MXPA06006037A - Organic compounds - Google Patents

Abstract

Disclosed are ?-amino-&ggr;-hydroxy-&ohgr;-aryl-alkanoic acid amide compounds of formula (I) and the salts thereof, having renin-inhibiting properties. Also disclosed are pharmaceutical compositions comprising these compounds and methods of administering them for the treatment of hypertension, atherosclerosis, unstable coronary syndrome, congestive heart failure, cardiac hypertrophy, cardiac fibrosis, cardiomyopathy postinfarction, unstable coronary syndrome, diastolic dysfunction, chronic kidney disease, hepatic fibrosis, complications resulting from diabetes, such as nephropathy, vasculopathy and neuropathy, diseases of the coronary vessels, restenosis following angioplasty, raised intra-ocular pressure, glaucoma, abnormal vascular growth, hyperaldosteronism, cognitive impairment, alzheimers, dementia, anxiety states and cognitive disorders.

Description

ORGANIC COMPOUNDS This invention relates to novel d-amino-α-hydroxy-α-aryl-alkanoic acid amides of Formula (I): wherein: R1 is hydrogen, halogen, optionally halogenated alkyl, cycloalkyl, hydroxyl, optionally halogenated alkoxy, cycloalkoxy, lower alkoxy-lower alkoxy, or carboxy-lower alkoxy or free lower alkyl or esterified or amidated; R2 is hydrogen, halogen, optionally halogenated lower alkyl, hydroxyl, cycloalkyl, cycloalkoxy, lower alkoxy-optionally halogenated lower alkyl, lower alkoxy-optionally substituted lower alkyl, cycloalkoxy-lower alkyl; lower hydroxy-lower alkoxy optionally lower alkanoylated, halogenated, or sulfonylated; amino-lower alkyl which is unsubstituted or substituted by lower alkyl, by lower alkanoyl, and / or by lower alkoxy-carbonyl, optionally hydrogenated heteroaryl-lower alkyl, lower amino-alkoxy which is substituted by lower alkyl, by lower alkanoyl, and / or by lower alkoxycarbonyl; oxo-lower alkoxy, lower alkoxy, lower alkenyloxy, cycloalkoxy-lower alkoxy, lower alkoxy-lower alkoxy, lower alkoxy-lower alkenyl, lower alkenyloxy-lower alkoxy, lower alkoxy-lower alkenyloxy, lower alkenyloxy-lower alkyl, lower alkanoxy-alkoxy lower, lower thioalkyl-optionally S-oxidized lower alkoxy, lower thioalkyl- (hydroxy) -lower alkoxy, aryl-lower alkoxy, arylalkyl, aryl-lower alkoxy, optionally hydrogenated heteroaryl-lower alkoxy, optionally hydrogenated heteroaryl-lower alkyl, cyano lower alkoxy, lower cyanoalkyl, free lower or esterified or amidated carboxy lower alkoxy, or free lower or esterified or amidated carboxy lower alkyl; R3 and R4 are independently hydrogen, halogen, optionally halogenated lower alkyl, hydroxyl, optionally halogenated lower alkoxy or cycloalkoxy, lower alkoxy-lower alkyl, cycloalkoxy-lower alkyl, hydroxy-lower alkyl, lower-thioalkyl-optionally S-oxidized lower alkyl, heterotioaryl optionally hydrogenated lower alkyl, heteroaryl-optionally hydrogenated lower alkyl; amino-lower alkyl that is unsubstituted or N-mono- or N, N-di-alkylated lower, N-lower alkanoylated, or N-lower alkane-sulfonylated, or N, N- disubstituted by lower alkylene, by unsubstituted lower aza-alkylene or lower N'-alkylated or lower N'-alkanoylated, by lower oxa-alkylene, or by optionally lower thia-alkylene S-oxidized, cyano-lower alkyl, carboxy-lower alkyl free or esterified or amidated, cycloalkyl, aryl, hydroxyl, lower alkoxy, cycloalkoxy, lower alkoxy-lower alkoxy, cycloalkoxy lower alkoxy, hydroxy lower alkoxy, aryl lower alkoxy, optionally halogenated lower alkoxy, lower thioalkyl-lower alkoxy optionally S -oxidated, optionally hydrogenated lower heteroaryl-lower alkoxy, optionally hydrogenated lower heteroxyaryl-lower alkoxy; lower amino-alkoxy which is unsubstituted or lower N-mono- or N, N-di-alkylated, lower N-alkanoylated, or lower-N-sulphonylated alkane, or substituted by lower alkylene, by unsubstituted lower aza-alkylene or N ' lower alkyl or lower N-alkanoylated, lower oxa-alkylene, or optionally lower S-oxidized thia-alkylene, lower cyano-lower alkoxy, or free lower or esterified or amidated carboxy-lower alkoxy; or R4, together with R3, is lower alkenoxyl, lower alkylene dioxy, or an aryl fused on, optionally hydrogenated heteroaryl or a cycloalkyl ring; X is methylene, hydroxymethylene, oxygen, nitrogen optionally substituted by lower alkyl, sulfur optionally oxidized; R5 is lower alkyl or cycloalkyl; R6 is hydrogen, lower alkyl, hydroxyl, alkoxy, or halogen; R7 is unsubstituted amino or N-mono- or N, N-dialkylated lower or N-lower alkanoylated; R8 is lower alkyl, lower alkenyl, cycloalkyl, or aryl-lower alkyl; R9 is optionally substituted lower alkyl, optionally substituted cycloalkyl, cycloalkyl-alkyl, cycloalkyl-carboxamides.cycloalkyl-carboxamides substituted by N-mono- or N, N-di-alkyl, optionally substituted arylalkyl, optionally substituted aryloxy-aryl, hetero optionally substituted aryloxy-alkyl, hydroxy-free lower alkyl or aliphatically esterified or etherified; amino-lower alkyl which is unsubstituted or lower N-alkanoylated or N-mono- or lower N, N-di-alkylated or N, N-di-substituted by lower alkylene, by hydroxy-, lower alkoxy-, or lower alkanoyloxy- lower alkylene, lower unsubstituted aza-alkylene or lower N'-alkanoylated or lower N-alkylated, lower oxa-alkylene, or optionally lower-thio-alkylene S-oxidized, carboxy-free lower alkyl or esterified or amidated, dicarboxy- free lower alkyl or esterified or amidated, carboxy-hydroxy-hydroxy-lower alkyl free or esterified or amidated, carboxy-cycloalkyl-free lower alkyl or esterified or amidated, cyano-lower alkyl, lower alkane-sulfonyl-lower alkyl, thiocarbamoyl-unsubstituted lower alkyl or N- mono- or N, N-di-alkylated lower, sulfamoyl-unsubstituted lower alkyl or N-mono- or lower N, N-di-alkylated, or a heteroaryl radical linked by means of a carbon atom and optionally hydrogenated and / or oxo-substituted, or lower alkyl substituted by a heteroaryl radical linked via of a carbon atom and optionally hydrogenated and / or oxo-substituted; and pharmaceutically acceptable salts thereof, to processes for the preparation of the compounds according to the invention, to pharmaceutical compositions containing them, and to their use as medicinal active ingredients. The compounds of the present invention exhibit an inhibitory activity on the natural renin enzyme. Accordingly, the compounds of Formula (I) can be used for the treatment of hypertension, atherosclerosis, unstable coronary syndrome, congestive heart failure, cardiac hypertrophy, cardiac fibrosis, post-infarct cardiomyopathy, unstable coronary syndrome, diastolic dysfunction, chronic disease. of the kidney, liver fibrosis, complications resulting from diabetes, such as nephropathy, vasculopathy and neuropathy, diseases of the coronary vessels, restenosis following angioplasty, elevated infraocular pressure, glaucoma, abnormal vascular growth, hyperaldosteronism, cognitive impairment, Alzheimer's disease, dementia, anxiety states, and cognitive disorders. The definitions of different terms used to describe the compounds of the present invention are listed below. These definitions apply to terms as they are used throughout the specification, unless otherwise limited in specific cases, either individually or as part of a larger group. Aryl and aryl in aryl-alkyl, aryl-lower alkoxy, aryl-lower alkyl, and the like, is, for example, phenyl or naphthyl which is unsubstituted or mono-, di-, or tri-substituted by lower alkyl, lower alkoxy optionally substituted with halogens, hydroxyl, lower alkyl-amino, di-lower alkyl-amino, halogen, and / or trifluoromethyl. Cycloalkoxy and cycloalkoxy in cycloalkoxy-lower alkoxy is, for example, cycloalkoxy of 3 to 8 members, preferably 3, 5, or 6 members, such as cyclo-propyloxy, cyclo-pentyloxy, cyclohexyloxy, and also cyclobutyloxy , cyclo-heptyloxy, or cyclo-octyloxy. Cycloalkyl and cycloalkyl in cycloalkyl-alkyl refers, for example, to monocyclic hydrocarbon groups, bicyclic, or tricyclics of 3 to 12 optionally substituted carbon atoms, each of which may be optionally substituted by one or more substituents, such as alkenyl, alkynyl, halogen, hydroxyl, alkoxy, alkoxy-alkoxy, thioalkyl, thioaryl, aryl -alkoxyl, carbamoyl, sulfamoyl, sulfonyl, optionally substituted amino, cyano, carboxyl, alkoxycarbonyl, aryl, aryloxy, heterocyclyl, or alkyl optionally substituted by amino, halogen, hydroxyl, alkoxy, carboxyl, carbamoyl, or heterocyclyl, and the like. Exemplary monocyclic hydrocarbon groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, and cyclohexenyl, and the like. Exemplary bicyclic hydrocarbon groups include bornyl, indyl, hexahydroindyl, tetrahydronaphthyl, decahydro-naphthyl, bicyclo- [2.1.1] -hexyl, bicyclo- [2.2.1] -heptyl, bicyclo- [2.2.1] -heptenyl, , 6-dimethyl-bicyclo- [3.1.1] -heptyl, 2,6,6-trimethyl-bicyclo- [3.1.1] -heptyl, bicyclo- [2.2.2] -octyl, and the like. Exemplary tricyclic hydrocarbon groups include adamantyl and the like. "Optionally substituted amino" refers to a primary or secondary amino group which optionally may be substituted, for example by acyl, sulfonyl, alkoxy- carbonyl, cycloalkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, aralkoxycarbonyl, heteroaralkoxycarbonyl, carbamoyl, and the like. Carbamoyl refers, for example, to H2NNC (0) -, alkyl-HNC (O) -, (alq ui I o) 2N H (O) -, ari I oN HC (O) -, alkyl- Cari I o) - NC (O) -, heteroaryl-NHC (O) -, alkyl- (heteroaryl) - NC (O) -, aralkyl-NHC (O) -, alkyl- (aralkyl) -NC (O) -, and sim Lares. Sulphamoyl refers, for example, to H2NS (0) 2-, alkyl-NHS (0) 2-, (alkyl) 2-NS (0) 2-, aryl-N HS (0) 2-, alkyl- ( aryl) -NS (0) 2-, (aryl) 2NS (0) 2-, hetero-aryl-NHS (0) 2-, hetero-aralkyl-N HS (0) 2-, and the like. Carboxy-free lower alkoxy or esterified or amidated is, for example, carboxy-lower alkoxy, lower alkoxy-carbonyl-lower alkoxy, carbamoyl-lower alkoxy, or N-mono- or N, N-di-lower alkyl-carbam oil- lower alkoxy. Lower optionally substituted, lower alkanoylated, halogenated, or sulfonylated lower alkoxy is, for example, lower alkanoyloxy-lower alkyl, hydroxy-lower alkoxy, halo- (hydroxy) -alkoxy, or lower alkane -sulfonyl- (hydroxy) - lower alkoxy. Amino-lower alkyl that is unsubstituted or substituted by lower alkyl, lower alkanoyl, and / or lower alkoxycarbonyl is, for example, amino-alkyl lower, lower alkyl-amino-lower alkyl, di-lower alkyl-amino-lower alkyl, lower alkanoyl-amino-lower alkyl, or lower alkoxy-carbon i-amino-lower alkyl. Amino lower alkoxy which is unsubstituted or substituted by lower alkyl, lower alkanoyl, and / or lower alkoxycarbonyl is, for example, amino-lower alkoxy, lower alkyl-amino-lower alkoxy, di-lower alkyl-amino-alkoxy lower, lower alkanoyl-amino-lower alkoxy, or lower alkoxy-carbonyl-amino-lower alkoxy. Lower thioalkyl-optionally S-oxidized lower alkoxy is, for example, lower thioalkyl-lower alkoxy, or lower alkane-sulfonyl-lower alkoxy. Optionally hydrogenated heteroaryl lower alkoxy is, for example, optionally partially hydrogenated or N-oxidized lower pyridyl-lower alkoxy, thiazolyl-lower alkoxy, or especially lower morpholino-lower alkoxy. Heterothioaryl-optionally hydrogenated lower alkoxy is, for example, optionally partially or completely hydrogenated heterothioaryl-lower alkoxy, such as thiothiazolyl-lower alkoxy or thiothiazolinyl-lower alkoxy, thioimidazolyl-lower alkoxy, thiopyridyl-lower alkoxy or thiopyrim idinyl-lower alkoxy optionally N - rusted Carboxy-free lower alkyl or esterified or oxidized is, for example, carboxy-lower alkyl, lower alkoxy-carbonyl-lower alkyl, carbamoyl-lower alkyl, or N-mono- or N, N-di-lower alkyl-carbamoyl-alkyl lower. Optionally halogenated lower alkyl is, for example, lower alkyl or poly-halo-lower alkyl. Lower optionally halogenated alkoxy is, for example, lower alkoxy or poly-halo lower alkoxy. Lower alkylthio-optionally S-oxidized lower alkyl is, for example, lower thioalkyl-lower alkyl, or lower alkane-sulfonyl-lower alkyl. Lower thioalkyl lower optionally S-oxidized lower alkoxy is, for example, lower thioalkyl-lower alkoxy, or lower alkane-sulfonyl lower alkoxy. Heteroaryl-optionally hydrogenated lower alkyl is, for example, optionally partially hydrogenated or N-oxidized pyridyl-lower alkyl. Heterothioaryl-optionally hydrogenated lower alkyl is, for example, thiothiazolyl-lower alkyl or thiothiazolinyl-lower alkyl, thioimidazolyl-lower alkyl, optionally N-oxidized -thiopyridyl-lower alkyl or thiopyrimidinyl-lower alkyl. Amino-lower alkyl that is unsubstituted or N-mono- or lower N, N-di-alkylated, N-lower alkanoylated, or N- lower alkylsulfonylated, or N, N-disubstituted by lower alkylene, by lower unsubstituted alkylene or lower N'-alkylated or lower N'-alkanoylated, by lower oxa-alkylene; or optionally S-oxidized lower thia-alkylene is, for example, amino-lower alkyl, lower alkyl-amino-lower alkyl, di-lower alkyl-amino-lower alkyl, lower alkanoyl-amino-lower alkyl, lower alkane-sulfonyl -amino-lower alkyl, polyhalo-lower alkane-sulfonyl-amino-lower alkyl, pyrrolidino-lower alkyl, piperidino-lower alkyl, piperazino-, N'-lower alkyl-piperazino-, or N'-lower alkanoyl-piperazino- lower alkyl; morpholino-lower alkyl, thiomorpholino-, S-oxo-thiomorpholino-, or S, S-dioxo-thiomorpholino-lower alkyl. Lower thioalkyl-optionally S-oxidized lower alkoxy is, for example, lower thioalkyl-lower alkoxy, or lower alkane-sulfonyl-lower alkoxy. Amino-lower alkoxy which is unsubstituted or N-mono- or lower N, N-di-alkylated, lower N-alkanoylated, or N-lower-sulfonylated, or N, N-disubstituted by lower alkylene, by lower aza-alkylene unsubstituted or lower N'-alkylated or lower N'-alkanoylated, by lower oxa-alkylene, or by optionally S-oxidized lower thia-alkylene is, for example, amino-lower alkoxy, lower alkyl-amino-lower alkoxy, di -lower-amino-lower alkoxy, lower alkanoyl-amino-lower alkoxy, lower alkane- sulfonyl-amino-lower alkoxy, polyhalo-lower alkane-sulfonyl-amino-lower alkoxy, pyrrolidino-lower alkoxy, piperidino-lower alkoxy, piperazino-, N'-lower alkyl-piperazino-, or N'-lower alkanoyl-piperazino- lower alkoxy; morpholino-lower alkoxy, thiomorpholino-, S-oxo-thiomorpholino, or S, S-dioxo-thiomorpholino-lower alkoxy. Unsubstituted amino or N-mono- or lower N, N-di-alkylated or lower N-alkanoylated is, for example, amino, lower alkyl-amino, di-lower alkyl-amino, or lower alkanoyl-amino. Free hydroxy-free or aliphatically esterified or etherified lower alkyl is, for example, hydroxy-lower alkyl, lower alkanoyloxy-lower alkyl, lower alkoxy-lower alkyl, or lower alkenyloxy-lower alkyl. Amino-lower alkyl which is unsubstituted or lower N-alkanoylated, lower N-mono- or N, N-di-alkylated, or N, N-disubstituted by lower alkylene, by hydroxy-, lower alkoxy-, or lower alkanoyloxy-alkylene lower, by unsubstituted lower aza-alkylene or lower N'-alkanoylated, by lower oxa-alkylene; or optionally S-oxidized lower thia-alkylene is, for example, amino-lower alkyl, lower alkanoyl-amino-lower alkyl, N-mono- or N, Nd i-al qui I or lower-amino-lower alkyl, piperidino optionally hydroxylated or alkoxylated lower alkyl lower, such as piperidino-lower alkyl, hydroxypiperidino-lower alkyl, or lower alkoxy-piperidino-lower alkyl, piperazino-, W-lower alkyl-piperazino-, or N'-lower alkanoyl-piperazino-lower alkyl; morpholino-unsubstituted or lower alkylated lower alkyl, such as morpholino-al. lower alkyl, or dimethyl-morpholino-lower alkyl; or thio-morpholino-optionally S-oxidized lower alkyl, such as thio-morpholino-lower alkyl or S, S-dioxo-thio-morpholino-lower alkyl. Dicarboxy-free lower alkyl or esterified or amidated is, for example, dicarboxy-lower alkyl, lower di-lower alkoxycarbonyl-lower alkyl, dicarbamoyl-lower alkyl, or di- (N-mono- or N, N-di- lower alkylcarbamoyl) -alkyl lower alkyl. Carboxy- (hydroxy) -free or esterified or amidated lower alkyl is, for example, carboxy (hydroxy) -lower alkyl, lower alkoxy-carbonyl- (hydroxy) -lower alkyl, or carbamoyl- (hydroxy) -lower alkyl. Carboxy-cycloalkyl-free lower alkyl or esterified or amidated is, for example, carboxy-cycloalkyl-lower alkyl of 5 or 6 members, lower alkoxy-carbonyl-cycloalkyl-lower alkyl, carbamyl-cycloalkyl-lower alkyl, or N- mono- or N, N-di-lower alkyl-carbamoyl-cycloalkyl-lower alkyl. Sulfamoyl-unsubstituted lower alkyl or N-mono- or Lower N, N-di-alkylated is, for example, sulfamoyl-lower alkyl, lower alkyl-sulfamoyl-lower alkyl, or di-lower alkyl-sulfamoyl-lower alkyl. Thiocarbamoyl-unsubstituted lower alkyl or lower N-mono- or N, N-di-alkylated is, for example, thiocarbamoyl-lower alkyl, lower alkyl-thiocarbamoyl-lower alkyl; or di-lower alkyl-thiocarbamoyl-lower alkyl, such as N, N-dimethyl-thiocarbamoyl-methyl. Previously herein and below, it should be understood that radicals and lower compounds are, for example, those having up to and including 7 carbon atoms, preferably up to and including 4 carbon atoms. Carboxy-cycloalkyl-lower alkyl of 5 or 6 members, lower alkoxyl-carbonyl-cycloalkyl-lower alkyl, carbamoyl-cycloalkyl-lower alkyl, N-mono- or N, N-di-lower alkyl-carbamoyl-cycloalkyl-lower alkyl is , for example,? - (1-carboxy-cycloalkyl) -alkyl of 1 to 4 carbon atoms,? - (1-lower alkoxy-carbonyl-cycloalkyl) -alkyl of 1 to 4 carbon atoms,? - (1 - carbamoyl-cycloalkyl) -alkyl of 1 to 4 carbon atoms,? - (1-lower alkyl-carbamoyl-cycloalkyl) -alkyl of 1 to 4 carbon atoms, or? - (1-di-lower alkyl-carbamoyl-cycloalkyl) ) -alkyl of 1 to 4 carbon atoms, wherein cycloalkyl is, for example, cyclopentyl or cyclohexyl; lower alkoxycarbonyl is, for example, alkoxy of 1 to 4 carbon atoms-carbonyl, such as methoxy- or ethoxycarbonyl; lower alkylcarbamoyl is, for example, alkyl of 1 to 4 carbon atoms-carbamoyl, such as methyl carbamoyl; di-lower alkylcarbamoyl is, for example, di-alkyl of 1 to 4 carbon atoms-carbamyl, such as di-methyl-carbamoyl; and lower alkyl is, for example, alkyl of 1 to 4 carbon atoms, such as methyl, ethyl, propyl, or butyl, especially (1-carboxy-cyclopentyl) -methyl. Cycloalkoxy-lower alkoxy of 5 or 6 members is, for example, cyclopentyloxy- or cyclohexyloxy-alkoxy of 1 to 4 carbon atoms, such as cyclopentyloxy- or cyclohexyloxy-methoxy, 2-cyclopentyloxy- or 2-cyclohexyloxy-ethoxy, 2- or 3-cyclopentyloxy- or 2- or 3-cyclohexyloxy-propyl loxyl, or 4-cyclopentyl-oxy- or 4-cyclohexyloxy-butyloxy, especially cyclopentyloxy- or cyclohexyloxy-methoxy. Cycloalkoxy-lower alkyl of 5 or 6 members is, for example, cyclopentyloxy- or cyclohexyloxy-alkyl of 1 to 4 carbon atoms, such as cyclopentyloxy- or cyclohexyloxy-methyl, 2-cyclopentyloxy- or 2-cyclohexyloxy-ethyl, 2- or 3-cyclopentyloxy- or 2- or 3-cyclohexyloxy-propyl, 2-cyclopentyloxy- or 2-cyclohexyloxy-2-methyl-propyl, 2-cyclopentyloxy- or 2-cyclohexyloxy-2-ethyl-butyl, or 4- cyclopentyloxy- or 4-cyclohexyloxy-butyl, especially cyclopentyloxy- or cyclohexyloxymethyl. Amino-lower alkoxy is, for example, amino- alkoxy of 1 to 4 carbon atoms, such as 2-amino-ethoxy or 5-amino-pentyloxy, and also 3-amino-pentyloxy or 4-a m i n o -b u t i I o x i I o. Amino-lower alkyl is, for example, aminoalkyl of 1 to 4 carbon atoms, such as 2-amino-ethyl, 3-amino-propyl, or 4-amino-butyl. Carbamoyl- (hydroxy) -lower alkyl is, for example, carbamoyl- (hydroxy) -alkyl of 1 to 7 carbon atoms, such as 1-carbamoyl-2-hydroxy-ethyl. Carbamoyl-lower alkoxy is, for example, carbamoyl-alkoxy of 1 to 4 carbon atoms, such as carbamoyl-methoxy, 2-carbamoyl-ethoxy, 3-carbamoyl-propyloxy, or 4-carbamoyl-butyloxy, especially carbamoyl-m ethoxy Carbamoyl-lower alkyl is, for example, carbamoyl-C 1-7 -alkyl, such as carbamoyl-methyl, 2-carbamoyl-ethyl, 3-carbamoyl-propyl, 2- (3-carbamoyl) -propyl, 2- carbamoyl-propyl, 3- (1-carbamoyl) -propyl, 2- (2-carbamoyl) -propyl, 2- (carbamoyl-2-methyl) -propyl, 4-carbamoyl-butyl, 1 -carbamoyl-butyl, 1- (1-carbamoyl-2-methyl) -butyl, 3- (4-carbamoyl-2-methyl) -butyl. Carboxy- (hydroxy) -lower alkyl is, for example, carboxy (hydroxy) -alkyl of 1 to 7 carbon atoms, such as 1-carboxy-2-hydroxy-ethyl. Carboxy-lower alkoxy is, for example, carboxy- C 1 -C 4 alkoxy, such as carboxymethoxy, 2-carboxy-ethoxy, 2- or 3-carboxy-propyloxy, or 4-carboxy-butyloxy, especially carboxy-methoxy. Carboxy-lower alkyl is, for example, carboxy-C 1-4 alkyl, such as carboxymethyl, 2-carboxy-ethyl, 2- or 3-carboxy-propyl, 2-carboxy-2-methyl-propyl. , 2-carboxy-2-ethyl-butyl, or 4-carboxy-butyl, especially carboxymethyl. Cyano-lower alkoxy is, for example, cyano-alkoxy of 1 to 4 carbon atoms, such as cyano-methoxy, 2-cyano-ethoxy, 2- or 3-cyano-propyloxy, or 4-cyano-butyloxy, in particular cyano-methoxy. Cyano-lower alkyl is, for example, cyano-alkyl of 1 to 4 carbon atoms, such as cyano-methyl, 2-cyano-ethyl, 2- or 3-cyano-propyl, 2-cyano-2-methyl-propyl. , 2-cyano-2-ethyl-butyl, or 4-cyano-butyl, especially cyano-methyl. Di- (N-mono- or N, N-di-lower alkyl-carbamoyl) -lower alkyl is, for example, di- (N-mono- or, N-di-alkyl of 1 to 4 carbon atoms-carbamoyl) ) -alkyl of 1 to 4 carbon atoms, such as 1,2-di- (N-mono- or N, N-di-alkyl of 1 to 4 carbon atoms-carbamoyl) -ethyl, or 1,3- di- (N-mono- or N, N-di-alkyl of 1 to 4 carbon atoms-carbam ori) -pro-pyl. Dicarbamoyl-lower alkyl is, for example, dicarbamoyl-alkyl of 1 to 4 carbon atoms, such as 1,2- dicarbamoyl-ethyl or 1,3-dicarbamoyl-propyl. Dicarboxy-lower alkyl is, for example, dicarboxy-alkyl of 1 to 4 carbon atoms, such as 1,2-dicarboxy-ethyl or 1,3-dicarboxy-propyl. Dimethyl-morpholino-lower alkoxy can be N-oxidized, and is, for example, 2,6-dimethyl-morphoino- or 3,5-dimethyl-morpholino-alkoxy of 1 to 4 carbon atoms, such as 2,6- dimethyl-morpholino- or 3,5-dimethyl-morpholino-methoxy, 2- (2,6-dimethyl-morpholino- or 3,5-dimethyl-morpholino) -ethoxy, 3- (2,6-dimethyl-morpholino-) 3,5-dimethyl-morpholine) -propyloxy, 2- (2,6-dimethyl-morpholino- or 3,5-dimethyl-morpholino-3-methy1) -propyloxy, or 1- or 2- [4- (2,6-dimethyl-morpholino- or 3,5-dimethyl-morpholino)] - butyloxy. Dimethyl-morpholino-lower alkyl can be N-oxidized, and is, for example, 2,6-dimethyl-morpholino- or 3,5-dimethyl-morpholino-alkyl of 1 to 4 carbon atoms, such as 2,6- dimethyl-morpholino- or 3,5-dimethyI-morpholino-methoxy, 2- (2,6-dimethyl-morpholino- or 3,5-dimethyl-morphino) -ethoxy, 3- (2,6-dimethyl-morpholino- or 3,5-dimethyl-m orfolino) -propyl, 2- (2,6-dimethyl-morpholino- or 3,5-dimethyl-morpholino-3-methyl) -propyl, or 1- or 2- [4- (2,6-dimethyl-morpholino- or 3,5-dimethyl-morpholino)] - butyl. Di-lower alkoxy-carbonyl-lower alkyl is, for example, lower di-lower alkoxycarbonyl-alkyl of 1 to 4 carbon atoms, such as 1,2-dimethoxy-carbonyl-ethyl, 1,3- dimethoxy-carbonyl-propyl, 1,2-dimethoxy-carbonyl-ethyl, or 1,3-diethoxy-carbonyl-propyl. Di-lower alkyl amino is, for example, di-alkyl of 1 to 4 carbon atoms ammo, such as dimethylamino, N-methyl-N-ethyl-amino, diethyl-amino, N-methyl-N -propyl-amino, or N-butyl-N-methyl-amino. Di-lower alkyl-amino-lower alkoxy is, for example, N-di-alkyl of 1 to 4 carbon atoms-amino-alkoxy of 1 to 4 carbon atoms, such as 2-dimethylamino-ethoxyl, -dimethyl-amino-propyloxy, 4-dimethyl-amino-butyloxy, 2-diethyl-amino-ethoxy, 2- (N-methyl-N-ethyl-amino) -ethoxy, or 2- (N-buty-N-methyl) -amino) -ethoxy. Di-lower alkyl-amino-lower alkyl is, for example, N, N-di-alkyl of 1 to 4 carbon atoms-amino-alkyl of 1 to 4 carbon atoms, such as 2-dimethyl-amino-ethyl, 3-dimethyl-amino-propyl, 4-dimethyl-amino-butyl, 2-diethyl-amino-ethyl, 2- (N-methyl-N-ethyl-amino) -ethyl, or 2- (N-butyl-N- methyl-amino) -ethyl. Di-lower alkyl-carbamoyl-lower alkoxy is, for example, N, N-di-alkyl of 1 to 4 carbon atoms-carbamoyl-alkoxy of 1 to 4 carbon atoms, such as methyl- or dimethyl-carbamoyl-alkoxy from 1 to 4 carbon atoms, such as N-methyl-, N-butyl-, or N, N-dimethyl-carbam or i-methoxy, 2- (N-methyl-carbamoyl) -ethoxy, 2- ( N-butyl carbamoyl) -ethoxy, 2- (N, N-dimethyl-carbamoyl) -ethoxy, 3- (N-methyl- carbamoyl) -propyloxy, 3- (N-butyl-carbamoyl) -propyloxy, 3- (N, N-dimethyl-carbamoyl) -propyloxy, or 4- (N-methyl-carbamoyl) -butyloxy, 4- (N-butyl) -carbamoyl) -butyloxyl, or 4- (N, N-dimethylcarbamoyl) -butyloxyl, especially N-methyl-, N-butyl-, or N, N-dimethyl-carbamoyl-methoxy. Di-lower alkyl-carbamyl-lower alkyl is, for example, N, N-di-alkyl of 1 to 4 carbon atoms-carbamoyl-alkyl of 1 to 4 carbon atoms, such as 2-dimethyl-carbamoyl-ethyl , 3-dimethyl-carbamoyl-propyl, 2-dimethyl-carbamoyl-propyl, 2- (dimethyl-carbamoyl-2-methyl) -propyl, or 2- (1-dimethyl-carbamoyl) -3-methyl) -butyl. Di-lower alkyl-sulfamoyl-lower alkyl is, for example, N, N-di-alkyl of 1 to 4 carbon atoms-sulfamoyl-alkyl of 1 to 4 carbon atoms, N, N-dimethyl-sulfamino - Alkyl from 1 to 4 carbon atoms, such as N, N-dimethyl-sulphamoM-methyl, 2- (N, N-dimethyI-carbamoyl) -ethyl, 3- (N, N-dimethyl-carbamoyl) -propy , or 4- (N, N-dimethyl-carbamoyl) -butyl, especially N, N-dimethyl-carbamoyl-methyl. Piperidyl-unsubstituted or lower N-alkanoylated lower alkyl is, for example, lower 1-lower alkanoyl of 1 to 7 carbon atoms-piperidin-4-yl-alkyl of 1 to 4 carbon atoms, such as 1-acetyl-piperidinyl- methyl, 2- (1-acetyl-piperidinyl) -ethyl. Optionally partially hydrogenated or N-oxidized lower pyridyl-lower alkoxy is, for example, pyridyl- or N-oxide- optionally partially hydrogenated C 1 -C 4 pyridyl-alkoxy, such as pyridyl- or N-oxide-pyridyl-methoxy, 2-pyridyl-ethoxy, 2- or 3-pyridyl-1-propyloxy, or 4-pyridyl-butyloxy, especially 3- or 4-pyridyl-methoxy. Pyridyl-optionally partially hydrogenated or N-oxidized lower alkyl is, for example, pyridyl- or N-oxide-pyridyl-alkyl of 1 to 4 carbon atoms optionally partially hydrogenated, such as pyridyl- or N-oxide-pyridyl-methyl, 2-pyridyl-ethyl, 2- or 3-pyridyl-propyl, or 4-pyridyl-butyl, especially 3- or 4-pyridyl-methyl. Halo- (hydroxy) -lower alkoxy is, for example, halo- (hydroxy) -alkoxy of 2 to 7 carbon atoms, especially halo- (hydroxy) -alkoxy of 2 to 4 carbon atoms, such as 3-halo -, such as 3-chloro-2-hydroxy-propyloxy. Hydroxy-lower alkoxy is, for example, hydroxy-alkoxy of 2 to 7 carbon atoms, especially hydroxy-alkoxy of 2 to 4 carbon atoms, such as 2-hydroxy-butyloxy, 3-hydroxy-propyloxy, or 4- hydroxybutyloxy Hydroxy-lower alkyl is, for example, hydroxyalkyl of 2 to 7 carbon atoms, especially hydroxyalkyl of 2 to 4 carbon atoms, such as 2-hydroxy-ethyl, 3-hydroxy-propyl, or 4-hydroxy-butyl. Hydroxy-piperidino-lower alkyl is, for example, 3- or 4-hydroxy-piperidino-alkoxy of 1 to 4 carbon atoms, such as 3- or 4-hydroxy-piperidino-methoxy, 2- (3- or 4-) hydroxy- piperidino) -ethoxy, 3- (3- or 4-hydroxy-piperidino) -propyloxy, or 4- (3- or 4-hydroxy-piperidino) -butyloxyl. Imidazolyl-lower alkyl is, for example, imidazolyl-C 1 -C 4 -alkyl, such as midazole-4-M-methyl, 2- (imidazol-4-yl) -ethyl, 3- (imidazol-4-) il) -propyl, or 4- (imidazol-4-yl) -butyl. Imidazolyl-lower alkoxy is, for example, imidazolyl-alkoxy of 1 to 4 carbon atoms, such as midazol-4-yl-methoxy, 2- (imidazol-4-yl) -ethoxy, 3- (midazole-4) -yl) -propyloxyl, or 4- (imidazol-4-yl) -butyloxyl. Imidazolyl-lower alkyl is, for example, imidazolyl-C 1 -C 4 -alkyl, such as imidazole-4-methyl, 2- (imidazol-4-yl) -ethyl, 3 - (imidazo I-4-i) ) -propyl, or 4- (imidazol-4-yl) -butyl. Morph oli non-carbonyl-lower alkyl is, for example, morpholino-carbonyl-alkyl of 1 to 4 carbon atoms, such as 1-morpholino-carbonyl-ethyl, 3-morpholino-carbonyl-propyl, or 1- (morpholino- carbonyl-2-methyl) -propyl. Morpholino-lower alkoxy can be N-oxidized, and is, for example, morpholino-alkoxy of 1 to 4 carbon atoms, such as 1-morpholino-ethoxy, 3-m-orpholino-propyloxy, or 1 - (m-orpholino-2) -methyl) -propyloxyl. Morpholino-lower alkyl can be N-oxidized, and is, for example, morpholino-alkyl of 1 to 4 carbon atoms, such as morpholino-methyl, 2-morpholino-ethyl, 3- morpholino-propyl, or 1- or 2- (4-morpholino) -butyl. Lower alkanoyl is, for example, alkanoyl of 1 to 7 carbon atoms, especially alkanoyl of 2 to 6 carbon atoms, such as acetyl, propionyl, butyryl, isobutyryl, or pivaloyl. Lower alkanoyl amino is, for example, N-alkanoyl of 1 to 7 carbon atoms-amino, such as acetylamino or pivaloyl-amino. Lower alkanoyl amino is, for example, N-alkanoyl of 1 to 7 carbon atoms-amino, such as acetylamino or pivaloyl-amino. Lower alkanoyl-amino-lower alkyl is, for example, N-alkanoyl of 1 to 4 carbon atoms-amino-alkyl of 1 to 4 carbon atoms, such as 2-acetoxy-amino-ethyl. Lower alkanoyl-amino-lower alkyl is, for example, N-alkanoyl of 1 to 4 carbon atoms-amino-alkyl of 1 to 4 carbon atoms, such as 2-acetoxy-amino-ethyl. Lower alkanoyl-lower alkoxy (lower oxo-lower alkoxy) carries the lower alkanoyl group in a higher position than the -al position, and is, for example, alkanoyl of 1 to 7 carbon atoms-alkoxy of 1 to 4 carbon atoms , such as 4-acetyl-butoxyl. Lower alkanoxyloxy-lower alkyl leads the group lower alkanoyloxy in a position higher than position-a, and is, for example, alkanoyloxy of 1 to 7 carbon atoms-alkyl of 1 to 4 carbon atoms, such as 4-acetoxy-butyl. Lower alkanesulfonyl- (hydroxy) -alkoxyl lower is, for example, alkane of 1 to 7 carbon atoms-sulphonyl- (hydroxy) -alkoxyl of 1 to 4 carbon atoms, such as 3-methanesulfonyl- 2-hydroxy-propyloxy Lower alkyl sulfonyl lower alkoxy is, for example, alkane of 1 to 7 carbon atoms-sulfonyl-alkoxy of 1 to 4 carbon atoms, such as methanesulfonyl-methoxy, or 3-methanesulfonyl-2- hydroxy-propyloxy Lower alkane-sulfonyl-amino-lower alkoxy is, for example, alkane of 1 to 7 carbon atoms-sulfonyl-amino-alkoxy of 1 to 4 carbon atoms, such as ethanesulfonyl-amino-methoxy, 2-ethane -sulfonyl-amino-ethoxy, 3-ethanesulfonyl-amino-propyloxy, or 3- (1,1-dimethyl-ethansulfonyl-amino) -propyl I oxy. Lower alkanesulfonyl-amino-lower alkyl is, for example, alkane of 1 to 7 carbon atoms-sulfonyl-amino-alkyl of 1 to 4 carbon atoms, such as ethanesulfonyl-amino-methyl, -ethan-su If onil-am ino-ethyl, 3-ethansulfonyl-amino-propyl, or 3- (1,1-d-imethyl-ethanesulfonyl-amino) -propyl. Lower alkane-sulfonyl-lower alkyl is, by example, alkane of 1 to 7 carbon atoms-sulfonyl-alkyl of 1 to 4 carbon atoms, such as ethanesulfonyl-methyl, 2-ethansulfonyl-ethyl, 3-ethanesulfonyl-propyl, or - (1,1-dimethyl-ethanesulfonyl) -propyl. Lower alkenyl is, for example, alkenyl of 1 to 7 carbon atoms, such as vinyl or allyl. Lower alkenyloxy is, for example, alkenyloxy of 1 to 7 carbon atoms, such as allyloxy. Lower alkenyloxy-lower alkoxy is, for example, alkenyloxy of 1 to 7 carbon atoms-alkoxy of 1 to 4 carbon atoms, such as allyloxy-methoxy. Lower alkenyloxy-lower alkyl is, for example, alkenyloxy of 1 to 7 carbon atoms-alkyl of 1 to 4 carbon atoms, such as allyloxymethyl. Lower alkoxy is, for example, alkoxy of 1 to 7 carbon atoms, preferably alkoxy of 1 to 5 carbon atoms, such as methoxy, ethoxy, propyloxy, isopropyloxy, butyloxy, butyloxy, secondary butyloxy, Tertiary lutyloxy, pentyloxy, or a hexyloxy or heptyloxy group Lower alkoxycarbonyl is, for example, C 1 -C 7 alkoxycarbonyl, preferably C 1 -C 5 alkoxycarbonyl, such as methoxycarbonyl , ethoxy-carbonyl, prop i lox i -ca iri bonyl, isopropyloxy-carbonyl, butyloxy-carbonyl, isobutyloxy-carbonyl, butyloxy secondary carbonyl, tertiary butyloxy, pentyloxycarbonyl, or a hexyl loxylcarbonyl or heptyloxycarbonyl group. Lower alkoxy-carbonyl (hydroxy) -lower alkyl is, for example, alkoxy of 1 to 4 carbon atoms-carbonyl (hydroxy) -alkyl of 1 to 7 carbon atoms, such as 1-methoxy-carbonyl- or -ethoxy-carbonyl-2-hydroxy-ethyl. Lower alkoxyl-carbonyl-amino-lower alkoxy is, for example, alkoxy of 1 to 7 carbon atoms-carbonyl-amino-alkoxy of 2 to 7 carbon atoms, preferably alkoxy of 2 to 5 carbon atoms-carbonyl-amino -alkoxy of 2 to 7 carbon atoms, such as methoxy-carbonyl-amino-alkoxy of 2 to 7 carbon atoms, ethoxy-carbonyl-amino-alkoxy of 2 to 7 carbon atoms, propyloxy-carbonyl-amino-alkoxy 2 to 7 carbon atoms, isobutyloxy-carbonyl-amino-alkoxy of 2 to 7 carbon atoms, butyloxy-carbonyl-amino-alkoxy of 2 to 7 carbon atoms, iso-butyloxy-carbonyl-amino-alkoxy of 2 to 7 carbon atoms, secondary butyloxy-carbonyl-amino-alkoxy of 2 to 7 carbon atoms, or tertiary butyloxy-amino-alkoxy of 2 to 7 carbon atoms, wherein alkoxy of 2 to 7 carbon atoms is, for example, methoxy, ethoxy, propyloxy, butyloxy, pentyloxy, or hexyloxy. Lower alkoxyl-carbonyl-amino-lower alkyl is, for example, alkoxy of 1 to 7 carbon atoms-carbonyl-amino-alkyl of 2 to 7 carbon atoms, preferably C 2 -C 5 alkoxycarbonyl-amino-C 2 -C 7 -alkoxy, such as methoxy-carbonyl-alkyl of 2 to 7 carbon atoms, ethoxy-carbonyl-amino-alkyl of 2 to 7 carbon atoms carbon, propyloxy-carbonyl-amino-alkyl of 2 to 7 carbon atoms, isopropyloxy-carbonyl-amino-alkyl of 2 to 7 carbon atoms, butyloxy-carbonyl-amino-alkyl of 2 to 7 carbon atoms, isobutyloxy-carbonyl -amino-alkyl of 2 to 7 carbon atoms, secondary butyloxy-carbonyl-amino-alkyl of 2 to 7 carbon atoms, or tertiary butyloxy-amino-alkyl of 2 to 7 carbon atoms, wherein alkyl of 2 to 7 carbon atoms; to 7 carbon atoms is, for example, methyl, ethyl, propyl, butyl, pentyl, or hexyl. Lower alkoxyl-carbonyl-lower alkoxy is, for example, alkoxy of 1 to 4 carbon atoms-carbonyl-alkoxy of 1 to 4 carbon atoms, such as methoxy-carbonyl- or ethoxy-carbonyl-methoxy, 2-methoxy-carbon M - or 2-ethoxy-carbonyl-ethoxy, 2- or 3-methoxy-carbonyl- or 2- or 3-ethoxycarbonyl-propyloxy, or 4-methoxy-carbonyl- or 4-ethoxycarbonyl-utiloxy, especially methoxy-carbonyl- or ethoxy-carbonyl-methoxy or 3-methoxy-carbonyl- or 3-ethoxy-carbonyl-propyloxy. Lower alkoxyl-carbonyl-lower alkyl is, for example, alkoxy of 1 to 4 carbon atoms-carbonyl-alkyl of 1 to 4 carbon atoms, such as methoxy-carbonyl- or ethoxy-carbonyl-methoxy, 2-methoxy-carbonyl - or 2-ethoxy-carbonyl-ethoxy, 3-methoxy-carbonyl- or 3-ethoxy-carbonyl-propyloxy, or 4- ethoxy-carbonyl-butyloxy Lower alkoxy-lower alkenyl is, for example, alkoxy of 1 to 4 carbon atoms-alkenyl of 2 to 4 carbon atoms, such as 4-methoxy-but-2-enyl. Lower alkoxyl-lower alkoxy is, for example, alkoxy of 1 to 4 carbon atoms-alkoxy of 2 to 4 carbon atoms, such as 2-methoxy-, 2-ethoxy-, or 2-propyloxy-ethoxy, 3-methoxy - or 3-ethoxy-propyloxy, or 4-methoxy-butyloxy, especially 3-methoxy-propyloxy or 4-methoxy-butyloxy. Lower alkoxy-lower alkoxy-lower alkyl is, for example, alkoxy of 1 to 4 carbon atoms-alkoxy of 1 to 4 carbon atoms-alkyl of 1 to 4 carbon atoms, such as 2-methoxy-, 2-ethoxy -, or 2-propyloxy-ethoxy-methyl, 2- (2-methoxy-, 2-ethoxy-, or 2-propyloxy-ethoxy) -ethyl, 3- (3-methoxy- or 3-ethoxy- propyloxy) -propyl, or 4- (2-methoxy-butyloxy) -butyl, especially 2- (3-methoxy-propyloxy) -ethyl or 2- (4-methoxy-butyloxy) -ethyl. Lower alkoxy-lower alkyl is, for example, alkoxy of 1 to 4 carbon atoms-alkyl of 1 to 4 carbon atoms, such as ethoxy-methyl, propyloxy-methyl, butyloxy-methyl, 2-methoxy-, 2-ethoxy -, or 2-propyloxy-ethyl, 3-methoxy- or 3-ethoxy-propyl, or 4-methoxy-butyl, especially 3-methoxy-propyl or 4-methoxy-butyl. Lower alkoxy-piperidino-lower alkyl is, for example, piperidino-, hydroxy-piperidino-, or lower alkoxy- piperidino-C 1 -C 4 -alkyl, such as piperidino-methyl, 4-hydroxy-piperidino-methyl, or 4-alkoxy-1 to 4-carbon atoms, such as 4-methoxy-piperidino-methyl. Lower alkoxyl-piperidino-lower alkyl is, for example, alkoxy of 1 to 4 carbon atoms-piperidino-alkyl of 1 to 4 carbon atoms, such as 4-alkoxy of 1 to 4 carbon atoms-piperidino-methyl, in special 4-methoxy-piperidino-methyl. Lower alkyl may be straight or branched chain, and / or may be bridged, and is, for example, the corresponding alkyl of 1 to 7 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secondary butyl. , or tertiary butyl, or a pentyl, hexyl, or heptyl group. Lower alkyl as R2 or R3 is in particular alkyl of 2 to 7 carbon atoms, lower alkyl as R5 or R7 is especially alkyl of 3 to 7 carbon atoms branched, and lower alkyl as R8 or R3 is, for example, alkyl 3 to 7 carbon atoms straight chain, branched, or bridged. Lower-amino alkyl is, for example, alkyl of 1 to 4 carbon atoms-amino, such as methyl-amino, ethyl-amino, propyl-amino, butyl-amino, isobutyl-amino, secondary-amino butyl, or tertiary butyl. -Not me. Lower alkyl-amino-lower alkoxy is, for example, alkyl of 1 to 4 carbon atoms-am ino-alkoxy from 1 to 4 carbon atoms, such as propyl-amino-methoxy, 2-methyl-amino-, 2-ethyl-amino-, 2-propyl-amino-, or 2-butyl-amino-ethoxy, 3-ethyl- amino-, or 3-propyl-amino-propyloxy, or 4-methyl-amino-butoxy. Lower alkyl-amino-lower alkyl is, for example, alkyl of 1 to 4 carbon atoms-amino-alkyl of 1 to 4 carbon atoms, such as propyl-amino-methyl, 2-methyl-amino-, 2-ethylene. -amino-, 2-propyl-amino-, or 2-butyl-amino-ethyl, 3-ethyl-amino- or 3-propyl-amino-propyl, or 4-methyl-amino-butyl. Lower alkyl-carbamoyl-lower alkoxy is, for example, N-alkyl of 1 to 7 carbon atoms-carbamoyl-alkoxy of 1 to 4 carbon atoms, such as methyl- or d-imethyl-carbamoyl-1-alkoxy from 1 to 4. carbon atoms, for example methylcarbamyl ether-methoxy, 2-methylcarbamoyl-1-ethoxy, or 3-methylcarbamoyl-propyloxy. Lower alkylenedioxyl is, for example, methylene dioxyl or ethylene dioxyl, but it can also be 1,3- or 1,2-propylene dioxyl. Lower alkyl sulfamoyl lower alkyl is, for example, N-alkyl of 1 to 7 carbon atoms-sulfamoyl-alkyl of 1 to 4 carbon atoms, such as N-methyl-, N-ethyl-, N-propyl- , or N-butyl-sulfamoyl-alkyl of 1 to 4 carbon atoms, such as N-methyl-, N-ethyl-, N-propyl-, or N-butyl-sulfamoyl-methyl, 2- (N-methyl- sulfamoyl) -ethyl, 2- (N-butyl- sulfamoyl) -ethyl, 3- (N-methyl-sulfamoyl) -propyl, 3- (N-butyl-sulfamoyl) -propyl, or 4- (N-methyl-sulfamoyl) -butyl, 4- (N-butylsulfamoyl) ) -butyl, or 4- (N, N-dimethyl-sulfamoyl) -butyl, especially N-methyl-, N-butyl-, or N, N-dimethyl-sulfamoyl-methyl. Lower erigene- (hydroxy) -alkoxyl lower alkylthio is, for example, N-thioalkyl of 1 to 4 carbon atoms- (hydroxy) -alkoxy of 1 to 4 carbon atoms, such as 2-hydroxy-3-thiomethyl- propyloxyl Oxazolyl-lower alkyl is, for example, oxazolyl-alkyl of 1 to 4 carbon atoms, such as 2- (1,2,4-oxadiazol-5-yl) -ethyl, 3- (1, 2,4-oxadiazole) -5-yl) -propyl, or 4- (1,2,4-oxadiazol-5-yl) -butyl. Lower thioalkyl-lower alkoxy is, for example, N-thioalkyl of 1 to 4 carbon atoms-alkoxy of 1 to 4 carbon atoms, such as thiomethyl-alkoxy of 1 to 4 carbon atoms, for example, thiomethyl-methoxy, -thiomethyl-ethoxy, or 3-thiomethyl-propyloxy. Lower alkylthio lower alkyl is, for example, N-thioalkyl of 1 to 4 carbon atoms-alkyl of 1 to 4 carbon atoms, such as thiomethyl-alkyl of 1 to 4 carbon atoms, for example thiomethyl-methyl, -thiomethyl-ethyl, or 3-thiomethyl-propyl. N'-lower alkanoyl-piperazino-lower alkoxy is, for example, N'-lower alkanoyl-piperazino-alkoxy of 1 to 4 carbon atoms, such as 4-acetyl-piperazino-methoxy.

N'-lower alkanoyl-piperazino-lower alkyl is, for example, N'-lower alkanoyl of 2 to 7 carbon atoms-piperazino-alkyl of 1 to 4 carbon atoms, such as 4-acetyl-piperazino-methyl. N'-lower alkyl-piperazino-lower alkyl is, for example, N'-alkyl of 1 to 4 carbon atoms-piperazino-alkyl of 1 to 4 carbon atoms, such as 4-methyl-piperazino-methyl. Oxo-lower alkoxy is, for example, oxo-alkoxy of 1 to 4 carbon atoms, such as 3,3-dimethyl-2-oxo-butyloxy. Piperazino-lower alkyl is, for example, piperazino-alkyl of 1 to 4 carbon atoms, such as piperazino-2-methyl, 2-piperazino-ethyl, or 3-piperazino-propyl. Piperidino-lower alkoxy is, for example, piperidino-alkoxy of 1 to 4 carbon atoms, such as piperidino-methoxy, 2-piperidino-ethoxy, or 3-piperidino-propyloxy. Piperidino-lower alkyl is, for example, piperidino-alkyl of 1 to 4 carbon atoms, such as piperidino-methyl, 2-pi peridino-ethyl, or 3-piperidino-propyl. Poly-halo-lower alkane-sulfonyl-amino-lower alkoxy is, for example, trifluoro-alkane of 1 to 7 carbon atoms-sulfonyl-alkoxy of 1 to 4 carbon atoms, as trifluoro-methansulfonyl-amino-butyloxy. Poly-halo-lower alkane-sulfonyl-amino-lower alkyl is, for example, trifluoro-alkane of 1 to 7 carbon atoms-sulfonyl-alkyl of 1 to 4 carbon atoms, such as trifluoro-methanesulfonyl-amino- butyl. Lower pyrimidinyl-alkoxy is, for example, pyrimidinyl-alkoxy of 1 to 4 carbon atoms, such as pyrimidinyl-methoxy, 2-pyrimidinyl-ethoxy, or 3-pyrimidinyl-propyloxy. Pyrimidinyl-lower alkyl is, for example, pyrimidinyl-alkyl of 1 to 4 carbon atoms, such as pyrimidinyl-methyl, 2-pyrimidinyl-ethyl, or 3-pyrimidinyl-propyl. Pyrrolidino-lower alkoxy is, for example, pyrrolidino-alkoxy of 2 to 4 carbon atoms, such as 2-pyrrolidino-ethoxy or 3-pyrrolidino-propyloxy. Pyrrolidino-lower alkyl is, for example, pyrrolidino-alkyl of 1 to 4 carbon atoms, such as non-methyl pi-rrolidi, 2-pyrrolidino-ethyl, or 3-pyrrolidino-propyl. S, S-dioxo-thiomorpholino-lower alkyl is, for example, S, S-dioxo-thiomorpholino-alkyl of 1 to 4 carbon atoms, such as S, S-dioxo-thiomorpholino-methyl, or 2- (S, S-dioxo) -thiomorpholino-ethyl. S-oxo-thiomorpholino-lower alkyl is, for example, S-oxo-thiomorpholino-alkyl of 1 to 4 carbon atoms, such as S-oxo-thiomorpholino-methyl, or 2- (S-oxo) -thiomorpholino- ethyl. Sulfamoyl-lower alkyl is, for example, sulfamoyl-C 1-4 -alkyl, such as sulfamoyl-methyl, 2-sulfamoyl-ethyl, 3-sulfamoyl-propyl., or 4- sulfamoyl-butyl. Tetrazolyl-lower alkyl is, for example, tetrazolyl-alkyl of 1 to 4 carbon atoms, such as tetrazol-5-yl-methyl, 2- (tetrazol-5-yl) -ethyl, 3- (tetrazol-5-yl) ) -propyl, or 4- (tetrazol-4-yl) -butyl. Thiazolinyl-lower alkoxy is, for example, thiazolinyl-alkoxy of 1 to 4 carbon atoms, such as thiazolinyl-methoxy, 2-thiazolinyl-methoxy, or 3-thiazolinyl-propyloxy. Thiazolinyl-lower alkyl is, for example, thiazolinyl-alkyl of 1 to 4 carbon atoms, such as thiazolinyl-methyl, 2-thiazolidinyl-ethyl, or 3-thiazolinyl-propyl. Thiazolyl-lower alkoxy is, for example, thiazolyl-alkoxy of 1 to 4 carbon atoms, such as thiazolyl-methoxy, 2-thiazolyl-ethoxy, or 3-thiazolyl-propyloxy. Thiazolyl-lower alkyl is, for example, thiazolyl-alkyl of 1 to 4 carbon atoms, such as ti azoli l-m eti I, 2-thiazolyl-ethyl, or 3-thiazolyl-propyl. Thiomorpholino-lower alkyl or S, S-dioxo-thiomorph olino-lower alkyl is, for example, thiomorpholino-alkyl of 1 to 4 carbon atoms, such as -methyl or -ethyl, or S, S-dioxo-thiomorpholino-alkyl of 1 to 4 carbon atoms, such as -methyl or -ethyl. Depending on whether asymmetric carbon atoms are present, the compounds of the invention may be present as mixtures of isomers, especially as racemates, or in the form of pure isomers, especially optical antipodes. The salts of the compounds having salt-forming groups are especially the acid addition salts, the salts with bases, or, when several salt-forming groups are present, they can also be mixed salts or internal salts. The salts are in particular the pharmaceutically acceptable or non-toxic salts of the compounds of the formula (I). These salts are formed, for example, by the compounds of Formula (I) having an acidic group, for example a carboxyl group or a sulfo group, and are, for example, salts thereof with suitable bases, such as the salts of non-toxic metals derived from the metals of groups la, Ib, Na, and llb of the Periodic Table of the Elements, for example the alkali metal salts, especially the lithium, sodium, or potassium salts; or the alkaline earth metal salts, for example the magnesium or calcium salts; also zinc salts or salts of ammonium, as well as salts formed with organic amines, such as unsubstituted or hydroxy-substituted mono-, di-, or tri-alkyl-amines, especially mono-, di-, or tri-lower alkyl-amines; or with quaternary ammonium bases, for example, with methyl-, ethyl-, diethyl-, or triethylamine; mono-, bis-, or tris- (2-hydroxy-lower alkyl) -amines, such as ethanol-, diethanol-, or triethanolamine; tris- (hydroxy-methyl) -methyl-amine or 2-hydroxy-tert-butyl-amines; N, N-di-lower alkyl-N- (hydroxy-lower alkyl) -amines, such as N, Nd-imethyl-N- (2-hydroxy-ethyl) -amine or N-methyl-D-glucamine; or quaternary ammonium hydroxides, such as tetrabutylammonium hydroxide. Compounds of Formula (I) having a basic group, for example an amino group, can form acid addition salts, for example, with suitable inorganic acids, for example hydrohalic acids, such as hydrochloric acid or hydrobromic acid.; or sulfuric acid with replacement of one or both protons; phosphoric acid with replacement of one or more protons, for example orthophosphoric acid or metaphosphoric acid; or pyrophosphoric acid with replacement of one or more protons; or with organic, sulfonic, sulfo, or phosphonic carboxylic acids; or N-substituted sulfamic acids, for example acetic acid, propionic acid, glycolic acid, succinic acid, maleic acid, hydroxymaleic acid, methylmaleic acid, fumaric acid, malic acid, tartaric acid, gluconic acid, acid glucaric, glucuronic acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, salicylic acid, 4-amino-salicylic acid, 2-phenoxy-benzoic acid, 2-acetoxybenzoic acid, embonic acid, nicotinic acid, or isonicotinic acid , as well as with amino acids, such as the a-amino acids mentioned hereinabove; and with methanesulfonic acid, ethanesulfonic acid, 2-hydroxy-ethanesulfonic acid, ethane-1,2-disulfonic acid, benzenesulfonic acid, 4-toluenesulfonic acid, naphthalene-2-sulfonic acid, - or 3-phosphoglycerate, glucose-6-phosphate, or N-cyclohexyl-sulfamic acid (forming cyclamates); or with other acidic organic compounds, such as ascorbic acid. Compounds of Formula (I) having acidic and basic groups can also form internal salts. For the purposes of isolation and purification, it is also possible to use pharmaceutically unacceptable salts. The compounds of the present invention have enzyme inhibiting properties. In particular, they inhibit the action of the natural renin enzyme. The latter passes from the kidneys to the blood, where it dissociates the angiotensinogen, releasing the decapeptide angiotensin I, which then dissociates in the lungs, kidneys, and other organs, to form the octapeptide angiotensinogen II. Octapeptide increases blood pressure both directly by arterial vasoconstriction, as indirectly by the release from the adrenal glands of the aldosterone hormone that retains the sodium ion, accompanied by an increase in extracellular fluid volume. This increase can be attributed to the action of angiotensin 11. Inhibitors of the enzymatic activity of renin cause a reduction in the formation of angiotensin I. As a result, a smaller amount of angiotensin II is produced. The reduced concentration of this active peptide hormone is the direct cause of the hypotensive effect of renin inhibitors. Accordingly, the compounds of the present invention can be used for the treatment of hypertension, atherosclerosis, unstable coronary syndrome, congestive heart failure, cardiac hypertrophy, cardiac fibrosis, post-infarct cardiomyopathy, unstable coronary syndrome, diastolic dysfunction, chronic kidney disease. , liver fibrosis, complications resulting from diabetes, such as nephropathy, vasculopathy and neuropathy, diseases of the coronary vessels, restenosis following angioplasty, elevated intraocular pressure, glaucoma, abnormal vascular growth, hyperaldosteronism, cognitive impairment, Alzheimer's disease, dementia, states of anxiety, and cognitive disorders.

The groups of compounds mentioned below should not be considered as exclusive; rather, for example, in order to replace the general definitions with more specific definitions, the parts of these groups of compounds can be exchanged for the definitions given above, or they can be omitted, as appropriate. Preferred are compounds of Formula (I), designated as group A, wherein: R9 is lower alkyl, optionally substituted cycloalkyl (alkyl, OH, alkoxy, alkoxy-alkano, halogen), optionally substituted cycloalkyl-alkyl (OH , alkoxy, alkoxy-alkyl, halogen, or cycloalkyl), cycloalkyl-carboxamides, cycloalkyl-carboxamides N-mono- or N, N-di-alkyl-substituted, aryl-alkyl optionally substituted, hydroxy-lower alkyl free or aliphatically esterified or etherified; amino-lower alkyl which is unsubstituted or lower N-alkanoylated or lower N-mono- or N, N-di-alkylated, or N, N-di-substituted by lower alkylene, by hydroxy-, lower alkoxy-, or lower alkanoyloxy lower alkylene, lower unsubstituted aza-lower alkanoylated or lower N'-alkylated, lower oxa-alkylene, or optionally lower-thio-lower alkylene, carboxy-free lower alkyl or esterified or amidated, dicarboxy-free lower alkyl or esterified or amidated, carboxy (hydroxy) - free lower alkyl or esterified or amidated, carboxy cycloalkyl-free lower alkyl or esterified or amidated, cyano-lower alkyl, lower alkane-sulfonyl-lower alkyl, thiocarbamoyl-unsubstituted lower alkyl or N-mono- or N, N-di- lower alkylated, sulfamoyl-unsubstituted or lower N- mono- or N, N-di-alkylated lower alkyl, or a heteroaryl radical linked via a carbon atom and optionally hydrogenated and / or oxo-substituted, or substituted lower alkyl by a heteroaryl radical linked by means of a carbon atom and optionally hydrogenated and / or oxo-substituted; or a pharmaceutically acceptable salt thereof. Preferred are compounds of group A wherein: R1 and R4 are hydrogen; R2 is lower alkoxy-lower alkoxy; R3 is halogen, or mono-, di-, or trisubstituted alkyl by halogen; or a pharmaceutically acceptable salt thereof. Further preferred are compounds of group A wherein the halogen / halo is fluoro or chloro; or a pharmaceutically acceptable salt thereof. The compounds of group A are more preferred where: R3 is fluorine or trifluoromethyl; or a pharmaceutically acceptable salt thereof. Most preferred are the compounds of group A wherein R2 is in the meta position, and R3 is in the position for; or a pharmaceutically acceptable salt thereof. Also more preferred are compounds of group A wherein R3 is in the ortho position; or a pharmaceutically acceptable salt thereof. Also more preferred are the compounds of group A wherein R3 is in the meta position; or a pharmaceutically acceptable salt thereof. Also preferred are compounds of group A, designated as group B, wherein R 2 is in the meta position and is lower alkoxy-lower alkoxy optionally substituted by halogen (s); or a pharmaceutically acceptable salt thereof. Further preferred are compounds of group B wherein the halogen (s) is fluorine or chlorine; or a pharmaceutically acceptable salt of the same. Further preferred are compounds of group B wherein the halogen (s) is fluorine; or a pharmaceutically acceptable salt thereof. Also preferred are compounds of group B, designated as group C, wherein: R3 is lower alkoxy substituted by halogen (s); or a pharmaceutically acceptable salt thereof. Preferred are compounds of group C wherein the halogen (s) is fluorine or chlorine; or a pharmaceutically acceptable salt thereof. Also preferred are compounds of group C wherein the halogen (s) is fluorine; or a pharmaceutically acceptable salt thereof. Also preferred are compounds of group B, designated as group D, wherein: R3 is in the para position; or a pharmaceutically acceptable salt thereof. Also preferred are the compounds of group D, wherein R3 is methoxy; or a pharmaceutically acceptable salt thereof. Also preferred are the compounds of group D, wherein R3 is trifluoromethoxyl; or a pharmaceutically acceptable salt thereof. Also preferred are compounds of Formula (1), wherein: R3 is located in the para position and is halogen; or a pharmaceutically acceptable salt thereof. Also preferred are the d-amino-α-hydroxy-α-aryl-alkanoic acid amide compounds of the Formula (I), designated as the E group, having the Formula (Ia): wherein: R1 is hydrogen, halogen, optionally halogenated alkyl, cycloalkyl, hydroxyl, optionally halogenated alkoxy, cycloalkoxy, lower alkoxy-lower alkoxy, or carboxy-lower alkoxy or free lower alkyl or esterified or amidated; R2 is hydrogen, halogen, optionally halogenated lower alkyl, hydroxyl, cycloalkyl, cycloalkoxy, lower alkoxy-optionally halogenated lower alkyl, lower alkoxy-optionally substituted lower alkoxy, cycloalkoxy-lower alkyl; lower hydroxy-lower alkoxy optionally lower alkanoylated, halogenated, or sulfonylated; amino-lower alkyl that is unsubstituted or substituted by lower alkyl, by lower alkanoyl, and / or by lower alkoxy-carbonyl; heteroaryl-optionally hydrogenated lower alkyl, amino-lower alkoxy that is substituted by lower alkyl, by lower alkanoyl, and / or by lower alkoxy-carbonyl; oxo-lower alkoxy, lower alkoxy, cycloalkoxy, lower alkenyloxy, cycloalkoxy-lower alkoxy, lower alkoxy-lower alkenyl, lower alkenyloxy-lower alkoxy, lower alkoxy-lower alkenyloxy, lower alkenyloxy-lower alkyl, lower alkanoy-lower alkoxy, lower alkylthio optionally S-oxidized lower alkoxy, lower thioalkyl- (hydroxy) -lower alkoxy, aryl-lower alkoxy, aryl-lower alkyl, aryl-lower alkoxy, optionally hydrogenated heteroaryl-lower alkoxy, optionally hydrogenated heteroaryl-lower alkyl, cyano-alkoxy lower, lower cyanoalkyl, free or esterified or amidated carboxy-lower alkoxy, or free carboxy-lower alkyl or esterified or amidated; R3 and R4 are independently hydrogen, halogen, optionally hydrogenated lower alkyl, hydroxyl, optionally halogenated lower alkoxy or cycloalkoxy, lower alkoxy-lower alkyl, cycloalkoxy-lower alkyl, hydroxy-lower alkyl, lower alkylthio-optionally S-oxidized lower alkyl, heterotyoaryl optionally hydrogenated lower alkyl, heteroaryl-optionally hydrogenated lower alkyl; amino-lower alkyl which is unsubstituted or N-mono- or lower N, N-di-alkylated, N-lower alkanoylated, or N-lower alkane-sulfonylated, or N, N-disubstituted by lower alkylene, by lower aza-alkylene unsubstituted or lower N'-alkylated, or lower N'-alkanoylated, by lower oxa-alkylene, or by optionally-S-oxidized lower thia-alkylene; cyano-lower alkyl, free or esterified or amidated carboxy-lower alkyl, cycloalkyl, aryl, hydroxyl, lower alkoxy, cycloalkoxy, lower alkoxy-lower alkoxy, cycloalkoxy-lower alkoxy, hydroxy-lower alkoxy, aryl-lower alkoxy, lower alkoxy optionally halogenated, lower thioalkyl-optionally S-oxidized lower alkoxy, optionally hydrogenated lower heteroaryl-lower alkoxy, optionally hydrogenated lower heteroxyaryl-lower alkoxy; amino-lower alkoxy which is unsubstituted or N-mono- or lower N, N-di-alkylated, lower N-alkanoylated, or lower-N-alkylated sulphonylated, or substituted by lower alkylene, by lower aza-alkylene unsubstituted or lower N'-alkylated, or lower N'-alkanoylated, by lower oxa-alkylene, or by optionally-S-oxidized lower thia-alkylene; cyano-lower alkoxy, or free lower or esterified or amidated carboxy lower alkoxy; or R 4, together with R 3, is lower alkenoxyl, alkylenedioxyl, or an aryl fused on, optionally hydrogenated heteroaryl, or a cycloalkyl ring; X is methylene, hydroxymethylene, oxygen, nitrogen optionally substituted by lower alkyl, or optionally oxidized sulfur; R5 is lower alkyl or cycloalkyl; R6 is hydrogen, lower alkyl, hydroxyl, alkoxy, or halogen; R7 is unsubstituted amino or lower N-mono- or N, N-di-alkylated or lower N-alkanoylated; R8 is lower alkyl, lower alkenyl, cycloalkyl, or aryl-lower alkyl; R9 is optionally substituted lower alkyl, optionally substituted cycloalkyl, cycloalkyl, optionally substituted cycloalkyl carboxamides, N-mono or N, N-di-alkyi-substituted cycloalkylcarboxamides, optionally substituted arylalkyl , optionally substituted aryloxy-aryl, optionally substituted heteroaryloxy-alkyl, hydroxy-free lower alkyl or aliphatically esterified or etherified; amino-lower alkyl that is unsubstituted or N- lower alkanoylate, or lower N-mono- or N, N-di-alkylated, or N, N-di-substituted by lower alkylene, by hydroxy-, lower alkoxy-, or lower alkanoyloxy-lower alkylene, by lower alkylene unsubstituted or lower N'-alkanoylated or lower N'-alkylated, by lower oxa-alkylene, or by optionally S-oxidized lower thia-alkylene, free or esterified or amidated carboxy-lower alkyl, dicarboxy-free lower alkyl or esterified or amidated , carboxy (hydroxy) -free or esterified or amidated lower alkyl, free or esterified or amidated carboxy-cycloalkyl-lower alkyl, cyano-lower alkyl, lower alkane-sulfonyl-lower alkyl, thiocarbamoyl-unsubstituted lower alkyl or N-mono- or N, lower N-alkylated, sulfamoyl-unsubstituted lower alkyl or lower N-mono- or N, N-di-alkylated, or a heteroaryl radical linked via a carbon atom and optionally hydrogenated and / or oxo- substituted, or substituted lower alkyl by a heteroaryl radical linked by means of a carbon atom and optionally hydrogenated and / or oxo-substituted; or a pharmaceutically acceptable salt thereof. The compounds of group E are preferred, wherein: R9 is cycloalkyl substituted with alkyl, hydroxyl, alkoxy, alkoxy-alkoxy, or halogens; cycloalkyl-alkyl optionally substituted with alkyl, hydroxyl, alkoxy, alkoxy-alkoxy, or halogens on cycloalkyl, or halogens on alkyl, or halogens on alkoxy; cycloalkylcarboxamides; N-mono- or N, N-di-alkyl-substituted cycloalkyl-carboxamides; or optionally substituted aryl-alkyl; or a pharmaceutically acceptable salt thereof. Also preferred are compounds of group E, designated as group F, wherein: R9 is hydrogen; halogenated alkyl; optionally substituted aryl-alkyl, optionally substituted aryloxy-alkyl, cycloalkyl substituted by 1 to 3 substituents selected from the group consisting of alkenyl, alkynyl, halogen, hydroxyl, alkoxy, alkoxy-alkoxy, thioalkyl, thioaryl, arylalkoxy, carbamoyl , sulfamoyl, sulfonyl, optionally substituted amino, cyano, carboxyl, alkoxycarbonyl, aryl, aryloxy, heterocyclyl, or alkyl optionally substituted by amino, halogen, hydroxyl, alkoxy, carboxyl, alkoxycarbonyl, carbamoyl, or heterocyclyl; or optionally substituted cycloalkyl-alkyl; or a pharmaceutically acceptable salt thereof. The compounds of group F are preferred, wherein: R 1 is hydrogen; R 2 is alkoxy of 1 to 4 carbon atoms-alkoxy of 1 to 4 carbon atoms, or alkoxy of 1 to 4 carbon atoms-alkyl of 1 to 4 carbon atoms; R3 is alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms; R4 is hydrogen; X is methylene; R5 is lower alkyl; R6 is hydrogen; R7 is amino unsubstituted; R8 is alkyl of 3 to 4 carbon atoms branched; R9 is optionally substituted cycloalkyl-alkyl; or a pharmaceutically acceptable salt thereof. Further preferred are compounds of group F, wherein: R 2 is 3-methoxy-propyloxy; R3 is methoxy; R5 is isopropyl; R8 is isopropyl; or a pharmaceutically acceptable salt thereof. Also preferred are compounds of group F, designated as group G, wherein: R 1 is hydrogen; R2 is alkoxy of 1 to 4 carbon atoms-alkoxy of 1 to 4 carbon atoms, or alkoxy of 1 to 4 carbon atoms carbon-alkyl of 1 to 4 carbon atoms; R3 is alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms; R4 is hydrogen; X is methylene; R5 is lower alkyl; R6 is hydrogen; R7 is amino unsubstituted; R8 is alkyl of 3 to 4 carbon atoms branched; R9 is aryl-alkyl optionally substituted; or a pharmaceutically acceptable salt thereof. The compounds of group G are preferred, wherein: R 2 is 3-methoxy-propyloxy; R3 is methoxy; R5 is isopropyl; R8 is isopropyl; or a pharmaceutically acceptable salt thereof. Also preferred are compounds of group G, wherein aryl-alkyl is alkyl substituted with phenyl; or a pharmaceutically acceptable salt thereof. In addition, the compounds of group G are preferred, wherein aryl-alkyl is methyl substituted with phenyl. More preferred are the compounds of group G, wherein: R 2 is 3-methoxy-propyloxy; R3 is methoxy; R5 is isopropyl; R8 is isopropyl; or a pharmaceutically acceptable salt thereof. As a result of the close relationship between the novel compounds in free form and in the form of their salts, hereinafter and hereinafter, any reference to the free compounds and their salts, it should be understood that it also includes the corresponding salts and the free compounds, respectively, as appropriate and convenient. The compounds of the present invention can be prepared in general by the methods disclosed in U.S. Patent No. 5,559,111, incorporated herein by reference in its entirety, as if absolutely stipulated herein. The present invention further provides pharmaceutical compositions comprising a therapeutically effective amount of a pharmacological compound- of the present invention, alone or in combination with one or more pharmaceutically acceptable carriers. The pharmaceutical compositions according to the present invention are those suitable for enteral, such as oral or rectal, transdermal, and parenteral administration to mammals, including man, for the purpose of inhibiting the activity of renin, and for the treatment of conditions associated with the activity of renin. These conditions include hypertension, atherosclerosis, unstable coronary syndrome, congestive heart failure, cardiac hypertrophy, cardiac fibrosis, post-infarction cardiomyopathy, unstable coronary syndrome, diastolic dysfunction, chronic kidney disease, hepatic fibrosis, complications resulting from diabetes, such as nephropathy, vasculopathy and neuropathy, diseases of the coronary vessels, restenosis following angioplasty, elevated intraocular pressure, glaucoma, abnormal vascular growth, hiraldosteronism, cognitive impairment, Alzheimer's disease, dementia, anxiety states, and cognitive disorders. Accordingly, the pharmacologically active compounds of the invention can be used in the manufacture of pharmaceutical compositions comprising an effective amount thereof together or in admixture with suitable excipients or vehicles for their application enteral or parenteral. Preferred are gelatin capsules and tablets comprising the active ingredient together with: a) diluents, for example lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, and / or glycine; b) lubricants, for example silica, talc, stearic acid, its magnesium or calcium salt, and / or polyethylene glycol; for tablets also, c) binders, for example magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethyl cellulose, and / or polyvinylpyrrolidone; if desired, d) disintegrants, for example starches, agar, alginic acid or its sodium salt, or effervescent mixtures; and / or e) absorbers, colorants, flavors, and sweeteners. The injectable compositions are preferably aqueous isotonic solutions or suspensions, and the suppositories are conveniently prepared from fat emulsions or suspensions. These compositions can be sterilized and / or contain adjuvants, such as preservatives, stabilizers, wetting agents, or emulsifiers, solution promoters, salts for regulating the osmotic pressure, and / or pH regulators. In addition, they may also contain other therapeutically valuable substances. These Compositions are prepared according to conventional mixing, granulating, or coating methods, respectively, and contain from about 0.1 to 75 percent, preferably from about 1 to 50 percent, of the active ingredient. Formulations suitable for transdermal application include a therapeutically effective amount of a compound of the invention with a carrier. Convenient carriers include pharmacologically acceptable absorbable solvents to aid passage through the skin of the host. Characteristically, the transdermal devices are in the form of a patch comprising a backup member, a reservoir containing the compound optionally with carriers, optionally a speed control barrier to deliver the compound to the skin of the host at a time. speed controlled and previously determined for a prolonged period of time, and elements to secure the device to the skin. In accordance with the above, the present invention provides pharmaceutical compositions as described above, for the treatment of conditions mediated by renin activity, preferably hypertension, atherosclerosis, unstable coronary syndrome, congestive heart failure, cardiac hypertrophy, cardiac fibrosis, post-infarction cardiomyopathy, unstable coronary syndrome, diastolic dysfunction, chronic kidney disease, hepatic fibrosis, complications resulting from diabetes, such as nephropathy, vasculopathy and neuropathy, diseases of the coronary vessels, restenosis following angioplasty, intraocular pressure elevated, glaucoma, abnormal vascular growth, hyperaldosteronism, cognitive impairment, Alzheimer's disease, dementia, anxiety states, and cognitive disorders. The pharmaceutical compositions may contain a therapeutically effective amount of a compound of the invention as defined above, either alone or in a combination with another therapeutic agent, for example, each in an effective therapeutic dose, as reported in the art. These therapeutic agents include: a) anti-diabetic agents, such as insulin, insulin derivatives, and mimetics; insulin secretagogues, such as the sulfonyl-ureas, for example glipizide, glyburide, and Amaril; insulinotropic sulfonyl urea receptor ligands, such as meglitinides, for example nateglinide and repaglinide; ligands of the peroxisome proliferator-activated receptor (PPAR); inhibitors of protein tyrosine-1B phosphatase (PTP-1B), such as PTP-112; inhibitors of GSK3 (glycogen synthase kinase) 3), such as SB-517955, SB-4195052, SB-216763, NN-57-05441 and NN-57-05445; RXR ligands, such as GW-0791 and AGN-194204; inhibitors of the sodium-dependent glucose co-transporter, such as T-1095; inhibitors of glycogen A phosphorylase, such as BAY R3401; biguanides, such as metformin; alpha-glucosidase inhibitors, such as acarbose; GLP-1 (glucagon-1 type peptide), GLP-1 analogs, such as Exendin-4, and GLP-1 mimetics; and inhibitors of DPPIV (dipeptidyl peptidase IV), such as LAF237; b) hypolipidemic agents, such as inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) -reductase, for example lovastatin, pitavastatin, simvastatin, pravastatin, cerivastatin, mevastatin, velostatin, fluvastatin, dalvastatin, atorvastatin , rosuvastatin, and rivastatin; squalene synthase inhibitors; ligands of FXR (farnesoid receptor X) and LXR (liver receptor X); cholestyramine; fibrates; nicotinic acid, and aspirin; c) anti-obesity agents, such as orlistat; and d) anti-hypertensive agents, for example cycle diuretics, such as ethacrynic acid, furosemide, and torsemide; Angiotensin-converting enzyme (ACE) inhibitors, such as benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perinodopril quinapril, ramipril, and trandolapril; inhibitors of the Na-K-ATPase membrane pump, such as digoxin; Neutralendopeptidase (NEP) inhibitors; ACE / NEP inhibitors, such as omapatrilate, sampatrilate, and fasidotril; angiotensin II antagonists, such as candesartan, eprosartan, irbesartan, losartan, telmisartan, and valsartan, in particular valsartan; ß-adrenergic receptor blockers, such as acebutolol, atenolol, betaxolol, bisoprolol, metoprolol, nadolol, propanolol, sotalol, and timolol; inotropic agents such as digoxin, dobutamine, and milrinone; calcium channel blockers, such as amlodipine, bepridil, diltiazem, felodipine, nicardipine, nimodipine, nifedipine, nisoldipine, and verapamil; Aldosterone receptor antagonists; and inhibitors of aldosterone synthase. Other specific anti-diabetic compounds are described by Patel Mona in Expert Opin Investig. Drugs, 2003, 12 (4), 623-633, in Figures 1 to 7, which are incorporated herein by reference. A compound of the present invention can be administered either simultaneously, before, or after the other active ingredient, either separately by the same or different route of administration, or together in the same pharmaceutical formulation.

The structure of the therapeutic agents identified by code numbers, generic or commercial names, can be taken from the current edition of the standard compendium "The Merck Index", or from the databases, for example Patents International (for example, IMS World Publications). The corresponding content thereof is incorporated herein by reference. In accordance with the foregoing, the present invention provides pharmaceutical compositions comprising a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of another therapeutic agent, preferably selected from anti-diabetic, hypolipidemic agents, anti-obesity agents, or anti-hypertensive agents, more preferably from antidiabetics, anti-hypertensive agents, or hypolipidemic agents, as described above. The present invention further relates to pharmaceutical compositions as described above, for use as a medicament. The present invention further relates to the use of pharmaceutical compositions or combinations as described above, for the preparation of a medicament for the treatment of conditions mediated by renin activity, preferably hypertension, atherosclerosis, unstable coronary syndrome, congestive heart failure, cardiac hypertrophy, cardiac fibrosis, post-infarction cardiomyopathy, unstable coronary syndrome, diastolic dysfunction, chronic kidney disease, hepatic fibrosis, complications resulting from diabetes, such as nephropathy, vasculopathy and neuropathy, diseases of the coronary vessels, restenosis following angioplasty, elevated intraocular pressure, glaucoma, abnormal vascular growth, hyperaldosteronism, cognitive deterioration, Alzheimer's disease, dementia, anxiety states, and cognitive disorders. Therefore, the present invention also relates to a compound of the Formula (I), for use as a medicament, to the use of a compound of the Formula (I) for the preparation of a pharmaceutical composition for prevention and / or the treatment of conditions mediated by the activity of renin, and a pharmaceutical composition for use under conditions mediated by renin activity, which comprises a compound of Formula (I), or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable diluent or vehicle therefor. The present invention further provides a method for the prevention and / or treatment of conditions mediated by the activity of renin, which comprises administering a therapeutically effective amount of a compound of the present invention. A unit dosage for a mammal of about 50 to 70 kilograms may contain between about 1 milligram and 1,000 milligrams, conveniently between about 5 and 600 milligrams of the active ingredient. The therapeutically effective dosage of the active compound depends on the species of warm-blooded animal (mammal), the body weight, the age and individual condition, the form of administration, and the compound involved. In accordance with the foregoing, the present invention also provides a therapeutic combination, for example a kit, a kit of parts, for example for use in any method as defined herein, which comprises a compound of Formula (I) , or a pharmaceutically acceptable salt thereof, for use concomitantly or in sequence with at least one pharmaceutical composition comprising at least one other therapeutic agent, preferably selected from anti-diabetic agents, hypolipidemic agents, anti-obesity agents , or agents against hypertension. The case may comprise instructions for its administration. In a similar manner, the present invention provides a kit of parts comprising: (i) a pharmaceutical composition of the invention; and (ii) a pharmaceutical composition comprising a compound selected from an anti-diabetic, a hypolipidemic agent, an anti-obesity agent, an anti-hypertensive agent, or a pharmaceutically acceptable salt thereof, in the form of two separate units of components (i) to (ii). In the same manner, the present invention provides a method as defined above, which comprises the co-administration, for example in a concomitant or sequential manner, of a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and a second drug substance, this second drug substance being an anti-diabetic, a hypolipidemic agent, an anti-obesity agent, or an antihypertensive agent, for example as indicated above. Preferably, a compound of the invention is administered to a mammal in need thereof. Preferably, a compound of the invention is used for the treatment of a disease that responds to the modulation of renin activity. Preferably, the condition associated with renin activity is selected from hypertension, atherosclerosis, unstable coronary syndrome, congestive heart failure, cardiac hypertrophy, cardiac fibrosis, post-infarction cardiomyopathy, unstable coronary syndrome, diastolic dysfunction, chronic kidney disease, hepatic fibrosis, complications resulting from diabetes, such as nephropathy, vasculopathy and neuropathy , diseases of the coronary vessels, restenosis following angioplasty, elevated intraocular pressure, glaucoma, abnormal vascular growth, hyperaldosteronism, cognitive impairment, Alzheimer's disease, dementia, anxiety states, and cognitive disorders. Finally, the present invention provides a method or use, which comprises administering a compound of Formula (I) in combination with a therapeutically effective amount of an anti-diabetic agent, a hypolipidemic agent, an anti-obesity agent, or an agent against hypertension. Finally, the present invention provides a method or use, which comprises administering a compound of Formula (I) in the form of a pharmaceutical composition as described herein. As used throughout the specification and in the claims, the term "treatment" encompasses all different forms or modes of treatment known to those skilled in the pertinent art, and in particular includes preventive, curative, delaying establishment and / or progress, and palliative treatment. The aforementioned properties can be demonstrated in in vitro and in vivo tests, conveniently using mammals, for example mice, rats, rabbits, dogs, monkeys, or isolated organs, tissues, and preparations thereof. These compounds can be applied in vitro in the form of solutions, for example preferably aqueous solutions, and in vivo either enterally, parenterally, conveniently intravenously, for example as a suspension or in an aqueous solution. The in vitro dosage can be in the range of concentrations between about 10"3 molar and 10" 10 molar. A therapeutically effective amount in vivo may be in the range, depending on the route of administration, of between about 0.001 and 500 milligrams / kilogram, preferably between about 0.1 and 100 milligrams / kilogram. As described above, the compounds of the present invention have enzyme inhibiting properties. In particular, they inhibit the action of the natural renin enzyme. Renin passes from the kidneys to the blood, where it dissociates the angiotensinogen, releasing the decapeptide angiotensin I, which then dissociates into the lungs, kidneys, and in other organs, to form the octapeptide angiotensin II. The octapeptide increases blood pressure, both directly by arterial vasoconstriction, and indirectly by releasing the hormone retention of sodium aldosterone from the adrenal glands, accompanied by an increase in the volume of the extracellular fluid, the increase of which can be attributed to the action of angiotensin II. Inhibitors of the enzymatic activity of renin lead to a reduction in the form of angiotensin I, and consequently, a smaller amount of angiotensin II is produced. The reduced concentration of this active peptide hormone is the direct cause of the hypotensive effect of renin inhibitors. The action of renin inhibitors can be demonstrated, inter alia, experimentally, by means of in vitro tests, measuring the reduction in the formation of angiotensin I in different systems (human plasma, purified human renin together with synthetic renin substrate). or natural). Among other things, the following in vitro tests can be used: A human kidney renin extract (0.5 mGU [milli-units GoldblattJ / milliliter) is incubated for 1 hour at 37 ° C and at a pH of 7.2 in an aqueous buffer of 2-N- (tris-hydroxy-methyl-methyl) -amino-ethanesulfonic acid 1M with 23 micrograms / milliliter of synthetic renin substrate, the tetradecapeptide H-Asp-Arg-Val-Tyr-I le-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser-OH. The amount of angiotensin I formed is determined by radioimmunoassay. Each of the inhibitors according to the invention is added to the incubation mixture in different concentrations. The IC50 is defined as the concentration of a particular inhibitor that reduces the formation of angiotensin I by 50 percent. Recombinant human renin (expressed in Chinese Hamster Ovary cells, and purified using conventional methods) in a concentration of 4 nM, is incubated with the test compound in different concentrations for 1 hour at room temperature, in regulator tris-HCl 0.1 M, pH 7.4, containing 0.05M NaCl, 0.5 mM EDTA, and 0.05 percent CHAPS. The synthetic peptide substrate Arg-Glu (EDANS) -lle-His-Pro-Phe-His-Leu-VaI-lle_His_Thr-Lys (DABCYL) -Arg9 is added to a final concentration of 2 μM, and the increase in fluorescence at an excitation wavelength of 340 nanometers, and at an emission wavelength of 485 nanometers, in a microplate lumen-f-spectrum. The IC50 values are calculated from the percentage of inhibition of renin activity as a function of the concentration of the test compound (Fluorescence Resonance Energy Transfer Test, FRET). Recombinant human renin (expressed in Chinese Hamster Ovary cells, and purified using conventional methods) at a concentration of 1 nM, is incubated with the test compound in different concentrations for 1.5 hours at 37 ° C, in tris / 0.1 HCl M, pH 7.4, containing 0.05M NaCl, 0.5 mM EDTA, and 0.025 percent (weight / volume) CHAPS. The synthetic Ac-I peptide substrate le-H is-Pro-Phe-His-Leu-Val-l le-His-Asn-Lys- [DY-505-X5] is added to a final concentration of 5 μM. The enzymatic reaction is stopped by adding 6 microliters of 1.0 percent trifluoroacetic acid. The product of the reaction is separated by HPLC, and quantified by spectrophotometric measurement at a wavelength of 505 nanometers. IC50 values are calculated from the percentage inhibition of renin activity as a function of the concentration of the test compound. Recombinant human renin (expressed in Chinese Hamster Ovary cells, and purified using conventional methods), at a concentration of 3.3 nM, 125 I-NVP-AJI891-NX-1 (0.27 μCi / ml, and 1 liter), and beads of streptavidin-SPA (0.67 milligrams / milliliter), incubated with the test compound in different concentrations for 2.0 hours at room temperature, in tris / 0.1M HCl, pH 7.4, containing 0.5M NaCl, and B ri j 35 0.5 percent (weight / volume). At the end of the incubation time, the plates are centrifuged (55 g, 60 seconds), and counted in a Wallac MicroBeta reader. The IC 50 values are calculated from the percent displacement of the radioligand linkage with the renin as a function of the concentration of the test compound. In animals deficient in salt, renin inhibitors cause a reduction in blood pressure. The human reniña may differ from the renin of other species. In order to test inhibitors of human renin, primates, for example marmosets (Callithrix jacchus), may be used, because human renin and primate renin are substantially homologous in the enzymatically active region. Among other things, the following in vivo tests may be employed: Test compounds are tested on norm offensive marmosets of both sexes with a body weight of approximately 350 grams that are conscious, allowed to move freely, and are in their normal cages . The blood pressure and heart rate are measured by means of a catheter in the descending aorta, and they are recorded radiometrically. The release of endogenous renin is stimulated by the combination of a low-salt diet of one week, and a single intramuscular injection of furosemide (5- (amino-sulfonyl) -4-chloro-2 - [(2-furanyl- methyl) -amino] -benzoic acid (5 milligrams / kilogram). Sixteen hours after the injection of furosemide, the test compounds are administered either directly into the femoral artery using an injection cannula, or in the form of a suspension or solution, by means of an esophageal tube into the stomach, and Its action on blood pressure and heart rate is evaluated. In the described in vivo test, the compounds of the present invention have a hypotensive action in doses of about 0.003 to about 1 milligram / kilogram intravenously, and in doses of about 0.3 to about 100 milligrams / kilogram orally. Alternatively, renin inhibitors can be tested on male normotensive marmosets weighing 250 to 500 grams that are conscious, allowed to move freely, and are in their normal cages. The blood pressure and heart rate are measured by means of a catheter placed in the descending aorta, and they are recorded radiometrically. The electrocardiogram is obtained by placing electrodes of the transmitter in conductor II. The release of endogenous renin is stimulated by two intramuscular injections of furosemide (5- (amino-sulfonyl) -4-chloro-2 - [(2-furanyl-methyl] -benzoic acid) (10 milligrams / kilogram), 43 and 19 hours before the application of the compound.The test compounds are administered either directly in the femoral artery using an injection cannula, or in the form of a suspension or solution, by means of an esophageal tube into the stomach, and its action on blood pressure, heart rate, and ECG is evaluated . In the described in vivo test, the compounds of the present invention have a hypotensive action in doses of about 0.003 to about 0.3 milligrams / kilogram intravenously, and in doses of about 0.31 to about 30 milligrams / kilogram orally. The compounds of the present invention also have the property of regulating, in particular of reducing, the intraocular pressure. The degree of reduction in intraocular pressure after administration of a pharmaceutical active ingredient of Formula (I) according to the present invention can be determined, for example, in animals, for example in rabbits or monkeys. Thereafter, two typical experimental procedures illustrating the present invention, but not limiting it in any way, are described herein. The in vivo test on a rabbit of the "Fauve de Bourgogne" type, to determine the reducing activity of the intraocular pressure of the topically applied compositions, can be designed, for example, as follows: measures intraocular pressure (lOP) using a flattening tonometer, both before the experiment and at regular time intervals. After a local anesthetic has been administered, the test compound suitably formulated topically at a precisely defined concentration (eg, 0.000001 to 5 weight percent) is applied to an eye of the animal in question. The contralateral eye is treated, for example, with physiological saline solution. The measured values thus obtained are statistically evaluated. In vivo tests in monkeys of the species Macaca Fascicularis, to determine the reducing activity of the infra-ocular pressure of the topically applied compositions, can be carried out, for example, as follows: the suitably formulated test compound is applied in a concentration precisely defined (e.g., 0.000001 to 5 percent by weight) to one eye of each monkey. The other eye of the monkey is treated in a corresponding manner, for example, with physiological saline. Before the start of the test, the animals are anesthetized with intramuscular injections, for example, of ketamine. At regular time intervals, intraocular pressure (IOP) is measured. The test is carried out and evaluated in accordance with the rules of "good laboratory practice" (GLP). Illustrating the invention, the compound of Example 29 demonstrates an inhibition of renin activity with an IC50 value of approximately 0.3 mM in the FRET assay.

The following Examples are intended to illustrate the invention, and should not be construed as limitations thereon. If not mentioned otherwise, all evaporations are carried out under reduced pressure, preferably between about 10 and 100 mmHg (= 20-133 mbar). The structure of the final products, intermediates, and starting materials is confirmed by conventional analytical methods, for example microanalysis, melting point (p.f.), and spectroscopic characteristics for example, MS, LC / MS, IR, NMR. In general, the abbreviations used are those conventional in this field.

Eiem pío 1. General Procedure (I).

Preparation of the starting acid: a) Acid (2S, 4S, 5S, 7S) -5-terbutoxy-carbonyl-amino-4- (tert-butyl-dimethyl-silanyloxy) -2-isopropyl-7- [4-methoxy-3- (3-methoxy) propoxy) -benzyl] -8-methyl-nonanoic acid.

Add triethylamine (NEt3) (7.2 milliliters, 51.6 millimoles, 3.0 equivalents), followed by dimethylaminopyridine (DMAP) (640 milligrams, 5.2 millimoles, 0.3 equivalents), to a solution of the acid (2S, 4S, 5S, 7S) -5-terbutoxy-carbonyl-amino-4-hydroxy-2-isopropyI-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid (9.53 grams, 17.2 millimoles, 1.0 equivalents), and TBDMSCI (10.3 grams, 68.7 millimoles, 4.0 equivalents) in dimethylformamide (DMF) (100 milliliters) at room temperature (RT). The reaction mixture is stirred at room temperature for 16 hours before adding water (H2O). The extraction with acetate ethyl (EtOAc), drying [sodium sulfate (Na2SO4)], and evaporation of the solvent, provide the crude product. Column chromatography by evaporation [600 grams of silicon dioxide (SiO2), hexane: EtOAc, 5: 1], produces the doubly protected product by TBDMS as a colorless oil. A portion of it (904 milligrams, 1.24 millimoles, 1.0 equivalents) is dissolved in methyl alcohol (MeOH) (20 milliliters), and 1M HCl is added (2 milliliters, 2 millimoles, 1.6 equivalents). The mixture is stirred at room temperature for 10 minutes, before adding 1M sodium hydroxide (NaOH) (2 milliliters), followed by H20 and a 10 percent citric acid solution for processing. Extraction with EtOAc, drying (Na2SO4) of the combined organic extracts and evaporation of the solvent give the crude product, which is purified by flash column chromatography [50 grams of SiO2, CH2Cl2: MeOH (9: 1 )], to provide the desired product as a colorless oil. MS (LC / MS): 691.3 [M + Na] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 7.63 minutes. b) ((1S, 2S, 4S) -4-benzylcarbamoyl-2- (tert-butyl-dimethyl-silanyloxy) -substantyl ester - [(S) -2- [4- methoxy-3- (3-methoxy-propoxy) -benzyl] -3-methyl-butyl] -5-methyl-hexyl) -carbamic acid.

HBTU (400 milligrams, 1.03 millimole, 1.2 equivalents) is added to a solution of (2S, 4S, 5S, 7S) -tertbutoxy-carbonyl-amino-4- (tert-butyl-dimethyl-alanyloxy) -2-isopropyl-7 acid. [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid (575 milligrams, 0.86 millimoles, 1.0 equivalents) in acetonitrile (CH3CN) (15 milliliters) and dimethyl formamide (1 milliliter) at 0 ° C. After 5 minutes, add a solution of benzyl amine (94 microliters, 0.86 mmol, 1.0 equivalents) and NEt 3 (1.2 milliliters, 8.6 mmol, 10 equivalents) in CH3CN (3 milliliters), and the reaction mixture is stirred at room temperature for 5 minutes. For processing, EtOAc is added, and the organic layer is washed with 1N HCl, a saturated solution of sodium bicarbonate (NaHCO3), and brine. Drying (Na2SO4) of the organic phase, and evaporation of the solvent, provide the crude product, which is purified by flash column chromatography [50 grams of SiO2, hexane: EtOAc (4: 1)], to provide the desired product as a colorless foam. MS (LC-MS): 780.4 [M + Na] +; Rf [Hexane: EtOAc (1: 1)]; 0.65 minutes. c) ((1S, 2S, 4S) -4-benzylcarbamoyl-2-hydroxy-1 - [(S) -2- [4-methoxy-3- (3-methoxy-propoxy) -benz-tert-butyl ester) L] -3-methyl-butyl] -5-methyl-hexyl) -carbamic acid.

TBAF * 3H20 (302 milligrams, 0.96 millimoles, 1.5 equivalents) is added to a solution of ((1S, 2S, 4S) -4-benzyl-carbamoyl-2- (tert-butyl-dimethylsilyoxy) tert-butyl ester. ) -1- { (S) -2- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -3-methyl-butyl} -5-methyl-hexyl) -carbamic acid (485) milligrams, 0.64 millimoles, 1.0 equivalents) in tetrahydrofuran (THF) (6 milliliters) at room temperature. After 1 hour, H2O is added, and the mixture is extracted with EtOAc. The combined extracts are dried (Na2SO4), and the solvent is evaporated. Flash column chromatography [50 grams of SiO 2, hexane: EtOAc (3: 1)], produces the desired product as a colorless foam. MS (LC-MS): 665.3 [M + Na] +; Rf [Hexane: EtOAc (1: 1)]; 0.33 minutes d) (2S, 4S, 5S, 7S) -5-am i non-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) benzyl] benzyl-amide 8-methyl-nonanoic.

At 0 ° C, 4N HCl / dioxane (7 milliliters, 28 mmol) is added to the ((1S, 2S, 4S) -4-benzyl-carbamoyl-2-hydroxy-1-yl ester. ) -2- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -3-methyl-butyl] -5-methyl-hexyl) -carbamic acid (214 milligrams, 0.34 mmol, 1.0 equivalents). The resulting solution is stirred at room temperature for 15 minutes, over which, a saturated solution of NaHCO3 is carefully added. The mixture is extracted with EtOAc, the combined extracts are dried (Na2SO), and the solvent is evaporated. Flash column chromatography [20 grams of SiO2, CH2Cl2: MeOH (9: 1) to CH2Cl2: MeOH (9: 1) + 1% NEt3] gives the product as a colorless oil. MS (LCMS): 544.3 [M + H] +; Rf [CH2Cl2: MeOH (9: 1)]; 0.19 minutes Eiem pío 2. General Procedure (II).

Preparation of the starting acid: a) Acid (2S, 4S, 5S, 7S) -5-azido-4- (tert-butyl-dimethylsilanyloxy) -2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl) ] -8-methyl-nonanoic.

Lithium hydroxide (LiOH) «H20 (2.18 grams, 52.0 mmol) is added to a solution of (3S, 5S) -5-. { (1S, 3S) -1-azido-3- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -4-methyl-pentyl} -3-isopropyl-dihydro-furan-2-one (20.0 grams, 43. 3 mmol) in dimethoxy-ethane (DME) (400 milliliters) and H2O (200 milliliters), and the resulting solution is stirred at room temperature for 2 hours. The solvent is coevaporated with toluene, and the resulting solid is dried under a high vacuum. This residue is dissolved in dimethylformamide (160 milliliters), and added in sequence NEt3 (32 milliliters, 227.6 millimoles), TBDMSOTf (41.8 milliliters, 182.1 millimoles), and DMAP (556 milligrams, 4.6 millimoles). The mixture is stirred at room temperature for 16 hours. For processing, EtOAc is added, and the mixture is quenched by the addition of a saturated solution of NaHCO3. The organic phase is separated, and the aqueous phase is extracted with EtOAc. Evaporation of the solvent from the combined organic extracts provides the product protected by bis-TBDMS (32.4 grams), while acidification of the basic aqueous layer with 1N HCl, followed by extraction with EtOAc and evaporation of the solvent, produces the free acid m ono-silylated corresponding (8.8 grams). Both isolated products are combined and flash chromatographed [hexane: EtOAc (4: 1) to hexane: EtOAc (1: 1)], to give the desired mono-silylated acid as a viscous oil (complete desilylation of the acid protected by silyl during chromatography). MS (LC-MS): 616.0 [M + Na] +; tR (HPLC, column C8, from 20 to 95 percent CH3CN / H20 (3.5 minutes, 95 percent CH3CN / 1 minute, flow: 0.8 milliliters / minute): 3.93 minutes. b) (2S, 4S, 5S, 7S) -5- azido-4- (tert-butyl-dimethylallanxyl) -2-isopropyl (2-piperidin-1-ethyl-ethyl) -amide. -7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid.

HBTU (1.20 grams, 3.0 mmol) was added to a solution of (2S, 4S, 5S, 7S) -5-azido-4- (tert-butyl-dimethyl-silanyloxy) -2-isopropyl-7- [4- methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid (1.50 grams, 2.5 mmol) in CH2CN (50 milliliters). Then 2-amino-ethyl-piperidine (324 milligrams, 2.5 mmol) and NEt3 (3.9 milliliters) were added, and the resulting solution was stirred at room temperature for 2.5 hours. For workup, EtOAc was added, and the organic phase was washed with 1N HCl, a saturated solution of NaHCO 3, and brine. Drying of the organic phase (Na 2 SO 4), and evaporation of the solvent, gives the crude product, which is purified by flash column chromatography [CH 2 Cl 2: MeOH (95: 5)], to give the Desired product as a colorless oil. MS (LC-MS): 705. 1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H2O / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3N / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 6.82 minutes. c) (2S, 4S, 5S, 7S) -5- azido-4-hydroxy-2-isopropyl-7- [4-methoxy] -amide (2-piperidin-1 -i-ethyl) -amide. 3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid.

TABF "3 H20 (1.73 grams, 5.5 mmol) is added to a solution of the (2S, 4S, 5S, 7S) -5-azido-4- (2-piperidin-1-ethyl-ethyl) -amide ( terbutyl-dimethyI-silanyloxy) -2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid (1.54 grams, 2.2 mmol) in tetrahydrofuran (15 milliliters). The reaction mixture is stirred at room temperature for 72 hours. For processing, H2O is added, and the mixture is extracted with CH2Cl2. The combined organic extracts are dried (Na2SO4), and the solvent is evaporated. Flash column chromatography [CH2Cl2: MeOH (9: 1)] produces the desired product like a yellowish oil. MS (LC-MS): 590.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H2O / 3 minutes, flow: 1.5 milliliters / minute ): 5.24 minutes. d) (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (2-piperidin-1-ethyl-ethyl) -amide. 3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid.

Palladium on charcoal (Pd / C) at 10 percent (200 milligrams) is added to a solution of the (2-piperidin-1-yl-ethyl-1-a) acid (2S, 4S, 5S, 7S) ) -5-azido-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid (780 milligrams, 1.32 mmol) ) in MeOH (40 milliliters) under Ar. Then, the suspension of the reaction is stirred under an atmosphere of hydrogen (H2) for 8 hours. The catalyst is filtered over Celite, and washed with MeOH. The evaporation of the solvent gives the crude product, which is pure according to the analysis, and is used without further purification.

MS (LC-MS): 564.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH2CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 4.31 minutes.

Example 3, General Procedure (III).

Cyclopropyl-methyl-amino acid (2S, 4S, 5S, 7S) -5-am ino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic.

A solution of (3S, 5S) -5-. { (1S, 3S) -1-azido-3- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -4-methyl-pentyl} -3-isopropyl-dihydro-furan-2-one (2.00 grams, 4.3 mmol), and cyclopropan-methyl-amine (1.9 milliliters, 21.7 mmol) in acetic acid (0.78 milliliters), was heated at 100 ° C in a tube sealed for 30 minutes. Water was added, and the mixture was extracted with CH2Cl2. Drying (Na2SO4) of the combined extracts, and evaporation of the solvent, provided the crude product, which was used without further purification. percent Pd / C (1.10 grams, 1.0 mmol) was added to a solution of the crude product (2.58 grams) in MeOH (16 milliliters), and the reaction mixture was stirred under an atmosphere of H2 for 9 hours. The catalyst was filtered over Celite, and the solvent was evaporated. Purification of the crude product by flash column chromatography [CH2Cl2 to CH2Cl2: MeOH (8: 2)], afforded the desired product as a colorless foam. MS [LC-MS]: 508.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 4.91 minutes.

Example 4: General Procedure (IV), a) 4-Bromo-1-fluoro-2- (3-methoxy-propoxy) -benzene.

Di-isopropyl ester of azodicarbonic acid is added to a solution of 4-bromo-1-f luoro-2-hydroxy-benzene [see Maleczak, Jr., Shi, Holmes and Smith, J. Am. Chem. Soc. Volume 125, Number 26, pages 7792-7793 (2003)] (5.52 grams, 28.9 millimoles, 1 equivalent), triphenylphosphine (8.4 grams, 31.8 millimoles, 1.1 equivalents) in tetrahydrofuran (20 milliliters), and 3-methoxy-propanol ( 3 milliliters, 31.8 mmol, 1.1 equivalents) in tetrahydrofuran at room temperature, and the solution is stirred for 16 hours, before evaporating the solvents. Column chromatography by flash evaporation [hexane: EtOAc (9: 1) to hexane.EtOAc (4: 1)] gives the product as a light yellow oil. MS (LC-MS): 264.9 [M + H] +; Rf [to hexane: EtOAc (4: 1)]: 0.6 minutes. b) (3S.5S) -5 - ((1S, 3S) -1-azido-3 { [4-fluoro-3- (3-methoxypropoxy) -phenyl] -hydroxy-methyl) -4 -methyl-pentyl) -3- isopropyl-dihydro-furan-2-one.

To a solution of 4-bromo-1-fluoro-2- (3-methoxy-propoxy) -benzene (1.94 grams, 13.3 mmol, 1.4 equivalents) and N-methyl-morpholine (1.6 milliliters, 14.7 mmol, 3 equivalents) in tetrahydrofuran (20 milliliters), N-butyl lithium in hexane (1.6 M, 5.5 milliliters, 8.8 mmol, 1.8 equivalents) is added dropwise at -78 ° C. The solution is stirred at -78 ° C for 1 hour, when a solution of MgBr2 (14.7 millimoles) in tetrahydrofuran (50 milliliters), freshly prepared from magnesium (0.36 grams, 14.7 millimoles, 3 equivalents) is added dropwise and 1,2-dibromo-ethane (1.3 milliliters, 14.7 millimoles, 3 equivalents) at -78 ° C. The reaction is stirred at the same temperature for 45 minutes, when added by drip (S) -2 - [(S) -2-azido-2 - ((2S, 4S) -4-isopropyl-5-oxo-tetrahydro-furan-2-yl) -ethyl] -3-methyl-butyraldehyde ( 1.4 grams, 4.9 mmol, 1 equivalent) in tetrahydrofuran (14 milliliters) at -78 ° C. The reaction mixture is stirred for an additional 1 hour at the same temperature, before being quenched with saturated aqueous NH 4 Cl (20 milliliters), and warmed to room temperature. The mixture is extracted with EtOAc, the combined extracts are washed with brine, dried over Na2SO4, and the solvent is evaporated. Flash column chromatography [CH2Cl2 to CH2Cl2: acetone (9: 1)] gives the product as a light yellow oil. MS (LC-MS): 488 [M + Na] +; Rf [CH2Cl2: acetone (98: 2): 0.25 minutes. The starting material of (S) -2 - [(S) -2-azido-2 - ((2S, 4S) -4-isopropyl-5-oxo-tetrahydro-furan-2-yl) -ethyl] -3 -methyl-butyraldehyde, is prepared according to the methods described in European Patent Numbers EP 0,678,503 B1, and EP 0,678,514 A1. c) (3S, 5S) -5-. { (1S, 3S) -1-amino-3- [4-fluoro-3- (3-methoxy-propoxy) -benzyl] -4-methyl-pentyl} -3-isopropyl-dihydro-furan-2-one.

A solution of (S) -2 - [(S) -2-azido-2 - ((2S, 4S) -4- isopropyl-5-oxo-tetrahydro-furan-2-yl) -ethyl] -1- [ 4-Fluoro-3- (3-methoxy-propoxy) -phenyl] -3-methyl-butyl-ester of isobutyric acid (1.45 grams, 2.7 millimoles, 1 equivalent), Pd / C (10 percent, 2.9 grams) , and ethanol-amine (0.17 milliliters, 2.7 millimoles, 1 equivalent) in ethanol (135 milliliters), was stirred under H2 (1 atmosphere) for 24 hours. The reaction mixture is filtered, before evaporating the solvent, to give the product as a light gray gum. MS (LC-MS): 424 [M + H] +. d) [(1S, 3S) -3- [4-f] luoro-3- (3-methoxy-propoxy) -benzyl] -1 - ((2S, 4S) -4-isopropyl-5-tert-butyl ester -oxo-tetrahydro-furan-2-yl) -4-methyl-pentyl] -carbamic acid.

A solution of (3S, 5S) -5-. { [1 S, 3 S) -1-amino-3- [4-fluoro-3- (3-methoxy-propoxy) -benzyl] -4-methyl-pentyl} -3-isopropyl-dihydro-furan-2-one (1.13 grams, 2.7 millimoles, 1 equivalent), diterbutyl dicarbonate (2.1 grams, 9.4 millimoles), and di-isopropyl-ethyl-amine (1.83 milliliters, 10.7 millimoles, 4 equivalents) in CH2Cl2 (20 milliliters), is stirred at room temperature for 164 hours. The solution is washed with aqueous HCl (1M), saturated aqueous NaHCO3, and brine, dried over Na2SO4, and the solvents are evaporated. Flash column chromatography [CH2Cl2 to CH2Cl2: acetone (95: 5)] gives the product as a light yellow oil. MS (LC-MS): 546 [M + Na] +; Rf (CH2Cl2: acetone (95: 5)]: 0.71 minutes. e) Terbutil-acid ester. { (1S, 2S, 4S) -1 - [(S) -2- [4-f luoro 3- (3-methoxy-propoxy) -benzyl] -3-methyl-butyl) -2-hydroxy-4- [ (1-hydroxy-methyl-cyclopropyl-methyl) -carbamoyl] -5-methyl-hexy I} - c a r b a mi c o. [(1 S, 3S) -3- [4-fluoro-3- (3-methoxy-propoxy) -benzyl] -1 - ((2S, 4S) -4-isopropyl-5-oxo-ter-butyl ester -tetrahydro-furan-2-yl) -4-methyl-pentyl] -carbamic acid (100 grams, 0.19 millimoles, 1 equivalent), 3-am ino-2, 2-dimethyl-propanol (0.3 grams, 2.8 millimoles, 15 equivalents ), and acetic acid (0.11 microliters, 0.002 millimoles, 0.01 equivalents), are stirred at 60 ° C for 24 hours, when the solvent. Flash column chromatography (CH2Cl2 / MeOH, 95: 5, to CH2Cl2 / MeOH, 9: 1), gives the product as a light yellow solid. MS (LC-MS): 627 [M + H] +; Rf (C H2C l2 / M eO H, 9: 1): 0.25. f) ((2S, 4S, 5S, 7S) -5-amino-7- [4-fluoro-3- (3-methoxy) -amido] -amidohydroxymethyl-cyclopropyl-1-methyl) -amide. propoxy) -benzyl] -4-hydroxy-2-isopropyl-8-methyl-nonanoic acid.

At 5 ° C, 4N HCl / dioxane (0.97 milliliters) is added to the ((1S, 2S, 4S) -4-cyclopropyl-carbamoyl-1 -. {(S) -2- [4-tert-butyl ester. -fluoro-3- (3-methoxy-propoxy) -benzyl] -3-methyl-butyl.} -2-hydroxy-5-methyl-hexyl) -carbamic acid (89 milligrams, 0.14 mmol, 1.0 equivalents) in dioxane (0.8 milliliters). The resulting solution is stirred at 5 ° C for 1 hour, upon which it is lyophilized. Flash column chromatography (CH2Cl2 / MeOH (10 percent NH4OH), 95: 5, to CH2Cl2 / MeOH (10 percent NH4OH), 9: 1), gives the product as a light yellow solid. MS (LC-MS): 527.1 [M + H] +; Rf (CH2Cl2 / MeOH (NH4OH at 10 percent) 9: 1): 0.16 minutes.

Example 5. (3-Hydroxy-2, 2-dim and I-p-pil) -am of the acid (2S, 4S.5S.7S) -5-amino-7- [4-fluoro-3 - (3-methoxy-propoxy) -benzyl] -4-hydroxy-2-isopropyl-8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (IV).

MS (LC-MS): 527.1 [M + H] +; Rf [CH2Cl2: MeOH (10 percent NH3) (9: 1)]: 0.16 minutes.

Example 6: (3-h id rox¡-2, 2-d imeti l-propi l) -amide of the acid (2S, 4S, 5S, 7S) -5-amino-7- [4-fluoro- 3- (3-methoxy-propoxy) -benzyl] -4-hydroxy-2-isopropyl-8-methylene-nonanoic. The title compound is prepared according to General Procedure (IV).

MS (LC-MS): 606.1 [M + H] +; Rf [CH2Cl2: MeOH (9: 1)]: 0.16 minutes. Example 7: [1 - ( { (2S, 4S, 5S, 7S) -5-am ino-7- [4-f luoro-3- (3-methoxy-propoxy) -benzyl] -4-hydroxy- 2-isopropyl-8-methyl-n-nanoi I -am in o.} -m eti I) -c icl op ro pi I] -am id a cyclopropane-carboxylic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 590.1 [M + H] +; Rf [CH2Cl2: MeOH (10 percent NH3) (9: 1)]: 0.16 minutes.

Eiem pio 8. (1-methoxy-methyl-cyclop-pyrrol-m-ethyl) -amide of (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4] -methoxy-3- (3-methoxy-propoxy) -benzyl-8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 551 [M + H] +; Rf [C H 2 Cl 2: M e O H (9: 1)]: 0.16 minutes. Example 9 (1S-hydroxy-methyl-cyclopropyl-methyl) -amide of (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy] 3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 537 [M + H] +; Rf [CH2Cl2: MeOH (9: 1)]: 0.15 minutes.

Example 10. (2-f I or ro-eti l) -am id to the acid (2S.4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 499.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 4.63 minutes.

Eiem pio 11. (2,2-d if luoro-ethyl) -amide of (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3] acid - (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 518.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 4.75 minutes.

Eiem pio 12. (3,3,3-trif luoro-p ropi l) -am ida (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4- methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared in accordance with the General Procedure (I).

MS (LC-MS): 535.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 4.9 minutes.

Example 13: Cyclopropyl-methyl-amino acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 508.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 4.91 minutes.

Example 14: (1-p ro p i 1-1 -methyl-ethyl) -amide of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 536.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 min., flow: 1.5 milliliters / minute ): 5.21 minutes.

Eiem pio 15. ((R) -1-cyclopropi l-ethyl) -amide of acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 522.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 4.95 minutes.

Eiem pio 16. ((S) -1 -ci cl op pyl I -eti l) -am ida (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7 - [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 522.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 4.93 minutes.

Eiem pio 17. (2, 2-d m eti I -cic lo p ro pi I -m eti I) -am ida acid (2S, 4S, 5S.7S) -5-amino-4-hydroxy-2 -isopropM-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 536.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 4.81 minutes.

Example 18. [(1R, 3S) -2,2-dimethyl-3- (2-methyl-propenyl) -cyclopropyl-ethyl] -amide of (2S, 4S, 5S, 7S) -5-am i no- 4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 590.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.70 minutes.

Eiem pio 19. ((2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- ((R) -1-cyclobutyl-ethyl) -amide. (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 536.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.12 minutes.

Example 20. ((S) -1-cyclobutyl-1-ethyl) -amide of (2S, 4S.5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy] 3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 536.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.15 minutes.

Eiem pio 21. ci cl o pen ti I -m eti-am ida ida (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 535.4 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.15 minutes.

Eiem pio 22. ((S) -1-cyclopentyl-1-ethyl) -amide of (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4] -methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 550.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.25 minutes.

Eiem pío 23. ((R) -1-ci clopenti l-etl) -am i da (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [ 4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 550.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.24 minutes.

Eiem pio 24. ((R) -2,2-d im eti l-cyclopentyl) -amide of acid (2S, 4S.5S.7S) -5-amino-4-hydroxy-2-isopropyI-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 550.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.27 minutes.

Example 25. ((S) -2, 2-d m eti I -c icl or pen ti I) -am id to acid (2S, 4S, 5S.7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 550.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.25 minutes.

Eiem pio 26. (1-ethyl-cyclopenti l) -amide of the acid (2S, 4S, 5S.7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 535.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H2O / I minute, flow: 0.5 milliliters / minute): 5.08 m inutes.

Eiem pio 27. (1-f I uo ro-cycle penti l) -am i da of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared in accordance with the General Procedure (I) MS (LC-MS): 554 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H2O / I minute, flow: 0.5 milliliters / minute): 5.42 minutes.

Eiem pio 28. cyclohexyl-methyl-1-amino acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyI-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 549.3 [M] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H2O / I minute, flow: 0.5 milliliters / minute): 3.87 minutes.

Eiem pío 29. ((S) -1-cyclohexyl-eti l) -amide of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 564.0 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.36 minutes.

Eiem pio 30. ((R) -1-cyclohexyl-1-yl) -amide of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 564.0 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.38 minutes.

Eiem pio 31. cyclohexyl-m eti-amide of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 563.2 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.62 minutes.

Example 32. ((2S, 4S, 5S, 7S) -5-am ino-4-hydroxy-2-iso (1.7,7-trimethyl-bicyclo- [2.2.1] -hept-2-yl) -amide) -propyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared in accordance with the General Procedure (I) MS (LC-MS): 590.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CHsCN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.71 minutes.

EXAMPLE 33. Meti-ester of 1 - ( { (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy -propoxy) -benzyl] -8-methyl-nonanoyl-amino.}. -methyl) -cyclopropane-carboxylic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 566.0 [M + H] +; tR (HPLC, column C8, 20 to 95 percent CH3CN / H20 / 3.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow rate: 0.8 milliliters / minute): 2.44 minutes Example 34. Methyl ester of 1 - ( { (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy) propoxy) -benzyl] -8-methyl-nonanoyl-amino.} - methyl) -cyclobutane-carboxylic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 580.0 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.11 minutes.

Example 35. Methyl ester of 1 - acid. { (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoylamino} -cyclopentane-carboxylic acid.

The title compound is prepared according to General Procedure (I).

MS (LC-MS): 580.0 [M + HJ +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.02 minutes.

Example 36. Methyl ester of 1 - ( { (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy) propoxy) -benzyl] -8-methyl-nonanoyl-amino.} - methyl) -cyclopentanecarboxylic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 594.0 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute): 5.19 minutes.

Example 37. Methyl ester of 1 - acid. { (2S.4S.5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoylamino} -cyclohexanecarboxylic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 594.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.13 minutes.

Example 38. Methyl ester of 1 - ( { (2S, 4S, 5S, 7S) -5 amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy ) -benzyl] -8-methyl-nonanoyl-amino.} - methyl) -cyclohexane-carboxylic acid.

The title compound is prepared according to General Procedure (I).

MS (LC-MS): 608.0 [M + H] +; IR (HPLC, column C8, from 20 to 95 per cent of CH3CN / H20 / 3.5 min., 95 percent of CH3CN / I minute, flow: 0.8 milliliters / minute): 2.74 minutes.

Example 39. Methyl ester of (S) - acid. { (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoyl-amino) -cyclohexyl-acetic. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 608.0 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.26 minutes.

Example 40. Methyl ester of (1S, 3R) -3- acid. { (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoyl- amino] -cyclopentane-carboxylic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 580.0 [M + H] +; tR (HPLC, column C18, from 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent of CHsCN / 3 minutes, from 100 to 10 percent of CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute): 5.10 minutes. Example 41. Methyl ester of (1S.3R) -3- acid. { (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoyl-amino] -cyclopentane-carboxylic acid. The title compound is prepared according to the procedure MS (LC-MS): 580.0 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 4.36 inutes.

Example 42. Methyl ester of 4- acid. { (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoyl-amino } -cyclohexane carboxylic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 594.0 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.08 minutes.

Example 43. Methyl ester of 4- acid. { (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoylamino) - cyclohexane carboxylic The title compound is prepared according to General Procedure (I).

MS (LC-MS): 594.0 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CHsCN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.01 minutes.

Example 44. 1 - ( { (2S, 4S, 5S, 7S) -5-am ino-4-h idroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy acid ) -benzyl] -8-methyl-nonanoyl-amino.} - methyl) -cyclopentane-carboxylic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 579.1 [M + H] +; tR (HPLC, column C8, from 20 to 95 percent of CH3CN / H20 / 3.5 minutes, 95 percent of CH3CN / H20 / 1 minute, flow: 0.8 milliliters / minute): 2.48 minutes.

Example 45. Amide of (2S.4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8- acid methyl-nonanoic. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 453.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 4.41 minutes.

Example 46. Amide of acid 1 - ( { (2S, 4S, 5S, 7S) -5-am ino 4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoyl-amino) -methyl} -cyclopropane-carboxylic acid.

The title compound is prepared according to General Procedure (I).

MS (LC-MS): 550.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 5.05 minutes.

Example 47. Amide of 1 - ( { (2S, 4S, 5S, 7S) -5-am ino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy ) -benzyl] -8-methyl-nonanoyl-amino.}. -methyl) -cyclobutane-carboxylic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 564.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H2O / I minute, flow: 0.5 milliliters / minute): 4.54 minutes.

Example 48. Amide of 1 - ( { (2S, 4S, 5S, 7S) -5-am ino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy ) - benzyl] -8-methyl-nonanoyl-amino.} - methyl) - cyclopentanecarboxylic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 578.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 4.2 minutes.

Example 49. Amide of acid 1 - ( { (2S, 4S, 5S, 7S) -5-am ino 4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoyl-amino.}. methyl) -cyclohexan-carboxylic acid.

The title compound is prepared according to General Procedure (I).

MS (LC-MS): 592.2 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 m i I i t ro s / m u n uto): 5.02 minutes.

Example 50. Amide of acid 1 -. { (2S, 4S, 5S, 7S) -5-am ino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoyl-amino } -cyclopentane-carboxylic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 564.2 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H2O / 1 minute, flow: 0.5 milliliters / minute): 4.66 minutes.

Example 51. 2- Acid Amide. { (2Ss4S, 5S, 7S) -5-am ino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-m etyl-nonanoyl-am i no } -cyclopentan -carboxylic. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 564.3 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 4.3 minutes.

Example 52. 2- Acid amide. { (2S, 4S, 5S, 7S) -5-am ino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoyl-amino } -cyclohexanecarboxylic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 578.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 4.84 minutes.

Example 53. Methyl-amide of 1 - ( { (2S.4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy) propoxy) -benzyl] -8-methyl-nonanoyl-amino.} - methyl) -cyclopentanecarboxylic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 592.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H2O / I minute, flow: 0.5 milliliters / minute): 4.51 minutes.

Example 54. (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyI-7- [4-methoxy-3] (1-formyl-amino-cyclopropyl [-methyl] -amide. - (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared in accordance with the General Procedure (I) MS (LC-MS): 551 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 4.41 minutes.

Example 55. (1 -a cet i I -am ino -cic I op ro pi I -m eti I) -amide of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl -7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methy! -nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 565.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 4.46 m inutes.

Eiem pio 56. ((2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxyl] -amido-cyclopentyl-methyl -3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 579.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 4.7 minutes.

Eiem pio 57. (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-acetyl-ami-cyclopentyl-methyl ethyl] -amide. methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 592.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 4.68 minutes.

Eiem pio 58. (2S, 4S, 5S, 7S) -5-am ino-4-hydroxy-2-isopropyl- [1- (2,2-dimethyl-propionyl-amino-cyclopentyl-methyl) -amide. 7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 634.2 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H2O / I minute, flow: 0.5 milliliters / minute): 5.18 minutes.

Eiem pío 59.. { 1 - [(2,2-dimethyl-proponyl-amino) -methyl] -cyclopentyl} -am ida (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-m eti I-no nano ico.

The title compound is prepared according to General Procedure (I).

MS (LC-MS): 635.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 illiliters / minute): 5.34 minutes.

Example 60. [1- ( { (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl) ] -8-methyl-nonane-1-amino-cyclopentyl-1-cyclopentyl-cyclopentyl-1-cyclopropane-carboxylic acid The title compound is prepared according to General Procedure (I).

S (LC-MS): [M + H] +; Rf [CH2Cl2: Me0H (9: 1)]; 0.18 minutes, Example 61. [1 - ( { (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy)] -butyl ester. -propoxy) -benzyl] -8-methyl-nonanoyl-amino.} - methyl) -cyclopropyl-carbamic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 623.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent C H3CN / H20 / 6.5 minutes, 95 percent CH3CN / H2O / I minute, flow: 0.5 milliliters / minute): 5.22 minutes. Example 62. Terbutil-ester of acid [1 - ( { (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy -propoxy) -benzyl] -8-methyl-nonanoyl-amino.} - methyl) -cyclopentyl I] -carbamic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 650.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H2O / I minute, flow: 0.5 milliliters / minute): 5.43 minutes.

Example 63. (1 -am ino-cyclopropi l-meti I) -am ida acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyI-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 523.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H2O / I minute, flow: 0.5 milliliters / minute): 4.33 minutes.

Eiem pío 64. (1 -am ino-ciclopentil-m eti l) -am ida acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 550.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 4.31 minutes.

Eiem pio 65. (4-am i non-cyclohexy l) -amide of the acid (2S.4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 550.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 4.18 minutes.

Eiem pio 66. (4-amo-cyclohexyl) -amide of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 550.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 4.14 minutes.

Example 67. (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (1-dimethyl-amino-cyclopropyl-1-ethyl) -amide) (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 551.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 4.36 minutes.

Eiem pio 68. (1 -dim eti I-am in oc i cio pen ti I -m eti I) -am ida of the acid (2S.4S, 5S.7S) -5-amino-4-hydroxy-2-isopropil -7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methylene-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 578.2 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H2O / I minute, flow: 0.5 milliliters / minute): 4.29 minutes.

Eiem pio 69. (1-M-ethoxy-methyl-cyclopentyl) -amide of acid (2S.4S.5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 565.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 5.11 minutes.

Eiem pío 70. (1-m ethoxy-cyclopentyl-methyl) -amide of acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 566 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 5.01 minutes.

Eiem pio 71. ((1 S, 2S) -2-be n ci loxi-cicio pen ti l) -am ida of the acid (2S, 4S.5S, 7S) -5-amino-4-hydroxy-2- isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 628.0 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.38 minutes.

Example 72. ((2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4- (2R, 2R) -2-benzyloxy-cyclopentyl] -amide. methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 628.0 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.42 minutes.

Eiem pio 73. (4-methoxy-cyclohexyl) -amide of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid.

MS (LC-MS): 565.1 [M + H] +; tR (HPLC, column C8, from 5 to 95 percent of CH3CN / H20 / 6.5 minutes, 95 percent of CH3CN / H2O / I minute, flow: 0.5 milliliters / minute): 4.59 minutes. Eiem pio 74. (4-m ethoxy-cyclohexyl) -amide of acid (2S.4S, 5S.7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid.

MS (LC-MS): 565.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 4.67 minutes.

Eiem pio 75. ((2S, 4S.5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4 (2S, 2S) -2-benzyloxy-cyclohexyl) -amide. -methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 641.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CHsCN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 6.10 minutes.

Eiem pio 76. ((2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyI-7- ((1R, 2R) -2-benzyloxy-cyclohexyl] -amide. 4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 641.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 6.00 minutes.

Eiem pio 77. (1-hydroxy-cyclopropyl-methyl) -amide of acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 523.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H2O / I minute, flow: 0.5 milliliters / minute): 4.52 minutes.

Eiem pio 78. ((1R, 2R) -2-hydroxycyclopentyl) -amide of (2S.4S, 5S, 7S) -5-amino-4-hydroxy-2-ysopropyl-7 acid - [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 538.0 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 4.74 minutes.

Example 79. ((1S, 2S) -2-hydroxy-cyclopentyl) amide of the acid (2S.4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy] -3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 537.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.37 minutes.

Eiem pío 80. (1 -hid roxi-m eti I -ci cl open ti I) -am ida acid (2S, 4S.5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid . The title compound is prepared according to General Procedure (I).

MS (LC-MS): 551.1 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H2O / I minute, flow: 0.5 milliliters / minute): 4.77 minutes.

Eiem pio 81. (1-h id roxi-cyclopenti l-m ethyl) -am ida acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 552 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H2O / 6.5 minutes, 95 percent CH3CN / H2O / I minute, flow: 0.5 milliliters / minute): 4.72 m inutes.

Eiem pio 82. ((1 R, 2R) -2-h id roxy-cyclohexy l) -am ida of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 551.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 4.62 minutes.

Example 83. ((1 S, 2S) -2-h id roxy-cyclohexy l) -am ida of (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [ 4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 551.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 4.41 minutes.

Example 84. (4-h id roxy-cyclohexy l) -amide of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 551.3 [M] +; Rf [CH2Cl2: MeOH (9: 1)]: 0.61 minutes.

Eiem pío 85. (4-h idroxi-ciclohexi l) -am ida of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 552.0 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.81 minutiae.

Eiem pio 86. (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-hydroxy-cyclohexyl-methyl) -amide. -methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid.

The title compound is prepared according to General Procedure (I).

MS (LC-MS): 565.2 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H2O / I minute, flow: 0.5 milliliters / minute): 5.07 minutes.

Eiem pio 87. ((R) -1-f en il-eti l) -am ida of the acid (2S, 4S.5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4- methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 558.3 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H2O / I minute, flow: 0.5 milliliters / minute): 4.63 minutes.

Example 88. ((S) -1-f in i 1 -eti 1) -am id a of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxr-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 558.3 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 4.69 minutes.

Eiem pio 89. (1-methyl-1-f in il-eti l) -am ida acid (2S.4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyI-7- [4-methoxy-3- (3-m-ethoxy-p -roxy) -benz I] -8-m ethi I-not nano ico The title compound is prepared according to General Procedure (I).

MS (LC-MS): 572.0 [M + HJ +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H2O / 1 minute, flow: 0.5 milliliters / minute): 3.85 min.

Eiem pio 90. (Naphtal in -1 -yl m eti l) -am id to acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 594.5 [M + H] +; Rf [CH2Cl2: MeOH (9: 1)]: 0.21 minutes.

Example 91. i ndan-2-i lam ida acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy ) -benzyl] -8-methyl-nonanoic acid.

The title compound is prepared according to General Procedure (I).

MS (LC-MS): 569.1 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.16 minutes.

Example 92. 2-methyl-benzyl-amide acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 558.3 [M + H] +; Rf [CH2Cl2: MeOH (9: 1)]: 0.17 minutes. Eiem pio 93. 3-methyl-benzyl-amide acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid.

The title compound is prepared according to General Procedure (I).

MS (LC-MS): 558.3 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH.CN/3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute): 5.28 minutes.

Eiem pío 94. 4-m eti l-benci l-am ida acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 558.3 [M + H] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 3.76 minutes Example 95. ((R) -1-p-tol-1-ethyl) -amide of (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 571.1 [M + H] +; tR (HPLC, column C18, from 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent of CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute): 5.24 minutes. Example 96. ((S) -1-p-toli l-eti l) -amide of the acid (2S.4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 571.2 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.25 minutes.

Eiem pío 97. 4-isopropi l-benzyl-am ida acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 586.3 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 4.26 minutes.

Example 98. 2-Methoxy-benzyl-amino acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 573.3 [M] +; Rf [CH2Cl2: Me0H (9: 1)]: 0.15 minutes.

Eiem pío 99. 3-m ethoxy-be n ci Iam ida (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- ( 3-methoxy-propoxy) -benzyl] -8-m ethi I-not nanoic. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 573.3 [M] +; Rf [CH2Cl2: Me0H (9: 1)]: 0.17 minutes.

Eiem pío 100. 4-m ethoxy-benzyl-amide acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared in accordance with the General Procedure (I) MS (LC-MS): 573.3 [M] +; Rf [CH2Cl2: Me0H (9: 1)]: 0.14 minutes.

Eiem pio 101. [(S) -1 - (3-methoxy-f in i I) -e t i I] -am ida acid (2S, 4S, 5S.7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (1).

MS (LC-MS): 587.2 [M + H] +; tR (HPLC, column C18, from 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent of CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute): 5.10 minutes. Eiem pio 102. [(R) -1 - (3-methoxy-phenyl) -ethyl] -amide of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 587.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute): 5.10 minutes.

Example 103. [(S) -1 - (4-m ethoxy-f in i I) -et i I] -am i d a of the acid (2S, 4S, 5S.7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 587.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute): 5.07 minutes.

Example 104. [(R) -1 - (4-methoxy-f in i l) -eti l] -am ida acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 587.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.09 minutes.

Eiem pio 105. 2-methyl-sulf an il-benzyl amide of acid (2S, 4S.5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid.

The title compound is prepared according to General Procedure (I).

MS (LC-MS): 589.3 [M] +; Rf [CH2Cl2: Me0H (9: 1)]: 0.10 minutes.

Eiem pío 106. 4-meti l-sulf an il-benzyl-am ida acid (2S, 4S.5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 589.0 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.12 minutes.

Eiem pio 107. 2,5-d-imethoxy-benzyl-amide of (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- ( 3- methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 603.3 [M] +; Rf [CH2Cl2: Me0H (9: 1)]: 0.13 minutes.

Eiem pio 108. 2,3-d imethoxy-benzyl-amino acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 603.3 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute): 5.03 minutes. Example 109. 2,4-dimethoxy-benzyl-amino acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 603.3 [M] +; R, [CH2Cl2: MeOH (9: 1)]: 0.23 minutes. Eiem pio 110. 3,4-d imethoxy-benzyl-amide acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyI-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 603.3 [M] +; Rf [CH2Cl2: MeOH (9: 1)]: 0.18 minutes.

Eiem pio 111. 2, 6-d imethoxy-benzyl-amide acid (2S.4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyI-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 603.3 [M] +; R, [CH2Cl2: MeOH (9: 1)]: 0.24 minutes.

Eiem pio 112. 3,5-dimethoxy-benzyl-amino acid (2S.4S, 5S.7S) -5-amino-4-hydroxy-2-isopropM-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to the Procedure MS (LC-MS): 603.3 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute): 5.04 minutes. Eiem pio 113. 2-trifluoro-methoxy-benzyl-amide acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 627.3 [M] +; Rf [CH2Cl2: MeOH (9: 1)]: 0.31 minutes.

Eiem pio 114. 3-trif I u o ro-m ethoxy-ben ci I -am id a of acid (2S, 4S, 5S.7S) -5-amino-4-hydroxy-2-isopropyI-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 627.2 [M] +; R, [CH2Cl2: MeOH (9: 1)]: 0.17 minutes. Example 115. 4-trifluoro-m-ethoxy-benzyl-amide acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyI-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 627.3 [M] +; Rf [CH2Cl2: MeOH (9: 1)]: 0.26 minutes.

Eiem pio 116. 2-f I u-ro-ben ci I -am id a of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 561.3 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.03 minutes.

Eiem pio 117. 3-f I u-ro-ben cil -am id a of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 561.3 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.09 minutes.

Eiem pio 118. 4-f luoro-benzyl-amide acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The compound of the title is prepared according to General Procedure (I).

MS (LC-MS): 561.3 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CHsCN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.08 minutes.

Eiem pio 119. [(R) -1 - (4-f luoro-f en il) -ethyl] -am ida acid (2S.4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methylene-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 575.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.11 minutes.

Example 120. [(S) -1 - (4-f luoro-f en il) -eti l] -am ida of the acid (2S, 4S, 5S.7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 575.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.09 minutes.

Example 121. 2-chloro-benzyl-amide acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 577.3 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.15 minutes.

Example 122. 3-cl or ro -ben ci I -am ida acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 577.3 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.18 minutes.

Eiem pio 123. 4-cl or ro-ben ci I -am ida acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared in accordance with the General Procedure (I).

MS (LC-MS): 577.3 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CHsCN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.14 minutes.

Eiem pío 124. 2, 5-d if I u-ro-ben ci I -am of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 579.1 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 illiliters / minute ): 5.13 minutes.

Eiem pio 125. 2,4-d if luoro-benz l-am ida acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 579.1 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.07 minutes.

Eiem pio 126. 2,6-difluoro-benzyl-amide acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 579.0 [M] +; tR (HPLC, column C8, 5 to 95 percent CH3CN / H20 / 6.5 minutes, 95 percent CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 4.63 minutes.

Eiem pio 127. 3,4-d if I uoro-benz l-am ida acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 579.0 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.11 minutes.

Example 128. 3,5-d if luoro-benz l-am ida acid (2S.4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyI-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 579.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CHsCN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.12 minutes.

Eiem pio 129. 2-trif I u o ro-m eti l-ben ci I -am id a of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 611.1 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.43 minutes.

Eiem pio 130. 3-trif I uoro-m ethyl-benzyl-amide acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 611.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 min, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.59 minutes.

Eiem pio 131. 4-trif I uoro-m eti l-ben ci l-am of acid (2S, 4S.5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 611.0 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.43 minutes.

Eiem pio 132. 4-cia n o-ben ci I -am ida acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 568.3 [M] +; Rf [CH2Cl2: Me0H (9: 1)]: 0.25 minutes.

Eiem pio 133. 4-d imethyl-amino-benzyl-amino acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid.

The title compound is prepared according to General Procedure (I).

MS (LC-MS): 586.3 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 4.26 minutes.

Example 134. (2S, 4S, 5S, 7S) -5-am ino-4-h id roxi-2 (2,3-dihydro-benzo- [1,4] -dioxin-6-ylmethyl) -amide. -iso-propyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 601.3 [M] +; Rf [CH2Cl2: Me0H (9: 1)]: 0.25 minutes. Example 135. (2S, 4S, 5S, 7S) -5-am ino-4-h id roxy -2 (2,3-dihydro-benzo- [1,4] -dioxin-5-ylmethyl) -amide. -iso- propyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 601.3 [MJ +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.07 minutes.

Example 136. (3,4-Dihydro-2H-benzo [b] [1,4] -dioxepin-7-imethyl) -amide of (2S, 4S, 5S, 7S) -5-am i -4-h id roxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 615.3 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.07 minutes.

Example 137. (2, 3-dih id ro-benzof u ra n -5-i I m eti l) -am id a (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2 acid -isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 585.3 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.07 minutes.

Eiem pio 138. (benzofu ran-4-ylme ethyl) -amide of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 583.3 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.11 minutes.

Eiem pío 39. 2-p i pe rid i n -1 -i I -ben ci l-am id a of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-ylpropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 626.4 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 4.58 minutes.

Eiem pio 140. 3-piperidin-1-yl-benzyl-amide of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 626.3 [M] +; tR (HPLC, column C18, from 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent of CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute): 4.35 minutes. Eiem pio 141. 4-p i peri d i n -1-yl-benzyl-amide of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 626.4 [M] +; R, (CH2Cl2: Me0H (9: 1)]: 0.35 minutes.

Example 142. 2-Morph olin-4-yl-ben-cyl-ida acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 628.4 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 4.58 minutes.

Eiem pio 143. 4-mo rf o I in -4-i l-ben ci l-am id a of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7 [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid.

The title compound is prepared according to General Procedure (I).

MS (LC-MS): 628.3 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 4.61 minutes.

Eiem pío 144. 4-morph ol i n -4-I-ben c i l-am ida acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to the procedure MS (LC-MS): 628.4 [M] +; tR (HPLC, column C18, from 10 a) 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute): 4.55 minutes.

Eiem pío 145. 2-pyrrole id in-1 -i l-benzyl-am ida acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 612.4 [M + H] +; tR (HPLC, column C18, from 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent of CHsCN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute): 4.46 minutes. Eiem pio 146. 3-pyrrolidin-1-yl-benzyl-amide of (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to the Procedure MS (LC-MS): 612.3 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 4.66 minutes.

Example 147. 4-pyrrolidin-1-yl-benzyl-amide acid (2S, 4S, 5S.7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 612.4 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 4.37 minutes.

Example 148. 3-pyrrol-1-yl-benzyl-amide acid (2S.4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 608.3 [M] +; R, [CH2Cl2: M eOH] (9: 1)]: 0.37 minutes.

Eiem pio 149. 4-pyrrol-1-yl-benzyl-amide of (2S, 4S, 5SJ 7 S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 608.3 [M] +; Rf [CH2Cl2: MeOH] (9: 1)]: 0.35 minutes.

Eiem pio 150. 4-thiof en-3-yl-benzyl amide of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid.

The title compound is prepared according to General Procedure (I).

MS (LC-MS): 625.3 [M] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.45 minutes.

Example 151. (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl) phenethyl-amide -8-methyl-nonanoic. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 557.1 [MJ +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute): 5.18 minutes. Example 152. [(2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7-1-phen-1-phenylpropyl] -amide] - [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 611.1 [M + H] +; tR (HPLC, column C8, from 5 to 95 percent of CH3CN / H20 / 6.5 minutes, 95 percent of CH3CN / H20 / 1 minute, flow: 0.5 milliliters / minute): 5.6 m inutes. Eiem pio 53. [2- (2-f luoro-f in i I) -et i I] -am ida acid. { 2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 575.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.12 minutes.

Eiem pio 154. [2- (3-f I u o ro-f in i I) -et i I] -am id a of the acid (2S, 4S.5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 575.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.11 minutes.

Example 155. [2- (4-f luoro-f-enyl) -ethyl] -amide of the acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 575.0 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.06 minutes.

Example 156. (2-f in oxy-ethyl) -amide of the acid (28.48.58, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The title compound is prepared according to General Procedure (I).

MS (LC-MS): 573.3 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.08 minutes.

Eiem pio 157. [2- (4-methoxy-f-enoxy) -eti l] -am ida acid (2S, 4S, 5S, 7S) -5-amino-4-hydroxy-2-isopropyl-7- [4-methoxy-3- (3-methoxy-propoxy) -benzyl] -8-methyl-nonanoic acid. The compose of the title is prepared in accordance with General Procedure (I).

MS (LC-MS): 603.1 [M + H] +; tR (HPLC, column C18, 10 to 100 percent CH3CN / H20 / 5 minutes, 100 percent CH3CN / 3 minutes, 100 to 10 percent CH3CN / H20 / 3 minutes, flow: 1.5 milliliters / minute ): 5.09 minutes.

Eiem pío 158. Gelatin solution. A sterile filtered aqueous solution, containing 20 percent cyclodextrins as a solubilizer, of one of the compounds of Formula (I), mentioned in the Examples above, as an active ingredient, is mixed in such a manner, with the application of heat and low aseptic conditions, with a sterile gelatin solution containing phenol as a preservative, that 1.0 milliliter of the solution has the following composition: Eiem pío 159. Sterile dry substance for injection. Five (5) milligrams of one of the compounds of Formula (I), mentioned in the preceding Examples, as an active ingredient, are dissolved in 1 milliliter of an aqueous solution containing 20 milligrams of mannitol, and 20 percent cyclodextrins as solubilizer. The solution is sterile filtered, and, under aseptic conditions, it is placed in a 2-milliliter vial, deep-frozen, and lyophilized. Before use, the lyophilisate is dissolved in 1 milliliter of distilled water, or in 1 milliliter of physiological saline solution. The solution is administered intramuscularly or intravenously. The formulation can also be filled into double-chamber disposable syringes.

Example 160. Nasal spray. Five hundred (500) milligrams of a finely ground powder (< 5.0 gm) of one of the compounds of Formula (I), mentioned in the preceding Examples, are suspended, as active ingredient, in a mixture of 3.5 milliliters of "Myglyol 8 12", and 0.08 grams of benzyl alcohol. The suspension is introduced in a performance that has a metering valve. Five (5.0) grams of "Freon 12" are introduced under pressure through the valve in the container. The "Freon" is dissolved in the mixture of Myglyol / benzyl alcohol by stirring. The atomizer container contains approximately 100 individual doses, which can be administered individually.

Eiem pío 161. Tablets covered with film. The following constituents are processed for the preparation of 10,000 tablets, each containing 100 milligrams of active ingredient.

A mixture of one of the compounds of Formula (I), mentioned in the preceding Examples, as active ingredient, 50 grams of corn starch, and colloidal silicic acid, is processed to form a wet mass with starch paste prepared from 250 grams of corn starch and 2.2 kilograms of demineralized water. The mass is forced through a sieve having a mesh size of 3 millimeters, and dried at 45 ° C for 30 minutes in a fluidized bed dryer. The dried granules are compressed through a sieve having a mesh size of 1 millimeter, mixed with a previously sieved mixture (1 millimeter sieve) of 330 grams of corn starch, magnesium stearate, stearic acid, and sodium carboxymethyl starch, and compressed to form slightly biconvex tablets.

Although the present invention has been described in considerable detail with reference to certain preferred versions thereof, other versions are possible without departing from the spirit and scope of the preferred embodiments contained herein. All references and patents (of the United States of America and others) referred to herein, are hereby incorporated by reference in their entirety, as if they were absolutely stipulated herein.

Claims (30)

1. An amide compound of d-amino-α-hydroxy-α-aryl-alkanoic acid of Formula (I): wherein: R1 is hydrogen, halogen, optionally halogenated alkyl, cycloalkyl, hydroxyl, optionally halogenated alkoxy, cycloalkoxy, lower alkoxy-lower alkoxy, or carboxy-lower alkoxy or free lower alkyl or esterified or amidated; R2 is hydrogen, halogen, optionally halogenated lower alkyl, hydroxyl, cycloalkyl, cycloalkoxy, lower alkoxy-optionally halogenated lower alkyl, lower alkoxy-optionally substituted lower alkyl, cycloalkoxy-lower alkyl; lower hydroxy-lower alkoxy optionally lower alkanoylated, halogenated, or sulfonylated; amino-lower alkyl which is unsubstituted or substituted by lower alkyl, by lower alkanoyl, and / or by lower alkoxy-carbonyl, heteroaryl-optionally hydrogenated lower alkyl, amino-lower alkoxy which is substituted by lower alkyl, by lower alkanoyl, and / or by lower alkoxycarbonyl; oxo-lower alkoxy, lower alkoxy, lower alkenyloxy, cycloalkoxy-lower alkoxy, lower alkoxy-lower alkoxy, lower alkoxy-lower alkenyl, lower alkenyloxy-lower alkoxy, lower alkoxy-lower alkenyloxy, lower alkenyloxy-lower alkyl, lower alkanoxy-alkoxy lower, lower thioalkyl-optionally S-oxidized lower alkoxy, lower thioalkyl- (hydroxy) -alowcoxyl, aryl-lower alkoxy, arylalkyl, aryl-lower alkoxy, optionally hydrogenated heteroaryl-lower alkoxy, optionally hydrogenated heteroaryl-lower alkyl, cyano lower alkoxy, lower cyanoalkyl, free lower or esterified or amidated carboxy lower alkoxy, or free lower or esterified or amidated carboxy lower alkyl; or R2 is in the meta position and is lower alkoxy-lower alkoxy optionally substituted by halogen (s); R3 is halogen or trifluoromethyl; R 4 is hydrogen, halogen, optionally halogenated lower alkyl, hydroxyl, optionally halogenated lower alkoxy or cycloalkoxy, lower alkoxy-lower alkyl, cycloalkoxy-lower alkyl, hydroxy-lower alkyl, lower thioalkyl-optionally S-oxidized lower alkyl, heterotyoaryl-lower alkyl optionally hydrogenated, heteroaryl-optionally hydrogenated lower alkyl; amino-lower alkyl that is unsubstituted or N- mono- or, lower N-di-alkylated, lower N-alkanoylated, or lower N-sulphonylated alkane, or N, N-disubstituted by lower alkylene, by unsubstituted lower aza-alkylene or lower N'-alkylated or N'- lower alkanoylate, lower oxa-alkylene, or optionally S-oxidized lower thia-alkylene, lower cyanoalkyl, free or esterified or amidated carboxy-lower alkyl, cycloalkyl, aryl, hydroxyl, lower alkoxy, cycloalkoxy, lower alkoxy-lower alkoxy , cycloalkoxy lower alkoxy, hydroxy lower alkoxy, aryl lower alkoxy, optionally halogenated lower alkoxy, lower thioalkyl optionally S-oxidized lower alkoxy, optionally hydrogenated heteroaryl lower alkoxy, optionally hydrogenated lower heteroxyaryl-lower alkoxy; lower amino-alkoxy which is unsubstituted or lower N-mono- or N, N-di-alkylated, lower N-alkanoylated, or lower N-alkylsulfonylated, or substituted by lower alkylene, by unsubstituted lower aza-alkylene or N ' lower alkyl or lower N-alkanoylated, lower oxa-alkylene, or optionally lower S-oxidized thia-alkylene, lower cyano-lower alkoxy, or free lower or esterified or amidated carboxy-lower alkoxy; or X is methylene, hydroxymethylene, oxygen, nitrogen optionally substituted by lower alkyl, optionally oxidized sulfur; R5 is lower alkyl or cycloalkyl; R6 is hydrogen, lower alkyl, hydroxyl, alkoxy, or halogen; R7 is unsubstituted amino or N-mono- or N, N-di-alkylated lower or N-lower alkanoylated; R8 is lower alkyl, lower all, cycloalkyl, or aryl-lower alkyl; R9 is optionally substituted lower alkyl, optionally substituted cycloalkyl, cycloalkyl-alkyl, cycloalkyl-carboxamides. Cycloalkyl-carboxamides substituted by N-mono- or N, N-di-alkyl, optionally substituted arylalkyl, optionally substituted aryloxy-aryl, hetero optionally substituted aryloxy-alkyl, hydroxy-free lower alkyl or aliphatically esterified or etherified; amino-lower alkyl which is unsubstituted or lower N-alkanoylated or lower N-mono- or N, N-di-alkylated or N, -disubstituted by lower alkylene, by hydroxy-, lower alkoxy-, or lower alkanoyloxy-lower alkylene, by unsubstituted lower aza-alkylene or lower N'-alkanoylated or lower N-alkylated, by lower oxa-alkylene, or by optionally lower thia-alkylene S-oxidized, carboxy-free lower alkyl or esterified or amidated, dicarboxy-free lower alkyl or esterified or amidated, carboxy-hydroxy- (hydroxy) -free or esterified or amidated lower alkyl, carboxy-cycloalkyl-free lower alkyl or esterified or amidated, cyano-lower alkyl, lower alkane-sulphonyl- lower alkyl, thiocarbamoyl-unsubstituted lower alkyl or N- mono- or N, N-di-alkylated lower, sulfamoyl-unsubstituted lower alkyl or N-mono- or N, N-di-alkylated lower, or a heteroaryl radical linked by means of a carbon atom and optionally hydrogenated and / or oxo-substituted, or lower alkyl substituted by a heteroaryl radical linked via a carbon atom and optionally hydrogenated and / or oxo-substituted; or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1, wherein: R9 is lower alkyl, optionally substituted cycloalkyl (alkyl, OH, alkoxy, alkoxy-alkyl, halogen), optionally substituted cycloalkyl-alkyl (OH, alkoxy, alkoxy-alkyl, halogen, or cycloalkyl), cycloalkylcarboxamides, N-mono- or NN-di-alkyl-substituted cycloalkyl-carboxamides, optionally substituted aryl-alkyl, hydroxy-lower alkyl free or aliphatically esterified or etherified; amino-lower alkyl which is unsubstituted or lower N-alkanoylated or lower N-mono- or N, -di-alkylated, or N, N-di-substituted by lower alkylene, by hydroxy-, lower alkoxy-, or lower alkanoyloxy- lower alkylene, unsubstituted lower aza-alkylene or lower N'-alkanoylated or lower N'-alkylated, by lower oxa-alkylene, or by thia- optionally S-oxidized lower alkylene, free or esterified or amidated carboxy-lower alkyl, free or esterified or amidated dicarboxy-lower alkyl, carboxy (hydroxy) -free or esterified or amidated lower alkyl, free carboxy-cycloalkyl-lower alkyl or esterified or amidated, cyano-lower alkyl, lower alkane-sulfonyl-lower alkyl, thiocarbamoyl-unsubstituted lower alkyl or N-mono- or N, N-di-alkylated lower, sulfamoyl-unsubstituted lower alkyl or N-mono- or N, N -di-alkylated lower, or a heteroaryl radical linked by means of a carbon atom and optionally hydrogenated and / or oxo-substituted, or lower alkyl substituted by a heteroaryl radical linked via a carbon atom and optionally hydrogenated and / or oxo-substituted; or a pharmaceutically acceptable salt thereof.

3. A compound according to claim 2, wherein: R1 and R4 are hydrogen; R2 is lower alkoxy-lower alkoxy; R3 is halogen; or a pharmaceutically acceptable salt thereof.

4. A compound according to claim, wherein the halogen / halo is fluorine or chlorine; or a pharmaceutically acceptable salt thereof.

5. A compound according to the claim 4, wherein: R3 is fluorine or trifluoromethyl; or a pharmaceutically acceptable salt thereof.

6. A compound according to the claim 5, where R2 is in the meta position, and R3 is in the para position; or a pharmaceutically acceptable salt thereof.

7. A compound according to claim 5, wherein R3 is in the ortho position; or a pharmaceutically acceptable salt thereof.

8. A compound according to the claim 5, where R3 is in the meta position; or a pharmaceutically acceptable salt thereof.

9. A compound according to claim 2, wherein R2 is in the membered position and is lower alkoxy-lower alkoxy optionally substituted by halogen (s); or a pharmaceutically acceptable salt thereof.

10. A compound according to the claim 9, wherein the halogen (s) is fluorine or chlorine; or a pharmaceutically acceptable salt thereof.

11. A compound according to claim 10, wherein the halogen (s) is fluorine; or a pharmaceutically acceptable salt thereof.

12. A compound according to claim 9, wherein R3 is in the para position; or a pharmaceutically acceptable salt thereof.

13. A compound according to claim wherein R is located in the para position, and is halogen; or a pharmaceutically acceptable salt thereof.

14. An amide compound of d-amino-α-hydroxy-α-aryl-alkanoic acid having Formula (Ia): wherein: R1 is hydrogen, halogen, optionally alkyl halogenated, cycloalkyl, hydroxyl, optionally halogenated alkoxy, cycloalkoxy, lower alkoxy-lower alkoxy, or carboxy-lower alkoxy or free lower alkyl or esterified or amidated; R2 is hydrogen, halogen, optionally halogenated lower alkyl, hydroxyl, cycloalkyl, cycloalkoxy, lower alkoxy-optionally halogenated lower alkyl, lower alkoxy-optionally substituted lower alkoxy, cycloalkoxy-lower alkyl; lower hydroxy-lower alkoxy optionally lower alkanoylated, halogenated, or sulfonylated; amino-lower alkyl that is unsubstituted or substituted by lower alkyl, by lower alkanoyl, and / or by lower alkoxy-carbonyl; heteroaryl-optionally hydrogenated lower alkyl, amino-lower alkoxy that is substituted by lower alkyl, by lower alkanoyl, and / or by lower alkoxy-carbonyl; oxo-lower alkoxy, lower alkoxy, lower alkenyloxy, cycloalkoxy-lower alkoxy, lower alkoxy-lower alkenyl, lower alkenyloxy-lower alkoxy, lower alkoxy-lower alkenyloxy, lower alkenyloxy-lower alkyl, lower alkanoylen-lower alkoxy, lower thioalkyl-alkoxy optionally S-oxidized lower thioalkyl- (hydroxy) -lower alkoxy, aryl-lower alkoxy, aryl-lower alkyl, aryl-lower alkoxy, optionally hydrogenated heteroaryl-lower alkoxy, heteroaryl-lower alkyl optionally hydrogenated, cyano-lower alkoxy, cyano-lower alkyl, carboxy-lower alkoxy-free or esterified or amidated, or free carboxy-lower alkyl or esterified or amidated; R3 and R4 are independently hydrogen, halogen, optionally hydrogenated lower alkyl, hydroxyl, optionally halogenated lower alkoxy or cycloalkoxy, lower alkoxy-lower alkyl, cycloalkoxy-lower alkyl, hydroxy-lower alkyl, lower alkylthio-lower alkyl optionally S-oxidized , optionally hydrogenated heterotioaryl-lower alkyl, optionally hydrogenated heteroaryl-lower alkyl; amino-lower alkyl which is unsubstituted or N-mono- or lower N, N-di-alkylated, N-lower alkanoylated, or N-lower alkane-sulfonylated, or N, N-disubstituted by lower alkylene, by lower aza-alkylene unsubstituted or lower N'-alkylated, or lower N'-alkanoylated, by lower oxa-alkylene, or by optionally-S-oxidized lower thia-alkylene; cyano-lower alkyl, free or esterified or amidated carboxy-lower alkyl, cycloalkyl, aryl, hydroxyl, lower alkoxy, cycloalkoxy, lower alkoxy-lower alkoxy, cycloalkoxy-lower alkoxy, hydroxy-lower alkoxy, aryl-lower alkoxy, lower alkoxy optionally halogenated, lower thioalkyl-optionally S-oxidized lower alkoxy, optionally hydrogenated lower heteroaryl-lower alkoxy, optionally hydrogenated lower heteroxyaryl-lower alkoxy; amino-lower alkoxy that is unsubstituted or N-mono- or lower N, N-di-alkylated, lower N-alkanoylated, or lower-N-sulphonylated alkane, or substituted by lower alkylene, by lower unsubstituted or lower N'-alkylated alkylene, or N '-low alkanoylated, by oxa-lower alkylene, or by optionally-S-oxidized lower thia-alkylene; cyano-lower alkoxy, or free lower or esterified or amidated carboxy-lower alkoxy; or R 4, together with R 3, is lower alkenoxyl, alkylenedioxyl, or an aryl fused on, optionally hydrogenated heteroaryl, or a cycloalkyl ring; X is methylene, hydroxymethylene, oxygen, nitrogen optionally substituted by lower alkyl, or optionally oxidized sulfur; R5 is lower alkyl or cycloalkyl; R6 is hydrogen, lower alkyl, hydroxyl, alkoxy, or halogen; R7 is unsubstituted amino or lower N-mono- or N, N-di-alkylated or lower N-alkanoylated; R8 is lower alkyl, lower alkenyl, cycloalkyl, or aryl-lower alkyl; R9 is cycloalkyl substituted with alkyl, hydroxyl, alkoxy, alkoxy-alkoxy, or halogens; cycloalkyl-alkyl optionally substituted with alkyl, hydroxyl, alkoxy, alkoxy-alkoxy, or halogens on cycloalkyl, or halogens on alkyl, or halogens on alkoxy; cycloalkyl- carboxamides; N-mono- or N, N-di-alkyl-substituted cycloalkyl-carboxamides; or optionally substituted aryl-alkyl; or R9 is hydrogen; halogenated alkyl; optionally substituted aryl-alkyl, optionally substituted aryloxy-alkyl, cycloalkyl substituted by 1 to 3 substituents selected from the group consisting of alkenyl, alkynyl, halogen, hydroxyl, alkoxy, alkoxy-alkoxy, thioalkyl, thioaryl, arylalkoxy, carbamoyl , sulfamoyl, sulfonyl, optionally substituted amino, cyano, carboxyl, alkoxycarbonyl, aryl, aryloxy, heterocyclyl, or alkyl optionally substituted by amino, halogen, hydroxyl, alkoxy, carboxyl, alkoxycarbonyl, carbamoyl, or heterocyclyl; or optionally substituted cycloalkyl-alkyl; or a pharmaceutically acceptable salt thereof.

15. A compound according to claim 14, wherein: R1 is hydrogen; R 2 is alkoxy of 1 to 4 carbon atoms-alkoxy of 1 to 4 carbon atoms, or alkoxy of 1 to 4 carbon atoms-alkyl of 1 to 4 carbon atoms; R3 is alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms; R4 is hydrogen; X is methylene; R5 is lower alkyl; R6 is hydrogen; R7 is amino unsubstituted; R8 is alkyl of 3 to 4 carbon atoms branched; R9 is optionally substituted cycloalkyl-alkyl; or a pharmaceutically acceptable salt thereof.

16. A compound according to claim 15, wherein: R 2 is 3-methoxy-propyloxy; R3 is methoxy; R5 is isopropyl; R8 is sopropyl; or a pharmaceutically acceptable salt thereof.

17. The compound of claim 14, wherein: R1 is hydrogen; R 2 is alkoxy of 1 to 4 carbon atoms-alkoxy of 1 to 4 carbon atoms, or alkoxy of 1 to 4 carbon atoms-alkyl of 1 to 4 carbon atoms; R3 is alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms; R4 is hydrogen; X is methylene; R5 is lower alkyl; R6 is hydrogen; R7 is amino unsubstituted; R8 is alkyl of 3 to 4 carbon atoms branched; R9 is aryl-alkyl optionally substituted; or a pharmaceutically acceptable salt thereof.

18. A compound according to claim 17, wherein: R 2 is 3-methoxy-propyloxy; R3 is methoxy; R5 is sopropyl; R8 is isopropyl; or a pharmaceutically acceptable salt thereof.

19. The compound of claim 17, wherein aryl-alkyl is alkyl substituted with phenyl; or a pharmaceutically acceptable salt thereof.

20. The compound of claim 19, wherein aryl-alkyl is methyl substituted by phenyl.

21. The compound according to the claim 20, wherein: R2 is 3-methoxy-propyloxy; R3 is methoxy; R5 is isopropyl; R8 is isopropyl; or a pharmaceutically acceptable salt thereof.

22. A method for the treatment of hypertension, atherosclerosis, unstable coronary syndrome, congestive heart failure, cardiac hypertrophy, cardiac fibrosis, post-infarction cardiomyopathy, unstable coronary syndrome, diastolic dysfunction, chronic kidney disease, hepatic fibrosis, complications resulting from diabetes, such as nephropathy, vasculopathy and neuropathy, diseases of the coronary vessels, restenosis following angioplasty, elevated intraocular pressure, glaucoma, abnormal vascular growth, hyperaldosteronism, cognitive impairment, Alzheimer's disease, dementia, anxiety states, and cognitive disorders, whose method comprises administering a therapeutically effective amount of the compound of claim 1 or 14, to a warm-blooded animal in need thereof.

23. A pharmaceutical composition comprising the compound of claim 1 or 14, and one or more pharmaceutically acceptable excipients.

24. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 or 14, in combination with a therapeutically effective amount of an anti-diabetic agent., a hypolipidemic agent, an anti-obesity agent, or an anti-hypertensive agent.

25. A pharmaceutical composition according to claim 23 or 24, for the treatment of hypertension, atherosclerosis, unstable coronary syndrome, congestive heart failure, cardiac hypertrophy, cardiac fibrosis, post-infarction cardiomyopathy, unstable coronary syndrome, diastolic dysfunction, chronic disease of the kidney, liver fibrosis, complications resulting from diabetes, such as nephropathy, vasculopathy and neuropathy, diseases of the coronary vessels, restenosis following angioplasty, elevated intraocular pressure, glaucoma, abnormal vascular growth, hyperaldosteronism, cognitive impairment, Alzheimer's disease, dementia, states of anxiety, and cognitive disorders.

26. A pharmaceutical composition according to claim 23 or 24, for use as a medicament.

27. The use of a pharmaceutical composition of according to claim 23 or 24, for the preparation of a medicament for the treatment of conditions associated with the activity of renin.

28. The use of a pharmaceutical composition according to claim 1 or 14, for the preparation of a pharmaceutical composition for the treatment of conditions associated with the activity of renin.

29. The use according to claim 27 or 28, wherein the condition associated with the activity of the renin is selected from hypertension, atherosclerosis, unstable coronary syndrome, congestive heart failure, cardiac hypertrophy, cardiac fibrosis, cardiomyopathy subsequent to infarction, unstable coronary syndrome, diastolic dysfunction, chronic kidney disease, hepatic fibrosis, complications resulting from diabetes, such as nephropathy, vasculopathy and neuropathy, diseases of the coronary vessels, restenosis following angioplasty, elevated intraocular pressure, glaucoma, vascular growth abnormal, hyperaldosteronism, cognitive impairment, Alzheimer's disease, dementia, anxiety states, and cognitive disorders.

30. A compound according to claim 1 or 14, for use as a medicament.