JP2002527520A - New compounds, their production and use - Google Patents

Abstract

  (57) [Summary] The invention relates to compounds of general formula (Ia). The compounds are useful for treating and / or preventing conditions mediated by nuclear receptors, particularly peroxisome proliferator-activated receptors (PPARs).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001] Field of the Invention: The present invention relates to novel compounds, pharmaceutical compositions containing them, processes for the manufacture of said compounds,
And their use as medicaments. More specifically, the compounds of the present invention
It can be used for the treatment of conditions mediated by nuclear receptors, in particular peroxisome proliferator-activated receptors (PPAR). The compounds of the present invention lower blood glucose and triglyceride levels and are therefore useful for the treatment of chronic diseases and disorders such as diabetes and obesity.

The present invention also relates to the above novel compounds, their derivatives, their analogs, their tautomers, their stereovariants, their polymorphs, and their pharmaceutically acceptable salts. And a pharmaceutically acceptable solvate and a method for producing a pharmaceutical composition containing the same.

The compounds include insulin resistance (type II diabetes), glucose tolerance disorder, dyslipidemia,
Treatment of disorders associated with Syndrome X, such as hypertension, obesity, insulin resistance, hyperglycemia, atherosclerosis, hyperlipidemia, coronary artery disease and other cardiovascular disorders and / or
Or it is useful for prevention. The compounds of the present invention are also useful for the treatment of certain renal diseases, such as glomerulonephritis, filar sclerosis, nephrotic syndrome, hypertensive renal sclerosis. The compounds are also useful for improving cognitive function in dementia, treating diabetic complications, psoriasis, polycystic ovary syndrome (PCOS), and preventing and treating bone loss, such as osteoporosis.

[0004] Background of the Invention: Coronary artery disease (CAD) is, II diabetes and metabolic syndrome patients (i.e., impaired glucose tolerance, insulin resistance, hyperglycemia and / or obesity in "fatal quartet" Category Patients) are the leading cause of death.

[0005] Hypolipidemic fibrates and antidiabetic thiazolidinedions are the only treatments for dyslipidemia often observed in patients with type II diabetes or metabolic candidate syndrome. Shows moderately effective triglyceride-lowering activity, though not as effective or efficacious. Thiazolidinediones also effectively reduce circulating glucose levels in animal models of type II diabetes and humans. However, compounds of the fibrate type are:
Has no beneficial effect on glycemia. Studies on the molecular effects of these compounds have shown that thiazolidinediones and fibrates exert their effects by activating distinct transcription factors of the peroxisome proliferator-activated receptor (PPAR) family, each of which is identified. It has been suggested that increased and decreased expression of enzymes and apolipoproteins, a key player in regulating plasma triglyceride content. On the one hand, fibrates are PPARα activators that act mainly in the liver. On the other hand, thiazolidinediones are high affinity ligands for PPARγ, which mainly act on adipose tissue.

[0006] Adipose tissue plays a central role in maintaining lipid homeostasis and energy balance in vertebrates. Fat cells store energy in the form of triglycerides during nutrient influx and release it in the form of free fatty acids at the time of nutrient deficiency. The growth of white adipose tissue is the result of a continuous differentiation process throughout life. Much evidence indicates a central role for PPARγ activation in initiating and regulating the differentiation of this cell. Several highly specialized proteins are induced during adipocyte differentiation, and most of these proteins are involved in fat storage and metabolism. The exact link from activation of PPARγ to change in glucose metabolism, most notably the reduction in insulin resistance in mice, is also unclear. Activation of PPARγ occurs in lipoprotein lipase (LPL), fatty acid transport protein (FATP) and acyl-
A possible linkage that triggers CoA synthase (ACS) is through free fatty acids. This dramatically lowers the concentration of free fatty acids in plasma and, due to substrate competition at the cellular level, skeletal muscle and other tissues with high metabolic rates result in a shift from fatty acid oxidation to glucose oxidation. Convert and ultimately have reduced insulin resistance.

[0007] PPARα is involved in stimulating β-oxidation of fatty acids. In rodents, PPARα-mediated alterations in the expression of genes involved in fatty acid metabolism are restricted to peroxisomal proliferation, ie, primarily in the liver and kidney, and pleiotropic cells leading to hepatocellular carcinogenesis in rodents Present based on the phenomenon of response. The phenomenon of peroxisome proliferation is not seen in humans. In addition to its role in peroxisomal proliferation in rodents, PPARα has also been implicated in the control of HDL cholesterol in rodents and humans. This effect is the main H
It is based, at least in part, on PPARα-mediated transcriptional regulation of the DL apolipoproteins, apoA-I and apo-II. The hypotriglyceridemic effects of fibrates and fatty acids are also involved in PPARα and can be summarized as follows: (I) Enhanced lipolysis and clearance of residual particles due to changes in lipoprotein lipase and apoC-III levels (II) Stimulation of cellular fatty acid uptake by induction of fatty acid binding proteins and acyl-CoA synthase and their subsequent conversion to acyl-CoA derivatives, (III) induction of fatty acid b-oxidation pathway, (
IV) Induction of fatty acid and triglyceride synthesis and, ultimately, (V) reduced VLDL production. Thus, both the enhanced catabolism of triglyceride-rich particles and the reduced secretion of VLDL particles constitute a mechanism that contributes to the hypolipidemic effect of fibrate.

[0008] Many compounds have been reported to be useful in the treatment of hyperglycemia, hyperlipidemia and hypercholesterolemia (US Pat. No. 5,306,726, P.S.
CT application numbers WO91 / 19702, WO95 / 03038, WO96 / 0
4260, WO94 / 13650, WO94 / 01420, WO97 / 3
No. 6579, WO97 / 25042, WO95 / 17394, WO99 / 0
8501, WO 99/19313 and WO 99/16758).

Summary of the Invention : It seems increasingly clear that glucose lowering as a single approach does not overcome many of the complications associated with type II diabetes and metabolic syndrome.
Therefore, novel treatments for type II diabetes and metabolic syndrome should help reduce the apparent hypertriglyceridemia and reduce hyperglycemia associated with those syndromes.

[0010] The clinical activity of fibrate and thiazolidinedione is
Investigation of compounds that exhibit ARα and PPARγ activity has potential for effective treatment of type II diabetes and metabolic syndrome (ie, impaired glucose tolerance, insulin resistance, hypertriglyceridemia and / or obesity) Suggests that the discovery of glucose and triglyceride reducing drugs should be guided.

Detailed Description of the Invention According to the present invention, there is provided a compound of general formula (Ia):

Embedded image(Where ring A fused to a ring containing X and N represents a 5- to 6-membered ring,
One or more halogen, perhalomethyl, hydroxy, nitro, cyano, holmi
Or C_1-12Alkyl, C_4-12Alkenyl, C_2-12Alkenyl, C_2-12Al
Quinyl, C_1-12Alkoxy, aryl, aryloxy, aralkyl, aralco
Xy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryl
Oxy, heteroaralkoxy, acyl, acyloxy, hydroxy C_1-12Archi
, Amino, acylamino, C_1-12Alkylamino, arylamino, aralkyl
Ruamino, amino C_1-12Alkyl, C_1-12Alkoxycarbonyl, aryloxy
Cicarbonyl, aralkoxycarbonyl, C_1-12Alkoxy C_1-12Alkyl, a
Reeloxy C_1-12Alkyl, aralkoxy C_1-12Alkyl, C_1-12Alkyl
Oh, Thio C_1-12Alkyl, C_1-12Alkoxycarbonylamino, aryloxy
Carbonylamino, aralkoxycarbonylamino, -COR¹¹Or SO_Two R ¹² Where R¹¹And R¹²Are independently hydroxy, halogen,
Perhalomethyl, C_1-6 Alkoxy or one or more C_1-6 Alkyl, per
Selected from amino substituted with halomethyl or aryl; optionally one or more
Ring B fused to a ring containing X and N represents a 5- to 6-membered ring, which is optionally substituted by one or more halogen, perhalomethyl, hydroxy, nitro or cyano.
A number of halogens, perhalomethyl, hydroxy, nitro, cyano, formyl, or
C_1-12Alkyl, C_4-12Alkenyl, C_2-12Alkenyl, C_2-12Alkynyl,
C_1-12Alkoxy, aryl, aryloxy, aralkyl, aralkoxy, f
Telocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy,
Heteroaralkoxy, acyl, acyloxy, hydroxy C_1-12Alkyl, Ami
No, acylamino, C_1-12Alkylamino, arylamino, aralkylamino
, Amino C_1-12Alkyl, C_1-12Alkoxycarbonyl, aryloxycarbo
Nil, aralkoxycarbonyl, C_1-12Alkoxy C_1-12Alkyl, arylo
Kishi C_1-12Alkyl, aralkoxy C_1-12Alkyl, C_1-12Alkylthio, thio
C_1-12Alkyl, C_1-12Alkoxycarbonylamino, aryloxycarboni
Ruamino, aralkoxycarbonylamino, -COR¹¹Or SO_Two R¹²Replace with
Where R¹¹And R¹²Are independently of each other hydroxy, halogen, perha
Lomethyl, C_1-6 Alkoxy or optionally one or more C_1-6 Alkyl, per
Selected from amino substituted with halomethyl or aryl; optionally one or more
X is substituted with a number of halogens, perhalomethyl, hydroxy, nitro or cyano; X is a valence bond,-(CHR⁹ )-,-(CHR⁹ ) -CH_Two -, -CH = C
H-, -O-, -O- (CHR⁹ )-, -S- (CHR⁹ )-,-(NR⁹ )-
CH_Two -,-(CHR⁹ ) -CH = CH-,-(CHR⁹ ) -CH_Two -CH_Two −
,-(C = O)-,-O-CH_Two -O-,-(NR⁹ )-,-(NR⁹ ) -S (
O_Two )-, -CH = (CR⁹ )-,-(CO)-(CHR⁹ )-, -CH_Two − (
SO)-, -S-,-(SO)-,-(SO_Two )-, -CH_Two − (SO_Two ) −,
-CH_Two -O-CH_Two -, Where R⁹ Is hydrogen, halogen, hydroxy,
Nitro, cyano, formyl, C_1-12Alkyl, C_1-12Alkoxy, aryl, a
Reeloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl
, Heteroaralkyl, heteroaryloxy, heteroaralkoxy, acyl, a
Siloxy, hydroxyalkyl, amino, acylamino, C_1-12Alkylam
No, arylamino, aralkylamino, aminoC_1-12Alkyl, C_1-12Arco
Xycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, C_1-12 Alkoxy C_1-12Alkyl, aryloxy C_1-12Alkyl, aralkoxy C_{1- 12} Alkyl, C_1-12Alkylthio, thio-C_1-12Alkyl, C_1-12Alkoxycal
Bonylamino, aryloxycarbonylamino, aralkoxycarbonylamino
No, -COR¹¹Or SO_Two R¹²Where R¹¹And R¹²But independently of each other
, Hydroxy, halogen, C_1-6 Alkoxy, optionally one or more C_1-6 Al
Q is -O-, -S-,> SO_Two ,> NR¹³Where R¹³Is hydrogen or C _1-6 Ar is arylene, heteroarylene, or one or more C_1-6 Alkyl
Or a divalent heterocyclic group substituted with aryl;^Five Is hydrogen, hydroxy, halogen, C_1-12Alkoxy, C_1-12Alkyl, C _4-12 Alkenyl, C_2-12Alkenyl, C_2-12Represents alkynyl or aralkyl
It optionally comprises one or more halogen, perhalomethyl, hydroxy, nitro or
Is substituted with cyano; or R^Five Is R⁶ Forms a bond with⁶ Is hydrogen, hydroxy, halogen, C_1-12Alkoxy, C_1-12Alkyl, C _4-12 Alkenyl, C_2-12Alkenyl, C_2-12Alkynyl, acyl or aralkyl
Which optionally contains one or more halogen, perhalomethyl, hydroxy,
Substituted with nitro or cyano; or R⁶ Is R^Five Forms a bond with⁷ Is hydrogen, C_1-12Alkyl, C_4-12Alkenyl, C_2-12Alkenyl, C_{2- 12} Alkynyl, aryl, aralkyl, C_1-12Alkoxy C_1-12Alkyl, C_{1- 12} Alkoxycarbonyl, aryloxycarbonyl, C_1-12Alkylaminoka
Rubonyl, arylaminocarbonyl, acyl, heterocyclyl, heteroaryl
Or a heteroaralkyl group; optionally with one or more halogen, per
Substituted with halomethyl, hydroxy, nitro or cyano; R⁸ Is hydrogen, C_1-12Alkyl, C_4-12Alkenyl, C_2-12Alkenyl, C_{2- 12} Alkynyl, aryl, aralkyl, heterocyclyl, heteroaryl or
Represents a heteroalkyl group; optionally one or more halogen, perhalomethyl
, Hydroxy, nitro or cyano; Y is oxygen, sulfur or NR^TenWhere R^TenIs hydrogen, C_1-12Alkyl, a
Reel, Hydroxy C_1-12Represents an alkyl or aralkyl group, or Y is NR ^Ten When, R⁸ And R^TenMay form a ring containing 5 or 6 membered nitrogen,
Is optionally one or more C_1-6 N is an integer ranging from 1 to 4 and m is an integer ranging from 0 to 1 wherein A or B does not represent phenyl) or a pharmaceutically acceptable compound About its salt.

In another preferred embodiment, the present invention provides a compound of formula I, wherein Ring A fused to the ring containing X and N represents a 5- to 6-membered ring, optionally having one or more hydrogen, halogen, perhalomethyl. , Hydroxy, cyano, or C _1-7 alkyl, C _4-7 alkenyl,
C _2-7 alkenyl, C _2-7 alkynyl, C _1-7 alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, acyl, acyloxy, Hydroxy C _1-7 alkyl, amino, acylamino, C _1-7 alkylamino, arylamino, aralkylamino, amino C _1-7 alkyl, C _1-7 alkoxy C _1-7 alkyl, aryloxy C _1-7 alkyl, Aralkoxy C _1-7 alkyl, C _1-7 alkylthio, thio C _1-7 alkyl, C _1-7 alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino,-
COR ¹¹ , or SO ₂ R ¹² , wherein R ¹¹ and R ¹² are independently selected from hydroxy, perhalomethyl or amino substituted with one or more C _1-6 alkyl, perhalomethyl or aryl; Which is optionally substituted with one or more halogen, perhalomethyl, hydroxy or cyano).

In another preferred embodiment, the present invention provides a compound of formula I wherein ring A fused to the ring comprising X and N represents a 5- to 6-membered ring, optionally having one or more hydrogen, halogen, perhalomethyl , Hydroxy, cyano, or C _1-7 alkyl, C _4-7 alkenyl,
C _2-7 alkenyl, C _2-7 alkynyl, C _1-7 alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, acyl, amino,
Acylamino, C _1-7 alkylamino, arylamino, aralkylamino, amino C _1-7 alkyl, C _1-7 alkoxy C _1-7 alkyl, aryloxy C _1-7
Alkyl, aralkoxy C _1-7 alkyl, C _1-7 alkylthio, thio C _1-7 alkyl; which is optionally substituted with one or more halogen or hydroxy).

In another preferred embodiment, the present invention provides compounds of formula I wherein ring A fused to the ring containing X and N represents a 5-6 membered ring, optionally having one or more hydrogen, halogen, perhalomethyl , Hydroxy or C _1-7 alkyl, C _2-7 alkenyl, C _2-7 alkynyl, C _1-7 alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heteroaryloxy, heteroaralkoxy, acyl, Arylamino, aryloxy C _1-7 alkyl).

In another preferred embodiment, the present invention provides compounds of formula I wherein ring A fused to the ring containing X and N represents a 5- to 6-membered ring, optionally having one or more hydrogen, halogen, perhalomethyl , Substituted with hydroxy or C _1-7 alkyl, C _2-7 alkenyl, C _2-7 alkynyl, C _1-7 alkoxy or aryl).

In another preferred embodiment, the present invention provides a compound of formula I, wherein Ring A fused to the ring comprising X and N represents a 5- to 6-membered ring, optionally substituted with one or more hydrogen or halogen. Has been described).

In another preferred embodiment, the present invention provides compounds of formula I wherein ring B fused to the ring comprising X and N represents a 5- to 6-membered ring, which optionally comprises one or more hydrogen, halogen, perhalomethyl , Hydroxy, cyano, or C _1-7 alkyl, C _4-7 alkenyl,
C _2-7 alkenyl, C _2-7 alkynyl, C _1-7 alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, acyl, acyloxy, Hydroxy C _1-7 alkyl, amino, acylamino, C _1-7 alkylamino, arylamino, aralkylamino, amino C _1-7 alkyl, C _1-7 alkoxy C _1-7 alkyl, aryloxy C _1-7 alkyl, Aralkoxy C _1-7 alkyl, C _1-7 alkylthio, thio C _1-7 alkyl, C _1-7 alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino,-
COR ¹¹ , or SO ₂ R ¹² , wherein R ¹¹ and R ¹² independently from each other are amino, substituted with hydroxy, perhalomethyl or optionally one or more C _1-6 alkyl, perhalomethyl or aryl. Selected; this is optionally substituted with one or more halogen, perhalomethyl, hydroxy or cyano).

In another preferred embodiment, the present invention relates to a compound of the formula I wherein X and N are fused to a ring
Ring B represents 5 to 6 members, which may optionally contain one or more hydrogen, halogen, perha
Lomethyl, hydroxy, cyano, or C_1-7 Alkyl, C_4-7 Alkenyl, C _2-7 Alkenyl, C_2-7 Alkynyl, C_1-7 Alkoxy, aryl, arylo
Xy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, hetero
Aralkyl, heteroaryloxy, heteroaralkoxy, acyl, amino, a
Silamino, C_1-7 Alkylamino, arylamino, aralkylamino, amino
No C_1-7 Alkyl, C_1-7 Alkoxy C_1-7 Alkyl, aryloxy C_1-7 A
Lucil, Aralkoxy C_1-7 Alkyl, C_1-7 Alkylthio, thio-C_1-7 Archi
Which is optionally substituted with one or more halogen or hydroxy.
The compound).

In another preferred embodiment, the present invention provides a compound of formula I wherein Ring B fused to the ring comprising X and N represents a 5- to 6-membered ring, optionally having one or more hydrogen, halogen, perhalomethyl. , Hydroxy or C _1-7 alkyl, C _2-7 alkenyl, C _2-7 alkynyl, C _1-7 alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heteroaryloxy, heteroaralkoxy, acyl, Arylamino, aryloxy C _1-7 alkyl).

In another preferred embodiment, the present invention provides compounds of formula I wherein ring B fused to the ring containing X and N forms a 5- to 6-membered ring, optionally comprising one or more hydrogen, halogen, Perhalomethyl, hydroxy or C _1-7 alkyl, C _2-7 alkenyl, C _2-7 alkynyl, C _1-7 alkoxy or aryl).

In another preferred embodiment, the present invention provides compounds of formula I wherein ring B fused to the ring containing X and N represents a 5-6 membered ring, which is optionally substituted with one or more hydrogen or halogen. Has been described).

In another preferred embodiment, the present invention provides compounds of formula I wherein X is a valence bond,-(C
HR⁹ )-,-(CHR⁹ ) -CH_Two -, -CH = CH-, -O-, -O- (C
HR⁹ )-, -S- (CHR⁹ )-,-(NR⁹ ) -CH_Two -,-(CHR⁹ )
-CH = CH-,-(CHR⁹ ) -CH_Two -CH_Two -,-(C = O)-, -O-
CH_Two -O-,-(NR⁹ )-,-(NR⁹ ) -S (O_Two )-, -CH = (CR ⁹ )-,-(CO)-(CHR⁹ )-, -CH_Two − (SO) −, −S−, − (S
O)-,-(SO_Two )-, -CH_Two − (SO_Two )-, -CH_Two -O-CH_Two −,
Where R⁹ Is hydrogen, halogen, hydroxy, cyano, C_1-7 Alkyl,
C_1-7 Alkoxy, aryl, aryloxy, aralkyl, aralkoxy, f
Telocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy,
Heteroaralkoxy, acyl, acyloxy, hydroxyalkyl, amino, amino
Silamino, C_1-7 Alkylamino, arylamino, aralkylamino, amino
No C_1-7 Alkyl, C_1-7 Alkoxy C_1-7 Alkyl, aryloxy C_1-7 A
Lucil, Aralkoxy C_1-7 Alkyl, C_1-7 Alkylthio, thio-C_1-7 Archi
Is a compound of the formula

In another preferred embodiment, the present invention provides a compound of formula I wherein X is a valence bond,-(C
HR⁹ )-,-(CHR⁹ ) -CH_Two -, -CH = CH-, -O-, -O- (C
HR⁹ )-, -S- (CHR⁹ )-,-(NR⁹ ) -CH_Two -,-(CHR⁹ )
-CH = CH-,-(CHR⁹ ) -CH_Two -CH_Two -,-(C = O)-, -O-
CH_Two -O-,-(NR⁹ )-,-(NR⁹ ) -S (O_Two )-, -CH = (CR ⁹ )-,-(CO)-(CHR⁹ )-, -CH_Two − (SO) −, −S−, − (S
O)-,-(SO_Two )-, -CH_Two − (SO_Two )-, -CH_Two -O-CH_Two −,
Where R⁹ Is hydrogen, halogen, hydroxy, C_1-7 Alkyl, C_1-7 A
Alkoxy, aryl).

In another preferred embodiment, the present invention provides a compound of formula I wherein X is a valence bond,-(C
HR ⁹ )-,-(CHR ⁹ ) -CH _2- , -CH = CH-, -O- (CHR ⁹ )
^{-, - S- (CHR 9)} -, - (NR 9) -CH 2 -, - (CHR 9) -CH =
^{CH -, - (CHR 9)} -CH 2 -CH 2 -, - (C = O) -, - O-CH 2 -
O-,-(NR ⁹ ) -S (O ₂ )-, -CH = (CR ⁹ )-,-(CO)-(C
HR ⁹ )-, -CH _2- (SO)-,-(SO)-,-(SO ₂ )-, -CH ₂
— (SO ₂ ) —, —CH ₂ —O—CH ₂ —, wherein R ⁹ is hydrogen, halogen, hydroxy, C _1-4 alkyl, C _1-4 alkoxy.

In another preferred embodiment, the present invention provides a compound of formula I wherein X is a valence bond,-(C
HR ⁹ )-,-(CHR ⁹ ) -CH _2- , -CH = CH-, -O- (CHR ⁹ )
-,-(CHR ⁹ ) -CH = CH-,-(CHR ⁹ ) -CH ₂ -CH ₂ -,-(
C = O) -, - O -CH 2 -O -, - CH = (CR 9) -, - (CO) - (CH
R ⁹ )-, -CH _2- (SO)-,-(SO)-,-(SO ₂ )-, -CH _2-
(SO ₂ ) —, —CH ₂ —O—CH ₂ —, wherein R ⁹ is hydrogen.

In another preferred embodiment, the invention relates to compounds of formula I wherein Q is —O— or —S—.

In another preferred embodiment, the invention relates to compounds of formula I wherein Q is —O—.

In another preferred embodiment, the present invention provides a compound of formula I wherein Ar is arylene, hetene
Lower arylene or one or more C_1-6 Substituted with alkyl or aryl
R represents a divalent heterocyclic group;^Five Is hydrogen, hydroxy, halogen, C_1-7 Alkoxy, C_1-7 Alkyl, C _4-7 Alkenyl, C_2-7 Alkenyl, C_2-7 Represents-; or R^Five Is R⁶ 
Forms a bond with⁶ Is hydrogen, hydroxy, halogen, C_1-7 Alkoxy, C_1-7 Alkyl, C _4-7 Alkenyl, C_2-7 Alkenyl, C_2-7 Represents alkynyl; or R ⁶ Is R^Five Forms a bond with⁷ Is hydrogen, C_1-7 Alkyl, C_4-7 Alkenyl, C_2-7 Alkenyl, C_{2- 7} Alkynyl, aryl, aralkyl, C_1-7 Alkoxy C_1-7 Alkyl, C_{1- 7} Alkoxycarbonyl, aryloxycarbonyl, C_1-7 Alkylaminoka
Rubonyl, arylaminocarbonyl, acyl, heterocyclyl, heteroaryl
R or a heteroaralkyl group;⁸ Is hydrogen, C_1-7 Alkyl, C_4-7 Alkenyl, C_2-7 Alkenyl, C_{2- 7} Alkynyl, aryl, aralkyl, heterocyclyl, heteroaryl or
Represents a heteroaralkyl; Y is oxygen, sulfur or NR^TenWhere R^TenIs hydrogen, C_1-7 Alkyl, hide
Roxy C_1-7 N represents an integer ranging from 2 to 3 and m represents an integer ranging from 0 to 1)
About.

In another preferred embodiment, the present invention provides a compound of formula I wherein Ar represents arylene or heteroarylene and R ⁵ represents hydrogen, hydroxy, halogen; or R ⁵ forms a bond with R ⁶ R ⁶ represents hydrogen, hydroxy, halogen; or R ⁶ forms a bond with R ⁵ , wherein R ⁷ is hydrogen, C _1-7 alkyl, C _2-7 alkenyl, C _2-7 alkynyl, aryl, aralkyl, C _1-7 alkoxy C _1-7 alkyl, C _1-7 alkylaminocarbonyl, arylaminocarbonyl, acyl, heterocyclyl, represents heteroaryl or heteroaralkyl groups; R ⁸ is hydrogen, C Y represents oxygen or sulfur; n is an integer ranging from 2 to 3, and m is 1), representing _1-7 alkyl, C _2-7 alkenyl, C _2-7 alkynyl.

[0030] In another preferred embodiment, the present invention provides a compound of formula I (wherein, Ar represents an arylene or heteroarylene; R ⁵ represents hydrogen; R ⁶ represents hydrogen; R ⁷ is hydrogen, C _1-7 Alkyl, C _2-7 alkenyl, C _2-7 alkynyl, aryl, aralkyl, C _1-7 alkoxyC _1-7 alkyl; R ⁸ is hydrogen, C _1-7 alkyl, C _2-7 alkenyl, C ₂ It represents _-7 alkynyl; Y represents oxygen; an integer n spans 2-3, and relates to compounds of m is 1).

In another preferred embodiment, the present invention provides a compound of formula I wherein Ar represents arylene, R ⁵ represents hydrogen; R ⁶ represents hydrogen; R ⁷ is hydrogen, C _1-4 alkyl, C R ⁸ represents hydrogen, C _1-4 alkyl, Y represents oxygen; n is an integer ranging from 2-3, and m is 1) representing _2-4 alkenyl, C _2-4 alkynyl; The compound of

In another preferred embodiment, the present invention provides a compound of formula I wherein Ar represents phenylene; R ⁵ represents hydrogen; R ⁶ represents hydrogen; R ⁷ represents hydrogen, C _1-4 alkyl. R ⁸ represents hydrogen; Y represents oxygen; n is an integer ranging from 2 to 3 and m is 1.

In another preferred embodiment, the invention relates to compounds of formula I, wherein A is a 5-membered ring containing S.

In another preferred embodiment, the invention relates to compounds of formula I, wherein B is a 5-membered ring containing S.

In another preferred embodiment, the present invention provides a compound of formula I, wherein X is -CH = (CR ⁹ )
Wherein R ⁹ is H).

In another preferred embodiment, the invention relates to compounds of formula I, wherein n is 2.

In another preferred embodiment, the invention relates to compounds of formula I wherein Q is -O-.

In another preferred embodiment, the invention relates to compounds of formula I wherein m is 1.

In another preferred embodiment, the invention relates to compounds of formula I, wherein Ar is phenylene.

In another preferred embodiment, the invention relates to compounds of formula I wherein R ⁵ is H.

In another preferred embodiment, the invention relates to compounds of formula I wherein R ⁶ is H.

In another preferred embodiment, the invention relates to compounds of formula I wherein R ⁷ is ethyl.

In another preferred embodiment, the invention is concerned with compounds of formula I wherein Y is oxygen.

In another preferred embodiment, the invention relates to compounds of formula I wherein R ⁸ is H.

A preferred compound of the present invention is: 3- {4- [2- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -ethoxy] phenyl} -2-ethoxy-propionic acid, 3- {4- [2- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -ethoxy] -phenyl}- 2-methoxy-propionic acid, 3- {4- [2- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -ethoxy] -phenyl} -2 -Propoxy-
Propionic acid, 3- {4- [2- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -ethoxy] -phenyl} -2-benzyloxy- Propionic acid, 3- {4- [2- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -ethyl] -phenyl} -2-ethoxy-propion Acid, 3- {4- [2- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -ethyl] -phenyl} -2-methoxy-propionic acid 3- {4- [2- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -ethyl] -phenyl} -2-propoxy-propionic acid; 3- {4- [2- (8,9-Jihi B-3,5-Dithia-4-aza-cyclopenta [f] azulen-4-yl) -ethyl] -phenyl} -2-benzyloxy-propionic acid, 3- {4- [1- (8,9- Dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -methoxy] -phenyl} -2-ethoxy-propionic acid, 3- {4- [1- (8,9-dihydro) -3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -methoxy] -phenyl} -2-methoxy-propionic acid, 3- {4- [1- (8,9-dihydro- 3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -methoxy] -phenyl} -2-benzyloxy-propionic acid, 3- {4- [3- (8,9-dihydro- 3,5-dithia-4-aza-cyclo Printers [f] azulen-4-yl) - propoxy] - phenyl} -2-ethoxy -
Propionic acid, 3- {4- [3- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -propoxy] -phenyl} -2-methoxy-
Propionic acid, 3- {4- [3- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -propoxy] -phenyl} -2-benzyloxy- Propionic acid, 3- {4- [3- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -propyl] -phenyl} -2-ethoxy-propion Acid, 3- {4- [3- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -propyl] -phenyl} -2-methoxy-propionic acid 3- {4- [3- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -propyl] -phenyl} -2-benzyloxy-propionic acid , 2-ethoxy-3- 4- (2- (9H-1,8,10-triaza-anthracen-10-yl) -ethoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (2- (9H-1,8 , 10-Triaza-anthracen-10-yl) -ethoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (2- (9H-1,8,10-triaza-anthracen-10-yl) -Ethoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (2- (9H-1,8,10-triaza-anthracen-10-yl) -ethoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (1- (9H-1,8,10-triaza-anthracen-10-yl) -methoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (1 -(9 -1,8,10-Triaza-anthracen-10-yl) -methoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (1- (9H-1,8,10-triaza-anthracene) -10-yl) -methoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (3- (9H-1,8,10-triaza-anthracen-10-yl) -propoxy) -phenyl) -Propionic acid, 2-propoxy-3- (4- (3- (9H-1,8,10-triaza-anthracen-10-yl) -propoxy) -phenyl) -propionic acid, 2-methoxy-3- ( 4- (3- (9H-1,8,10-triaza-anthracen-10-yl) -propoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (3- (9H- 1,8,10-Triaza-anthracen-10-yl) -propoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (3- (9H-1,8,10-triaza-anthracene-10) -Yl) -propyl) -phenyl) -propionic acid, 2-propoxy-3- (4- (3- (9H-1,8,10-triaza-anthracen-10-yl) -propyl) -phenyl) -propionate Acid, 2-methoxy-3- (4- (3- (9H-1,8,10-triaza-anthracen-10-yl) -propyl) -phenyl) -propionic acid, 2-benzyloxy-3- (4 -(3- (9H-1,8,10-triaza-anthracen-10-yl) -propyl) -phenyl) -propionic acid, 2-ethoxy-3- (4- (2- (4,5,9- Thoria - fluoren-9
Yl) -ethoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (2- (4,5,9-triaza-fluorene-9-
Yl) -ethoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (2- (4,5,9-triaza-fluorene-9)
-Yl) -ethoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (1- (4,5,9-triaza-fluorene-9-
Yl) -methoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (1- (4,5,9-triaza-fluorene-9-
Yl) -methoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (1- (4,5,9-triaza-fluoren-9-yl) -methoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (3- (4,5,9-triaza-fluorene-9-
Yl) -propoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (3- (4,5,9-triaza-fluorene-9-
Yl) -propoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (3- (4,5,9-triaza-fluoren-9-yl) -propoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (3- (4,5,9-triaza-fluorene-9)
-Yl) -propoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (3- (4,5,9-triaza-fluorene-9-
Yl) -propyl) -phenyl) -propionic acid, 2-methoxy-3- (4- (3- (4,5,9-triaza-fluorene-9-
Yl) -propyl) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (3- (4,5,9-triaza-fluoren-9-yl) -propyl) -phenyl) -propionic acid, 2-propoxy-3- (4- (3- (4,5,9-triaza-fluorene-9)
-Yl) -propyl) -phenyl) -propionic acid, 2-ethoxy-3- (4- (2- (1,8,9-triaza-fluorene-9-
Yl) -ethoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (2- (1,8,9-triaza-fluorene-9-)
Yl) -ethoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (2- (1,8,9-triaza-fluorene-9)
-Yl) -ethoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (2- (1,8,9-triaza-fluoren-9-yl) -ethoxy) -phenyl) -propionic acid 2-methoxy-3- (4- (1- (1,8,9-triaza-fluorene-9-
Yl) -methoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (1- (1,8,9-triaza-fluorene-9-)
Yl) -methoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (1- (1,8,9-triaza-fluorene-9)
-Yl) -methoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (1- (1,8,9-triaza-fluoren-9-yl) -methoxy) -phenyl) -propionic acid 2-ethoxy-3- (4- (3- (1,8,9-triaza-fluorene-9-
Yl) -propoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (3- (1,8,9-triaza-fluorene-9-)
Yl) -propoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (3- (1,8,9-triaza-fluorene-9)
-Yl) -propoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (3- (1,8,9-triaza-fluoren-9-yl) -propoxy) -phenyl) -propionic acid 2-ethoxy-3- (4- (3- (1,8,9-triaza-fluorene-9-
Yl) -propyl) -phenyl) -propionic acid, 2-methoxy-3- (4- (3- (1,8,9-triaza-fluorene-9-
Yl) -propyl) -phenyl) -propionic acid, 2-propoxy-3- (4- (3- (1,8,9-triaza-fluorene-9)
-Yl) -propyl) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (3- (1,8,9-triaza-fluoren-9-yl) -propyl) -phenyl) -propionic acid 3- (4- (2- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -ethoxy) -phenyl) -2-ethoxy-propionic acid, 3- (4- (2- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -ethoxy) -phenyl) -2-methoxy-propionic acid, 3- (4- (2- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -ethoxy) -phenyl) -2-propoxy-propionic acid, 3- (4- (2- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -ethoxy) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (1- (dithieno [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -methoxy) -phenyl) -2-methoxy-propionic acid, 3- (4- (1- (dithieno [2,3-b; 3 ′, 2′-d] pyrrole-7-)
Yl) -methoxy) -phenyl) -2-ethoxy-propionic acid, 3- (4- (1- (dithieno [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -methoxy) -phenyl) -2-propoxy-propionic acid, 3- (4- (1- (dithieno [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -methoxy) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (3- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propoxy) -phenyl) -2-ethoxy-propionic acid, 3- (4- (3- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propoxy) -phenyl) -2-methoxy-propionic acid, 3- (4- (3- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propoxy) -phenyl) -2-propoxy-propionic acid, 3- (4- (3- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propoxy) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (3- (dithieno [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -propyl) -phenyl) -2-ethoxy-propionic acid, 3- (4- (3- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propyl) -phenyl) -2-methoxy-propionic acid, 3- (4- (3- (dithieno [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -propyl) -phenyl) -2-propoxy-propionic acid, 3- (4- (3- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propyl) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (2- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -ethoxy) -phenyl) -2-ethoxy-propionic acid, 3- (4- (2- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -ethoxy) -phenyl) -2-methoxy-propionic acid, 3- (4- (2- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -ethoxy) -phenyl) -2-propoxy-propionic acid, 3- (4- (2- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -ethoxy) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (1- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -methoxy) -phenyl) -2-ethoxy-propionic acid, 3- (4- (1- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -methoxy) -phenyl) -2-methoxy-propionic acid, 3- (4- (1- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -methoxy) -phenyl) -2-propoxy-propionic acid, 3- (4- (1- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -methoxy) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (3- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -propoxy) -phenyl) -2-ethoxy-propionic acid, 3- (4- (3- (difurano [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propoxy) -phenyl) -2-propoxy-propionic acid, 3- (4- (3- (difurano [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propoxy) -phenyl) -2-methoxy-propionic acid, 3- (4- (3- (difurano [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propoxy) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (3- (difurano [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propyl) -phenyl) -2-ethoxy-propionic acid, 3- (4- (3- (difurano [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propyl) -phenyl) -2-propoxy-propionic acid, 3- (4- (3- (difurano [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propyl) -phenyl) -2-methoxy-propionic acid, 3- (4- (3- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -propyl) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (2- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -ethoxy) -phenyl) -2-ethoxy-propionic acid, 3- (4- (2- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -ethoxy) -phenyl) -2-methoxy-propionic acid, 3- (4- (2- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -ethoxy) -phenyl) -2-propoxy-propionic acid, 3- (4- (2- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -ethoxy) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (1- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -methoxy) -phenyl) -2-ethoxy-propionic acid, 3- (4- (1- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -methoxy) -phenyl) -2-methoxy-propionic acid, 3- (4- (1- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -methoxy) -phenyl) -2-propoxy-propionic acid, 3- (4- (1- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -methoxy) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (3- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -propoxy) -phenyl) -2-ethoxy-propionic acid, 3- (4- (3- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -propoxy) -phenyl) -2-methoxy-propionic acid, 3- (4- (3- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -propoxy) -phenyl) -2-propoxy-propionic acid, 3- (4- (3- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -propoxy) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (3- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -propyl) -phenyl) -2-ethoxy-propionic acid, 3- (4- (3- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -propyl) -phenyl) -2-methoxy-propionic acid, 3- (4- (3- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -propyl) -phenyl) -2-propoxy-propionic acid, 3- (4- (3- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -propyl) -phenyl) -2-benzyloxy-propionic acid, 2-ethoxy-3- (4- (2- (4-oxa-1,7-dithia-8-aza-
s-Indacene-8-yl) -ethoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (2- (4-oxa-1,7-dithia-8-aza-)
s-Indacene-8-yl) -ethoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (2- (4-oxa-1,7-dithia-8-aza-s-indacene-8). -Yl) -ethoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (2- (4-oxa-1,7-dithia-8-aza-s-indacene-8-yl) -ethoxy). ) -Phenyl) -propionic acid, 2-benzyloxy-3- (4- (2- (4-oxa-1,7-dithia-8-
Aza-s-indacen-8-yl) -ethoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (1- (4-oxa-1,7-dithia-8-aza-)
s-Indacene-8-yl) -methoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (1- (4-oxa-1,7-dithia-8-aza-)-
s-Indacene-8-yl) -methoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (1- (4-oxa-1,7-dithia-8-aza-s-indacene-8). -Yl) -methoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (1- (4-oxa-1,7-dithia-8-).
Aza-s-indacen-8-yl) -methoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (3- (4-oxa-1,7-dithia-8-aza-
s-Indacene-8-yl) -propoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (3- (4-oxa-1,7-dithia-8-aza-)-
s-Indacene-8-yl) -propoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (3- (4-oxa-1,7-dithia-8-aza-s-indacene-8). -Yl) -propoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (3- (4-oxa-1,7-dithia-8-).
Aza-s-indacen-8-yl) -propoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (3- (4-oxa-1,7-dithia-8-aza-)
s-Indacene-8-yl) -propyl) -phenyl) -propionic acid, 2-methoxy-3- (4- (3- (4-oxa-1,7-dithia-8-aza-)
s-Indacene-8-yl) -propyl) -phenyl) -propionic acid, 2-propoxy-3- (4- (3- (4-oxa-1,7-dithia-8-aza-s-indacene-8). -Yl) -propyl) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (3- (4-oxa-1,7-dithia-8-).
Aza-s-indacen-8-yl) -propyl) -phenyl) -propionic acid; or a pharmaceutically acceptable salt thereof.

Further preferred compounds of the present invention are: 3- {4- [2- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -ethoxy]- Phenyl} -2-ethoxy-propionic acid; or a pharmaceutically acceptable salt thereof.

In the above structural formulas and throughout this specification, the following terms have the indicated meanings.

The term “C _1-12 alkyl” as used herein, alone or in combination, refers to those alkyl groups of a length designed in either a linear or branched or cyclic configuration. It is meant to include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like. Typical C _1-6 alkyl groups are methyl, ethyl, n-propyl, isopropyl,
Butyl, iso-butyl, sec-butyl, tert-butyl, pentyl, iso-pentyl, hexyl, iso-hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like, but only to these. Is not limited.

The term “C _{2-n ′} alkenyl” (where n ′ can be 3 to 15), as used herein, refers to a group of 2 to a specified number of carbon atoms and at least one carbon atom. Represents an olefinically unsaturated branched or straight-chain group having a heavy bond. Examples of such groups are vinyl, 1-propenyl, 2-propenyl, allyl, iso-propenyl,
Includes, but is not limited to 1,3-butadienyl, 1-butenyl, hexenyl, pentenyl and the like.

The term “C _{2-n ′} alkynyl” (where n ′ can be 3 to 15), as used herein, refers to a number of carbon atoms and at least one triple. Represents an unsaturated branched or linear group having a bond. Examples of such groups are 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 1-pentynyl, 2-
Including, but not limited to, pentynyl and the like.

The term “C _{4-n ′} alkenyl” (where n ′ can be 5 to 15), as used herein, refers to four to the specified number of carbon atoms and at least one divalent carbon atom. Represents an unsaturated branched or straight-chain hydrocarbon group having a heavy bond and at least one triple bond. Examples of such groups are 1-penten-4-yne, 3-pentene-1
-In, 1,3-hexadiene-5-yne and the like, but is not limited thereto.

The term “C _1-12 alkoxy,” as used herein, alone or in combination, refers to a straight-chain or linked alkyl group having its free valence bond from the ether oxygen. It is meant to include those C _1-12 alkyl groups of designed length in either a branched or cyclic configuration. Examples of linear alkoxy groups are methoxy, ethoxy, propoxy, butoxy, pentoxy and hexoxy. Examples of branched alkoxy are isopropoxy, sec-butoxy, tert-butoxy, isopentoxy and isohexoxy. Examples of cyclic alkoxy are cyclopropyloxy, cyclobutyloxy, cyclopentyloxy and cyclohexyloxy.

The term “C _1-6 alkoxycarbonyloxy” refers to a C _1-6 alkoxy group as defined above attached to a carbonyloxy moiety, such as methoxycarbonyloxy,
Ethoxycarbonyloxy, and the like.

As used herein, the term “C _4-12- (cycloalkylalkyl) refers to a branched or straight-chain alkyl group substituted by a carbon atom with a cycloalkyl group. Examples of groups include, but are not limited to, cyclopropylethyl, cyclobutylmethyl, 2- (cyclohexyl) ethyl, cyclohexylmethyl, 3- (cyclopentyl) -1-propyl, and the like.

[0055] The term "C _1-12 alkylthio", as used herein alone or in combination, attached through a divalent sulfur atom having its free valence bond from the sulfur atom C _1- Reference is made to linear or branched or cyclic monovalent substituents comprising ₁₂ alkyl groups and having 1 to 12 carbon atoms, for example methylthio, ethylthio, propylthio, butylthio, pentylthio. Examples of cyclic alkylthio are cyclopropylthio, cyclobutylthio, cyclopentylthio and cyclohexylthio.

The term “C _1-12 alkylamino” as used herein, alone or in combination, refers to a C _1-12 alkyl group attached through an amino having a free valence bond from a nitrogen atom. Reference is made to linear, branched or cyclic monovalent substituents comprising, for example, methylamino, ethylamino, propylamino, butylamino, pentylamino. Examples of cyclic alkylamino are cyclopropylamino, cyclobutylamino, cyclopentylamino and cyclohexylamino.

The term “hydroxy C _1-12 alkyl,” as used herein, alone or in combination, refers to a C _1-12 alkyl, as defined herein, attached to a hydroxy group, For example, hydroxyethyl, 1-hydroxypropyl, 2
-Hydroxypropyl, and the like.

The term “arylamino,” as used herein, alone or in combination, is linked through an amino having a free valence bond from the nitrogen atom.
Reference is made to aryl as defined herein, such as phenylamino, naphthylamino, and the like.

The term “aralkylamino,” as used herein, alone or in combination, refers to an aralkyl, as defined herein, attached through an amino having a free valence bond from the nitrogen atom. For example, benzylamino, phenethylamino, 3-phenylpropylamino, 1-naphthylmethylamino, 2-
(1-Naphthyl) ethylamino and the like.

[0060] The term "amino C _1-12 alkyl", alone or when used herein in combination, combined with an amino group, C _{1 -12} alkyl, as defined herein, For example, aminoethyl, 1-aminopropyl, 2-aminopropyl, and the like are mentioned.

The term “aryloxycarbonyl,” as used herein, alone or in combination, as defined herein, attached through a carbonyl having a free valence bond from a carbon atom Reference is made to aryloxy, such as phenoxycarbonyl, 1-naphthyloxycarbonyl or 2-naphthyloxycarbonyl.

The term “aralkoxycarbonyl” as used herein, alone or in combination, as defined herein, attached through a carbonyl having a free valence bond from a carbon atom. Aralkoxy, such as benzyloxycarbonyl, phenethoxycarbonyl, 3-phenylpropoxycarbonyl, 1-naphthylmethoxycarbonyl, 2- (1-naphthyl) ethoxycarbonyl, and the like.

The term “C _1-12 alkoxyC _1-12 alkyl” as used herein, alone or in combination, as defined herein, attached to a C _1-12 alkoxy _C1-12 alkyl, such as methoxymethyl, ethoxymethyl, methoxyethyl, ethoxyethyl, and the like.

The term “ _{aryloxyC 1-12} alkyl,” as used herein, alone or in combination, is as defined herein, attached to an aryloxy as defined herein. Reference is made to C _1-12 alkyl, such as phenoxymethyl, phenoxydodecyl, 1-naphthyloxyethyl, 2-naphthyloxypropyl, and the like.

The term “aralkoxy C _1-12 alkyl,” as used herein, alone or in combination, is as defined herein, attached to aralkoxy, as defined herein. Such _C1-12 alkyl, such as benzyloxymethyl, phenethoxydodecyl, 3-phenylpropoxyethyl, 1-naphthylmethoxypropyl, 2- (1-naphthyl) ethoxymethyl, and the like.

The term “thio C _1-12 alkyl,” as used herein, alone or in combination, refers to a compound of the formula —SR ″ ′, where R ′ ″ is hydrogen, C _1-6 (Which is alkyl or aryl), refers to a C _1-12 alkyl as defined herein, eg, thiomethyl, methylthiomethyl, phenylthiomethyl, and the like.

The term “C _1-12 alkoxycarbonylamino,” as used herein, alone or in combination, is defined herein as attached through an amino having a free valence bond from a nitrogen atom. _C1-12 alkoxycarbonyl such as methoxycarbonylamino, carbethoxyamino, propoxycarbonylamino, isopropoxycarbonylamino, n-butoxycarbonylamino, tert-butoxycarbonylamino, and the like.

The term “aryloxycarbonylamino” as used herein, alone or in combination, as defined herein, attached through an amino having a free valence bond from a nitrogen atom Aryloxycarbonyl, such as phenoxycarbonylamino, 1-naphthyloxycarbonylamino or 2-
Naphthyloxycarbonylamino, and the like.

The term “aralkoxycarbonylamino,” as used herein, alone or in combination, is defined herein as attached through an amino having a free valence bond from the nitrogen atom. Such as aralkoxycarbonyl, such as benzyloxycarbonylamino, phenethoxycarbonylamino, 3-phenylpropoxycarbonylamino, 1-naphthylmethoxycarbonylamino,
Reference is made to 2- (1-naphthyl) ethoxycarbonylamino, and the like.

The term “aryl” refers to a phenyl, naphthyl, (1) aryl group optionally substituted by an aromatic ring such as halogen, amino, hydroxy, C _1-6 alkyl or C _1-6 alkoxy.
-Naphthyl or 2-naphthyl).

The term “arylene” refers to a divalent aromatic ring, for example, a carboxylic acid selected from the group consisting of phenylene, naphthylene optionally substituted by halogen, amino, hydroxy, C _1-6 alkyl or C _1-6 alkoxy. It is meant to contain an acid aromatic ring.

The term “halogen” refers to fluorine, chlorine, bromine or iodine.

The term “perhalomethyl” means trifluoromethyl, trichloromethyl, tribromomethyl or triiodomethyl.

The term “C _1-6 dialkylamino” as used herein refers to a straight or branched chain saturated hydrocarbon wherein two hydrogen atoms independently have the indicated number of carbon atoms. Amino group substituted by a chain, for example dimethylamino, N-ethyl-N-methylamino, diethylamino, dipropylamino, N- (n-butyl)
-N-methylamino, di (n-pentyl) amino and the like.

The term “acyl” as used herein refers to a monovalent substituent comprising a C _1-6 alkyl group attached through a carbonyl group, for example, acetyl, propionyl, butyryl, isobutyryl, pivaloyl, Valeryl and others are mentioned.

The term “acyloxy” as used herein refers to an acyl as defined herein, eg, acetyloxy, attached to an oxygen atom having its free valence bond from an oxygen atom , Propionyloxy, butyryloxy, isobutyryloxy, pivaloyloxy, valeryloxy and the like.

The term “C _1-12 alkoxycarbonyl” as used herein, refers to a monovalent substituent comprising a C _1-12 alkoxy group attached through a carbonyl group,
For example, methoxycarbonyl, carbethoxy, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, sec-butoxycarbonyl, tert-
Reference is made to butoxycarbonyl, 3-methylbutoxycarbonyl, n-hexoxycarbonyl and the like.

The term “ring containing 5 to 7 carbon atoms” as used herein refers to a monocyclic saturated or unsaturated, or aromatic system such as cyclopentyl, cyclopentenyl, cyclohexyl, phenyl Or cycloheptyl.

The term “bicycloalkyl” as used herein refers to 6-12
Monovalent substituents comprising bicyclic structures made from carbon atoms, such as 2-norbornyl, 7-norbornyl, 2-bicyclo [2.2.2] octyl and 9-
Reference is made to bicyclo [3.3.1] nonanyl.

The term “heteroaryl,” as used herein, alone or in combination, refers to a 5 to 6 membered monocyclic ring containing one or more heteroatoms selected from nitrogen, oxygen and sulfur Monovalent substituents comprising a formula aromatic system or a 9-10 membered bicyclic aromatic system such as furan, thiophene, pyrrole, imidazole, pyrazole, triazole, pyridine, pyrazine, pyrimidine, pyridazine, isothiazole, isoxazole , Oxazole, oxadiazole, thiadiazole, quinoline,
Isoquinoline, quinazoline, quinoxaline, indole, benzimidazole,
Reference is made to benzofurans, pteridines and purines.

The term “heteroarylene,” as used herein, alone or in combination, refers to a 5- to 6-membered monocyclic ring containing one or more heteroatoms selected from nitrogen, oxygen and sulfur. Divalent substituents comprising a formula aromatic system or a 9-10 membered bicyclic aromatic system, such as furan, thiophene, pyrrole, imidazole, pyrazole, triazole, pyridine, pyrazine, pyrimidine, pyridazine, isothiazole,
Refer to isoxazole, oxazole, oxadiazole, thiadiazole, quinoline, isoquinoline, quinazoline, quinoxaline, indole, benzimidazole, benzofuran, pteridine and purines.

The term “heteroaryloxy,” as used herein, alone or in combination, is defined herein as attached to an oxygen atom that has its free valence bond from an oxygen atom. Such heteroaryl, such as pyrrole, imidazole, pyrazole, triazole, pyridine, pyrazine, pyrimidine, pyridazine, isothiazole, isoxazole, oxazole, attached to oxygen;
Reference is made to oxadiazole, thiadiazole, quinoline, isoquinoline, quinazoline, quinoxaline, indole, benzimidazole, benzofuran, pteridine and purines.

The term “aralkyl,” as used herein, refers to a straight or branched saturated carbon chain containing 1-6 carbon atoms, such as benzyl, substituted by an aromatic carbon hydride. Reference is made to phenethyl, 3-phenylpropyl, 1-naphthylmethyl, 2- (1-naphthyl) ethyl and the like.

The term “aryloxy” as used herein refers to phenoxy, 1-naphthyloxy or 2-naphthyloxy.

The term “aralkoxy,” as used herein, refers to a C _1-6 alkoxy group substituted by an aromatic carbon hydride, such as benzyloxy, phenethoxy, 3-phenylpropoxy, 1-naphthylmethoxy. , 2- (1-naphthyl) ethoxy and the like.

The term “heteroaralkyl” as used herein, refers to a straight or branched saturated carbon chain containing 1 to 6 carbons, such as (2-furyl), substituted by a heteroaryl group. Methyl, (3-furyl) methyl, (2-thienyl) methyl, (3-thienyl) methyl, (2-pyridyl) methyl, 1-methyl-1- (2
-Pyrimidyl) ethyl and the like.

The term “heteroaralkoxy,” as used herein, refers to a heteroaralkyl, as defined herein, attached to an oxygen atom having its free valence bond from an oxygen atom. For example, (2-furyl) methyl, (3-furyl) methyl, (2-thienyl) methyl, (3-thienyl) methyl, (2-pyridyl) methyl, 1-methyl-1- (2 -Pyrimidyl) ethyl.

The term “C _1-6 alkylsulfonyl”, as used herein, refers to a monovalent substituent comprising a C _1-6 alkyl group attached through a sulfonyl group, eg, methylsulfonyl, ethylsulfonyl , N-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, sec-butylsulfonyl, isobutylsulfonyl, tert-butylsulfonyl, n-pentylsulfonyl, 2-methylbutylsulfonyl, 3-methylbutylsulfonyl, n-hexylsulfonyl, 4 -Methylpentylsulfonyl, neopentylsulfonyl, n-hexylsulfonyl and 2
, 2-Dimethylpropylsulfonyl.

The term “C _1-6 monoalkylaminosulfonyl” as used herein refers to a monovalent substituent comprising a C _1-6 monoalkylamino group attached through a sulfonyl group, eg, methyl Aminosulfonyl, ethylaminosulfonyl, n-propylaminosulfonyl, isopropylaminosulfonyl, n-butylaminosulfonyl, sec-butylaminosulfonyl, isobutylaminosulfonyl, tert
-Butylaminosulfonyl, n-pentylaminosulfonyl, 2-methylbutylaminosulfonyl, 3-methylbutylaminosulfonyl, n-hexylaminosulfonyl, 4-methylpentylaminosulfonyl, neopentylaminosulfonyl, n-hexylaminosulfonyl and 2 , 2-Dimethylpropylaminosulfonyl.

The term “C _1-6 dialkylaminosulfonyl” as used herein refers to a monovalent substituent comprising a C _1-6 dialkylamino group attached through a sulfonyl group, eg, dimethylaminosulfonyl , N-ethyl-N-methylaminosulfonyl, diethylaminosulfonyl, dipropylaminosulfonyl, N- (n-butyl) -N-methylaminosulfonyl, di (n-pentyl) aminosulfonyl and the like.

The term “C _1-6 alkylsulfinyl” refers to a monovalent substituent comprising a straight or branched C _1-6 alkyl group attached through a sulfinyl group (—S (＝ O) —), for example, methyl Reference is made to sulfinyl, ethylsulfinyl, isopropylsulfinyl, butylsulfinyl, pentylsulfinyl and the like.

The term “acylamino,” as used herein, refers to one of the hydrogen atoms
Mention is made of amino groups, one of which is substituted by an acyl group, such as acetamido, propionamido, isopropylcarbonylamino and the like.

[0093] The term "(C _3-6 cycloalkyl) C _1-6 alkyl", as used herein alone and in combination, have from 1 to 6 carbon atoms, and C ₃ Linear or branched saturated hydrocarbon mono-substituted by _-6 cycloalkyl, wherein said cycloalkyl group is optionally mono- or polysubstituted by C _1-6 alkyl, halogen, hydroxy or C _1-6 alkoxy Reference is made to chains such as cyclopropylmethyl, (1-methylcyclopropyl) methyl, 1- (cyclopropyl) ethyl, cyclopentylmethyl, cyclohexylmethyl and the like.

The term “arylthio,” as used herein, alone or in combination, refers to an aryl group attached through a divalent sulfur atom having its free valence bond from a sulfur group, wherein the aryl group is Optionally substituted by C _1-6 alkyl, halogen, hydroxy or C _1-6 alkoxy), for example, phenylthio, (4-methylphenyl) thio, (2-chlorophenyl) thio and the like. .

The term “arylsulfinyl” as used herein refers to an aryl group attached through a sulfinyl group (—S (＝ O) —), wherein the aryl group is optionally a C _1-6 alkyl. , Halogen, hydroxy or C _1-6 alkoxy), for example phenylsulfinyl, (4-chlorophenyl) sulfinyl and the like.

The term “arylsulfonyl” as used herein refers to an aryl group attached through a sulfonyl group, wherein said aryl group is optionally a C _1-6 alkyl, halogen, hydroxy or C ₁ -alkyl. ₆ mono- or polysubstituted), for example, phenylsulfonyl, tosyl and the like.

The term “C _1-6 monoalkylaminocarbonyl,” as used herein, refers to a monovalent substituent comprising a C _1-6 monoalkylamino group attached through a carbonyl group, eg, methyl Aminocarbonyl, ethylaminocarbonyl, n-propylaminocarbonyl, isopropylaminocarbonyl, n-butylaminocarbonyl, sec-butylaminocarbonyl, isobutylaminocarbonyl, tert
-Butylaminocarbonyl, n-pentylaminocarbonyl, 2-methylbutylaminocarbonyl, 3-methylbutylaminocarbonyl, n-hexylaminocarbonyl, 4-methylpentylaminocarbonyl, neopentylaminocarbonyl, n-hexylaminocarbonyl and 2 , 2-dimethylpropylaminocarbonyl.

The term “C _1-6 dialkylaminocarbonyl” as used herein refers to a monovalent substituent comprising a C _1-6 dialkylamino group attached through a carbonyl group, eg, dimethylaminocarbonyl , N-ethyl-N-methylaminocarbonyl, diethylaminocarbonyl, dipropylaminocarbonyl, N- (n-butyl) -N-methylaminocarbonyl, di (n-pentyl) aminocarbonyl and the like.

The term “C _1-6 monoalkylaminocarbonylamino” as used herein refers to an amino group in which one of the hydrogen atoms has been replaced by a C _1-6 monoalkylaminocarbonyl group, for example, Methylaminocarbonylamino, ethylamino-
Carbonylamino, n-propylaminocarbonylamino, isopropylaminocarbonylamino, n-butylaminocarbonylamino, sec-butylaminocarbonylamino, isobutylaminocarbonylamino, tert-butylaminocarbonylamino, and 2-methylbutylaminocarbonylamino Mention.

The term “C _1-6 dialkylaminocarbonylamino,” as used herein, refers to an amino group in which one of the hydrogen atoms has been replaced by a C _1-6 dialkylaminocarbonyl group, such as dimethylamino Carbonylamino, N-ethyl-N-methylaminocarbonylamino, diethylaminocarbonylamino, dipropylaminocarbonylamino, N- (n-butyl) -N-methylaminocarbonylamino, di (n-pentyl) aminocarbonylamino and the like Mention.

As used herein, the term “heterocyclyl” is monocyclic and is one or more, for example, having 1 to 4 carbon atoms and 1 to 4 N, O or S A monovalent saturated or unsaturated group containing atoms, or a combination thereof. The term “heterocyclyl” refers to a 5-membered heterocycle having one heteroatom (eg, pyrrolidine, pyrroline); a 5-membered heterocycle having two heteroatoms at the 1,2, or 1,3 position (eg, , Pyrazoline, pyrazolidine, 1,2-oxathiolane, imidazolidine, imidazoline, 4-oxazolone); 5 having three heteroatoms
Membered heterocycle (eg, tetrahydrofuran); five-membered heterocycle having four heteroatoms; six-membered heterocycle having one heteroatom (eg, piperidine)
A 6-membered heterocycle having 2 heteroatoms (eg, piperazine, morpholine); a 6-membered heterocycle having 3 heteroatoms; and a 6-membered heterocycle having 4 heteroatoms. But not limited to them.

As used herein, the term “divalent heterocyclic group” is monocyclic and may be one or more, for example, having 1 to 4 carbon atoms and 1 to 4 N, A divalent saturated or unsaturated group containing an O or S atom or a combination thereof is meant. The term “divalent heterocyclic group” refers to a 5-membered heterocycle having one heteroatom (eg, pyrrolidine, pyrroline); a 5-membered heterocycle having two heteroatoms at the 1,2, or 1,3 positions. Ring (e.g., pyrazoline, pyrazolidine, 1,2-oxathiolane, imidazolidine, imidazoline, 4-oxazolone); 5 having 3 heteroatoms
Membered heterocycle (eg, tetrahydrofurazan); 5 having 4 heteroatoms
Six-membered heterocycle with one heteroatom (eg, piperidine); six-membered heterocycle with two heteroatoms (eg, piperazine, morpholine); three heteroatoms 6-membered heterocycles; and, but not limited to, 6-membered heterocycles having 4 heteroatoms.

As used herein, the term “5- to 6-membered cyclic ring” refers to one or more carbon atoms and optionally one to four N, O or S atoms or the same. A saturated or unsaturated or aromatic system is meant, including combinations. The term "5- to 6-membered cyclic ring" refers to cyclopentyl, cyclohexyl, phenyl, cyclohexenyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, pyrazolidinyl, pyrazolinyl, piperidyl, piperazinyl, pyrrolyl, 2H-pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl. , Pyrazinyl, pyrimidinyl, pyridazinyl, morpholinyl, thiomorpholinyl, isothiazolyl, isoxazolyl, oxazolyl, oxadiazolyl, thiadiazolyl, 1,3-dioxolanyl, 1,4-dioxolanyl, 5-membered heterocycles having one heteroatom (eg, thiophene, pyrrole , Furan); a 5-membered heterocycle having two heteroatoms at the 1,2 or 1,3 positions (eg, oxazole, pyrazole, imidazole, thiazole, Phosphorus)
A 5-membered heterocycle having 3 heteroatoms (eg, thiazole, thiadiazole); a 5-membered heterocycle having 4 heteroatoms; a 6-membered heterocycle having 1 heteroatom (eg, pyridine, Quinoline, isoquinoline, phenanthridine, cyclohepta [b] pyridine); a 6-membered heterocycle having two heteroatoms (eg, pyridazine, cinnoline, phthalazine, pyrazine, pyrimidine, quinazoline, morpholine); three heteroatoms 6-membered heterocycle (eg, 1
, 3,5-triazine); and six-membered heterocycles having four heteroatoms, but are not limited thereto.

As used herein, the term “5- or 6-membered nitrogen-containing ring” is defined as
Or a monovalent unsaturated or saturated monovalent substituent having 5 or 6 members, or a monovalent substituent comprising an aromatic system, comprising a plurality of carbon, nitrogen, oxygen or sulfur atoms, or a combination thereof, such as pyrrolidinyl, Pyrrolinyl, imidazolidinyl, pyrazolidinyl,
Pyrazolinyl, piperidyl, piperazinyl, pyrrolyl, 2H-pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, morpholinyl, thiomorpholinyl, isothiazolyl, isoxazolyl, oxazolyl, oxadiazolyl, thiadiazolyl, 1,3-dioxolanyl Reference is made to dioxolanyl.

Certain terms as defined above may occur more than once in Formula (Ia) above, and based on such occurrence, each term will be defined independently of the other .

Pharmaceutically acceptable salts forming part of the present invention include salts of the carboxylic acid component, for example alkali metal salts such as Li, Na and K salts, alkaline earth metals such as Ca and Mg salts. Salts, organic bases such as salts of lysine, arginine, guanidine, diethanolamine, choline and the like, ammonium or substituted ammonium salts, aluminum salts are included. Salts include, where appropriate, acid addition salts, which include sulfates, nitrates, phosphates, perchlorates, borates, halides, acetates, tartrates, maleates, citrates, Succinate, palmoate, methanesulfionate, benzoate, salicylate, hydroxynaphthoate, benzenesulfonate, ascorbate, glycerophosphate, ketoglutarate and the like. Pharmaceutically acceptable solvents are hydrates or can include other solvents for crystallization, such as alcohols.

Pharmaceutically acceptable salts include compounds of formula (Ia) and 1-4 equivalents of a base, such as sodium hydroxide, sodium methoxide, sodium hydride, potassium t-butoxide, calcium hydroxide, magnesium hydroxide And the like in a solvent such as ether, THF, methanol, t-butanol, dioxane, isopropanol, ethanol and the like. Mixtures of solvents can be used. Organic bases such as lysine, arginine, diethanolamine, choline, guandin and their derivatives and the like can also be used. On the other hand, acid addition salts
Where applicable, solvents such as ethyl acetate, ether, alcohol, acetone,
Acids in THF, dioxane, etc., such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid,
p-toluenesulfonic acid, methanesulfonic acid, acetic acid, citric acid, maleic acid, salicylic acid, hydroxynaphthoic acid, ascorbic acid, palmitic acid, succinic acid,
It is prepared by treatment with benzoic acid, benzenesulfonic acid, tartaric acid and the like. Mixtures of solvents can also be used.

The stereoisomers of the compounds forming part of the present invention may be prepared by using the reactants in their single enantiomeric form in the possible manner or in the presence of reagents or catalysts. Or by fractionating a mixture of stereoisomers by conventional methods. Some preferred methods include chiral acids such as mandelic acid, camphorsulfonic acid, tartaric acid,
Includes the use of microbial degradation to degrade diastereomers formed by lactic acid or the like, or by chiral bases such as brucine, cinchona alkaloids and their derivatives. Commonly used methods are Jaques et al. “Enantiomer, Racemates and
Resolution "(Wiley Interscience, 1981). More specifically, the compounds of formula (Ia) are prepared by treatment with a chiral amine, an amino acid, an amino alcohol derived from an amino acid into a 1: 1 mixture of diastereomeric amides. Conventional reaction conditions may be used to convert the acid to the amide; diastereomers may be separated by fractional recrystallization or chromatography and the stereochemistry of a compound of formula (Ia) Isomers can be prepared by hydrolyzing pure diastereomeric amides.

The various polymorphs of the compounds of the general formula (Ia) which form part of the invention can be prepared by crystallization of the compounds of the formula (Ia) under different conditions. For example, different solvents or mixtures thereof commonly used for recrystallization; crystallization at different temperatures; various cooling modes ranging from very fast to very slow during crystallization. Polymorphs can also be obtained by heating or melting the compound followed by gradual or rapid cooling. The presence of a polymorph may be determined by solid probe NMR spectroscopy, IR spectroscopy, differential scanning calorimetry, powder X-ray diffraction or other such techniques.

The present invention further relates to a method for producing the compound described above.

The compounds of the formula (Ia) can be used as compounds of the formula VI when m is 1 or b) when m is 0
Can be prepared as any of the compounds of formula XII.

Alkylation of I to II with a suitable electrophile (examples of electrophiles are: ethylene oxide, ethyl bromoacetate where the ester is reduced to an alcohol, 2-
Bromoethanol and 3-bromopropanol).

Embedded image

The hydroxy group is a suitable leaving group (eg, a halogen under Mitsunobu conditions,
Sulphonate, phosphate) and then reacts with HQ-Ar-R, III

Embedded image And if R = CHO, then III can react with the Wittig reagent and be converted to IV.

Embedded image

The addition of the double bond to the appropriate reagent

Embedded image give.

V can be hydrolyzed to the corresponding carboxylic acid or reacted further with appropriate reagents to form VI

Embedded image Can be given or one of them.

The molecule VII mentioned in the formation of II can be synthesized in a similar way starting from HQ-Ar-CHO.

VII is reacted with a suitable alkylating reagent to form VIII

Embedded image Which can be further reacted with I to give VI.

Yet another method for synthesizing compounds of the present invention is to react I with the appropriate propargyl analog IX,

Embedded image Is to give.

X is further cross-coupled with I-Ar-R using a Pd catalyst such as Pd (PPh ₃ ) ₄ or PdCl ₂ (PPh) ₂ to form XI

Embedded image Can be given.

If R = CHO, the above synthetic sequence (Wittig reaction, hydrogenation, followed by hydrolysis or derivatization of the carboxylic acid) results in the desired product XII

Embedded image Will give.

Compound XIII may further comprise a Pd catalyst such as Pd (PPh ₃ ) ₄ or PdCl ₂ (PP
h) Cross-coupling with propargyl derivative IX using ₂ to give product XIV

Embedded image Can be given.

XIV can further react with I to give XI, which can further react as described above to give XII.

L is a leaving group, and all other symbols are as previously described.

Pharmacological Methods PPAR Alpha and PPAR Gamma Activation Principles of Activity In Vitro The transcriptional activation assay of the PPAR gene involves the transfer of two plasmids, each encoding a chimeric test protein and a reporter protein, to human HEK293 cells. Based on transient transfection. The chimeric test protein is
DNA binding domain (DBD) derived from yeast GAL4 transcription factor and human PPAR
It is a fusion with the ligand binding domain (LBD) of the protein. The above-mentioned PPA
RLBD has, in addition to the ligand binding pocket, a natural activation domain (activating function 2 = AF2) that allows the fusion protein to function as a PPAR ligand-dependent transcription factor. The GAL4 DBD will only bind the fusion protein to the Gal4 enhancer (not present in HEK293 cells). The reporter plasmid contains a Gal4 enhancer that drives expression of the firefly luciferase protein. After transfection, HEK293 cells expressed the GAL4-DBD-PPAR-LBD fusion protein. The fusion protein then regulates the expression of the luciferase in G
It binds to the al4 enhancer and will do nothing in the absence of ligand. By adding a PPAR ligand to the cells, a luciferase protein will be produced in an amount corresponding to activation of the PPAR protein. The amount of luciferase protein is measured by light emission after addition of the appropriate substrate.

Methods Cell culture and transfection: HEK293 cells were transferred to DMEM + 10%
FCS was grown in 1% PS. Cells were seeded in 96-well plates the day before transfection, so that they were 80% confluent at the time of transfection. 0.8 μg DNA per well was transfected using FuGene transfection reagent according to the manufacturer's instructions (Boehringer-Mannhei
m). The cells were allowed to express the protein for 48 hours, after which the compound was added.

Plasmids: Human PPARα and γ were obtained by PCR amplification using cDNA templates from liver, intestine and adipose tissue, respectively. The amplified cDNA was converted to pC
It was cloned into R2.1 and sequenced. LBD derived from each isotype PPAR
Is generated by PCR (PPARα: aa167-C terminus; PPARγ: a
a165-C-terminal), and the plasmids pM1αLBD and pM1γLBD. The fragment was fused to GAL4-DBD by subcloning the fragment in reading frame into the vector pM1. Following fusion, it was confirmed by sequencing. The reporter contained Gal4 in a pGL2 vector (Promega).
It was constructed by inserting an oligonucleotide encoding 5 repeats of the recognition sequence.

Compounds: All compounds are dissolved in DMSO and 1: 1 upon addition to cells
000. Cells are incubated for 24 hours with test compound (200 μl containing delipidated serum)
(1: 1000) in a culture medium, followed by a luciferase assay.

Luciferase assay: The medium containing the test compound is aspirated and 1 mM Mg ⁺⁺ And Ca⁺⁺Was added to each well. Luciferase ass
A was performed using the LucLite kit according to the instruction manual (Packard In
struments). The light emission is on a Packard Instruments Top-counter
It was quantified by counting the SPC mode.

Pharmaceutical Compositions In another aspect, the present invention provides a pharmaceutical composition comprising within its scope at least one compound of general formula (Ia) as active ingredient, or a pharmaceutically acceptable carrier or diluent. Or a pharmaceutical composition comprising the salt thereof.

Pharmaceutical compositions containing the compounds of the present invention may be prepared according to the prior art, for example, from Remington: The Scien.
^{ce and Practice of Pharmacy, 19 th} Ed., can be prepared according to what is described in 1995. The compositions may also be presented in conventional forms, for example, capsules, tablets, aerosols, solutions, suspensions or topical applications.

A typical composition comprises a compound of Formula (Ia) or a pharmaceutically acceptable acid addition salt thereof, which may be a carrier or diluent, or may be diluted with a carrier. Associated with a pharmaceutically acceptable excipient, or enclosed in a carrier, which may be in the form of a capsule, satchet, paper or other container. In preparing the compositions described above, conventional techniques for the manufacture of pharmaceutical compositions can be used. For example, the active compound will usually be mixed with or diluted with a carrier, or enclosed in a carrier which may be in the form of an ampoule, capsule, sachet, paper or other container. When the carrier serves as a diluent, it is a solid,
It may be a semi-solid or liquid material, which acts as an excipient, excipient or solvent for the active compound. The active compound may be adsorbed on a solid container of granules, for example a sachet. Examples of suitable carriers are water, saline, alcohol, polyethylene glycol, polyhydroxyethoxylated castor oil, peanut oil, olive oil, gelatin, lactose, terra alba, sucrose, cyclodextrin, amylose,
Magnesium stearate, talc, gelatin, agar, pectin, acacia, lower alkyl ethers of stearic acid or cellulose, silicic acid, fatty acids, fatty acid amines, fatty acid monoglycerides and diglycerides, pentaerythritol fatty acid esters, polyoxyethylene, hydroxymethylcellulose and polyvinylpyrrolidone It is. Similarly, the carrier or diluent may include any sustained release agent known in the art, such as glyceryl monostearate or glyceryl distearate, alone or in combination with a wax. The formulations may also contain wetting, emulsifying and suspending agents, preserving, sweetening or flavoring agents. The formulations of the present invention can be prepared to provide a rapid, sustained or delayed release of the active ingredient after administration to the patient by applying methods known in the art.

The pharmaceutical compositions may be sterilized and mixed, if desired, with adjuvants, emulsifiers, salts which affect osmotic pressure, buffers and / or coloring agents, etc., which may contain any of the active ingredients Does not react harmfully with compounds.

The route of administration in the present case may be any route which effectively delivers the active compound to a suitable or desired site of action, for example oral, nasal, pulmonary, transdermal or parenteral. For example, rectal, depot, subcutaneous, intravenous, urethral, intramuscular, intranasal, ophthalmine solution or ointment, the oral route being preferred.

If a solid carrier is used for oral administration, the preparation may be tabletted and placed in a hard gelatin capsule in powder or pill form, or it may be in the form of a troche or lozenge. There is. If a liquid carrier is used, the preparation may be in the form of a syrup, emulsifier, soft gelatin capsule or sterile injectable solution, for example, an aqueous or non-aqueous liquid suspension or solution.

For nasal administration, the preparation may contain a compound of formula (Ia) dissolved or suspended in a liquid carrier, especially an aqueous carrier for spray application. The carrier may include solubilizers, for example, propylene glycol, surfactants, adsorption enhancers, for example, lecithin (phosphatidylcholine) or cyclodextrin, or preservatives, for example, additives such as parabens.

Particularly suitable for parenteral application are injectable solutions or suspensions,
Preferred is an aqueous liquid having the active compound dissolved in polyhydroxylated castor oil.

Tablets, dragees or capsules with talc and / or carbohydrate carriers or binders and the like are particularly suitable for oral application. Preferred carriers for tablets, dragees, or capsules include lactose, corn starch, and / or potato starch. Syrups or elixirs can be used where sweetened excipients can be applied.

Typical tablets that can be manufactured by conventional tableting techniques are: Core: Active compound (as an independent compound or a salt thereof) 5 mg Colloidal silicon dioxide (Aerosil) 1.5 mg Cellulose, Microcrist (Avicel) 70 mg Modified Cellulose Gum (Ac-Di-Sol) 7.5 mg Magnesium Stearate Adding Coating: HPMC about 9 mg ^* Mywacet 9-40T May contain about 0.9 mg. ^* Acylated monoglycerides used as plasticizers for film coating.

The compounds of the present invention can be administered to mammals, especially humans, in need of the treatment, prevention, elimination, reduction or amelioration of the above-mentioned diseases associated with the regulation of blood glucose. Such mammals further include both livestock, eg, domestic pets, and non-domestic animals, eg, wildlife.

The compounds of the present invention are effective over a wide dosage range. For example, in the treatment of adults, from about 0.05 to about 100 mg, preferably from about 0.1 to about 10 mg per day.
A dose of 0 mg may be used. The most preferred dosage is about 0.1 mg per day
About 70 mg. In selecting a regimen for the patient, from about 2 to about 7 per day
It may often be necessary to start with a dose of 0 mg, and if conditions are adjusted to reduce the dose, from about 0.1 to about 10 mg per day. Precise dosages will depend on the mode of administration, the treatment desired, the type of administration, the subject to be treated and the weight of the subject to be treated, and the preferences and experience of the attending physician and veterinarian.

Generally, the compounds of the present invention are suspended in unit dosage form comprising from about 0.1 to about 100 mg of the active ingredient per unit dosage form, together with a pharmaceutically acceptable carrier.

Typically, dosage forms suitable for oral, nasal, pulmonary, or transdermal administration will comprise from about 0.001 mg to about 100 mg, preferably about 0.0 mg, mixed with a pharmaceutically acceptable carrier or diluent.
1 mg to about 50 mg of a compound of formula (Ia).

In a further aspect, the present invention relates to a method for treating and / or preventing type I or type II diabetes.

In a still further aspect, the invention relates to the use of one or more compounds of general formula (Ia) or a pharmaceutically acceptable salt thereof, for the treatment and / or prevention of type I or type II diabetes. For use for manufacturing.

Any novel features or combinations described herein are considered essential to the invention.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61P 3/04 A61P 3/04 3/06 3/06 3/10 3/10 9/00 9/00 9 / 12 9/12 13/12 13/12 17/06 17/06 19/10 19/10 43/00 111 43/00 111 C07D 471/14 101 C07D 471/14 101 491/153 491/153 495/14 495/14 CD (81) Designated countries EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), OA (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH, GM, KE, LS, MW, SD, SL, SZ, TZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, U, TJ, TM), AE, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CR, CU, CZ, DE, DK, DM, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU , LV, MA, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, TZ, UA, UG, UZ, VN, YU, ZA, ZW (72) Inventor Jepessen, Rone Denmark, DECO-2830 Birm, Malmosebai 121 (72) Inventor Bury, Paul Stanley Denmark, DECO-2400 Kebenhaun Embe, Yorsol Suarere 48 (72) Inventor Sauerberg, Perk Denmark-3520 Farm, Silenbeyet 27 F-term (reference) BB02 CC01 CC22 EE13 FF03 FF06 GG03 JJ01 KK11 LL01 4C086 AA01 AA03 AA04 BC31 CB05 CB09 CB22 CB26 CB27 MA01 MA04 MA52 MA56 MA59 MA63 ZA15 ZA36 ZA42 ZA70 ZA81 ZA89 ZA96 ZA97 ZCZ ZC35

Claims (49)

[Claims] 1. A compound of the formula (Ia)(Where ring A fused to a ring containing X and N represents a 5- to 6-membered ring,
One or more halogen, perhalomethyl, hydroxy, nitro, cyano, holmi
Or C_1-12Alkyl, C_4-12Alkenyl, C_2-12Alkenyl, C_2-12Al
Quinyl, C_1-12Alkoxy, aryl, aryloxy, aralkyl, aralco
Xy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryl
Oxy, heteroaralkoxy, acyl, acyloxy, hydroxy C_1-12Archi
, Amino, acylamino, C_1-12Alkylamino, arylamino, aralkyl
Ruamino, amino C_1-12Alkyl, C_1-12Alkoxycarbonyl, aryloxy
Cicarbonyl, aralkoxycarbonyl, C_1-12Alkoxy C_1-12Alkyl, a
Reeloxy C_1-12Alkyl, aralkoxy C_1-12Alkyl, C_1-12Alkyl
Oh, Thio C_1-12Alkyl, C_1-12Alkoxycarbonylamino, aryloxy
Carbonylamino, aralkoxycarbonylamino, -COR¹¹Or SO_Two R ¹² Where R¹¹And R¹²Are independently hydroxy, halogen,
Perhalomethyl, C_1-6 Alkoxy or one or more C_1-6 Alkyl, per
Selected from amino substituted with halomethyl or aryl; optionally one or more
Ring B fused to a ring containing X and N represents a 5- to 6-membered ring, which is optionally substituted by one or more halogen, perhalomethyl, hydroxy, nitro or cyano.
A number of halogens, perhalomethyl, hydroxy, nitro, cyano, formyl, or
C_1-12Alkyl, C_4-12Alkenyl, C_2-12Alkenyl, C_2-12Alkynyl,
C_1-12Alkoxy, aryl, aryloxy, aralkyl, aralkoxy, f
Telocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy,
Heteroaralkoxy, acyl, acyloxy, hydroxy C_1-12Alkyl, Ami
No, acylamino, C_1-12Alkylamino, arylamino, aralkylamino
, Amino C_1-12Alkyl, C_1-12Alkoxycarbonyl, aryloxycarbo
Nil, aralkoxycarbonyl, C_1-12Alkoxy C_1-12Alkyl, arylo
Kishi C_1-12Alkyl, aralkoxy C_1-12Alkyl, C_1-12Alkylthio, thio
C_1-12Alkyl, C_1-12Alkoxycarbonylamino, aryloxycarboni
Ruamino, aralkoxycarbonylamino, -COR¹¹Or SO_Two R¹²Replace with
Where R¹¹And R¹²Are independently of each other hydroxy, halogen, perha
Lomethyl, C_1-6 Alkoxy or optionally one or more C_1-6 Alkyl, per
Selected from amino substituted with halomethyl or aryl; optionally one or more
X is substituted with a number of halogens, perhalomethyl, hydroxy, nitro or cyano; X is a valence bond,-(CHR⁹ )-,-(CHR⁹ ) -CH_Two -, -CH = C
H-, -O-, -O- (CHR⁹ )-, -S- (CHR⁹ )-,-(NR⁹ )-
CH_Two -,-(CHR⁹ ) -CH = CH-,-(CHR⁹ ) -CH_Two -CH_Two −
,-(C = O)-,-O-CH_Two -O-,-(NR⁹ )-,-(NR⁹ ) -S (
O_Two )-, -CH = (CR⁹ )-,-(CO)-(CHR⁹ )-, -CH_Two − (
SO)-, -S-,-(SO)-,-(SO_Two )-, -CH_Two − (SO_Two ) −,
-CH_Two -O-CH_Two -, Where R⁹ Is hydrogen, halogen, hydroxy,
Nitro, cyano, formyl, C_1-12Alkyl, C_1-12Alkoxy, aryl, a
Reeloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl
, Heteroaralkyl, heteroaryloxy, heteroaralkoxy, acyl, a
Siloxy, hydroxyalkyl, amino, acylamino, C_1-12Alkylam
No, arylamino, aralkylamino, aminoC_1-12Alkyl, C_1-12Arco
Xycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, C_1-12 Alkoxy C_1-12Alkyl, aryloxy C_1-12Alkyl, aralkoxy C_{1- 12} Alkyl, C_1-12Alkylthio, thio-C_1-12Alkyl, C_1-12Alkoxycal
Bonylamino, aryloxycarbonylamino, aralkoxycarbonylamino
No, -COR¹¹Or SO_Two R¹²Where R¹¹And R¹²But independently of each other
, Hydroxy, halogen, C_1-6 Alkoxy, optionally one or more C_1-6 Al
Q is -O-, -S-,> SO_Two ,> NR¹³Where R¹³Is hydrogen or C _1-6 Ar is arylene, heteroarylene, or one or more C_1-6 Alkyl
Or a divalent heterocyclic group substituted with aryl;^Five Is hydrogen, hydroxy, halogen, C_1-12Alkoxy, C_1-12Alkyl, C _4-12 Alkenyl, C_2-12Alkenyl, C_2-12Represents alkynyl or aralkyl
It optionally comprises one or more halogen, perhalomethyl, hydroxy, nitro or
Is substituted with cyano; or R^Five Is R⁶ Forms a bond with⁶ Is hydrogen, hydroxy, halogen, C_1-12Alkoxy, C_1-12Alkyl, C _4-12 Alkenyl, C_2-12Alkenyl, C_2-12Alkynyl, acyl or aralkyl
Which optionally contains one or more halogen, perhalomethyl, hydroxy,
Substituted with nitro or cyano; or R⁶ Is R^Five Forms a bond with⁷ Is hydrogen, C_1-12Alkyl, C_4-12Alkenyl, C_2-12Alkenyl, C_{2- 12} Alkynyl, aryl, aralkyl, C_1-12Alkoxy C_1-12Alkyl, C_{1- 12} Alkoxycarbonyl, aryloxycarbonyl, C_1-12Alkylaminoka
Rubonyl, arylaminocarbonyl, acyl, heterocyclyl, heteroaryl
Or a heteroaralkyl group; optionally with one or more halogen, per
Substituted with halomethyl, hydroxy, nitro or cyano; R⁸ Is hydrogen, C_1-12Alkyl, C_4-12Alkenyl, C_2-12Alkenyl, C_{2- 12} Alkynyl, aryl, aralkyl, heterocyclyl, heteroaryl or
Represents a heteroalkyl group; optionally one or more halogen, perhalomethyl
, Hydroxy, nitro or cyano; Y is oxygen, sulfur or NR^TenWhere R^TenIs hydrogen, C_1-12Alkyl, a
Reel, Hydroxy C_1-12Represents an alkyl or aralkyl group, or Y is NR ^Ten When, R⁸ And R^TenMay form a ring containing 5 or 6 membered nitrogen,
Is optionally one or more C_1-6 N is an integer ranging from 1 to 4 and m is an integer ranging from 0 to 1 wherein A or B does not represent phenyl) or a pharmaceutically acceptable compound Its salt. 2. A ring fused to a ring containing X and N represents a 5- to 6-membered ring,
Is optionally one or more of hydrogen, halogen, perhalomethyl, hydroxy, cyano,
Or C_1-7 Alkyl, C_4-7 Alkenyl, C_2-7 Alkenyl, C_2-7 Alkini
Le, C_1-7 Alkoxy, aryl, aryloxy, aralkyl, aralkoxy
, Heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy
Si, heteroaralkoxy, acyl, acyloxy, hydroxy C_1-7 Alkyl,
Amino, acylamino, C_1-7 Alkylamino, arylamino, aralkyl
Mino, amino C_1-7 Alkyl, C_1-7 Alkoxy C_1-7 Alkyl, aryloxy
C_1-7 Alkyl, aralkoxy C_1-7 Alkyl, C_1-7 Alkylthio, thio-C _1-7 Alkyl, C_1-7 Alkoxycarbonylamino, aryloxycarbonyl
Amino, aralkoxycarbonylamino, -COR¹¹Or SO_Two R¹²Replaced by
Where R¹¹And R¹²Are independently hydroxy, perhalomethyl or
Is one or more C_1-6 Amino substituted with alkyl, perhalomethyl or aryl
Which is optionally selected from one or more halogen, perhalomethyl, hydroxy
2. The compound according to claim 1, wherein the compound is substituted with cyano or cyano. 3. Ring A fused to a ring containing X and N represents a 5- to 6-membered ring, optionally having one or more hydrogen, halogen, perhalomethyl, hydroxy, cyano,
Or C _1-7 alkyl, C _4-7 alkenyl, C _2-7 alkenyl, C _2-7 alkynyl, C _1-7 alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, Heteroaryloxy, heteroaralkoxy, acyl, amino, acylamino, C _1-7 alkylamino, arylamino, aralkylamino, amino C _1-7 alkyl, C _1-7 alkoxy C _1-7 alkyl, aryloxy C _{1 -7} alkyl, aralkoxy C _1-7 alkyl, substituted with C _1-7 alkylthio, thio C _1-7 alkyl; this is optionally substituted with one or more halogen or hydroxy, as defined in claim 1 or 2 Compound. 4. Ring A fused to a ring containing X and N represents a 5- to 6-membered ring, optionally having one or more hydrogen, halogen, perhalomethyl, hydroxy or C _1-7.
Alkyl, C _2-7 alkenyl, C _2-7 alkynyl, C _1-7 alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heteroaryloxy, heteroaralkoxy, acyl, arylamino, aryloxy C _{1 - 7} alkyl substituted compound according to any one of claims 1 to 3. 5. Ring A fused to a ring containing X and N represents a 5- to 6-membered ring, optionally having one or more hydrogen, halogen, perhalomethyl, hydroxy or C _1-7.
The compound according to any one of claims 1 to 4, substituted with alkyl, _C2-7 alkenyl, _C2-7 alkynyl, _C1-7 alkoxy or aryl. 6. The method of claim 1, wherein the ring A fused to the ring containing X and N represents a 5- to 6-membered ring, which is optionally substituted with one or more hydrogen or halogen. The compound according to the above. 7. A ring B fused to a ring containing X and N represents a 5- to 6-membered ring,
Is optionally one or more of hydrogen, halogen, perhalomethyl, hydroxy, cyano,
Or C_1-7 Alkyl, C_4-7 Alkenyl, C_2-7 Alkenyl, C_2-7 Alkini
Le, C_1-7 Alkoxy, aryl, aryloxy, aralkyl, aralkoxy
, Heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy
Si, heteroaralkoxy, acyl, acyloxy, hydroxy C_1-7 Alkyl,
Amino, acylamino, C_1-7 Alkylamino, arylamino, aralkyl
Mino, amino C_1-7 Alkyl, C_1-7 Alkoxy C_1-7 Alkyl, aryloxy
C_1-7 Alkyl, aralkoxy C_1-7 Alkyl, C_1-7 Alkylthio, thio-C _1-7 Alkyl, C_1-7 Alkoxycarbonylamino, aryloxycarbonyl
Amino, aralkoxycarbonylamino, -COR¹¹Or SO_Two R¹²Replaced by
Where R¹¹And R¹²Are independently of each other, hydroxy, perhalomethyl
Or one or more C_1-6 Substituted with alkyl, perhalomethyl or aryl
Which is optionally selected from one or more halogen, perhalomethyl,
The compound according to any one of claims 1 to 6, which is substituted with hydroxy or cyano.
object. 8. Ring B fused to a ring containing X and N represents 5 to 6 members, optionally having one or more hydrogen, halogen, perhalomethyl, hydroxy, cyano, or C _1-7 alkyl, C _{4 -7} alkenynyl, C _2-7 alkenyl, C _2-7 alkynyl, C _1-7 alkoxy, aryl, aryloxy, aralkyl, aralkoxy,
Heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, acyl, amino, acylamino, C _1-7 alkylamino, arylamino, aralkylamino, amino C _1-7 alkyl, C _1-7 alkoxy Substituted with C _1-7 alkyl, aryloxy C _1-7 alkyl, aralkoxy C _1-7 alkyl, C _1-7 alkylthio, thio C _1-7 alkyl; which is optionally substituted with one or more halogen or hydroxy. A compound according to any one of claims 1 to 7. 9. Ring B fused to a ring containing X and N represents a 5- to 6-membered ring, optionally having one or more hydrogen, halogen, perhalomethyl, hydroxy or C _1-7.
Alkyl, C _2-7 alkenyl, C _2-7 alkynyl, C _1-7 alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heteroaryloxy, heteroaralkoxy, acyl, arylamino, aryloxy C _{1 - 7} alkyl substituted compound according to any one of claims 1 to 8. 10. A ring B fused to a ring containing X and N to form a 5- to 6-membered ring,
This is optionally one or more of hydrogen, halogen, perhalomethyl, hydroxy or C _1-7 Alkyl, C_2-7 Alkenyl, C_2-7 Alkynyl, C_1-7 Alkoxy or a
10. The compound according to any one of claims 1 to 9, substituted with a reel. 11. The method according to claim 1, wherein the ring B fused to the ring containing X and N represents a 5- to 6-membered ring, which is optionally substituted with one or more hydrogen or halogen. The compound according to the above. 12. X is a valence bond,-(CHR⁹ )-,-(CHR⁹ ) -C
H_Two -, -CH = CH-, -O-, -O- (CHR⁹ )-, -S- (CHR⁹ )
−, − (NR⁹ ) -CH_Two -,-(CHR⁹ ) -CH = CH-,-(CHR⁹ )
-CH_Two -CH_Two -,-(C = O)-, -O-CH_Two -O-,-(NR⁹ ) −,
− (NR⁹ ) -S (O_Two )-, -CH = (CR⁹ )-,-(CO)-(CHR⁹ 
)-, -CH_Two -(SO)-, -S-,-(SO)-,-(SO_Two )-, -CH _Two − (SO_Two )-, -CH_Two -O-CH_Two -, Where R⁹ Is hydrogen, halo
Gen, hydroxy, cyano, C_1-7 Alkyl, C_1-7 Alkoxy, aryl, a
Reeloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl
, Heteroaralkyl, heteroaryloxy, heteroaralkoxy, acyl, a
Siloxy, hydroxyalkyl, amino, acylamino, C_1-7 Alkylam
No, arylamino, aralkylamino, aminoC_1-7 Alkyl, C_1-7 Arco
Kishi C_1-7 Alkyl, aryloxy C_1-7 Alkyl, aralkoxy C_1-7 Al
Kill, C_1-7 Alkylthio, thio-C_1-7 Any of claims 1 to 11, which is alkyl.
A compound according to any one of the preceding claims. 13. X is a valence bond,-(CHR⁹ )-,-(CHR⁹ ) -C
H_Two -, -CH = CH-, -O-, -O- (CHR⁹ )-, -S- (CHR⁹ )
−, − (NR⁹ ) -CH_Two -,-(CHR⁹ ) -CH = CH-,-(CHR⁹ )
-CH_Two -CH_Two -,-(C = O)-, -O-CH_Two -O-,-(NR⁹ ) −,
− (NR⁹ ) -S (O_Two )-, -CH = (CR⁹ )-,-(CO)-(CHR⁹ 
)-, -CH_Two -(SO)-, -S-,-(SO)-,-(SO_Two )-, -CH _Two − (SO_Two )-, -CH_Two -O-CH_Two -, Where R⁹ Is hydrogen, halo
Gen, hydroxy, C_1-7 Alkyl, C_1-7 Is an alkoxy or aryl
Item 13. The compound according to any one of Items 1 to 12. 14. X is a valence bond,-(CHR ⁹ )-,-(CHR ⁹ ) -C
H _2- , -CH = CH-, -O- (CHR ⁹ )-, -S- (CHR ⁹ )-,-(
NR ⁹ ) -CH ₂ -,-(CHR ⁹ ) -CH = CH-,-(CHR ⁹ ) -CH _{2
-CH 2 -, - (C =} O) -, - O-CH 2 -O -, - (NR 9) -S (O 2)
-, -CH = (CR ⁹ )-,-(CO)-(CHR ⁹ )-, -CH _2- (SO)
-, - (SO) -, - (SO 2) -, - CH 2 - (SO 2) -, - CH 2 -O-
CH ₂ -, a, wherein R ⁹ is hydrogen, halogen, hydroxy, C _1-4 alkyl, C _1-4 alkoxy, A compound according to any one of claims 1 to 13. 15. X is a valence bond,-(CHR ⁹ )-,-(CHR ⁹ ) -C
H ₂ —, —CH ＝ CH—, —O— (CHR ⁹ ) —, — (CHR ⁹ ) —CH ＝ CH
^{-, - (CHR 9) -CH} 2 -CH 2 -, - (C = O) -, - O-CH 2 -O-
, -CH = (CR ⁹ )-,-(CO)-(CHR ⁹ )-, -CH _2- (SO)-
, - (SO) -, - (SO 2) -, - CH 2 - (SO 2) -, - CH 2 -O-C
H ₂ -, a, wherein R ⁹ is hydrogen, A compound according to any one of claims 1 to 14. 16. The compound according to any one of claims 1 to 15, wherein Q is -O- or -S-. 17. The compound according to any one of claims 1 to 16, wherein Q is -O-. 18. Ar is arylene, heteroarylene, or one or more
Number C_1-6 R represents a bivalent heterocyclic group substituted with alkyl or aryl;^Five Is hydrogen, hydroxy, halogen, C_1-7 Alkoxy, C_1-7 Alkyl, C _4-7 Alkenyl, C_2-7 Alkenyl, C_2-7 Represents-; or R^Five Is R⁶ 
Forms a bond with⁶ Is hydrogen, hydroxy, halogen, C_1-7 Alkoxy, C_1-7 Alkyl, C _4-7 Alkenyl, C_2-7 Alkenyl, C_2-7 Represents alkynyl; or R ⁶ Is R^Five Forms a bond with⁷ Is hydrogen, C_1-7 Alkyl, C_4-7 Alkenyl, C_2-7 Alkenyl, C_{2- 7} Alkynyl, aryl, aralkyl, C_1-7 Alkoxy C_1-7 Alkyl, C_{1- 7} Alkoxycarbonyl, aryloxycarbonyl, C_1-7 Alkylaminoka
Rubonyl, arylaminocarbonyl, acyl, heterocyclyl, heteroaryl
R or a heteroaralkyl group;⁸ Is hydrogen, C_1-7 Alkyl, C_4-7 Alkenyl, C_2-7 Alkenyl, C_{2- 7} Alkynyl, aryl, aralkyl, heterocyclyl, heteroaryl or
Represents a heteroaralkyl; Y is oxygen, sulfur or NR^TenWhere R^TenIs hydrogen, C_1-7 Alkyl, hide
Roxy C_1-7 18. A compound according to any one of claims 1 to 17, wherein n represents an integer ranging from 2 to 3 and m represents an integer ranging from 0 to 1. 19. Ar represents an arylene or heteroarylene, R ⁵ is hydrogen, hydroxy, or halogen; or R ⁵ forms a bond together with R ^6, Table R ⁶ is hydrogen, hydroxy, halogen Or R ⁶ forms a bond with R ⁵ , wherein R ⁷ is hydrogen, C _1-7 alkyl, C _2-7 alkenyl, C _2-7 alkynyl, aryl, aralkyl, C _1-7 alkoxy C _{1 -7} alkyl, C _1-7 alkylaminocarbonyl, arylaminocarbonyl, acyl, heterocyclyl, heteroaryl or heteroaralkyl group; R ⁸ is hydrogen, C _1-7 alkyl, C _2-7 alkenyl, C ₂ It represents _-7 alkynyl; Y represents oxygen or sulfur; an integer n spans 2-3, and m is 1, a compound according to any one of claims 1-18. 20. Ar represents arylene or heteroarylene; R ⁵ represents hydrogen; R ⁶ represents hydrogen; R ⁷ is hydrogen, C _1-7 alkyl, C _2-7 alkenyl, C _2-7 alkynyl , Aryl, aralkyl, C _1-7 alkoxyC _1-7 alkyl; R ⁸ represents hydrogen, C _1-7 alkyl, C _2-7 alkenyl, C _2-7 alkynyl; Y represents oxygen; n Is an integer ranging from 2 to 3, and m is 1. 20. The compound according to any one of claims 1 to 19, wherein m is 1. 21. Ar 21 represents arylene; R ⁵ represents hydrogen; R ⁶ represents hydrogen; R ⁷ represents hydrogen, C _1-4 alkyl, C _2-4 alkenyl, C _2-4 alkynyl; R ⁸ represents hydrogen, C _1-4 alkyl, Y represents oxygen; n is an integer ranging 2-3, and m is 1, according to any one of claims 1 to 20 Compound. 22. Ar represents phenylene; R ⁵ represents hydrogen; R ⁶ represents hydrogen; R ⁷ represents hydrogen, C _1-4 alkyl; R ⁸ represents hydrogen; Y represents oxygen. 22. The compound according to any one of claims 1-21, wherein n is an integer ranging from 2 to 3 and m is 1. 23. The compound according to any one of claims 1 to 22, wherein A is a 5-membered ring containing S. 24. The compound according to any one of claims 1 to 23, wherein B is a 5-membered ring containing S. 25. X is -CH = (CR ⁹⁾ - a, where in R ⁹ is H, A compound according to any one of claims 1 to 24. 26. The compound according to any one of claims 1 to 25, wherein n is 2. 27. The compound according to any one of claims 1-26, wherein Q is -O-. 28. The compound according to any one of claims 1-27, wherein m is 1. 29. The compound according to any one of claims 1 to 28, wherein Ar is phenylene [In another preferred embodiment, the present invention relates to a compound of formula I, wherein R ⁵ is H.
Related to the compound of formula (1). 30. The compound according to any one of claims 1-29, wherein R ⁶ is H. 31. The compound according to any one of claims 1 to 30, wherein R ⁷ is ethyl. 32. The compound according to any one of claims 1 to 31, wherein Y is oxygen. 33. The compound according to any one of claims 1 to 32, wherein R ⁸ is H. 34. 3- {4- [2- (8,9-dihydro-3,5-dithia-
4-aza-cyclopenta [f] azulen-4-yl) -ethoxy] phenyl}-
2-ethoxy-propionic acid, 3- {4- [2- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -ethoxy] -phenyl} -2 -Methoxy-propionic acid, 3- {4- [2- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -ethoxy] -phenyl} -2- Propoxy
Propionic acid, 3- {4- [2- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -ethoxy] -phenyl} -2-benzyloxy- Propionic acid, 3- {4- [2- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -ethyl] -phenyl} -2-ethoxy-propion Acid, 3- {4- [2- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -ethyl] -phenyl} -2-methoxy-propionic acid 3- {4- [2- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -ethyl] -phenyl} -2-propoxy-propionic acid; 3- {4- [2- (8,9-Jihi B-3,5-Dithia-4-aza-cyclopenta [f] azulen-4-yl) -ethyl] -phenyl} -2-benzyloxy-propionic acid, 3- {4- [1- (8,9- Dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -methoxy] -phenyl} -2-ethoxy-propionic acid, 3- {4- [1- (8,9-dihydro) -3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -methoxy] -phenyl} -2-methoxy-propionic acid, 3- {4- [1- (8,9-dihydro- 3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -methoxy] -phenyl} -2-benzyloxy-propionic acid, 3- {4- [3- (8,9-dihydro- 3,5-dithia-4-aza-cyclo Printers [f] azulen-4-yl) - propoxy] - phenyl} -2-ethoxy -
Propionic acid, 3- {4- [3- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -propoxy] -phenyl} -2-methoxy-
Propionic acid, 3- {4- [3- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -propoxy] -phenyl} -2-benzyloxy- Propionic acid, 3- {4- [3- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -propyl] -phenyl} -2-ethoxy-propion Acid, 3- {4- [3- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -propyl] -phenyl} -2-methoxy-propionic acid 3- {4- [3- (8,9-dihydro-3,5-dithia-4-aza-cyclopenta [f] azulen-4-yl) -propyl] -phenyl} -2-benzyloxy-propionic acid , 2-ethoxy-3- 4- (2- (9H-1,8,10-triaza-anthracen-10-yl) -ethoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (2- (9H-1,8 , 10-Triaza-anthracen-10-yl) -ethoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (2- (9H-1,8,10-triaza-anthracen-10-yl) -Ethoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (2- (9H-1,8,10-triaza-anthracen-10-yl) -ethoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (1- (9H-1,8,10-triaza-anthracen-10-yl) -methoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (1 -(9 -1,8,10-Triaza-anthracen-10-yl) -methoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (1- (9H-1,8,10-triaza-anthracene) -10-yl) -methoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (3- (9H-1,8,10-triaza-anthracen-10-yl) -propoxy) -phenyl) -Propionic acid, 2-propoxy-3- (4- (3- (9H-1,8,10-triaza-anthracen-10-yl) -propoxy) -phenyl) -propionic acid, 2-methoxy-3- ( 4- (3- (9H-1,8,10-triaza-anthracen-10-yl) -propoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (3- (9H- 1,8,10-Triaza-anthracen-10-yl) -propoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (3- (9H-1,8,10-triaza-anthracene-10) -Yl) -propyl) -phenyl) -propionic acid, 2-propoxy-3- (4- (3- (9H-1,8,10-triaza-anthracen-10-yl) -propyl) -phenyl) -propionate Acid, 2-methoxy-3- (4- (3- (9H-1,8,10-triaza-anthracen-10-yl) -propyl) -phenyl) -propionic acid, 2-benzyloxy-3- (4 -(3- (9H-1,8,10-triaza-anthracen-10-yl) -propyl) -phenyl) -propionic acid, 2-ethoxy-3- (4- (2- (4,5,9- Thoria - fluoren-9
Yl) -ethoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (2- (4,5,9-triaza-fluorene-9-
Yl) -ethoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (2- (4,5,9-triaza-fluorene-9)
-Yl) -ethoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (1- (4,5,9-triaza-fluorene-9-
Yl) -methoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (1- (4,5,9-triaza-fluorene-9-
Yl) -methoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (1- (4,5,9-triaza-fluoren-9-yl) -methoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (3- (4,5,9-triaza-fluorene-9-
Yl) -propoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (3- (4,5,9-triaza-fluorene-9-
Yl) -propoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (3- (4,5,9-triaza-fluoren-9-yl) -propoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (3- (4,5,9-triaza-fluorene-9)
-Yl) -propoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (3- (4,5,9-triaza-fluorene-9-
Yl) -propyl) -phenyl) -propionic acid, 2-methoxy-3- (4- (3- (4,5,9-triaza-fluorene-9-
Yl) -propyl) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (3- (4,5,9-triaza-fluoren-9-yl) -propyl) -phenyl) -propionic acid, 2-propoxy-3- (4- (3- (4,5,9-triaza-fluorene-9)
-Yl) -propyl) -phenyl) -propionic acid, 2-ethoxy-3- (4- (2- (1,8,9-triaza-fluorene-9-
Yl) -ethoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (2- (1,8,9-triaza-fluorene-9-)
Yl) -ethoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (2- (1,8,9-triaza-fluorene-9)
-Yl) -ethoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (2- (1,8,9-triaza-fluoren-9-yl) -ethoxy) -phenyl) -propionic acid 2-methoxy-3- (4- (1- (1,8,9-triaza-fluorene-9-
Yl) -methoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (1- (1,8,9-triaza-fluorene-9-)
Yl) -methoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (1- (1,8,9-triaza-fluorene-9)
-Yl) -methoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (1- (1,8,9-triaza-fluoren-9-yl) -methoxy) -phenyl) -propionic acid 2-ethoxy-3- (4- (3- (1,8,9-triaza-fluorene-9-
Yl) -propoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (3- (1,8,9-triaza-fluorene-9-)
Yl) -propoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (3- (1,8,9-triaza-fluorene-9)
-Yl) -propoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (3- (1,8,9-triaza-fluoren-9-yl) -propoxy) -phenyl) -propionic acid 2-ethoxy-3- (4- (3- (1,8,9-triaza-fluorene-9-
Yl) -propyl) -phenyl) -propionic acid, 2-methoxy-3- (4- (3- (1,8,9-triaza-fluorene-9-
Yl) -propyl) -phenyl) -propionic acid, 2-propoxy-3- (4- (3- (1,8,9-triaza-fluorene-9)
-Yl) -propyl) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (3- (1,8,9-triaza-fluoren-9-yl) -propyl) -phenyl) -propionic acid 3- (4- (2- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -ethoxy) -phenyl) -2-ethoxy-propionic acid, 3- (4- (2- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -ethoxy) -phenyl) -2-methoxy-propionic acid, 3- (4- (2- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -ethoxy) -phenyl) -2-propoxy-propionic acid, 3- (4- (2- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -ethoxy) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (1- (dithieno [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -methoxy) -phenyl) -2-methoxy-propionic acid, 3- (4- (1- (dithieno [2,3-b; 3 ′, 2′-d] pyrrole-7-)
Yl) -methoxy) -phenyl) -2-ethoxy-propionic acid, 3- (4- (1- (dithieno [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -methoxy) -phenyl) -2-propoxy-propionic acid, 3- (4- (1- (dithieno [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -methoxy) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (3- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propoxy) -phenyl) -2-ethoxy-propionic acid, 3- (4- (3- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propoxy) -phenyl) -2-methoxy-propionic acid, 3- (4- (3- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propoxy) -phenyl) -2-propoxy-propionic acid, 3- (4- (3- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propoxy) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (3- (dithieno [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -propyl) -phenyl) -2-ethoxy-propionic acid, 3- (4- (3- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propyl) -phenyl) -2-methoxy-propionic acid, 3- (4- (3- (dithieno [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -propyl) -phenyl) -2-propoxy-propionic acid, 3- (4- (3- (dithieno [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propyl) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (2- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -ethoxy) -phenyl) -2-ethoxy-propionic acid, 3- (4- (2- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -ethoxy) -phenyl) -2-methoxy-propionic acid, 3- (4- (2- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -ethoxy) -phenyl) -2-propoxy-propionic acid, 3- (4- (2- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -ethoxy) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (1- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -methoxy) -phenyl) -2-ethoxy-propionic acid, 3- (4- (1- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -methoxy) -phenyl) -2-methoxy-propionic acid, 3- (4- (1- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -methoxy) -phenyl) -2-propoxy-propionic acid, 3- (4- (1- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -methoxy) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (3- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -propoxy) -phenyl) -2-ethoxy-propionic acid, 3- (4- (3- (difurano [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propoxy) -phenyl) -2-propoxy-propionic acid, 3- (4- (3- (difurano [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propoxy) -phenyl) -2-methoxy-propionic acid, 3- (4- (3- (difurano [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propoxy) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (3- (difurano [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propyl) -phenyl) -2-ethoxy-propionic acid, 3- (4- (3- (difurano [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propyl) -phenyl) -2-propoxy-propionic acid, 3- (4- (3- (difurano [2,3-b; 3 ', 2'-d] pyrrole-7-
Yl) -propyl) -phenyl) -2-methoxy-propionic acid, 3- (4- (3- (difurano [2,3-b; 3 ′, 2′-d] pyrrole-7-
Yl) -propyl) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (2- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -ethoxy) -phenyl) -2-ethoxy-propionic acid, 3- (4- (2- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -ethoxy) -phenyl) -2-methoxy-propionic acid, 3- (4- (2- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -ethoxy) -phenyl) -2-propoxy-propionic acid, 3- (4- (2- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -ethoxy) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (1- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -methoxy) -phenyl) -2-ethoxy-propionic acid, 3- (4- (1- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -methoxy) -phenyl) -2-methoxy-propionic acid, 3- (4- (1- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -methoxy) -phenyl) -2-propoxy-propionic acid, 3- (4- (1- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -methoxy) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (3- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -propoxy) -phenyl) -2-ethoxy-propionic acid, 3- (4- (3- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -propoxy) -phenyl) -2-methoxy-propionic acid, 3- (4- (3- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -propoxy) -phenyl) -2-propoxy-propionic acid, 3- (4- (3- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -propoxy) -phenyl) -2-benzyloxy-propionic acid, 3- (4- (3- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -propyl) -phenyl) -2-ethoxy-propionic acid, 3- (4- (3- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -propyl) -phenyl) -2-methoxy-propionic acid, 3- (4- (3- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -propyl) -phenyl) -2-propoxy-propionic acid, 3- (4- (3- (4H-1,7-dithia-8-aza-s-indacene-8-).
Yl) -propyl) -phenyl) -2-benzyloxy-propionic acid, 2-ethoxy-3- (4- (2- (4-oxa-1,7-dithia-8-aza-
s-Indacene-8-yl) -ethoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (2- (4-oxa-1,7-dithia-8-aza-)
s-Indacene-8-yl) -ethoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (2- (4-oxa-1,7-dithia-8-aza-s-indacene-8). -Yl) -ethoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (2- (4-oxa-1,7-dithia-8-aza-s-indacene-8-yl) -ethoxy). ) -Phenyl) -propionic acid, 2-benzyloxy-3- (4- (2- (4-oxa-1,7-dithia-8-
Aza-s-indacen-8-yl) -ethoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (1- (4-oxa-1,7-dithia-8-aza-)
s-Indacene-8-yl) -methoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (1- (4-oxa-1,7-dithia-8-aza-)-
s-Indacene-8-yl) -methoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (1- (4-oxa-1,7-dithia-8-aza-s-indacene-8). -Yl) -methoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (1- (4-oxa-1,7-dithia-8-).
Aza-s-indacen-8-yl) -methoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (3- (4-oxa-1,7-dithia-8-aza-
s-Indacene-8-yl) -propoxy) -phenyl) -propionic acid, 2-methoxy-3- (4- (3- (4-oxa-1,7-dithia-8-aza-)-
s-Indacene-8-yl) -propoxy) -phenyl) -propionic acid, 2-propoxy-3- (4- (3- (4-oxa-1,7-dithia-8-aza-s-indacene-8). -Yl) -propoxy) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (3- (4-oxa-1,7-dithia-8-).
Aza-s-indacen-8-yl) -propoxy) -phenyl) -propionic acid, 2-ethoxy-3- (4- (3- (4-oxa-1,7-dithia-8-aza-)
s-Indacene-8-yl) -propyl) -phenyl) -propionic acid, 2-methoxy-3- (4- (3- (4-oxa-1,7-dithia-8-aza-)
s-Indacene-8-yl) -propyl) -phenyl) -propionic acid, 2-propoxy-3- (4- (3- (4-oxa-1,7-dithia-8-aza-s-indacene-8). -Yl) -propyl) -phenyl) -propionic acid, 2-benzyloxy-3- (4- (3- (4-oxa-1,7-dithia-8-).
Aza-s-indacen-8-yl) -propyl) -phenyl) -propionic acid,
The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein 35. 3- {4- [2- (8,9-dihydro-3,5-dithia-
4-aza-cyclopenta [f] azulen-4-yl) -ethoxy] -phenyl}
The compound according to claim 1, which is 2-ethoxy-propionic acid; or a pharmaceutically acceptable salt thereof. 36. A medicament comprising as active ingredient a compound according to any one of claims 1 to 35 or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier or diluent. Composition. 37. About 0.05 to about 100 mg, preferably about 0.1 to about 50 mg
37. The pharmaceutical composition according to claim 36, comprising a compound according to any one of claims 1 to 35 or a pharmaceutically acceptable salt thereof. 38. Nuclear receptors, in particular peroxisome proliferator-activated receptors (
A pharmaceutical composition useful for the treatment and / or prevention of conditions mediated by PPAR), wherein the compound according to any one of claims 1 to 35, or a pharmaceutically acceptable carrier or as an active ingredient. A composition comprising a pharmaceutically acceptable salt thereof together with a diluent. 39. A pharmaceutical composition useful for the treatment and / or prevention of diabetes and / or obesity, wherein the compound according to any one of claims 1 to 35 or a pharmaceutically acceptable compound is used as an active ingredient. A composition comprising a pharmaceutically acceptable salt thereof together with a carrier or diluent. 40. A pharmaceutical composition for diabetes and / or obesity, comprising as an active ingredient a compound according to any one of claims 1 to 35, or a pharmaceutically acceptable carrier or diluent. A composition comprising together a pharmaceutically acceptable salt thereof. 41. The pharmaceutical composition according to any one of claims 36 to 40, for oral, nasal, transdermal, pulmonary, or parenteral administration. 42. A method for the treatment of a disease, which comprises administering to a subject in need thereof a compound according to any one of claims 1 to 35 or a pharmaceutically acceptable salt thereof, or a method thereof. 42. A method comprising administering an effective amount of a composition according to any one of paragraphs 36 to 41. 43. A nuclear receptor, in particular a peroxisome proliferator-activated receptor (
35. A method for the treatment and / or prevention of a condition mediated by PPAR), wherein the compound according to any one of claims 1 to 35 is provided to a subject in need thereof.
42. A method comprising administering an effective amount of a pharmaceutically acceptable salt thereof, or a composition of any one of claims 36-41. 44. A method for treating and / or preventing diabetes and / or obesity, which is provided to a subject in need thereof as a compound or a medicine according to any one of claims 1 to 35. 42. A method comprising administering an effective amount of an acceptable salt thereof, or a composition according to any one of claims 36-41. 45. The effective amount of the compound according to any one of claims 1 to 35 or a pharmaceutically acceptable salt or ester thereof is about 0.05 to about 100 mg per day, preferably about 0 to about 100 mg per day. 43. The range of from about 0.1 to about 50 mg.
44. The method according to 46. Use of a compound according to any one of claims 1 to 35 or a pharmaceutically acceptable salt thereof for the manufacture of a medicament. 47. A compound according to any one of claims 1 to 35 or a pharmaceutically acceptable salt thereof, wherein said compound is a nuclear receptor, particularly a peroxisome proliferator-activated receptor (PPAR) mediated condition. Use for the manufacture of a medicament useful for treatment and / or prevention. 48. Use of a compound according to any one of claims 1 to 35 or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment and / or prevention of diabetes and / or obesity. . 49. Use of a compound according to any one of claims 1 to 35 or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment and / or prevention of diabetes and obesity.