NO841024L - Fremgangsmaate for fremstilling av nye forbindelser med virkning mot hypertensjon - Google Patents

Fremgangsmaate for fremstilling av nye forbindelser med virkning mot hypertensjon

Info

Publication number: NO841024L
Authority: NO; Norway
Prior art keywords: ethoxycarbonyl; phenylpropyl; chloro; alanyl; compound
Prior art date: 1983-03-16

Application number

NO841024A

Other languages

English (en)

Norwegian (no)

Inventor

John J Piwinski

John T Suh

Paul R Menard

Howard Jones

Edward S Neiss

Original Assignee

Usv Pharma Corp

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1983-03-16

Filing date

1984-03-16

Publication date

1984-09-17

1984-03-16 Application filed by Usv Pharma Corp filed Critical Usv Pharma Corp

1984-09-17 Publication of NO841024L publication Critical patent/NO841024L/no

Links

150000001875 compounds Chemical class 0.000 title claims description 119
238000000034 method Methods 0.000 title claims description 23
206010020772 Hypertension Diseases 0.000 title description 6
230000000694 effects Effects 0.000 title description 5
125000000217 alkyl group Chemical group 0.000 claims description 30
125000003118 aryl group Chemical group 0.000 claims description 24
239000001257 hydrogen Substances 0.000 claims description 20
229910052739 hydrogen Inorganic materials 0.000 claims description 20
125000004432 carbon atom Chemical group C* 0.000 claims description 17
150000003839 salts Chemical class 0.000 claims description 17
229920006395 saturated elastomer Polymers 0.000 claims description 17
239000002253 acid Substances 0.000 claims description 15
-1 acylaminoalkylamino Chemical group 0.000 claims description 15
125000000753 cycloalkyl group Chemical group 0.000 claims description 15
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
125000001424 substituent group Chemical group 0.000 claims description 12
229910052736 halogen Inorganic materials 0.000 claims description 10
150000002367 halogens Chemical class 0.000 claims description 10
238000002360 preparation method Methods 0.000 claims description 9
239000004471 Glycine Substances 0.000 claims description 7
125000003545 alkoxy group Chemical group 0.000 claims description 7
125000003710 aryl alkyl group Chemical group 0.000 claims description 7
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
229910000039 hydrogen halide Inorganic materials 0.000 claims description 7
239000012433 hydrogen halide Substances 0.000 claims description 7
125000004350 aryl cycloalkyl group Chemical group 0.000 claims description 6
230000015572 biosynthetic process Effects 0.000 claims description 6
OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 6
229910052757 nitrogen Inorganic materials 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
125000004103 aminoalkyl group Chemical group 0.000 claims description 5
125000004429 atom Chemical group 0.000 claims description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
229910052799 carbon Inorganic materials 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
150000007513 acids Chemical class 0.000 claims description 3
230000000903 blocking effect Effects 0.000 claims description 3
125000001072 heteroaryl group Chemical group 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
125000003107 substituted aryl group Chemical group 0.000 claims description 3
238000006467 substitution reaction Methods 0.000 claims description 3
125000004442 acylamino group Chemical group 0.000 claims description 2
125000004945 acylaminoalkyl group Chemical group 0.000 claims description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
125000004093 cyano group Chemical group *C#N 0.000 claims description 2
125000004367 cycloalkylaryl group Chemical group 0.000 claims description 2
125000004404 heteroalkyl group Chemical group 0.000 claims description 2
125000004475 heteroaralkyl group Chemical group 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims 2
229960002429 proline Drugs 0.000 claims 2
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims 1
239000004472 Lysine Substances 0.000 claims 1
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims 1
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
239000000825 pharmaceutical preparation Substances 0.000 claims 1
238000007086 side reaction Methods 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
239000000203 mixture Substances 0.000 description 65
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 51
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
239000000243 solution Substances 0.000 description 43
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 40
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 38
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 35
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 28
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
238000004128 high performance liquid chromatography Methods 0.000 description 25
238000006243 chemical reaction Methods 0.000 description 20
229910052943 magnesium sulfate Inorganic materials 0.000 description 20
235000019341 magnesium sulphate Nutrition 0.000 description 20
239000011541 reaction mixture Substances 0.000 description 20
239000000047 product Substances 0.000 description 18
239000007787 solid Substances 0.000 description 17
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
229960000583 acetic acid Drugs 0.000 description 14
238000002844 melting Methods 0.000 description 14
230000008018 melting Effects 0.000 description 14
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
239000000706 filtrate Substances 0.000 description 13
239000012299 nitrogen atmosphere Substances 0.000 description 13
239000007864 aqueous solution Substances 0.000 description 12
235000017557 sodium bicarbonate Nutrition 0.000 description 12
229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
239000011780 sodium chloride Substances 0.000 description 11
239000003921 oil Substances 0.000 description 10
235000019198 oils Nutrition 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
229940086542 triethylamine Drugs 0.000 description 10
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
229910000041 hydrogen chloride Inorganic materials 0.000 description 9
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
239000012267 brine Substances 0.000 description 8
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
150000002431 hydrogen Chemical class 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
239000004014 plasticizer Substances 0.000 description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 5
125000005842 heteroatom Chemical group 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
229910052938 sodium sulfate Inorganic materials 0.000 description 5
235000011152 sodium sulphate Nutrition 0.000 description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 4
108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 4
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical class C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
239000007788 liquid Substances 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 3
VOABBQIQCAKTIC-UHFFFAOYSA-N 2-[carboxymethyl(phenylmethoxycarbonyl)amino]acetic acid Chemical compound OC(=O)CN(CC(O)=O)C(=O)OCC1=CC=CC=C1 VOABBQIQCAKTIC-UHFFFAOYSA-N 0.000 description 3
101800000734 Angiotensin-1 Proteins 0.000 description 3
102400000344 Angiotensin-1 Human genes 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 3
239000002775 capsule Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
230000001882 diuretic effect Effects 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
239000006260 foam Substances 0.000 description 3
239000012362 glacial acetic acid Substances 0.000 description 3
239000011521 glass Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
238000010992 reflux Methods 0.000 description 3
239000002904 solvent Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
229910052717 sulfur Inorganic materials 0.000 description 3
LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 2
MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 2
MONMFXREYOKQTI-UHFFFAOYSA-N 2-bromopropanoic acid Chemical compound CC(Br)C(O)=O MONMFXREYOKQTI-UHFFFAOYSA-N 0.000 description 2
SCYSJFKWFQZRJW-UHFFFAOYSA-N 4-chloro-3-sulfamoylbenzoyl chloride Chemical compound NS(=O)(=O)C1=CC(C(Cl)=O)=CC=C1Cl SCYSJFKWFQZRJW-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
102000005862 Angiotensin II Human genes 0.000 description 2
101800000733 Angiotensin-2 Proteins 0.000 description 2
241000167854 Bourreria succulenta Species 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
108090000783 Renin Proteins 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
239000000370 acceptor Substances 0.000 description 2
239000013543 active substance Substances 0.000 description 2
229960003767 alanine Drugs 0.000 description 2
125000004448 alkyl carbonyl group Chemical group 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
229940024606 amino acid Drugs 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 2
229950006323 angiotensin ii Drugs 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
239000002585 base Substances 0.000 description 2
JHVLLYQQQYIWKX-UHFFFAOYSA-N benzyl 2-bromoacetate Chemical compound BrCC(=O)OCC1=CC=CC=C1 JHVLLYQQQYIWKX-UHFFFAOYSA-N 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
230000036772 blood pressure Effects 0.000 description 2
238000009835 boiling Methods 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
239000007795 chemical reaction product Substances 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
235000019693 cherries Nutrition 0.000 description 2
238000009833 condensation Methods 0.000 description 2
230000005494 condensation Effects 0.000 description 2
238000001816 cooling Methods 0.000 description 2
239000008120 corn starch Substances 0.000 description 2
239000007822 coupling agent Substances 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
238000001035 drying Methods 0.000 description 2
WFLQXECQLHZKMV-NSHDSACASA-N ethyl (2s)-2-amino-4-phenylbutanoate Chemical compound CCOC(=O)[C@@H](N)CCC1=CC=CC=C1 WFLQXECQLHZKMV-NSHDSACASA-N 0.000 description 2
LSXBNLARBXRUOW-UHFFFAOYSA-N ethyl 2,4-dichloro-5-sulfamoylbenzoate Chemical compound CCOC(=O)C1=CC(S(N)(=O)=O)=C(Cl)C=C1Cl LSXBNLARBXRUOW-UHFFFAOYSA-N 0.000 description 2
238000001914 filtration Methods 0.000 description 2
235000003599 food sweetener Nutrition 0.000 description 2
229910000042 hydrogen bromide Inorganic materials 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
125000003367 polycyclic group Chemical group 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
239000002002 slurry Substances 0.000 description 2
239000011734 sodium Substances 0.000 description 2
241000894007 species Species 0.000 description 2
239000007858 starting material Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
239000003765 sweetening agent Substances 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Chemical class OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical class OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
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239000007885 tablet disintegrant Substances 0.000 description 1
BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
CVAWKJKISIPBOD-UHFFFAOYSA-N tert-butyl 2-bromopropanoate Chemical compound CC(Br)C(=O)OC(C)(C)C CVAWKJKISIPBOD-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
238000001665 trituration Methods 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000003643 water by type Substances 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
239000009637 wintergreen oil Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/022—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2
- C07K5/0222—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2 with the first amino acid being heterocyclic, e.g. Pro, Trp
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Heart & Thoracic Surgery (AREA)
Public Health (AREA)
Cardiology (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

NO841024A 1983-03-16 1984-03-16 Fremgangsmaate for fremstilling av nye forbindelser med virkning mot hypertensjon NO841024L (no)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US47580483A	1983-03-16	1983-03-16

Publications (1)

Publication Number	Publication Date
NO841024L true NO841024L (no)	1984-09-17

Family

ID=23889224

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO841024A NO841024L (no)	1983-03-16	1984-03-16	Fremgangsmaate for fremstilling av nye forbindelser med virkning mot hypertensjon

Country Status (11)

Country	Link
EP (1)	EP0121830A3 (fr)
JP (1)	JPS59181247A (fr)
KR (1)	KR840009072A (fr)
AU (1)	AU2580184A (fr)
DK (1)	DK156484A (fr)
ES (2)	ES8602631A1 (fr)
FI (1)	FI841052A (fr)
IL (1)	IL71266A0 (fr)
NO (1)	NO841024L (fr)
NZ (1)	NZ207531A (fr)
ZA (1)	ZA841981B (fr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4482544A (en) *	1982-11-29	1984-11-13	Usv Pharmaceutical Corporation	Compounds for treating hypertension
GB8311286D0 (en) *	1983-04-26	1983-06-02	Searle & Co	Carboxyalkyl peptide derivatives
JPS6034993A (ja) *	1983-05-23	1985-02-22	ユーエスヴイー　フアーマシユーテイカル　コーポレーシヨン	高血圧治療用化合物
AU578489B2 (en) *	1984-09-12	1988-10-27	Rorer Pharmaceutical Corporation	Proline derivatives
DE3569368D1 (en) *	1984-11-30	1989-05-18	Fisons Plc	Angiotensin converting enzyme inhibitors and their production and use as pharmaceuticals
FR2578544A1 (en) *	1985-03-11	1986-09-12	Usv Pharma Corp	Antihypertension spirocyclic compounds
FR2578543B1 (fr) *	1985-03-11	1988-06-10	Usv Pharma Corp	Composes spiro-amidoamino anti-hypertenseurs
ATE62694T1 (de) *	1985-09-16	1991-05-15	Schering Corp	Antihypertensive mittel, deren pharmazeutische zusammensetzungen und verfahren zur herstellung von mitteln und zusammensetzungen.
AR033048A1 (es)	2001-03-19	2003-12-03	Kaneka Corp	Metodo para la purificacion de la n-(1(s)-etoxicarbonil-3-fenilpropil) -l-alanina
CN105001139B (zh) *	2015-07-08	2018-03-02	南京葆赫生物技术有限公司	一种抗高血压活性肽、其制备方法及应用

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3177130D1 (de) *	1980-08-30	1990-01-11	Hoechst Ag	Aminosaeurederivate, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung.
GR75019B (fr) *	1980-09-17	1984-07-12	Univ Miami
LU88621I2 (fr) *	1980-10-23	1995-09-01	Schering Corp	Sandopril
IN156096B (fr) *	1981-03-19	1985-05-11	Usv Pharma Corp
IE55867B1 (en) *	1981-12-29	1991-02-14	Hoechst Ag	New derivatives of bicyclic aminoacids,processes for their preparation,agents containing these compounds and their use,and new bicyclic aminoacids as intermediates and processes for their preparation
EP0083923B1 (fr) *	1982-01-11	1988-10-19	Merck & Co. Inc.	Dérivés dipeptidiques contenant le groupe aminoacyle, utilisables comme agents antihypertensifs
EP0088350B1 (fr) *	1982-03-08	1985-02-20	Schering Corporation	Carboxyalkyl dipeptides, leur procédé de préparation et leurs compositions pharmaceutiques les contenant
DE3210496A1 (de) *	1982-03-23	1983-10-06	Hoechst Ag	Neue derivate bicyclischer aminsaeuren, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung sowie neue bicyclische aminosaeuren als zwischenstufen und verfahren zu deren herstellung
DE3211676A1 (de) *	1982-03-30	1983-10-06	Hoechst Ag	Neue derivate von cycloalka (c) pyrrol-carbonsaeuren, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung sowie neue cycloalka (c) pyrrol-carbonsaeuren als zwischenstufen und verfahren zu deren herstellung
US4499079A (en) *	1982-11-18	1985-02-12	E. R. Squibb & Sons, Inc.	Carboxy and substituted carboxy alkanoyl and cycloalkanoyl peptides
DE3315464A1 (de) *	1983-04-28	1984-10-31	Hoechst Ag, 6230 Frankfurt	Verfahren zur herstellung von n-alkylierten dipeptiden und deren estern

1984
- 1984-03-15 DK DK156484A patent/DK156484A/da not_active IP Right Cessation
- 1984-03-15 FI FI841052A patent/FI841052A/fi not_active Application Discontinuation
- 1984-03-16 ES ES531077A patent/ES8602631A1/es not_active Expired
- 1984-03-16 NO NO841024A patent/NO841024L/no unknown
- 1984-03-16 EP EP84102941A patent/EP0121830A3/fr not_active Withdrawn
- 1984-03-16 KR KR1019840001335A patent/KR840009072A/ko not_active Application Discontinuation
- 1984-03-16 ZA ZA841981A patent/ZA841981B/xx unknown
- 1984-03-16 NZ NZ207531A patent/NZ207531A/en unknown
- 1984-03-16 JP JP59049384A patent/JPS59181247A/ja active Pending
- 1984-03-16 AU AU25801/84A patent/AU2580184A/en not_active Abandoned
- 1984-03-16 IL IL71266A patent/IL71266A0/xx unknown
1985
- 1985-06-28 ES ES545175A patent/ES8704875A1/es not_active Expired

Also Published As

Publication number	Publication date
DK156484A (da)	1984-09-17
FI841052A0 (fi)	1984-03-15
ES531077A0 (es)	1985-12-16
EP0121830A3 (fr)	1986-02-05
IL71266A0 (en)	1984-06-29
ES8704875A1 (es)	1987-05-01
DK156484D0 (da)	1984-03-15
EP0121830A2 (fr)	1984-10-17
JPS59181247A (ja)	1984-10-15
FI841052A (fi)	1984-09-17
AU2580184A (en)	1984-09-20
KR840009072A (ko)	1984-12-24
ES545175A0 (es)	1987-05-01
ZA841981B (en)	1984-10-31
NZ207531A (en)	1986-12-05
ES8602631A1 (es)	1985-12-16

Publication	Publication Date	Title
KR850000303B1 (ko)	1985-03-18	옥타히드로-1h-인돌-2-카복실산 치환 아실유도체의 제법
US4668797A (en)	1987-05-26	Bicyclic aminoacids as intermediates and processes for their preparation
EP0054862B1 (fr)	1985-11-27	Dipeptides substitués, leur procédé de préparation, compositions pharmaceutiques les contenant et leur emploi comme inhibiteurs de l'enképhalinase
US4350704A (en)	1982-09-21	Substituted acyl derivatives of octahydro-1H-indole-2-carboxylic acids
NO158740B (no)	1988-07-18	Analogifremgangsmaate ved fremstilling av terapeutisk aktive 4-substituerte 2-azetidinonforbindelser.
NO821037L (no)	1982-10-01	Fremgangsmaate ved fremstilling av n-substituerte amidoaminosyrer
US4496542A (en)	1985-01-29	N-substituted-amido-amino acids
SK64993A3 (en)	1994-01-12	Hydroxamic acid derivatives, method of their preparation and medicaments with their content
NO841024L (no)	1984-09-17	Fremgangsmaate for fremstilling av nye forbindelser med virkning mot hypertensjon
US4425355A (en)	1984-01-10	Substituted acyl derivatives of chair form of octahydro-1H-indole-2-carboxylic acids
NZ199310A (en)	1985-10-11	Peptides and peptide derivatives containing 3-5 amino acid residues;compositions
NO820903L (no)	1982-09-20	Fremgangsmaate ved fremstilling av amido-aminosyrer.
US5380872A (en)	1995-01-10	Modulators of cholecystokinin
CA1158236A (fr)	1983-12-06	Procede de preparation d'un nouveau compose amide de l'acide phenylacetique substitue
KR910001438B1 (ko)	1991-03-07	광학적 활성 비시클릭 이미노-α-카복실산 에스테르 라세미체의 분할방법
NO840102L (no)	1984-07-13	Analogifremgangsmaate for fremstilling av terapeutisk aktive hydroxylaminoeddiksyrederivater
JPS63295597A (ja)	1988-12-01	トリペプタイド誘導体及びそれを有効成分とする心血管系疾患治療剤
US4490386A (en)	1984-12-25	Phosphate salts of 1-[2-[(1-alkoxycarbonyl-3-aralkyl)-amino]-1-oxoalkyl]octahydro-1H-indole-2-carboxylic acids, preparation of, and medical compositions thereof
EP0127124A2 (fr)	1984-12-05	Composés pour le traitement de l'hypertension
EP0061768B1 (fr)	1986-05-14	Dipeptides N-amido substitués
EP0058567B1 (fr)	1984-07-25	Dérivés acyliques substitués des acides octahydro-1H-isoindole-1-carboxyliques et de ses esters
US4456594A (en)	1984-06-26	N-Carboxyalkylproline-containing tripeptides
JPH0247480B2 (fr)	1990-10-19
US4749698A (en)	1988-06-07	Antihypertensive derivatives
CA1247085A (fr)	1988-12-20	Preparation de tripeptides renfermant la n-carboxyalcoylproline