US5366973A — Mercaptoacetylamido pyridazo [1,2]pyridazine, pyr…

Claim 1

Independent Claim 151 words

A compound of the Formula ##STR3## wherein G represents a methylene, ethylene or vinylene group; R 1 represents a hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group wherein Ar is a phenyl or naphthyl group unsubstituted or substituted with from one to three substitutents selected from the gorup consisting of methylenedioxy, hydroxy, C 1 -C 4 alkoxy, amino, nitro, fluoro and chloro and Y is a saturated straight or branched chain hydrocarbyl radical of zero to four carbon atoms; R 2 represents a hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; R 3 represents a carboxyl, alkoxycarbonyl or an Ar--Y--O carbonyl group; R 4 and R 5 each represent a hydrogen atom or R 4 and R 5 together represent an oxo group; n stands for zero, 1 or 2, and pharmaceutically acceptable salts and individual optical isomers thereof.

Claim 2

Dependent Claim 151 words

A compound of the Formula ##STR3## wherein G represents a methylene, ethylene or vinylene group; R 1 represents a hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group wherein Ar is a phenyl or naphthyl group unsubstituted or substituted with from one to three substitutents selected from the gorup consisting of methylenedioxy, hydroxy, C 1 -C 4 alkoxy, amino, nitro, fluoro and chloro and Y is a saturated straight or branched chain hydrocarbyl radical of zero to four carbon atoms; R 2 represents a hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; R 3 represents a carboxyl, alkoxycarbonyl or an Ar--Y--O carbonyl group; R 4 and R 5 each represent a hydrogen atom or R 4 and R 5 together represent an oxo group; n stands for zero, 1 or 2, and pharmaceutically acceptable salts and individual optical isomers thereof.

Claim 3

Dependent Claim 8 words

A compound according to claim 1 wherein n=2.

Claim 4

Dependent Claim 12 words

A compound according to claim 2 wherein G is an ethylene group.

Claim 5

Dependent Claim 11 words

A compound according to claim 3 wherein R 1 is phenylmethyl.

Claim 6

Independent Claim 173 words

A method of inhibiting enkephalinase in a patient in need thereof comprising administering to said patient an effective enkephalinase inhibitory amount of a compound of the Formula ##STR4## wherein G represents a methylene, ethylene or vinylene group; R 1 represents a hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group wherein Ar is a phenyl or naphthyl group unsubstituted or substituted with from one to three substitutents selected from the gorup consisting of methylenedioxy, hydroxy, C 1 -C 4 alkoxy, amino, nitro, fluoro and chloro and Y is a saturated straight or branched chain hydrocarbyl radical of zero to four carbon atoms; R 2 represents a hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; R 3 represents a carboxyl, alkoxycarbonyl or an Ar--Y--O carbonyl group; R 4 and R 5 each represent a hydrogen atom or R 4 and R 5 together represent an oxo group; n stands for zero, 1 or 2, and pharmaceutically acceptable salts and individual optical isomers thereof.

Claim 7

Independent Claim 173 words

A method of inhibiting enkephalinase in a patient in need thereof comprising administering to said patient an effective enkephalinase inhibitory amount of a compound of the Formula ##STR4## wherein G represents a methylene, ethylene or vinylene group; R 1 represents a hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group wherein Ar is a phenyl or naphthyl group unsubstituted or substituted with from one to three substitutents selected from the gorup consisting of methylenedioxy, hydroxy, C 1 -C 4 alkoxy, amino, nitro, fluoro and chloro and Y is a saturated straight or branched chain hydrocarbyl radical of zero to four carbon atoms; R 2 represents a hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; R 3 represents a carboxyl, alkoxycarbonyl or an Ar--Y--O carbonyl group; R 4 and R 5 each represent a hydrogen atom or R 4 and R 5 together represent an oxo group; n stands for zero, 1 or 2, and pharmaceutically acceptable salts and individual optical isomers thereof.

Claim 8

Dependent Claim 19 words

A method according to claim 5 wherein the patient is in need of an endorphin- or enkephalin-mediated analgesic effect.

Claim 9

Dependent Claim 17 words

A method according to claim 5 wherein the patient is in need of an ANP-mediated hypotensive effect.

Claim 10

Dependent Claim 17 words

A method according to claim 5 wherein the patient is in need of an ANP-mediated diuretic effect.

Claim 11

Dependent Claim 15 words

A method according to claim 5 wherein the patient is suffering from congestive heart failure.

Claim 12

Dependent Claim 15 words

A method according to claim 5 wherein the patient is suffering from irritable bowel syndrome.

Claim 13

Independent Claim 173 words

A method of inhibiting ACE in a patient in need thereof comprising administering to said patient an effective ACE inhibitory amount of a compound of the Formula ##STR5## wherein G represents a methylene, ethylene or vinylene group; R 1 represents a hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group wherein Ar is a phenyl or naphthyl group unsubstituted or substituted with from one to three substitutents selected from the gorup consisting of methylenedioxy, hydroxy, C 1 -C 4 alkoxy, amino, nitro, fluoro and chloro and Y is a saturated straight or branched chain hydrocarbyl radial of zero to four carbon atoms; R 2 represents a hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; R 3 represents a carboxyl, alkoxycarbonyl or an Ar--Y--O carbonyl group; R 4 and R 5 each represent a hydrogen atom or R 4 and R 5 together represent an oxo group; n stands for zero, 1 or 2, and pharmaceutically acceptable salts and individual optical isomers thereof.

Claim 14

Independent Claim 173 words

A method of inhibiting ACE in a patient in need thereof comprising administering to said patient an effective ACE inhibitory amount of a compound of the Formula ##STR5## wherein G represents a methylene, ethylene or vinylene group; R 1 represents a hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group wherein Ar is a phenyl or naphthyl group unsubstituted or substituted with from one to three substitutents selected from the gorup consisting of methylenedioxy, hydroxy, C 1 -C 4 alkoxy, amino, nitro, fluoro and chloro and Y is a saturated straight or branched chain hydrocarbyl radial of zero to four carbon atoms; R 2 represents a hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; R 3 represents a carboxyl, alkoxycarbonyl or an Ar--Y--O carbonyl group; R 4 and R 5 each represent a hydrogen atom or R 4 and R 5 together represent an oxo group; n stands for zero, 1 or 2, and pharmaceutically acceptable salts and individual optical isomers thereof.

Claim 15

Dependent Claim 16 words

A method according to claim 11 wherein the patient is in need of a hypotensive effect.

Claim 16

Dependent Claim 17 words

A method according to claim 11 wherein the patient is in need of a cognition enhancing effect.

Claim 17

Dependent Claim 15 words

A method according to claim 11 wherein the patient is suffering from congestive heart failure.

Claim 18

Independent Claim 177 words

A method of inhibiting smooth cell proliferation in a patient in need thereof comprising administering to said patient an effective smooth cell proliferation inhibitory amount of a compound of the formula ##STR6## wherein G represents a methylene, ethylene or vinylene group; R 1 represents a hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group wherein Ar is a phenyl or naphthyl group unsubstituted or substituted with from one to three substitutents selected from the gorup consisting of methylenedioxy, hydroxy, C 1 -C 4 alkoxy, amino, nitro, fluoro and chloro and Y is a saturated straight or branched chain hydrocarbyl radical of zero to four carbon atoms; R 2 represents a hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; R 3 represents a carboxyl, alkoxycarbonyl or an Ar--Y--O carbonyl group; R 4 and R 5 each represent a hydrogen atom or R 4 and R 5 together represent an oxo group; n stands for zero, 1 or 2, and pharmaceutically acceptable salts and individual optical isomers thereof.

Claim 19

Independent Claim 177 words

A method of inhibiting smooth cell proliferation in a patient in need thereof comprising administering to said patient an effective smooth cell proliferation inhibitory amount of a compound of the formula ##STR6## wherein G represents a methylene, ethylene or vinylene group; R 1 represents a hydrogen, C 1 -C 8 alkyl, --CH 2 OCH 2 CH 2 OCH 3 or an Ar--Y-- group wherein Ar is a phenyl or naphthyl group unsubstituted or substituted with from one to three substitutents selected from the gorup consisting of methylenedioxy, hydroxy, C 1 -C 4 alkoxy, amino, nitro, fluoro and chloro and Y is a saturated straight or branched chain hydrocarbyl radical of zero to four carbon atoms; R 2 represents a hydrogen, acetyl, --CH 2 O--C(O)C(CH 3 ) 3 or benzoyl; R 3 represents a carboxyl, alkoxycarbonyl or an Ar--Y--O carbonyl group; R 4 and R 5 each represent a hydrogen atom or R 4 and R 5 together represent an oxo group; n stands for zero, 1 or 2, and pharmaceutically acceptable salts and individual optical isomers thereof.

Claim 20

Dependent Claim 22 words

A composition comprising an assayable amount of a compound of claim 1 in admixture or otherwise in association with an inert carrier.

Claim 21

Dependent Claim 29 words

A pharmaceutical composition comprising an effective immunosuppressive amount of a compound of claim 1 in admixture or otherwise in association with one or more pharmaceutically acceptable carriers or excipients.

Claim 22

Dependent Claim 11 words

A compound of claim 1 wherein the compound is 9-[(S)-(1-Oxo-2(R)-acetylthio-3-phenylpropyl)amino]-octahydro-10-oxo-6H-pyridazo[1,2-a][1,2]diazepine-1(S)-carboxylic acid.

Claim 23

Dependent Claim 11 words

A compound of claim 1 wherein the compound is 9-[(S)-(1-Oxo-2(R)-thio-3-phenylpropyl)amino]-octahydro-10-oxo-6H-pyridazo[1,2-a][1,2]diazepine-1(S)-carboxylic acid.

Claim 24

Dependent Claim 11 words

A compound of claim 1 wherein the compound is 9-[(S)-(1-Oxo-2(S)-acetylthio-3-phenylpropyl)amino]-octahydro-10-oxo-6H-pyridazo[1,2-a][1,2]diazepine-1(S)-carboxylic acid.

Claim 25

Dependent Claim 11 words

A compound of claim 1 wherein the compound is 9-[(S)-(1-Oxo-2(S)-thio-3-phenylpropyl)amino]-octahydro-10-oxo-6H-pyridazo[1,2-a][1,2]diazepine-1(S)-carboxylic acid.

Claim 26

Dependent Claim 13 words

A compound of claim 1 wherein the compound is 9-[(S)-(1-Oxo-2(S)-acetylthio-3-phenylpropyl)amino]-octahydro-10-oxo-6H-pyridazo[1,2-a][1,2]diazepine-1(S)-carboxylic acid, t-butyl ester.

Claim 27

Dependent Claim 13 words

A compound of claim 1 wherein the compound is 9-[(S)-(1-Oxo-2(S)-thio-3-phenylpropyl)amino]-octahydro-10-oxo-6H-pyridazo[1,2-a][1,2]diazepine-1(S)-carboxylic acid, t-butyl ester.

Claim 28

Dependent Claim 13 words

A compound of claim 1 wherein the compound is [(S)-(1-Oxo-2(S)-acetylthio-3-phenylpropyl)amino]-octahydro-10-oxo-6H-pyridazo[1,2-a][1,2]diazepine-1(R)-carboxylic acid, t-butyl ester.

Claim 29

Dependent Claim 13 words

A compound of claim 1 wherein the compound is 9-[(S)-(1-Oxo-2(S)-thio-3-phenylpropyl)amino]-octahydro-10-oxo-6H-pyridazo[1,2-a][1,2]diazepine-1(R)-carboxylic acid, t-butyl ester.

Claim 30

Dependent Claim 11 words

A compound of claim 1 wherein the compound is 9-[(S)-(1-Oxo-2(S)-acetylthio-3-phenylpropyl)amino]-octahydro-10-oxo-6H-pyridazo[1,2-a][1,2]diazepine-1(R)-carboxylic acid.

Claim 31

Dependent Claim 11 words

A compound of claim i wherein the compound is 9-[(S)-(1-Oxo-2(S)-thio-3-phenylpropyl)amino]-octahydro-10-oxo-6H-pyridazo[1,2-a][1,2]diazepine-1(R)-carboxylic acid.

Claim 32

Dependent Claim 13 words

A compound of claim 1 wherein the compound is 9-((S)-(1-Oxo-2(S)-acetylthio-3-phenylpropyl)amino)-octahydro-6,10-dioxo-6H-pyridazo[1,2-a][1,2]diazepine-1(S)-carboxylic acid, t-butyl ester.

Claim 33

Dependent Claim 11 words

A compound of claim 1 wherein the compound is 9-((S)-(1-Oxo-2(S)-acetylthio-3-phenylpropyl)amino)-octahydro-6,10-dioxo-6H-pyridazo[1,2-a][1,2]diazepine-1(S)-carboxylic acid.

Claim 34

Dependent Claim 11 words

A compound of claim 1 wherein the compound is 9-((S)-(1-Oxo-2(S)-thio-3-phenylpropyl)amino)-octahydro-6,10-dioxo-6H-pyridazo[1,2-a][1,2]diazepine-1(S)-carboxylic acid.

Claim 35

Dependent Claim 13 words

A compound of claim 1 wherein the compound is 9-((S)-(1-Oxo-2(S)-thio-3-phenylpropyl)amino)-octahydro-6,10-dioxo-6H-pyridazo[1,2-a][1,2]diazepine-1(S)-carboxylic acid, t-butyl ester.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1997-11-21	1998-05-23	1998-11-22	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	2001-11-21	2002-05-23	2002-11-22	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2005-11-21	2006-05-23	2006-11-22	$7700.00	Window Closed / Lapsed

Mercaptoacetylamido pyridazo [1,2]pyridazine, pyrazolo[1,2]pyridazine pyrazolo[1,2]pyridazine, pyridazol[1,2-a][1,2]diazepine and pyrazolol[1,2-a][1,2]diazepine

Abstract

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