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US4587258A Expired / Lapsed US ⏱️ 0.0 years remaining

Angiotensin-converting enzyme inhibitors

Assignee: Merck Sharp & Dohme LLC
•
Filing: 1984-07-30
•
Granted: 1986-05-06
•
Expires: 2004-07-30
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Abstract

Abstract Novel compounds with angiotensin-converting enzyme inhibitory activity are disclosed. Such compounds are useful in the treatment of cardiovascular disorders, especially hypertension and congestive heart failure, and are useful in the treatment of glaucoma.

Inventors

  • 👤 Elijah H. Gold
  • 👤 Bernard R. Neustadt
  • 👤 Elizabeth M. Smith

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-23 04:41
CPC Classifications
C; C07; C07K; C07K5/00; C07K5/02; C07K5/022; C07K5/0222; A; A61; A61P; A61P9/00; A61P9/12; A61K; A61K38/00

Claims Analysis

Total Claims: 31
Claim 1
Independent Claim 208 words
A compound represented by the formula ##STR23## and the pharmaceutically acceptable salts thereof, wherein R and R 6 are the same or different and are hydroxy, lower alkoxy, lower alkenoxy, dilower alkylamino lower alkoxy, acylamino lower alkoxy, acyloxy lower alkoxy, aryloxy, arylloweralkoxy, amino, lower alkylamino, dilower alkylamino, hydroxyamino, aryllower alkylamino, or substituted aryloxy or substituted aryllower alkoxy wherein the substituent is methyl, halo or methoxy; R 1 is hydrogen, alkyl of from 1 to 10 carbon atoms, including branched and cyclic and unsaturated alkyl groups, substituted lower alkyl wherein the substituent is hydroxy, lower alkoxy, aryloxy, substituted aryloxy, heteroaryloxy, substituted heteroaryloxy, amino, lower alkylamino, diloweralkylamino, acylamino, arylamino, substituted arylamino, guanidino, imidazolyl, indolyl, lower alkylthio, arylthio, substituted arylthio, carboxy, carbamoyl, lower alkoxycarbonyl, aryl, substituted aryl, aralkyloxy, substituted aralkyloxy, aralkylthio, or substituted aralkylthio, wherein the aryl or heteroaryl portion of said substituted aryloxy, heteroaryloxy, arylamino, arylthio, aryl, aralkyloxy or aralkylthio groups is substituted with a group selected from halo, loweralkyl, hydroxy, lower alkoxy, amino, aminomethyl, carboxyl, cyano and sulfamoyl; R 3 is hydrogen, lower alkyl, phenyl lower alkyl, aminomethylphenyl lower alkyl, hydroxyphenyl lower alkyl, hydroxy lower alkyl, acylamino lower alkyl, amino lower alkyl, dimethylamino lower alkyl, guanidino lower alkyl, imidazolyl lower alkyl, indolyl lower alkyl, or lower alkylthio lower alkyl.
Claim 2
Dependent Claim 208 words
A compound represented by the formula ##STR23## and the pharmaceutically acceptable salts thereof, wherein R and R 6 are the same or different and are hydroxy, lower alkoxy, lower alkenoxy, dilower alkylamino lower alkoxy, acylamino lower alkoxy, acyloxy lower alkoxy, aryloxy, arylloweralkoxy, amino, lower alkylamino, dilower alkylamino, hydroxyamino, aryllower alkylamino, or substituted aryloxy or substituted aryllower alkoxy wherein the substituent is methyl, halo or methoxy; R 1 is hydrogen, alkyl of from 1 to 10 carbon atoms, including branched and cyclic and unsaturated alkyl groups, substituted lower alkyl wherein the substituent is hydroxy, lower alkoxy, aryloxy, substituted aryloxy, heteroaryloxy, substituted heteroaryloxy, amino, lower alkylamino, diloweralkylamino, acylamino, arylamino, substituted arylamino, guanidino, imidazolyl, indolyl, lower alkylthio, arylthio, substituted arylthio, carboxy, carbamoyl, lower alkoxycarbonyl, aryl, substituted aryl, aralkyloxy, substituted aralkyloxy, aralkylthio, or substituted aralkylthio, wherein the aryl or heteroaryl portion of said substituted aryloxy, heteroaryloxy, arylamino, arylthio, aryl, aralkyloxy or aralkylthio groups is substituted with a group selected from halo, loweralkyl, hydroxy, lower alkoxy, amino, aminomethyl, carboxyl, cyano and sulfamoyl; R 3 is hydrogen, lower alkyl, phenyl lower alkyl, aminomethylphenyl lower alkyl, hydroxyphenyl lower alkyl, hydroxy lower alkyl, acylamino lower alkyl, amino lower alkyl, dimethylamino lower alkyl, guanidino lower alkyl, imidazolyl lower alkyl, indolyl lower alkyl, or lower alkylthio lower alkyl.
Claim 3
Dependent Claim 13 words
A compound of claim 1 which is a cis,endo isomer of octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid.
Claim 4
Dependent Claim 9 words
The compound of claim 1 which is 1-[N-(1(S)-carboethoxy-3-phenylpropyl)-(S)-alanyl]-cis,endo-octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid.
Claim 5
Dependent Claim 10 words
The compound of claim 1 which is 1[N-(1(S)-carboethoxy-3-phenylpropyl)-(S)-alanyl]-cis,endo-octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid hydrochloride.
Claim 6
Dependent Claim 8 words
The compound of claim 1 is 1-[N-(1(S)-carboxy-3-phenylpropyl)-(S)-alanyl]-cis,endo-octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid.
Claim 7
Dependent Claim 9 words
The compound of claim 1 is 1-[N-(1(S)-carboxy-3-phenylpropyl)-(S)-alanyl]-cis,endo-octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid hydrochloride.
Claim 8
Dependent Claim 9 words
The compound of claim 1 which is 1[Nα-(1(S)-carboethoxy-3-phenylpropyl)-(S)-lysyl]-cis,endooctahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid.
Claim 9
Dependent Claim 10 words
The compound of claim 1 which is 1[Nα-(1(S)-carboethoxy-3-phenylpropyl)-(S)-lysyl]-cis,endo-octahydrocyclopenta[b]pyrrole-2(S-carboxylic acid hydrochloride.
Claim 10
Dependent Claim 10 words
The compound of claim 1 which is 1[Nα-(1(S)-carboethoxy-3-phenylpropyl)-(S)-lysyl]-cis,endo-octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid dihydrochloride.
Claim 11
Dependent Claim 9 words
The compound of claim 1 which is 1-[Nα-(1(S)-carboxy-3-phenylpropyl)-(S)-lysyl]-cis,endo-octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid.
Claim 12
Dependent Claim 10 words
The compound of claim 1 which is 1-[Nα-(1(S)-carboxy-3-phenylpropyl)-(S)-lysyl]-cis,endo-octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid hydrochloride.
Claim 13
Dependent Claim 10 words
The compound of claim 1 which is 1-[Nα-(1(S)-carboxy-3-phenylpropyl)-(S)-lysyl]-cis,endo-octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid dihydrochloride.
Claim 14
Dependent Claim 9 words
The compound of claim 1 which is 1-[N-(1(S)-carboethoxybutyl)-(S)-alanyl]-cis,endo-octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid.
Claim 15
Dependent Claim 10 words
The compound of claim 1 which is 1-[N-(1(S)-carboethoxybutyl)-(S)-alanyl]-cis,endo-octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid hydrochloride.
Claim 16
Dependent Claim 9 words
The compound of claim 1 which is 1-[N-(1(S)-carboxybutyl)-(S)-alanyl]-cis,endo-octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid.
Claim 17
Dependent Claim 10 words
The compound of claim 1 which is 1-[N-(1(S)-carboxybutyl)-(S)-alanyl]-cis,endo-octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid hydrochloride.
Claim 18
Dependent Claim 9 words
The compound of claim 1 which is 1-[Nα-(1(S)-carboethoxybutyl)-(S)-lysyl]-cis,endo-octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid.
Claim 19
Dependent Claim 10 words
The compound of claim 1 which is 1-[Nα-(1(S)-carboethoxybutyl)-(S)-lysyl]-cis,endo-octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid hydrochloride.
Claim 20
Dependent Claim 10 words
The compound of claim 1 which is 1-[Nα-(1(S)-carboethoxybutyl)-(S)-lysyl]-cis,endo-octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid dihydrochloride.
Claim 21
Dependent Claim 9 words
The compound of claim 1 which is 1-[Nα-(1(S)-carboxybutyl)-(S)-lysyl]-cis,endo-octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid.
Claim 22
Dependent Claim 11 words
The compound of claim 1 which is 1-[Nα-(1(S)-carboxybutyl)-(S)-lysyl]-cis,endo-octahydrocyclopenta[b]- pyrrole-2(S)-carboxylic acid hydrochloride.
Claim 23
Dependent Claim 10 words
The compound of claim 1 which is 1-[Nα-(1(S)-carboxybutyl)-(S)-lysyl]cis,endo-octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid dihydrochloride.
Claim 24
Dependent Claim 13 words
A compound of claim 1 which is a cis,exo isomer of octahydrocyclopenta[b]pyrrole-2(S)-carboxylic acid.
Claim 25
Dependent Claim 10 words
A compound of claim 1, which is a hydrochloride salt.
Claim 26
Dependent Claim 10 words
A compound of claim 1 which is a maleate salt.
Claim 27
Dependent Claim 22 words
An antihypertensive pharmaceutical composition comprising an antihypertensive effective amount of a compound of claim 1 together with a pharmaceutically acceptable carrier therefor.
Claim 28
Dependent Claim 36 words
A method for reducing blood pressure in hypertensive mammals which comprises administering to such a mammal a composition comprising an antihypertensive effective amount of a compound of claim 1 together with a pharmaceutically acceptable carrier therefor.
Claim 29
Dependent Claim 41 words
A method for treating mammals suffering from congestive heart failure which comprises administering to such a mammal a composition comprising an amount of a compound of claim 1 effective in treating congestive heart failure together with a pharmaceutically acceptable carrier therefor.
Claim 30
Dependent Claim 37 words
A method for treating glaucoma in mammals suffering from glaucoma which comprises administering to such a mammal a composition comprising an anti-glaucoma effective amount of a compound of claim 1 together with a pharmaceutically acceptable carrier therefor.
Claim 31
Dependent Claim 41 words
A method for reducing blood pressure in hypertensive mammals which comprises administering to such a mammal a composition comprising an antihypertensive effective amount of a compound of claim 1 in combination with a diuretic, together with a pharmaceutically acceptable carrier therefor.

References Cited (Backward Citations)

US4404206A Cited
US4344949A Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1989-05-05 1989-11-04 1990-05-06 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1993-05-05 1993-11-04 1994-05-06 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1997-05-05 1997-11-04 1998-05-06 $7700.00 Window Closed / Lapsed

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