Patent US3827658A successfully refreshed from Google Patents.
US4456595A
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Carboxy and substituted carboxy aroly peptides
Assignee: ER Squibb and Sons LLC
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Filing: 1982-12-06
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Granted: 1984-06-26
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Expires: 2002-12-06
Abstract
Abstract Peptides of the formula ##STR1## wherein X is various amino or imino acids or esters are useful as hypotensive agents.
Inventors
- 👤 Harold N. Weller, III
- 👤 Eric M. Gordon
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 20:10
CPC Classifications
C; C07; C07K; C07K5/00; C07K5/04; C07K5/06; C07K5/06008; C07K5/06017; C07K5/06034; C07K5/06026; C07K5/06078; C07K5/06086; C07K5/06095; C07K5/06139; C07K5/06147; C07K5/06156; Y; Y10; Y10S; Y10S530/00; Y10S530/80
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
420 words
A compound of the formula ##STR122## and a pharmaceutically acceptable salt thereof wherein ##STR123## R is hydroxy, lower alkoxy, lower alkyl, ##STR124## R 1 is hydrogen, lower alkyl, halo substituted lower alkyl, ##STR125## --(CH 2 ) r --NH 2 , --(CH 2 ) r --SH, --(CH 2 ) r --S--lower alkyl, --(CH 2 ) r --S--lower alkyl, ##STR126## R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of hydrogen, lower alkyl of 1 to 4 carbons, lower alkoxy of 1 to 4 carbons, lower alkylthio of 1 to 4 carbons, ##STR127## hydroxy, nitro, halo, halo substituted lower alkyl of 1 to 4 carbons, hydroxy substituted lower alkyl of 1 to 4 carbons, lower ##STR128## wherein said lower alkyl is of 1 to 4 carbons, and ##STR129## R 7 is hydrogen, lower alkyl, halogen, keto, hydroxy, ##STR130## a 1- or 2-naphthyl of the formula ##STR131## a 1- or 2-naphthyloxy of the formula ##STR132## or a 1- or 2-naphthylthio of the formula ##STR133## R 10 is halogen or --Y--R 16 ; R 13 is hydrogen, lower alkyl of 1 to 4 carbons, lower alkoxy of 1 to 4 carbons, lower alkylthio of 1 to 4 carbons, chloro, bromo, fluoro, trifluoromethyl, hydroxy, phenyl, phenoxy, phenylthio, or phenylmethyl; R 14 is hydrogen, lower alkyl of 1 to 4 carbons, lower alkoxy of 1 to 4 carbons, lower alkylthio of 1 to 4 carbons, chloro, bromo, fluoro, trifluoromethyl, or hydroxy; n is zero, one, two, three, or four; p is one, two or three provided that p is more than one only if R 13 or R 14 is hydrogen, methyl, methoxy, chloro, or fluoro; R 15 is hydrogen or lower alkyl of 1 to 4 carbons; Y is oxygen or sulfur; R 16 is lower alkyl of 1 to 4 carbons, ##STR134## or the R 16 groups join to complete an unsubstituted 5- or 6-membered ring or said ring in which one or more of the carbons has a lower alkyl of 1 to 4 carbons or a di(lower alkyl of 1 to 4 carbons) substituent; r is an integer from 1 to 4; R 19 is lower alkyl, benzyl, or phenethyl; R 20 is hydrogen, lower alkyl, benzyl or phenethyl; R 6 is hydrogen, lower alkyl, benzyl, benzhydryl, salt forming ion, or ##STR135## R 17 is hydrogen, lower alkyl, cycloalkyl of 3 to 7 carbons or phenyl; R 18 is hydrogen, lower alkyl, lower alkoxy or phenyl; and M is a salt forming ion.
Claim 2
Dependent Claim
420 words
A compound of the formula ##STR122## and a pharmaceutically acceptable salt thereof wherein ##STR123## R is hydroxy, lower alkoxy, lower alkyl, ##STR124## R 1 is hydrogen, lower alkyl, halo substituted lower alkyl, ##STR125## --(CH 2 ) r --NH 2 , --(CH 2 ) r --SH, --(CH 2 ) r --S--lower alkyl, --(CH 2 ) r --S--lower alkyl, ##STR126## R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of hydrogen, lower alkyl of 1 to 4 carbons, lower alkoxy of 1 to 4 carbons, lower alkylthio of 1 to 4 carbons, ##STR127## hydroxy, nitro, halo, halo substituted lower alkyl of 1 to 4 carbons, hydroxy substituted lower alkyl of 1 to 4 carbons, lower ##STR128## wherein said lower alkyl is of 1 to 4 carbons, and ##STR129## R 7 is hydrogen, lower alkyl, halogen, keto, hydroxy, ##STR130## a 1- or 2-naphthyl of the formula ##STR131## a 1- or 2-naphthyloxy of the formula ##STR132## or a 1- or 2-naphthylthio of the formula ##STR133## R 10 is halogen or --Y--R 16 ; R 13 is hydrogen, lower alkyl of 1 to 4 carbons, lower alkoxy of 1 to 4 carbons, lower alkylthio of 1 to 4 carbons, chloro, bromo, fluoro, trifluoromethyl, hydroxy, phenyl, phenoxy, phenylthio, or phenylmethyl; R 14 is hydrogen, lower alkyl of 1 to 4 carbons, lower alkoxy of 1 to 4 carbons, lower alkylthio of 1 to 4 carbons, chloro, bromo, fluoro, trifluoromethyl, or hydroxy; n is zero, one, two, three, or four; p is one, two or three provided that p is more than one only if R 13 or R 14 is hydrogen, methyl, methoxy, chloro, or fluoro; R 15 is hydrogen or lower alkyl of 1 to 4 carbons; Y is oxygen or sulfur; R 16 is lower alkyl of 1 to 4 carbons, ##STR134## or the R 16 groups join to complete an unsubstituted 5- or 6-membered ring or said ring in which one or more of the carbons has a lower alkyl of 1 to 4 carbons or a di(lower alkyl of 1 to 4 carbons) substituent; r is an integer from 1 to 4; R 19 is lower alkyl, benzyl, or phenethyl; R 20 is hydrogen, lower alkyl, benzyl or phenethyl; R 6 is hydrogen, lower alkyl, benzyl, benzhydryl, salt forming ion, or ##STR135## R 17 is hydrogen, lower alkyl, cycloalkyl of 3 to 7 carbons or phenyl; R 18 is hydrogen, lower alkyl, lower alkoxy or phenyl; and M is a salt forming ion.
Claim 3
Dependent Claim
116 words
A compound of claim 1 wherein ##STR136## R 1 is hydrogen, straight or branched chain lower alkyl of 1 to 4 carbons, ##STR137## R 7 is hydrogen, cyclohexyl, lower alkoxy of 1 to 4 carbons, ##STR138## wherein n is zero, one or two and R 13 is hydrogen, methyl, methoxy, methylthio, Cl, Br, F or hydroxy; t is two or three; R 6 is hydrogen, an alkali metal salt ion, straight or branched chain alkyl of 1 to 4 carbons, or ##STR139## R 17 is hydrogen, straight or branched chain lower alkyl of 1 to 4 carbons, or cyclohexyl; and R 18 is straight or branched chain lower alkyl of 1 to 4 carbons or phenyl.
Claim 4
Dependent Claim
50 words
A compound of claim 2 wherein ##STR140## R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of hydrogen, methyl, methoxy, methylthio, phenyl, benzyl, nitro, halo, trifluoromethyl, ##STR141## R is hydroxy, ethoxy, --OM or ##STR142## M is an alkali metal salt ion.
Claim 5
Dependent Claim
36 words
A compound of claim 3 having the formula ##STR143## wherein R 6 is hydrogen, ethyl, ##STR144## or an alkali metal salt ion; and R is hydroxy or --OM wherein M is an alkali metal salt ion.
Claim 6
Dependent Claim
21 words
A compound of claim 4 wherein R 2 , R 3 , R 4 , and R 5 are all hydrogen.
Claim 7
Dependent Claim
6 words
The compound of claim 5, 1-[N-[(2-carboxyphenyl)carbonyl]-L-alanyl]-L-proline.
Claim 8
Dependent Claim
21 words
A compound of claim 4 wherein R 2 and R 5 are hydrogen; and R 3 and R 4 are chloro.
Claim 9
Dependent Claim
6 words
The compound of claim 7, 1-[N-(2-carboxy-4,5-dichlorobenzoyl)-L-alanyl]-L-proline.
Claim 10
Dependent Claim
21 words
A compound of claim 4 wherein R 2 , R 3 and R 4 are hydrogen and R 5 is nitro.
Claim 11
Dependent Claim
6 words
The compound of claim 9, 1-[N-(2-carboxy-6-nitrobenzoyl)-L-alanyl]-L-proline.
Claim 12
Dependent Claim
21 words
A compound of claim 4 wherein R 3 , R 4 and R 5 are hydrogen and R 2 is ##STR145##
Claim 13
Dependent Claim
6 words
The compound of claim 11, 1-[N-[3-(acetylamino)-2-carboxybenzoyl]-L-alanyl]-L-proline.
Claim 14
Dependent Claim
33 words
A compound of claim 2 wherein ##STR146## R 14 is hydrogen, methyl, methoxy, methylthio, chloro, bromo, fluoro, or hydroxy; R is hydroxy, ethoxy, --OM, or ##STR147## M is an alkali metal salt ion.
Claim 15
Dependent Claim
36 words
A compound of claim 13 having the formula ##STR148## wherein R 6 is hydrogen, ethyl, ##STR149## or an alkali metal salt ion; and R is hydroxy or --OM wherein M is an alkali metal salt ion.
Claim 16
Dependent Claim
10 words
A compound of claim 14 wherein R 14 is hydrogen.
Claim 17
Dependent Claim
8 words
The compound of claim 15, 1-[N-[[2-carboxy-1-naphthalenyl]carbonyl]-L-alanyl]-L-proline, dilithium salt.
Claim 18
Dependent Claim
8 words
The compound of claim 15, 1-[N-[[1-carboxy-2-naphthalenyl]carbonyl]-L-alanyl]-L-proline, dilithium salt.
Claim 19
Dependent Claim
45 words
The method of treating hypertension in a mammalian specie which comprises administering an effective amount of a composition comprising a pharmaceutically acceptable carrier and hypotensively active compound of the formula ##STR150## wherein R, R 1 , A and X are as defined in claim 1.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-06-26 | 1987-12-26 | 1988-06-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-06-26 | 1991-12-26 | 1992-06-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-06-26 | 1995-12-26 | 1996-06-26 | $7700.00 | Window Closed / Lapsed |