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US4499079A Expired / Lapsed US ⏱️ 0.0 years remaining

Carboxy and substituted carboxy alkanoyl and cycloalkanoyl peptides

Assignee: ER Squibb and Sons LLC
•
Filing: 1982-11-18
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Granted: 1985-02-12
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Expires: 2002-11-18
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Abstract

Abstract Peptides of the formula ##STR1## wherein X is various amino or imino acids or esters are useful as hypotensive agents.

Inventors

  • 👤 Eric M. Gordon
  • 👤 Harold N. Weller, III

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-07 11:58
CPC Classifications
C; C07; C07D; C07D311/00; A; A61; A61P; A61P43/00; A61P9/00; A61P9/12; C07C; C07C61/00; C07C61/16; C07C61/39; C07D217/00; C07D217/22; C07D217/26; C07D263/00; C07D263/02; C07D263/30; C07D263/34; C07D263/36; C07D263/42; C07K; C07K5/00; C07K5/04; C07K5/06; C07K5/06008; C07K5/06017; C07K5/06026; C07K5/06034; C07K5/06078; C07K5/06086; C07K5/06095; C07K5/06139; C07K5/06147; C07K5/08; C07K5/0819; A61K; A61K38/00

Claims Analysis

Total Claims: 24
Claim 1
Independent Claim 354 words
A compound of the formula ##STR96## and a pharmaceutically acceptable salt thereof wherein: R is hydroxy, lower alkoxy, lower alkyl, ##STR97## R 1 is hydrogen, lower alkyl, halo substituted lower alkyl, ##STR98## R 7 is hydrogen, lower alkyl, halogen, keto, hydroxy, ##STR99## 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, ##STR100## 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 ##STR101## R 17 is hydrogen, lower alkyl, cycloalkyl, or phenyl; R 18 is hydrogen, lower alkyl, lower alkoxy or phenyl; M is a salt forming ion; and Z completes a cycloalkyl ring of 3 to 10 carbons, said cycloalkyl ring in which one of the carbon atoms is substituted by a lower alkyl of 1 to 4 carbons, lower alkoxy of 1 to 4 carbons, lower alkylthio of 1 to 4 carbons, halo, trifluoromethyl, or hydroxy group, a cycloalkenyl ring of 5 to 7 carbons, or a cycloalkadienyl ring of 6 or 7 carbons.
Claim 2
Dependent Claim 354 words
A compound of the formula ##STR96## and a pharmaceutically acceptable salt thereof wherein: R is hydroxy, lower alkoxy, lower alkyl, ##STR97## R 1 is hydrogen, lower alkyl, halo substituted lower alkyl, ##STR98## R 7 is hydrogen, lower alkyl, halogen, keto, hydroxy, ##STR99## 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, ##STR100## 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 ##STR101## R 17 is hydrogen, lower alkyl, cycloalkyl, or phenyl; R 18 is hydrogen, lower alkyl, lower alkoxy or phenyl; M is a salt forming ion; and Z completes a cycloalkyl ring of 3 to 10 carbons, said cycloalkyl ring in which one of the carbon atoms is substituted by a lower alkyl of 1 to 4 carbons, lower alkoxy of 1 to 4 carbons, lower alkylthio of 1 to 4 carbons, halo, trifluoromethyl, or hydroxy group, a cycloalkenyl ring of 5 to 7 carbons, or a cycloalkadienyl ring of 6 or 7 carbons.
Claim 3
Dependent Claim 119 words
A compound of claim 1 wherein: ##STR102## R 1 is hydrogen, straight or branched chain lower alkyl of 1 to 4 carbons, --CH 2 OH, ##STR103## R 7 is hydrogen, cyclohexyl, lower alkoxy of 1 to 4 carbons, ##STR104## 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 ##STR105## 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 60 words
A compound of claim 2 wherein: Z completes a cycloalkyl ring of 4 to 7 carbons, a cycloalkyl ring of 4 to 7 carbons wherein one of the carbons is substituted by a methyl, methoxy, methylthio, Cl, Br, F, or hydroxy, or a cyclohexenyl ring; R is hydroxy, ethoxy, --OM, or ##STR106## and M is an alkali metal salt ion.
Claim 5
Dependent Claim 36 words
A compound of claim 3 having the formula ##STR107## wherein R 6 is hydrogen, ethyl, ##STR108## or an alkali metal salt ion; and R is hydroxy or --OM wherein M is an alkali metal salt ion.
Claim 6
Dependent Claim 30 words
A compound of claim 4 wherein Z completes a cyclobutyl ring; R is hydroxy or --OM; R 6 is hydrogen or --M; and M is an alkali metal salt ion.
Claim 7
Dependent Claim 8 words
The compound of claim 5, (cis)-1-[N-(2-carboxycyclobutyl)carbonyl]-L-alanyl]-L-proline, dilithium salt.
Claim 8
Dependent Claim 8 words
The compound of claim 5, (trans)-1-[N-(2-carboxycyclobutyl)carbonyl]-L-alanyl]-L-proline, dilithium salt.
Claim 9
Dependent Claim 30 words
A compound of claim 4 wherein: Z completes a cyclopentyl ring; R is hydroxy or --OM; R 6 is hydrogen or --M; and M is an alkali metal salt ion.
Claim 10
Dependent Claim 8 words
The compound of claim 8, (cis)-1-[N-(2-carboxycyclopentyl)carbonyl]-L-alanyl]-L-proline, dilithium salt.
Claim 11
Dependent Claim 8 words
The compound of claim 8, (trans)-1-[N-[(2-carboxycyclopentyl)carbonyl]-L-alanyl]-L-proline, dilithium salt.
Claim 12
Dependent Claim 30 words
A compound of claim 4 wherein Z completes a cyclohexyl ring; R is hydroxy or --OM; R 6 is hydrogen or --M; and M is an alkali metal salt ion.
Claim 13
Dependent Claim 6 words
The compound of claim 11, (cis)-1-[N-[(2-carboxycyclohexyl)carbonyl]-L-alanyl]-L-proline.
Claim 14
Dependent Claim 6 words
The compound of claim 11, (trans)-1-[N-[(2-carboxycyclohexyl)carbonyl]-L-alanyl]-L-proline.
Claim 15
Dependent Claim 6 words
The compound of claim 11, (d-trans)-1-[N-[(2-carboxycyclohexyl)carbonyl]-L-alanyl]-L-proline.
Claim 16
Dependent Claim 6 words
The compound of claim 11, (l-trans)-1-[N-[(2-carboxycyclohexyl)carbonyl]-L-alanyl]-L-proline.
Claim 17
Dependent Claim 30 words
A compound of claim 4 wherein Z completes a cycloheptyl ring; R is hydroxy or --OM; R 6 is hydrogen or --M; and M is an alkali metal salt ion.
Claim 18
Dependent Claim 8 words
The compound of claim 16, (cis)-1-[N-[(2-carboxycycloheptyl)carbonyl]-L-alanyl]-L-proline, dilithium salt.
Claim 19
Dependent Claim 31 words
A compound of claim 4 wherein Z completes a methoxy substituted cyclohexyl ring; R is hydroxy or --OM; R 6 is hydrogen or --M; and M is an alkali metal salt.
Claim 20
Dependent Claim 8 words
The compound of claim 17, (1α,2β,5α)-1-[N-[(2-carboxy-5-methoxycyclohexyl)carbonyl]-L-alanyl]-L-proline, dilithium salt.
Claim 21
Dependent Claim 30 words
A compound of claim 4 wherein Z completes a cyclohexenyl ring; R is hydroxy or --OM; R 6 is hydrogen or --M; and M is an alkali metal salt ion.
Claim 22
Dependent Claim 6 words
The compound of claim 20, (cis)-1-[N-[(6-carboxy-3-cyclohexen-1-yl)carbonyl]-L-alanyl]-L-proline.
Claim 23
Dependent Claim 8 words
The compound of claim 20, (trans)-1-[N-[(6-carboxy-3-cyclohexen-1-yl)carbonyl]-L-alanyl]-L-proline, dilithium salt.
Claim 24
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 ##STR109## wherein R, R 1 , X and Z are as defined in claim 1.

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1988-02-12 1988-08-13 1989-02-12 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1992-02-12 1992-08-13 1993-02-12 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1996-02-12 1996-08-13 1997-02-12 $7700.00 Window Closed / Lapsed

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