Patent US6197016B1 successfully refreshed from Google Patents.
US4381297A
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Substituted carbonyl phosphinyl-alkanoyl compounds
Assignee: ER Squibb and Sons LLC
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Filing: 1981-05-04
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Granted: 1983-04-26
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Expires: 2001-05-04
Abstract
Abstract Compounds of the formula ##STR1## wherein X is an imino acid or ester are disclosed as useful hypotensive agents due to their angiotensin converting enzyme inhibition activity.
Inventors
- 👤 Donald S. Karanewsky
- 👤 Edward W. Petrillo, Jr.
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 21:01
CPC Classifications
C; C07; C07F; C07F9/00; C07F9/02; C07F9/547; C07F9/6561; C07F9/65615; C07F9/553; C07F9/572; C07F9/6536; C07F9/6539
Claims Analysis
Total Claims: 16
Claim 1
Independent Claim
488 words
A compound of the formula ##STR266## wherein X is an imino acid of the formula ##STR267## R 7 is hydrogen, lower alkyl, halogen, keto, hydroxy, ##STR268## azido, amino, ##STR269## a 1- or 2-naphthyl of the formula ##STR270## --(CH 2 ) m -cycloalkyl, ##STR271## --O--lower alkyl, ##STR272## a 1- or 2-naphthyloxy of the formula ##STR273## --S--lower alkyl, ##STR274## or a 1- or 2-naphthylthio of the formula ##STR275## R 8 is keto, halogen, ##STR276## ##STR277## --O--lower alkyl, a 1- or 2-naphthyloxy of the formula ##STR278## --S--lower alkyl, ##STR279## or a 1- or 2-naphthylthio of the formula ##STR280## R 9 is keto or ##STR281## R 10 is halogen or --Y--R 16 ; R 11 , R 11 ', R 12 and R 12 ' are independently selected from hydrogen and lower alkyl or R 11 ', R 12 and R 12 ' are hydrogen and R 11 is ##STR282## 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; m is zero, one, two or three; 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, ##STR283## 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; n is zero or one; R 5 is hydrogen, lower alkyl, halo substituted lower alkyl, benzyl or phenethyl; R 3 and R 6 are independently selected from hydrogen, lower alkyl, benzyl, benzhydryl, or ##STR284## wherein R 17 is hydrogen, lower alkyl, or phenyl, and R 18 is hydrogen, lower alkyl, lower alkoxy, phenyl, or R 17 and R 18 taken together are ##STR285## R 4 is hydrogen, lower alkyl, halo substituted lower alkyl, ##STR286## wherein R 13 and p are as defined above and q is zero or an integer from 1 to 7, cycloalkyl, ##STR287## R 19 is lower alkyl, benzyl or phenethyl; R 20 is hydrogen, lower alkyl, benzyl or phenethyl; R 1 and R 2 are independently selected from the group consisting of hydrogen, lower alkyl, halo substituted lower alkyl, ##STR288## wherein q, R 13 , p and m are as defined above; and when either or both of R 3 and R 6 are hydrogen a basic addition salt or an amino acid addition salt thereof.
Claim 2
Dependent Claim
488 words
A compound of the formula ##STR266## wherein X is an imino acid of the formula ##STR267## R 7 is hydrogen, lower alkyl, halogen, keto, hydroxy, ##STR268## azido, amino, ##STR269## a 1- or 2-naphthyl of the formula ##STR270## --(CH 2 ) m -cycloalkyl, ##STR271## --O--lower alkyl, ##STR272## a 1- or 2-naphthyloxy of the formula ##STR273## --S--lower alkyl, ##STR274## or a 1- or 2-naphthylthio of the formula ##STR275## R 8 is keto, halogen, ##STR276## ##STR277## --O--lower alkyl, a 1- or 2-naphthyloxy of the formula ##STR278## --S--lower alkyl, ##STR279## or a 1- or 2-naphthylthio of the formula ##STR280## R 9 is keto or ##STR281## R 10 is halogen or --Y--R 16 ; R 11 , R 11 ', R 12 and R 12 ' are independently selected from hydrogen and lower alkyl or R 11 ', R 12 and R 12 ' are hydrogen and R 11 is ##STR282## 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; m is zero, one, two or three; 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, ##STR283## 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; n is zero or one; R 5 is hydrogen, lower alkyl, halo substituted lower alkyl, benzyl or phenethyl; R 3 and R 6 are independently selected from hydrogen, lower alkyl, benzyl, benzhydryl, or ##STR284## wherein R 17 is hydrogen, lower alkyl, or phenyl, and R 18 is hydrogen, lower alkyl, lower alkoxy, phenyl, or R 17 and R 18 taken together are ##STR285## R 4 is hydrogen, lower alkyl, halo substituted lower alkyl, ##STR286## wherein R 13 and p are as defined above and q is zero or an integer from 1 to 7, cycloalkyl, ##STR287## R 19 is lower alkyl, benzyl or phenethyl; R 20 is hydrogen, lower alkyl, benzyl or phenethyl; R 1 and R 2 are independently selected from the group consisting of hydrogen, lower alkyl, halo substituted lower alkyl, ##STR288## wherein q, R 13 , p and m are as defined above; and when either or both of R 3 and R 6 are hydrogen a basic addition salt or an amino acid addition salt thereof.
Claim 3
Dependent Claim
18 words
A compound of claim 1 wherein n is zero; R 2 is hydrogen; and R 5 is hydrogen.
Claim 4
Dependent Claim
80 words
A compound of claim 2 wherein R 4 is lower alkyl of 1 to 7 carbons, trifluoromethyl, ##STR289## cyclopentyl, cyclohexyl, ##STR290## R 3 is hydrogen or ##STR291## R 1 is lower alkyl of 1 to 7 carbons or ##STR292## q is zero or an integer from 1 to 4; R 13 is hydrogen, methyl, methoxy, methylthio, chloro, bromo, fluoro or hydroxy; R 17 is hydrogen or methyl; and R 18 is lower alkyl or 1 to 4 carbons or phenyl.
Claim 5
Dependent Claim
200 words
A compound of claim 3 wherein X is ##STR293## R 7 is hydrogen, hydroxy, amino, lower alkyl of 1 to 4 carbons, cyclohexyl, lower alkoxy of 1 to 4 carbons, ##STR294## or lower alkylthio of 1 to 4 carbons; R 8 is lower alkoxy of 1 to 4 carbons, lower alkylthio of 1 to 4 carbons, ##STR295## R 9 is phenyl, 2-hydroxyphenyl, or 4-hydroxyphenyl; m is zero, one or two; R 13 is hydrogen, methyl, methoxy, methylthio, chloro, bromo, fluoro, or hydroxy; R 10 is fluoro, chloro, or --Y--R 16 ; Y is O or S; R 16 is lower alkyl of 1 to 4 carbons 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 available carbon atoms has a methyl or dimethyl substituent; R 11 , R 11 ', R 12 and R 12 ' are all hydrogen or R 11 is phenyl, 2-hydroxyphenyl, or 4-hydroxyphenyl, and R 11 ', R 12 and R 12 ' are all hydrogen; R 6 is hydrogen or ##STR296## R 17 is hydrogen or methyl; and R 18 is lower alkyl or 1 to 4 carbons or phenyl.
Claim 6
Dependent Claim
50 words
A compound of claim 4 wherein X is ##STR297## R 7 is hydrogen, cyclohexyl, ##STR298## m is zero, one or two; R 13 is hydrogen, methyl, methoxy, methylthio, Cl, Br, F, or hydroxy; Y is O or S; r is two or three; and R 6 is hydrogen or ##STR299##
Claim 7
Dependent Claim
10 words
A compound of claim 5 wherein R 1 is ##STR300##
Claim 8
Dependent Claim
10 words
A compound of claim 6 wherein R 4 is phenyl.
Claim 9
Dependent Claim
18 words
The compound of claim 7 wherein R 1 is ##STR301## R 3 is hydrogen; and X is (L)-proline.
Claim 10
Dependent Claim
9 words
The dilithium salt of the compound of claim 8.
Claim 11
Dependent Claim
28 words
The compound of claim 6 wherein R 1 is ##STR302## R 4 is --(CH 2 ) 4 --CH 3 ; R 3 is hydrogen; and X is (L)-proline.
Claim 12
Dependent Claim
9 words
The dilithium salt of the compound of claim 10.
Claim 13
Dependent Claim
28 words
The compound of claim 5 wherein R 1 is --(CH 2 ) 5 --CH 3 ; R 4 is phenyl; R 3 is hydrogen; and X is (L)-proline.
Claim 14
Dependent Claim
9 words
The dilithium salt of the compound of claim 12.
Claim 15
Dependent Claim
25 words
A pharmaceutical composition useful for treating hypertension comprising a pharmaceutically acceptable carrier and one or more compounds of claim 1 or pharmaceutically acceptable salts thereof.
Claim 16
Dependent Claim
20 words
The method of treating hypertension in a mammalian specie comprising administering an effective amount of the composition of claim 14.
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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) | 1986-04-25 | 1986-10-25 | 1987-04-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1990-04-25 | 1990-10-25 | 1991-04-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1994-04-25 | 1994-10-25 | 1995-04-26 | $7700.00 | Window Closed / Lapsed |