US5217991A
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Cycloalkyl/cycloalkylalkyl-N-terminal cycloalkoxy-C-terminal amino hydroxy β-amino acid derivatives
Assignee: GD Searle LLC
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Filing: 1992-05-28
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Granted: 1993-06-08
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Expires: 2012-05-28
Abstract
Abstract Non-peptidyl compounds characterized generally as cycloalkyl/cycloalkylalkyl-N-terminal cycloalkoxy-C-terminal amino hydroxy β-amino acid derivatives are useful as renin inhibitors for treatment of hypertension. Compounds of particular interest are of the formula ##STR1## wherein R 1 is selected from cycloalkyl and cycloalkylalkyl groups, wherein said cycloalkyl group contains three to about eight carbon atoms and the acyclic alkyl portion of said cycloalkylalkyl group contains one to about eight carbon atoms; wherein each of R 2 and R 4 is independently selected from hydrido and methyl; wherein R 3 is methyl or ethyl: wherein R 5 is cyclohexylmethyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms, and which heterocyclic ring may be optionally substituted with lower alkyl; or a pharmaceutically-acceptable salt thereof.
Inventors
- 👤 Gunnar J. Hanson
- 👤 John S. Baran
- 👤 Dave Weissing
- 👤 Mark Russell
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-08 13:39
CPC Classifications
C; C07; C07D; C07D471/00; C07D471/02; C07D471/04; C07C; C07C237/00; C07C237/02; C07C237/22; C07D209/00; C07D209/02; C07D209/04; C07D209/10; C07D209/18; C07D209/30; C07D209/42; C07D215/00; C07D215/02; C07D215/16; C07D215/48; C07D241/00; C07D241/36; C07D241/38; C07D241/40; C07D241/44; C07D307/00; C07D307/77; C07D307/78; C07D307/82; C07D307/84; C07D307/85; C07D311/00; C07D311/02; C07D311/04; C07D311/22; C07D311/24; C07C2601/00; C07C2601/12; C07C2601/14
Claims Analysis
Total Claims: 15
Claim 1
Independent Claim
139 words
Compound of the formula ##STR27## wherein R 1 is selected from cycloalkyl and cycloalkylalkyl groups; wherein each of R 2 and R 4 is independently selected from hydrido and lower alkyl; wherein R 3 is selected from hydrido, alkyl, benzyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl and alkylthioalkyl; wherein R 5 is selected from cycloalkyl, phenyl, lower alkyl, cycloalkylalkyl and phenylalkyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms; and wherein any of the foregoing R 1 through R 7 substituents having a substitutable position may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano; or a pharmaceutically-acceptable salt thereof.
Claim 2
Dependent Claim
139 words
Compound of the formula ##STR27## wherein R 1 is selected from cycloalkyl and cycloalkylalkyl groups; wherein each of R 2 and R 4 is independently selected from hydrido and lower alkyl; wherein R 3 is selected from hydrido, alkyl, benzyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl and alkylthioalkyl; wherein R 5 is selected from cycloalkyl, phenyl, lower alkyl, cycloalkylalkyl and phenylalkyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms; and wherein any of the foregoing R 1 through R 7 substituents having a substitutable position may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano; or a pharmaceutically-acceptable salt thereof.
Claim 3
Dependent Claim
163 words
Compound of claim 1 wherein R 1 is selected from cycloalkyl and cycloalkylalkyl groups, wherein said cycloalkyl group contains three to about ten carbon atoms and the acyclic alkyl portion of said cycloalkylalkyl group contains one to about ten carbon atoms; wherein each of R 2 and R 4 is independently selected from hydrido and lower alkyl; wherein R 3 is selected from hydrido, alkyl, alkoxyalkyl and alkylthioalkyl; wherein R 5 is selected from substituted or unsubstituted lower alkyl, cycloalkylalkyl and phenylalkyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms; and wherein any of the foregoing R 1 through R 7 substituents having a substitutable position may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano; or a pharmaceutically-acceptable salt thereof.
Claim 4
Dependent Claim
137 words
Compound of claim 2 wherein R 1 is selected from cycloalkyl and cycloalkylalkyl groups, wherein said cycloalkyl group contains three to about eight carbon atoms and the acyclic alkyl portion of said cycloalkylalkyl group contains one to about eight carbon atoms; wherein each of R 2 and R 4 is independently selected from hydrido and methyl; wherein R 3 is selected from hydrido, methyl, ethyl, methoxymethyl and methylthiomethyl; wherein R 5 is selected from benzyl, cyclohexylmethyl, isobutyl and n-butyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms, and which heterocyclic ring may be optionally substituted with lower alkyl; or a pharmaceutically-acceptable salt thereof.
Claim 5
Dependent Claim
91 words
Compound of claim 3 wherein each of R 2 and R 4 is independently selected from hydrido and methyl; wherein R 3 is selected from methyl and ethyl; wherein R 5 is cyclohexylmethyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms, and which heterocyclic ring may be optionally substituted with lower alkyl; or a pharmaceutically-acceptable salt thereof.
Claim 6
Dependent Claim
164 words
A pharmaceutical composition comprising a therapeutically-effective amount of a renin-inhibiting compound and a pharmaceutically-acceptable carrier or diluent, said renin-inhibiting compound selected from a family of compounds of the formula ##STR28## wherein R 1 is selected from cycloalkyl and cycloalkylalkyl groups; wherein each of R 2 and R 4 is independently selected from hydrido and lower alkyl; wherein R 3 is selected from hydrido, alkyl, benzyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl and alkylthiaolkyl; wherein R 5 is selected from cycloalkyl, phenyl, lower alkyl, cycloalkylalkyl and phenylalkyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms; and wherein any of the foregoing R 1 through R 7 substituents having a substitutable position may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano; or a pharmaceutically-acceptable salt thereof.
Claim 7
Dependent Claim
164 words
A pharmaceutical composition comprising a therapeutically-effective amount of a renin-inhibiting compound and a pharmaceutically-acceptable carrier or diluent, said renin-inhibiting compound selected from a family of compounds of the formula ##STR28## wherein R 1 is selected from cycloalkyl and cycloalkylalkyl groups; wherein each of R 2 and R 4 is independently selected from hydrido and lower alkyl; wherein R 3 is selected from hydrido, alkyl, benzyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl and alkylthiaolkyl; wherein R 5 is selected from cycloalkyl, phenyl, lower alkyl, cycloalkylalkyl and phenylalkyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms; and wherein any of the foregoing R 1 through R 7 substituents having a substitutable position may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano; or a pharmaceutically-acceptable salt thereof.
Claim 8
Dependent Claim
164 words
The composition of claim 5 wherein R 1 is selected from cycloalkyl and cycloalkylalkyl groups, wherein said cycloalkyl group contains three to about ten carbon atoms and the acyclic alkyl portion of said cycloalkylalkyl group contains one to about ten carbon atoms; wherein each of R 3 and R 4 is independently selected from hydrido and lower alkyl; wherein R 3 is selected from hydrido, alkyl, alkoxyalkyl and alkylthioalkyl; wherein R 5 is selected from substituted or unsubstituted lower alkyl, cycloalkylalkyl and phenylalkyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms; and wherein any of the foregoing R 1 through R 7 substituents having a substitutable position may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano; or a pharmaceutically-acceptable salt thereof.
Claim 9
Dependent Claim
138 words
The composition of claim 5 wherein R 1 is selected from cycloalkyl and cycloalkylalkyl groups, wherein said cycloalkyl group contains three to about eight carbon atoms and the acyclic alkyl portion of said cycloalkylalkyl group contains one to about eight carbon atoms; wherein each of R 2 and R 4 is independently selected from hydrido and methyl; wherein R 3 is selected from hydrido, methyl, ethyl, methoxymethyl and methylthiomethyl; wherein R 5 is selected from benzyl, cyclohexylmethyl, isobutyl and n-butyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms, and which heterocyclic ring may be optionally substituted with lower alkyl; or a pharmaceutically-acceptable salt thereof.
Claim 10
Dependent Claim
92 words
The composition of claim 7 wherein each of R 2 and R 4 is independently selected from hydrido and methyl; wherein R 3 is selected from methyl and ethyl; wherein R 5 is cyclohexylmethyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms, and which heterocyclic ring may be optionally substituted with lower alkyl; or a pharmaceutically-acceptable salt thereof.
Claim 11
Dependent Claim
158 words
A therapeutic method for treating hypertension, said method comprising administering to a hypertensive patient a therapeutically-effective amount of a compound of the formula ##STR29## wherein R 1 is selected from cycloalkyl and cycloalkylalkyl groups; wherein each of R 2 and R 4 is independently selected from hydrido and lower alkyl; wherein R 3 is selected from hydrido, alkyl, benzyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl and alkylthioalkyl; wherein R 5 is selected from cycloalkyl, phenyl, lower alkyl, cycloalkylalkyl and phenylalkyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms; and wherein any of the foregoing R 1 through R 7 substituents having a substitutable position may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano; or a pharmaceutically-acceptable salt thereof.
Claim 12
Dependent Claim
158 words
A therapeutic method for treating hypertension, said method comprising administering to a hypertensive patient a therapeutically-effective amount of a compound of the formula ##STR29## wherein R 1 is selected from cycloalkyl and cycloalkylalkyl groups; wherein each of R 2 and R 4 is independently selected from hydrido and lower alkyl; wherein R 3 is selected from hydrido, alkyl, benzyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl and alkylthioalkyl; wherein R 5 is selected from cycloalkyl, phenyl, lower alkyl, cycloalkylalkyl and phenylalkyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms; and wherein any of the foregoing R 1 through R 7 substituents having a substitutable position may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano; or a pharmaceutically-acceptable salt thereof.
Claim 13
Dependent Claim
164 words
The method of claim 9 wherein R 1 is selected from cycloalkyl and cycloalkylalkyl groups, wherein said cycloalkyl group contains three to about ten carbon atoms and the acyclic alkyl portion of said cycloalkylalkyl group contains one to about ten carbon atoms; wherein each of R 2 and R 4 is independently selected from hydrido and lower alkyl; wherein R 3 is selected from hydrido, alkyl, alkoxyalkyl and alklthioalkyl; wherein R 5 is selected from substituted or unsubstituted lower alkyl, cycloalkylalkyl and phenylalkyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms; and wherein any of the foregoing R 1 through R 7 substituents having a substitutable position may be substituted with one or more groups selected from alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl and cyano; or a pharmaceutically-acceptable salt thereof.
Claim 14
Dependent Claim
138 words
The method of claim 10 wherein R 1 is selected from cycloalkyl and cycloalkylalkyl groups, wherein said cycloalkyl group contains three to about eight carbon atoms and the acyclic alkyl portion of said cycloalkylalkyl group contains one to about eight carbon atoms; wherein each of R 2 and R 4 is independently selected from hydrido and methyl; wherein R 3 is selected from hydrido, methyl, ethyl, methoxymethyl and methylthiomethyl; wherein R 5 is selected from benzyl, cyclohexylmethyl, isobutyl and n-butyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms, and which heterocyclic ring may be optionally substituted with lower alkyl; or a pharmaceutically-acceptable salt thereof.
Claim 15
Dependent Claim
93 words
The method of claim 11 wherein wherein each of R 2 and R 4 is independently selected from hydrido and methyl; wherein R 3 is selected from methyl and ethyl; wherein R 5 is cyclohexylmethyl; wherein R 6 and R 7 are taken together to form a partially saturated or fully saturated heterocyclic ring containing five to eight ring members with one or two ring members being oxygen atoms and the remaining ring members being carbon atoms, and which heterocyclic ring may be optionally substituted with lower alkyl; or a pharmaceutically-acceptable salt thereof.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1996-06-07 | 1996-12-07 | 1997-06-08 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2000-06-07 | 2000-12-07 | 2001-06-08 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2004-06-07 | 2004-12-07 | 2005-06-08 | $7700.00 | Window Closed / Lapsed |