Imidazolyl/imidazolylalkyl-N-terminal amino hydroxy
AssigneeG. D. Searle & Co.
InventorsGunnar J. Hanson, John S. Baran, Dave Weissing, Mark Russell
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Abstract
Non-peptidyl compounds characterized generally as imidazolyl/imidazolylalkyl-N-terminal amino hydroxy .beta.-amino acid derivatives are useful as renin inhibitors for treatment of hypertension. Compounds of particular interest are of the formula ##STR1## wherein R.sub.1 is imidazolyl or imidazolylmethyl; wherein each of R.sub.2 and R.sub.4 is independently selected from hydrido and methyl; wherein R.sub.3 is methyl or ethyl; wherein R.sub.5 is cyclohexylmethyl; wherein R.sub.6 is hydroxy; and wherein R.sub.7 is isobutyl or ethyl; or a pharmaceutically-acceptable salt thereof.
Claims12
Compound of the formula ##STR27## wherein R.sub.1 is selected from imidazolyl and imidazolyalkyl;
- wherein each of R.sub.2 and R.sub.4 is independently selected from hydrido and lower alkyl;
- wherein R.sub.3 is selected from hydrido, alkyl, benzyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, alkylthioalkyl, imidazolyl and imidazolyalkyl;
- wherein R.sub.5 is selected from cycloalkyl, phenyl, lower alkyl, cycloalkylalkyl and phenylalkyl;
- wherein R.sub.6 is selected from hydrido, hydroxy, alkoxy, amino, alkylamino, dialkylamino, lower alkyl and cycloalkyl;
- wherein R.sub.7 is selected from hydrido, alkyl, haloalkyl, cycloalkylalkyl, alkylcycloalkyl, alkylcycloalkenyl and alkoxycarbonyl;
- wherein R.sub.6 and R.sub.7 may further be taken together to form a carbocyclic ring consisting of from three to about eight ring members, or to form an imidazolyl or imidazolyalkyl group;
- and wherein any of the foregoing R.sub.1 through R.sub.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.
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.sub.1 is selected from imidazolyl and imidazolylalkyl;
- wherein each of R.sub.2 and R.sub.4 is independently selected from hydrido and lower alkyl;
- wherein R.sub.3 is selected from hydrido, alkyl, benzyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, alkylthioalkyl, imidazolyl and imidazolylalkyl;
- wherein R.sub.5 is selected from cycloalkyl, phenyl, lower alkyl, cycloalkylalkyl and phenylalkyl;
- wherein R.sub.6 is selected from hydrido, hydroxy, alkoxy, amino, alkylamino, dialkylamino, lower alkyl and cycloalkyl;
- wherein R.sub.7 is selected from hydrido, alkyl, haloalkyl, cycloalkylalkyl, alkylcycloalkyl, alkylcycloalkenyl and alcoxycarbonyl;
- wherein R.sub.6 and R.sub.7 may further be taken together to form a carbocyclic ring consisting of from three to about eight ring members, or to form an imidazolyl or imidazolylalkyl group;
- and wherein any of the foregoing R.sub.1 through R.sub.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.
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.sub.1 is selected from imidazolyl and imidazolylalkyl;
- wherein each of R.sub.2 and R.sub.4 is independently selected from hydrido and lower alkyl;
- wherein R.sub.3 is selected from hydrido, alkyl, benzyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, alkylthioalkyl, imidazolyl and imidazolylalkyl;
- wherein R.sub.5 is selected from cycloalkyl, phenyl, lower alkyl, cycloalkylalkyl and phenylalkyl;
- wherein R.sub.6 is selected from hydrido, hydroxy, alkoxy, amino, alkylamino, dialkylamino, lower alkyl and cycloalkyl;
- wherein R.sub.7 is selected from hydrido, alkyl, haloalkyl, cycloalkylalkyl, alkylcycloalkyl, alkylcycloalkenyl and alkoxycarbonyl;
- wherein R.sub.6 and R.sub.7 may further be taken together to form a carbocyclic ring consisting of from three to about eight ring members, or to form an imidazolyl or imidazolylalkyl group;
- and wherein any of the foregoing R.sub.1 through R.sub.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.
Dependencies are inferred from the claim text.