Mercaptoacetylamide bicyclic lactam derivatives useful as inhibitors of enkephalinase and ACE
AssigneeMerrell Pharmaceuticals Inc.
InventorGary A. Flynn
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Abstract
The present invention relates to certain novel mercaptoacetylamide bicyclic lactam derivatives useful as inhibitors of enkephalinase and of ACE. These mercaptoacetylamide bicyclic lactam derivatives can be described by the following formula: ##STR1## wherein R is hydrogen, a C.sub.1 -C.sub.4 alkyl, an Ar--Y--group, --CH.sub.2 O--C(O)C(CH.sub.3).sub.3 or diphenylmethyl; R.sub.1 is hydrogen, acetyl, --CH.sub.2 O--C(O)C(CH.sub.3).sub.3, benzoyl or a group of the formula ##STR2## R.sub.2 is hydrogen, C.sub.1 -C.sub.8 alkyl, --CH.sub.2 OCH.sub.2 CH.sub.2 OCH.sub.3 or an Ar--Y--group; A is --CH.sub.2 --, --O--, or --S--; B is --S--or --O--; and pharmaceutically acceptable salts thereof.
Claims32
A compound of the formula ##STR19## wherein R is hydrogen, a C.sub.1 -C.sub.4 alkyl or an Ar--Y-- group wherein Y is C.sub.0 -C.sub.4 alkyl, --CH.sub.2 O--C(O)C(CH.sub.3).sub.3 or diphenylmethyl;
- R.sub.1 is hydrogen, acetyl, --CH.sub.2 O--C(O)C(CH.sub.3).sub.3 or benzoyl or a group of the formula ##STR20## R.sub.2 is hydrogen, C.sub.1 -C.sub.8 alkyl, --CH.sub.2 OCH.sub.2 CH.sub.2 OCH.sub.3 or an Ar--Y-- group;
- A is --CH.sub.2 --, --O--, or --S--;
- ev1 B is --S-- or --O--;
- or
- the pharmaceutically acceptable salts thereof.
A method of inhibiting enkephalinase in a patient in need thereof comprising administering to said patient an effective enkephalinase inhibitory amount of a compound of the formula ##STR23## wherein R is hydrogen, a C.sub.1 -C.sub.4 alkyl or an Ar--Y-- group wherein Y is C.sub.0 -C.sub.4 alkyl, --CH.sub.2 O--C(O)C(CH.sub.3).sub.3 or diphenylmethyl;
- R.sub.1 is hydrogen, acetyl, --CH.sub.2 O--C(O)C(CH.sub.3).sub.3 or benzoyl or a group of the formula ##STR24## R.sub.2 is hydrogen, C.sub.1 -C.sub.8 alkyl, --CH.sub.2 OCH.sub.2 CH.sub.2 OCH.sub.3 or an Ar--Y-- group;
- A is --CH.sub.2 --, --O--, or --S--;
- B is --S-- or --O--;
- or
- the pharmaceutically acceptable salts thereof.
A method of inhibiting ACE in a patient in need thereof comprising administering to said patient an effective ACE inhibitory amount of a compound of the formula ##STR25## wherein R is hydrogen, a C.sub.1 -C.sub.4 alkyl or an Ar--Y-- group wherein Y is C.sub.0 -C.sub.4 alkyl, --CH.sub.2 O--C(O)C(CH.sub.3).sub.3 or diphenylmethyl;
- R.sub.1 is hydrogen, acetyl, --CH.sub.2 O--C(O)C(CH.sub.3).sub.3 or benzoyl or a group of the formula ##STR26## R.sub.2 is hydrogen, C.sub.1 -C.sub.8 alkyl, --CH.sub.2 OCH.sub.2 CH.sub.2 OCH.sub.3 or an Ar--Y-- group;
- A is --CH.sub.2 --, --O--, or --S--;
- B is --S-- or --O--;
- or
- the pharmaceutically acceptable salts thereof.
A method of inhibiting smooth cell proliferation in a patient in need thereof comprising administering to said patient an effective smooth cell proliferation inhibitory amount of a compound of the formula ##STR27## wherein R is hydrogen, a C.sub.1 -C.sub.4 alkyl or an Ar--Y-- group wherein Y is C.sub.0 -C.sub.4 alkyl, --CH.sub.2 O--C(O)C(CH.sub.3).sub.3 or diphenylmethyl;
- R.sub.1 is hydrogen, acetyl, --CH.sub.2 O--C(O)C(CH.sub.3).sub.3 or benzoyl or a group of the formula ##STR28## R.sub.2 is hydrogen, C.sub.1 -C.sub.8 alkyl, --CH.sub.2 OCH.sub.2 CH.sub.2 OCH.sub.3 or an Ar--Y-- group;
- A is --CH.sub.2 --, --O--, or --S--;
- B is --S-- or --O--;
- or
- the pharmaceutically acceptable salts thereof.
Dependencies are inferred from the claim text.