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US 5,508,272 AGranted
Compounds containing a fused bicycle ring and processes therefor
AssigneeBristol-Myers Squibb Company
InventorJeffrey A. Robl
Life of this patent
Estimating the term…
Abstract
Compounds of the formula ##STR1## wherein X is O or S--(O).sub.t ; n is one or two; m is zero or one; Y is CH.sub.2, O, or S--(O).sub.t provided that Y is O or S--(O).sub.t only when m is one; and A is ##STR2## are dual inhibitors of NEP and ACE. Compounds wherein A is ##STR3## are selective ACE inhibitors. Also disclosed are methods of preparation and intermediates.
Claims39
A compound of the formula ##STR87## or a pharmaceutically acceptable salt thereof wherein:
- A is ##STR88## X is O or S-(O).sub.t ;
- R.sub.1 and R.sub.12 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, substituted alkyl, substituted alkenyl, aryl, substituted aryl, heteroaryl, cycloalkyl- alkylene-, aryl-alkylene-, substituted aryl- alkylene-, and heteroaryl-alkylene- or R.sub.1 and R.sub.12 taken together with the carbon to which they are attached complete a cycloalkyl ring or a benzolused cycloalkyl ring;
- R.sub.2 is hydrogen, ##STR89## or R.sub.11 -S-;
- R.sub.3, R.sub.5 and R.sub.7 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl- (CH.sub.2) p-, substituted aryl- (CH.sub.2).sub.p -, heteroaryl-(CH.sub.2).sub.p - , ##STR90## R.sub.4 is alkyl, cycloalkyl-(CH.sub.2).sub.p -, substituted alkyl, aryl-(CH.sub.2).sub.p -, substituted aryl-(CH.sub.2).sub.p -, or heteroaryl-(CH.sub.2).sub.p -;
- R.sub.6 is alkyl, substituted alkyl, cycloalkyl-(CH.sub.2).sub.p -, aryl- (CH.sub.2).sub.p -, substituted aryl-(CH.sub.2).sub.p -, or heteroaryl-(CH.sub.2).sub.p -;
- R.sub.8 is hydrogen, lower alkyl, cycloalkyl, or phenyl;
- R.sub.9 is hydrogen, lower alkyl, lower alkoxy, or phenyl;
- R.sub.10 is lower alkyl or aryl-(CH.sub.2).sub.p -;
- R.sub.11 is hydrogen, alkyl, substituted alkyl, cycloalkyl-(CH.sub.2).sub.p -, aryl- (CH.sub.2).sub.p -, substituted aryl-(CH.sub.2).sub.p -, heteroaryl-(CH.sub.2).sub.p -, or -S-R.sub.11 completes a symmetrical disulfide wherein R.sub.11 is ##STR91## m is zero or one;
- Y is CH.sub.2, S-(O).sub.t or O provided that Y is S-(O).sub.t or O only when m is one;
- n is one or two;
- p is zero or an integer from 1 to 6;
- q is zero or an integer from 1 to 3;
- r is zero or one;
- and
- t is zero, one, or two.
13 more elements
A compound of the formula ##STR97## or a salt thereof wherein:
- X is O or S;
- n is two;
- m is zero or one;
- Y is CH.sub.2, O or S provided that Y is O or S only when m is one;
- R.sub.3 is hydrogen, lower alkyl, or aryl --(CH.sub.2).sub.p --;
- and
- p is zero or an integer from 1 to 6.
4 more elements
Dependencies are inferred from the claim text.