Hetero-benzazepine derivatives and their pharmaceutical use
AssigneeCiba-Geigy Corporation
InventorsJoel Slade, James L. Stanton
Life of this patent
Estimating the term…
Abstract
Disclosed are variously substituted 3-(carboxymethylamino)-(1,5-benzothiazepin-4-one, 1,5-benzoxazepin-4-one and 1,5-benzodiazepin-4-one)-5-alkanoic acids and derivatives as angiotensin-converting enzyme inhibitors and antihypertensive agents. Their synthesis, pharmaceutical compositions thereof, and methods of threatment utilizing such compounds are included.
Claims18
A compound of the formula ##STR20## wherein R.sub.1 is hydrogen, lower alkyl, amino-lower alkyl, acylamino-lower alkyl, aryl, aryl-lower alkyl, cycloalkyl or cycloalkyl-lower alkyl;
- R.sub.2 is hydrogen or lower alkyl;
- R.sub.3 and R.sub.4, each independently, represent hydrogen, lower alkyl, lowr alkoxy, lower alkanoyloxy, hydroxy, halogen or trifluoromethyl;
- or R.sub.3 and R.sub.4 taken together represent lower alkylenedioxy;
- R.sub.5 is hydrogen or lower alkyl;
- R.sub.6 and R.sub.7 represent independently hydroxy;
- lower alkoxy;
- (amino, mono- or di-lower alkylamino)-substituted lower alkoxy;
- carboxy-substituted lower alkoxy;
- lower alkoxycarbonyl-substituted lower alkoxy;
- aryl-substituted lower alkoxy;
- (hydroxy, lower alkanoyloxy or lower alkoxy)-substituted lower alkoxy;
- (hydroxy, lower alkanoyloxy or lower alkoxy)-substituted lower alkoxymethoxy;
- bicyclo[2,2,1]-heptyloxycarbonyl-substituted lower alkoxy;
- 3-phthalidoxy;
- (lower alkyl, lower alkoxy, halo)-substituted 3-phthalidoxy;
- amino;
- lower alkylamino;
- di-lower alkylamino;
- pyrrolidino, piperidino or perhydroazepino;
- (amino or acylamino)-substituted lower alkylamino;
- .alpha.-(carboxy or lower alkoxycarbonyl)-substituted lower alkylamino;
- aryl-substituted lower alkylamino which can be substituted on the .alpha.-carbon by carboxy or lower alkoxycarbonyl;
- X represents S(O).sub.p, N--R.sub.8 or O, in which radicals R.sub.8 represents hydrogen, lower alkyl or aryl, and p represents zero, one or two;
- and
- wherein the carbocylic ring may also be hexahydro;
- and
- wherein within the above definitions acylamino represents lower alkanoylamino;
- lower alkoxycarbonylamino;
- aryl-lower alkanoylamino;
- aryl-lower alkoxycarbonylamino;
- or aroylamino in which aroyl represents benzoyl or benzoyl substituted by lower alkyl, lower alkoxy or halogen, or nicotinoyl;
- and
- wherein within the above definitions aryl represents phenyl unsubstituted or mono- or di-substituted by lower alkyl, lower alkoxy, lower alkylenedioxy, lower alkanoyloxy, hydroxy, halogen or trifluoromethyl;
- and cycloalkyl contains 3 to 8 carbons;
- or a pharmaceutically acceptable salt thereof.
A compound having the formula ##STR21## wherein R.sub.1 is hydrogen, lower alkyl, amino-lower alkyl, acylamino-lower alkyl, aryl, aryl-lower alkyl, or cycloalkyl-lower alkyl;
- R.sub.2 and R.sub.5 represent hydrogen or lower alkyl;
- R.sub.3 and R.sub.4 represent hydrogen, lower alkyl, lower alkoxy, lower alkanoyloxy, hydroxy, halogen or trifluoromethyl;
- or R.sub.3 and R.sub.4 taken together represent lower alkylenedioxy;
- p represents zero, one or two;
- R.sub.6 and R.sub.7 independently represent hydroxy, amino, mono- or di-lower alkylamino, lower alkoxy, aryl-lower alkoxy, lower alkanoyloxymethoxy, (amino, mono- or di-lower alkylamino, carboxy, lower alkoxycarbonyl or bicyclo [2,2,1]-heptyloxycarbonyl)-lower alkoxy;
- and
- wherein within the above definitions acylamino represents lower alkanoylamino;
- lower alkoxycarbonylamino;
- aryl(lower)alkanoylamino;
- aryl(lower)alkoxycarbonylamino;
- or aroylamino in which aroyl represents benzoyl or benzoyl substituted by lower alkyl, lower alkoxy or halogen, or nicotinoyl;
- and
- wherein within the above definitions aryl represents phenyl unsubstituted or mono- or di-substituted by lower alkyl, lower alkoxy, lower alkylenedioxy, lower alkanoyloxy, hydroxy, halogen or trifluoromethyl;
- and cycloalkyl contains 3 to 8 carbons;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.