Hoffmann-la Roche Inc.

Jay P O'Brien

Erno Mohacsi

Richard W Kierstead

Hans Bruderer

John G Mullin

Keiji Nakamura

Mitsuru Tateishi

Sidney Teitel

Teitel Sidney

Compounds of the formula ##STR1## wherein R.sub.1 is phenyl substituted with 1 to 3 substituents selected from the group consisting of halogen and lower alkoxy; R.sub.2 is hydrogen, lower alkyl, lower alkanoyl, lower cycloalkanoyl, ##STR2## R.sub.3 and R.sub.4 are independently lower alkyl, phenyl lower alkyl or together form a piperidine or pyrrolidine ring; n is 2 ro 4; m is 1 to 2; and pharmaceutically acceptable acid addition salts thereof, with the proviso that when R.sub.1 is 4-methoxyphenyl, R.sub.2 is hydrogen and R.sub.3 and R.sub.4 are methyl; and n is 2, the compound of formula I cannot be in the (-)-cis form, are described. The compounds of formula I are active as calcium channel blockers and accordingly, are useful as agents for treating ischemia.

3-phenyl-thiazepinones as calcium regulating agents

Compounds of the formula ##STR1## wherein R.sub.1 is phenyl substituted with 1 to 3 substituents selected from the group consisting of halogen and lower alkoxy; R.sub.2 is hydrogen, lower alkyl, lower alkanoyl, lower cycloalkanoyl, ##STR2## R.sub.3 and R.sub.4 are independently lower alkyl, phenyl lower alkyl or together form a piperidine or pyrrolidine ring; n is 2 to 4; m is 1 to 2; and pharmaceutically acceptable acid addition salts thereof are described. The compounds of formula I are active as calcium channel blockers and accordingly, are useful as agents for treating ischemia.

Phenyl-thiazepinones as calcium regulating agents

(+)-Cis compounds of the formula ##STR1## wherein R is lower alkyl; R.sub.1 is ##STR2## wherein R.sub.3 is pyridyl, ##STR3## or phenyl unsubstituted or substituted by up to 3 substituents selected from the group consisting of hydroxy, halogen, lower alkoxy, and lower alkanoyloxy; (-)cis enantiomers, and (.+-.)-cis racemates thereof; or pharmaceutically acceptable acid addition salts thereof are described.

Analogs of naphtho[1,2-.beta.] [1,4] thiazepin-4(5H)-one

Compounds of the formula: ##STR1## wherein R.sub.1 is phenyl substituted with 1 to 3 substituents selected from the group consisting of lower alkoxy and halogen; R.sub.2 is hydroxy, lower alkoxy, lower alkanoyloxy, lower cycloalkylcarbonyloxy; ##STR2## or ##STR3## R.sub.3 and R.sub.4 are independently lower alkyl, phenyl lower alkyl or together form a piperidine or pyrrolidine ring; n is 2 to 4; m is 1 to 2; or pharmaceutically acceptable acid addition salts thereof are described. The compounds of formula I have activity as calcium channel blockers and accordingly, are useful as agents for lowering blood pressure, and as agents for treating ischemia.

Naphtho[1,2-b][1,4]thiazepin-4(5H)-ones and use thereof in treatment of

Compounds of the formula ##STR1## wherein R.sub.1 is phenyl substituted with 1 to 3 lower alkoxy groups or 1 to 3 halogens; R.sub.2 is hydroxy, lower alkoxy, lower alkanoyloxy, lower cycloalkylcarbonyloxy; ##STR2## R.sub.3 and R.sub.4 are independently lower alkyl, phenyl lower alkyl or together form a piperidine or pyrrolidine ring; n is 2 to 4; m is 1 to 2; or pharmaceutically acceptable acid addition salts thereof are described. The compounds of formula I have activity as calcium channel blockers and accordingly, are useful as agents for lowering blood pressure, and as agents for treating ischemia.

Naphtho[1,2-b]-1,4-thiazepinones

A compound of the formula ##STR1## wherein R.sub.1 is phenyl substituted with 1 to 3 lower alkoxy groups, or 1 to 3 halogens; R.sub.2 is hydroxy or lower alkanoyloxy; R.sub.3 and R.sub.4 are each independently lower alkyl or together form a pyrrolidine or piperidine ring; and n is 2 to 4, and pharmaceutically acceptable acid addition salts thereof are described. The compounds of formula I are active as calcium channel blockers and accordingly, are useful as agents for lowering blood pressure, and as agents for treating ischemia.

Naphtho(1,8-bc)-1,5-thiazocinones

Substituted isoquinolines of the formula ##STR1## wherein R is a lower alkoxy, n is the integer zero or 1, and

Substituted isoquinolines

Substituted isoquinolines of the formula ##STR1## wherein R is lower alkoxy, n is the integer zero or 1, and A is ##STR2## wherein R.sub.1 is phenyl, halophenyl, lower-alkylphenyl or lower-alkoxyphenyl, and pharmaceutically acceptable acid addition salts thereof, are described. The compounds of formula I are useful in the treatment of cerebral and cardiac ischemias.

Growing community of inventors

Cedar Grove, NJ, United States of America

Jay P O'Brien