Hoffmann-La Roche Inc.

Erno Mohacsi

Jay P O'Brien

A process for preparing optically active naphtho[1.2-b][1,4]thiazepin-4(5H)-ones comprising resolution of rac-.beta.-[(2-amino-1-naphthalenyl)thio]-.alpha.-hydroxy-4-methoxybenzene propanoic acid and converting the optically active acids so obtained into final products is described. The end product naphtho[1,2-b][1,4]thiazepin-4(5H)-ones have activity as calcium channel blockers and accordingly are useful as agents for lowering blood pressure, and as agents for treating ischemia.

Process for making optically active naphtho[1,2-b]thiazepin-4(5H)-ones

A process for preparing optically active naphtho[1,2-b][1,4]thiazepin-4(5H)-ones comprising resolution of rac-.beta.-[(2-amino-1-naphthalenyl)thio]-.alpha.- hydroxy-4-methoxybenzenepropanoic acid and converting the optically active acids so obtained into final products is described. The end product naphtho[1,2-b][1,4]thiazepin- 4(5H)-ones have activity as calcium channel blockers and accordingly are useful as agents for lowering blood pressure, and as agents for treating ischemia.

Enantiomers of .beta.-[(2-amino-1-naphthalenyl)

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

A process for preparing optically active naphtho[1,2-b][1,4]thiazepin-4(5H)-ones comprising resolution of rac-.beta.-[(2-amino-1-naphthalenyl)thio]-.alpha.-hydroxy-4-methoxybenzene propanoic acid and converting the optically active acids so obtained into final products is described. The end product naphtho[1,2-b][1,4]thiazepin-4(5H)-ones have activity as calcium channel blockers and accordingly are useful as agents for lowering blood pressure, and as agents for treating ischemia.

Process for making optically active

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.

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Summit, NJ, United States of America

Erno Mohacsi