US 4,736,031 AGranted

2-(piperazinylalkyl)-1-benzothiepin, 1-benzoxepin, and 1,5-benzodioxepin derivatives

AssigneeTakeda Chemical Industries, Ltd.

InventorsHirosada Sugihara, Minoru Hirata

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Abstract

Novel condensed seven-membered heterocyclic compounds of the formula: ##STR1## wherein R.sub.1 and R.sub.2 are independently hydrogen, halogen, hydroxy, lower alkyl or lower alkoxy, R.sub.3 and R.sub.4 are independently hydrogen, optionally substituted lower alkyl, optionally substituted cycloalkyl or optionally substituted aralkyl, or both jointly form an optionally substituted ring together with the adjacent nitrogen atom, X is hydrogen, optionally substituted lower alkyl, optionally substituted aryl or a carboxyl group which may be esterified or amidated, Y is >C.dbd.O or >CH--OR.sub.5 in which R.sub.5 is hydrogen, acyl or optionally substituted carbamoyl, A is oxygen atom or sulfur atom, E is oxygen atom or methylene, and G is lower alkylene, provided that when A is sulfur atom, E is methylene, and salts thereof exhibit serotonin S.sub.2 receptor blocking activity, actions to relieve cerebral vasospasm and antithrombotic activity, and are of value as a prophylactic and therapeutic agent for ischemic cardiopathies, thrombosis, hypertension and cerebral circulatory disorders.

Claims15

Dependent claims

A compound of the formula:

##STR82## wherein R.sub.1 and R.sub.2 are independently hydrogen, halogen, hydroxy, C.sub.1-4 alkyl or C.sub.1-4 alkoxy,
R.sub.3 and R.sub.4, taken together with the nitrogen atom, form 4-phenylpiperazinyl in which the phenyl group is unsubstituted or substituted by hydroxy,
X is (1) hydrogen, (2) C.sub.1-4 alkyl, (3) C.sub.1-4 alkanoyl, (4) hydroxymethyl, (5) C.sub.1-5 alkanoyloxymethyl, (6) phenyl-C.sub.1-4 alkyl which may be substituted by 1 to 3 members of halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, methylenedioxy, amino, nitro or hydroxy, (7) phenyl which may be substituted by 1 to 3 members of halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, methylenedioxy, amino, nitro or hydroxy, (8) C.sub.1-4 alkoxycarbonyl, (9) phenyl-C.sub.1-4 alkoxycarbonyl, (10) carbamoyl which may be substituted by 1 or 2 members of C.sub.1-4 alkyl, phenyl or phenyl-C.sub.1-4 alkyl or (11) carboxy,
Y is >C.dbd.O or >CH--OR.sub.5
in which
R.sub.5 is (i) hydrogen, (ii) C.sub.1-6 alkanoyl, (iii) phenyl-C.sub.1-6 alkanoyl unsubstituted or substituted by 1 to 3 members of halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, methylenedioxy, amino, nitro or hydroxy, (iv) carbamoyl unsubstituted or substituted by (1) C.sub.1-4 alkyl, (2) phenyl unsubstituted or substituted by 1 to 3 members of halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, methylenedioxy, amino, nitro or hydroxy or (3) phenyl-C.sub.1-4 alkyl unsubstituted or substituted by 1 to 3 members of halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, methylenedioxy, amino, nitro or hydroxy,
A is oxygen atom or sulfur atom, E is oxygen atom or methylene, and
G is C.sub.1-6 alkylene, provided that when A is sulfur atom, E is methylene,
or a pharmaceutically acceptable salt thereof.

6 more elements

Dependencies are inferred from the claim text.