Merrell Dow Pharmaceuticals

Merrell Pharmaceuticals, Inc.

Richardson-merrell Inc.

Albert A. Carr

John M. Kane

Hsien C. Cheng

Hsien C Cheng

John M Kane

Albert A Carr

George D Maynard

Mark W Dudley

Michael G Palfreyman

Norbert L Wiech

Richard C Dage

Winton D Jones

George P Claxton

Phillip J Robinson

Maurice W Gittos

Francis P Miller

Ronald C Bernotas

Jeffrey S Sprouse

Stephen M Sorensen

Stephen W Horgan

John R Fozard

James K Woodward

Paul Moser

Piperidinyl thiacyclic derivatives useful in the treatment of allergic diseases and diseases responding to antagonism of 5HT.sub.2 receptors, pharmaceutical compositions and a methods of treatment using these compounds.

Piperidinyl thiacyclic derivatives

Piperidinyl thiacyclic derivatives of the formula ##STR1## wherein X, Y, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are defined in the specification, are useful in the treatment of allergic diseases and diseases responding to antagonism of 5HT.sub.2 receptors. Pharmaceutical compositions and methods of treatment using these compounds are also disclosed.

Piperidinyl thiacyclic derivatives ##STR1## wherein X, Y, R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are defined in the specification. useful in the treatment of allergic diseases and diseases responding to antagonism of 5HT.sub.2 receptors, pharmaceutical compositions and a methods of treatment using these compounds.

The present invention is directed to a new class of 2-optionally substituted-4-piperazine-benzothiophene derivatives of the formula ##STR1## in which Y is represented by hydrogen or C.sub.1-3 alkyl; R is represented by a substituent selected from the group consisting of hydrogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, halogen, --CF.sub.3, --OCF.sub.3, and --OH; R.sub.1 is represented by hydrogen, cycloalkyl, C.sub.1-6 alkyl, phenyl optionally substituted, phenylalkyl, or phenylamidoalkyl; X is represented by hydrogen, --(CH.sub.2).sub.n X.sub.1, CH=CHX.sub.1 or CHX.sub.2 --(CH.sub.2).sub.q --CH.sub.3 ; n is an integer from 0-2; q is either the integer 0 or 1; X.sub.1 is represented by --OH--,--OR.sub.2, --NR.sub.2 R.sub.3, --CO.sub.2 R.sub.2, --CONR.sub.2 R.sub.3, --CN, or --COR.sub.2 ; R.sub.2 and R.sub.3 are each independently represented by hydrogen, C.sub.1-4 alkyl, phenyl optionally substituted, phenylalkyl, or R.sub.2 and R.sub.3 together form a (CH.sub.2).sub.m cycloalkyl, where m=2- 6; X.sub.2 is --OR.sub.4 or --NR.sub.4 R.sub.5 in which R.sub.4 and R.sub.5 are each independently hydrogen or C.sub.1-4 alkyl; and the pharmaceutically acceptable addition salts thereof; with the proviso that when n is O or X is --CH=CHX.sub.1, then X.sub.1 is not OH, OR.sub.2, or NR.sub.2 R.sub.3 ; that are serotonin 5HT.sub.1A and 5HT.sub.1D receptor agents.

Serotonin receptor agents

The present invention is directed to a new class of piperidinyl benzimidazoles that are useful in the treatment of allergic disorders.

Antiallergic compounds

Applicants have discovered that certain previously known lactamimide derivatives possess, as a class, valuable calcium channel blocking activity. By virtue of this calcium antagonism activity the compounds are antihypertensives and will have other activities associated with calcium antagonists.

Lactamimides as calcium antagonists

The present invention is directed to a new class of cyclic guanidines of the formula: ##STR1## in which Q is represented by a substituent selected from the group consisting of (CH.sub.2).sub.n in which n is an integer from 2-10, ##STR2## A is a substituent selected from the group consisting of --NH--(CH.sub.2).sub.m in which m is an integer from 0-5, a piperidino substituent, or a piperazino substituent; both Ar and Ar.sub.1 are each independently represented by a phenyl ring, each of which may be optionally substituted with up to 3 substituents, each selected from the group consisting of halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, and trifluoromethyl; and R is represented by either hydrogen or a C.sub.1-4 alkyl; R.sub.1 is represented by hydrogen or a C.sub.1-4 alkyl; the optional isomers and tautomers thereof; and the pharmaceutically acceptable acid addition salts thereof, and their use as calcium antagonists.

Calcium antagonists

Applicants have discovered that certain previously known lactamimide derivatives possess, as a class, valuable calcium channel blocking activity. By virtue of this calcium antagonism activity the compounds are antihypertensives and will have other activites associated with calcium antagonists.

Growing community of inventors

Cincinnati, OH, United States of America

Hsien C Cheng