G.d. Searle & Company

Chi-Dean Liang

Thomas Dale Penning

Stevan Wakefield Djuric

Michael John Clare

Mark Andrew Russell

Julie M Miyashiro

Barbara B Chen

Stella S Yu

Nizal S Chandrakumar

Alan Frank Gasiecki

Bipinchandra N Desai

Richard A Haack

Stephen Hermann Docter

Richard A Mueller

John Patrick McKearn

John M Farah, Jr

John S Baran

Kurt J Rorig

Kerry W Fowler

James W Malecha

Robert W Hamilton

Gerald M Walsh

Mark A, Russell

Stella Siu-tzyy Yu

The present invention provides compounds of the formula Ar &mdash;Q&mdash;Ar &mdash;Y&mdash;R&mdash;Z and pharmaceutically acceptable salts thereof wherein Ar and Ar are optionally substituted aryl moieties, Z is an optionally substituted nitrogen-containing moiety which may be an acyclic, cyclic or bicyclic amine or an optionally substituted monocyclic or bicyclic nitrogen-containing heteroaromatic moiety; Q is a linking group capable of linking two aryl groups; R is an alkylene moiety; Y is a linking moiety capable of linking an aryl group to an alkylene moiety and wherein Z is bonded to R through a nitrogen atom. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of inflammatory diseases which are mediated by LTB production, such as psoriasis, ulcerative colitis, IBD and asthma.

LTA4 hydrolase inhibitor pharmaceutical compositions and methods of use

Phenylacetonitrilealkylaminoalkyl-ortho-substituted aryl compounds as immunosuppressives

The present invention provides compounds having the of the formula I: ##STR1## and pharmaceutically acceptable salts and stereoisomers thereof that are useful in the treatment of inflammatory diseases which are mediated by LTB.sub.4 production, such as psoriasis, ulcerative colitis, IBD, and asthma.

LTA.sub.4 hydrolase inhibitors

The present invention provides compounds of the formula Ar.sup.1 --Q--Ar.sup.2 --Y--R--Z and pharmaceutically acceptable salts thereof wherein Ar.sup.1 and Ar.sup.2 are optionally substituted aryl moieties, Z is an optionally substituted nitrogen-containing moiety which may be an acyclic, cyclic or bicyclic amine or an optionally substituted monocyclic or bicyclic nitrogen-containing heteroaromatic moiety; Q is a linking group capable of linking two aryl groups; R is an alkylene moiety; Y is a linking moiety capable of linking an aryl group to an alkylene moiety and wherein Z is bonded to R through a nitrogen atom. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of inflammatory diseases which are mediated by LTB.sub.4 production, such as psoriasis, ulcerative colitis, IBD and asthma.

LTA.sub.4 Hydrolase inhibitors

A class of substituted phenylacetonitrile-alkylaminoalkyl-ortho-substituted aryl compounds having immunosuppressive properties is described. Compounds of this class would be useful in reducing recipient rejection of transplanted organs and for treatment of autoimmune or inflammatory diseases. Compounds of particular interest are of the formula ##STR1## wherein m is one or two; wherein n is a number selected from one to five, inclusive; wherein R.sup.1 is selected from hydrido, alkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, alkenyl and alkynyl; wherein R.sup.6 is selected from loweralkyl; wherein each of R.sup.8, R.sup.9, R.sup.10 and R.sup.12 through R.sup.16 is independently selected from hydrido, hydroxy, alkyl, hydroxyalkyl, alkoxy, alkenyl, alkynyl, alkylcarbonyl, alkoxycarbonyl, alkylcarbonylalkenyl, alkylaminocarbonyl and alkoxyalkyl; with the proviso that at least one of R.sup.12 and R.sup.16 must be selected from hydroxy, alkyl, hydroxyalkyl, alkoxy, alkenyl, alkynyl, alkylcarbonyl, alkoxycarbonyl, alkylcarbonylalkenyl, alkylaminocarbonyl and alkoxyalkyl; or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

Method of using phenylacetonitrilealkylaminoalkyl-ortho-substituted aryl

A class of substituted phenylacetonitrilealkylaminoalkyl-ortho-substituted aryl compounds having immunosuppressive properties is described. Compounds of this class would be useful in reducing recipient rejection of transplanted organs and for treatment of autoimmune or inflammatory diseases. Compounds of particular interest are of the formula ##STR1## wherein m is one or two; wherein n is a number selected from one to five, inclusive; wherein R.sup.1 is selected from hydrido, alkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, alkenyl and alkynyl; wherein R.sup.6 is selected from loweralkyl; wherein each of R.sup.8, R.sup.9, R.sup.10 and R.sup.12 through R.sup.16 is independently selected from hydrido, hydroxy, alkyl, hydroxyalkyl, alkoxy, alkenyl, alkynyl, alkylcarbonyl, alkoxycarbonyl, alkylcarbonylalkenyl, alkylaminocarbonyl and alkoxyalkyl; with the proviso that at least one of R.sup.12 and R.sup.16 must be selected from hydroxy, alkyl, hydroxyalkyl, alkoxy, alkenyl, alkynyl, alkylcarbonyl, alkoxycarbonyl, alkylcarbonylalkenyl, alkylaminocarbonyl and alkoxyalkyl; or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

Phenylacetonitrilealkylaminoalkyl-ortho-substituted aryl compounds as

Cyanoguanidines which have activity as Class III antiarrhythmic agents, acting by prolonging cardiac action potential repolarization. The invention further provides for compositions incorporating the compounds and methods of their use, as well as providing for pharmaceutically acceptable salts of the compounds.

Cyanoquanidine type III antiarrhythmic agents and use

The invention relates to compounds of the formula: ##STR1## which are useful cardiovascular agents.

Bicyclo-substituted phenylacetonitrile derivatives

N-(aralkoxybenzyl)-4(benzhydryl) piperidines

Substituted N-benzyl-4-(benzhydryl) piperidines

.beta.-Adrenergic receptor site activation by novel pyridinemethanol derivatives and pharmaceutical compositions and methods of use thereof are described.

.beta.-Adrenergic receptor agonist alkylaminoalkyl pyridinemethanol

The invention relates to octahydronapthalenes which are useful in antiatherosclerotic agents.

Octahydronapthalenes

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Chi-Dean Liang