Richardson-merrell Inc.

Merrell Dow Pharmaceuticals

Hoechst Marion Roussel

Other

Merrell Pharmaceuticals, Inc.

Aventis Pharmaceuticals Inc.

Aventis Pharma Limited

Robert A Farr

Albert A Carr

Norton P Peet

John M Kane

David A Janowick

Boyd Lynn Harrison

Joseph E Dolfini

Sai P Sunkara

Philip L Nyce

Viviane Van Dorsselaer

Daniel G Schirlin

Celine Tarnus

Craig E Thomas

Robert J Cregge

Thomas L Fevig

Mohinder S Kang

Brent L Podlogar

Stephen M Bowen

Charles A Lundberg, Jr

Daniel T Kohlman

Macrocyclic difluorostatone derivatives useful as antiviral agents

The present invention is directed to novel cyclic nitrones and their use in the prevention of oxidation tissue damage by free radicals, their use in the treatment of a number of disease states in which radicals either damage or destroy tissues via oxidation, and pharmaceutical compositions containing these cyclic nitrones.

Cyclic nitrones

The present invention is new 3-(heterocyclic)-propenoic acid derivatives and pharmaceutical compositions thereof. These new 3-(heterocyclic)-propenoic acid derivatives are useful as NMDA antagonist.

Heterocycle substituted propenoic acid derivatives and pharmaceutical

Glucohydrolase inhibitors useful as antidiabetic agents

Substituted (1.alpha., 2.beta., 3.alpha. or .beta.,4.alpha.,5.alpha. or .beta.)-2,3,4-trihydroxy-5-(hydroxymethyl)cyclopentylamines are inhibitors of alphamannosidase and alpha-fucosidase and are useful immunostimulants, antiviral and antimetastatic agents.

Alpha-mannosidase and fucosidase inhibitors

[4S-(4.alpha.,4a.beta.,5.beta.,6.alpha.,7.alpha.,7a.alpha.)]-Octahydro-1H-1 -pyrindine-4,5,6,7-tetrols and [4R-(4.alpha.,4a.alpha.,5.alpha.,6.beta.,7.beta.,7a.beta.)]-octahydro-1H-1 -pyrindine-4,5,6,7-tetrols are useful as inhibitors of alpha-mannosidase and are useful immunostimulants, chemoprotective and radioprotective agents and antimetastatic agents.

.alpha.-mannosidase inhibitors

Substituted (1.alpha.,2.beta.,3.alpha. or .beta.,4.alpha.,5.alpha. or .beta.)-2,3,4-trihydroxy-5-(hydroxymethyl)cyclopentylamines are inhibitors of alpha-mannosidase and alpha-fucosidase and are useful immunostimulants, antiviral and antimetastatic agents.

Novel analgesic and antipsychotic agents having the formula ##STR1## in which R.sub.1 is hydrogen, hydroxy or halogen and R.sub.4 is hydrogen or, R.sub.1 and R.sub.4 are both hydroxy; Z is hydrogen or straight chain lower alkyl having from 1 to 4 carbon atoms and X is methylene, carbonyl, hydroxymethylene, thio, sulfinyl or sulfonyl, or Z and X, taken together, are methylidenyl, with the proviso that when X is sulfonyl or sulfinyl, Z is other than hydrogen; R.sub.5 is hydrogen or halogen, and R.sub.2 is H, a straight or branched lower alkyl group having from 1 to 4 carbon atoms, the group ##STR2## or the group ##STR3## wherein R.sub.3 is hydroxy, amino, alkylamino or dialkylamino wherein the alkyl moiety is straight or branched and has from 1 to 4 carbon atoms, diastereomers, enantiomers and pharmaceutically acceptable salts thereof.

Substituted derivatives of 4-t-alkoxycarbonyl-piperazin-2-ones

Novel compounds of the formula ##STR1## wherein n is an integer of from 2 to 5, R is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl, R.sub.1 is hydrogen, alkyl, alkoxy or halogen, and Z is carbonyl or hydroxymethylene and their pharmaceutically acceptable acid addition salts are useful as antipsychotic agents having a low potential for extrapyramidal side effects. The novel compounds are prepared from novel intermediates of formula ##STR2## or their salts wherein R has the meanings defined above and R.sub.2 is hydrogen, lower alkyl or phenyl(lower alkyl).

Antipsychotic 4-(naphthalenyloxy)piperidine derivatives

The present invention relates to compounds of the formula ##STR1## wherein R' is hydrogen, straight or branched chain lower alkyl having from 1 to 4 carbon atoms or benzyl, Z is hydrogen or straight chain lower alkyl having from 1 to 4 carbon atoms, Y is hydrogen or a nitrogen blocking group selected from the group consisting of tertiary alkoxycarbonyl, benzyloxycarbonyl, cycloalkoxycarbonyl and vinyloxycarbonyl, R.sub.c is hydrogen, halogen or benzyloxy and R.sub.d is hydrogen, or R.sub.c and R.sub.d are benzyloxy; or an individual diastereomer thereof. Said compounds having use as intermediates in the production of enkephalin derivatives which in turn are used as analgesic and antipsychotic agents.

5-(Substituted benzyl)-6-oxo-2-piperazine carboxylic acids and esters

Novel analgesic and antipsychotic agents having the formula ##STR1## wherein Q is ##STR2## in which R.sub.1 is hydrogen, hydroxy or halogen and R.sub.4 is hydrogen or, R.sub.1 and R.sub.4 are both hydroxy; Z is hydrogen or straight chain lower alkyl having from 1 to 4 carbon atoms and X is methylene, carbonyl, hydroxymethylene, thio, sulfinyl or sulfonyl, or Z and X, taken together, are methylidenyl, with the proviso that when X is sulfonyl or sulfinyl, Z is other than hydrogen; R.sub.5 is hydrogen or halogen, and R.sub.2 is H, a straight or branched lower alkyl group having from 1 to 4 carbon atoms, the group ##STR3## or the group ##STR4## wherein R.sub.3 is hydroxy, amino, alkylamino or dialkylamino wherein the alkyl moiety is straight or branched and has from 1 to 4 carbon atoms, diastereomers, enantiomers and pharmaceutically acceptable salts thereof.

Enkaphalin derivatives

Compounds of the formula ##STR1## wherein R.sub.1 is hydrogen, a straight or branched chain alkyl of 1-5 carbon atoms or a straight or branched chain alkanoyl of 1-5 carbon atoms;

2-Amino-11b-aryl-benzo[a]quinolizines

Cinnamoylpiperidinobutyrophenone derivatives and pharmaceutically acceptable salts thereof of the following general structure: ##STR1## wherein R is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl; and R' is hydrogen or halogen; are useful as antipsychotic agents. The novel compounds are produced by aldol condensation of a benzaldehyde with a protected 4-(4-acetyl-1-piperidino)-butyrophenone.

Cinnamoylpiperidinobutyrophenone antipsychotic agents

4-Aroylethnyl-1-piperidinobutyrophenone derivatives and pharmaceutically acceptable salts thereof of the following general structure: ##STR1## wherein R is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl; and R' is hydrogen or halogen, are useful as antipsychotic agents. The novel compounds are produced by aldol condensation of an acetophenone with a protected 4-(4-formyl-1-piperidino)-butyrophenone.

Aroylethenylpiperidinobutyrophenone antipsychotic agents

2,4a-Ethanobenz[g]isoquinolin-5(1H)-one derivatives are described which are useful as analgesic and anti-fertility agents.

Growing community of inventors

Cincinnati, OH, United States of America

Robert A Farr