Schering Corporation

Schering Corportion

Wei K Chang

Joel G Berger

Elijah H Gold

Joseph A Kozlowski

John W Clader

Sundeep Dugar

Samuel Chackalamannil

Derek B Lowe

Michael J Green

Stuart W McCombie

Wayne D Vaccaro

Margaret H Sherlock

Wing C Tom

Theodros Asberom

Susan F Vice

Allen Barnett

Robert D McQuade

Margaret E Browne

Lian-Yong Chen

Jayaram R Tagat

Wang Yuguang

Yuguang Wang

Craig D Boyle

Guowei Zhou

Marjorie Peters

Esther Babad

Arthur J Elliott

Lydia Peer

Javaram R Tagat

Elijah J Gold

Muscarinic antagonists

Di-N-substituted piperazine or 1,4 di-substituted piperadine compounds in accordance with formula I (including all isomers, salts, esters, and solvates)

Di-N-substituted piperazine or 1,4 di-substituted piperadine compounds in accordance with formula I (including all isomers, salts, esters, and solvates) ##STR1## wherein R, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.21, R.sup.27, R.sup.28, X, Y, and Z are as defined herein are muscarinic antagonists useful for treating cognitive disorders such as Alzheimer's disease. Pharmaceutical compositions and methods of preparation are also disclosed. Also disclosed are synergistic combinations of compounds of the above formula with acetylcholinesterase inhibitors.

Di-N-substituted piperazine or 1,4 di-substituted piperadine compounds in accordance with formula I (including all isomers, salts, esters, and solvates) ##STR1## wherein R, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.21, R.sup.27, R.sup.28, X, Y, and Z are as defined herein are muscarinic antagonists useful for treating cognitive disorders such as Alzheimer's disease. Pharmaceutical compositions and methods of preparation are also disclosed. Also disclosed are synergistic combinations of compounds of the above formula or other compounds capable of enhancing acetylcholine release with acetylcholinesterase inhibitors.

1,4 Di-substituted piperidine muscarinic antagonists of formula I ##STR1## or an isomer, pharmaceutically acceptable salt, ester or solvate thereof, wherein

Ether muscarinic antagonists

Di-N-substituted piperazine or 1,4-di-substituted piperidine compounds in accordance with formula I (including all isomers, salts, esters, and solvates) ##STR1## wherein Q, n, R, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.21, R.sup.27, R.sup.28, X, and Z are as defined herein are muscarinic antagonists useful for treating cognitive disorders such as Alzheimer's disease. Pharmaceutical compositions and methods of preparation are also disclosed. Also disclosed are synergistic combinations with acetyl-cholinesterase inhibitors of compounds capable of enhancing acetylcholine release and having the above formula.

Di-N-substituted piperazine or 1,4 di-substituted piperadine compounds of formula I ##STR1## wherein one of Y and Z is N and the other is N, CH, or C-alkyl; X is --O--, --SO.sub.0-2 --, amino, substituted amino, --CO--, --CH.sub.2 --, mono or di-substituted methylene, --CS--, --CONR.sup.20 --, --NR.sup.20 --SO.sub.2 --, --NR.sup.20 CO--, --SO.sub.2 NR.sup.20 --, --CH.dbd.CH--, --C.tbd.C-- or --NHC(O)NH--; R is optionally substituted phenyl, aryl or cycloalkyl, or other substituents as defined in the specification; R.sup.1 and R.sup.21 are H, CN or optionally substituted alkyl, or other substituents as defined in the specification; R.sup.2 is optionally substituted cycloalkyl or piperidyl, or other substituents as defined in the specification; and R.sup.3, R.sup.4, R.sup.5, R.sup.20, R.sup.27 and R.sup.28 are as defined in the specification; are muscarinic antagonists useful for treating cognitive disorders such as Alzheimer's disease; pharmaceutical compositions and methods of preparation are also disclosed, as well as synergistic combinations of compounds of the above formula or other compounds capable of enhancing acetylcholine release with acetylcholinesterase inhibitors.

Synthesis of .alpha.-substituted-aryl ethylamines

Disclosed herein are compounds of the formula ##STR1## and pharmaceutically acceptable salts thereof, wherein Ar, R, X, and Y are as described herein are described. The compounds are useful for treating psychoses and depression and for providing analgesia. Compositions containing the compounds and methods for producing the compounds are also disclosed.

Indolyl-, pyrrolyl- and pyrazolyl substituted benzazepines

Bridged benzazepines

Disclosed are fused benzazepine compounds, pharmaceutical compositions including such compounds, methods of using such compounds, for example, in the treatment of psychoses and/or depression, and intermediates useful in the preparation of such compounds.

Fused benzazepines

Disclosed herein are novel compounds of formula II ##STR1## and pharmaceutically acceptable salts thereof, wherein: Q represents H, halo or --OSO.sub.2 R' wherein R' is CH.sub.3, CF.sub.3, phenyl or tolyl;

Substituted benzazepines useful as intermediates for producing

A novel process for the preparation of .alpha.-substituted arylacetamides wherein the substituent is an aromatic group or a 1-alkenyl or 1-cycloalkenyl group and wherein the nitrogen atom carries no hydrogen atoms comprises the reaction of an arylacetamide having one or two hydrogen atoms on the .alpha.-carbon atom, wherein the nitrogen atom carries no hydrogen atoms, with a strong base in an inert aprotic organic solvent, followed by reaction with a zerovalent transition metal catalyst and then with a compound of the formula R.sup.4 --X, wherein R.sup.4 is selected from aromatic groups, 1-alkenyl groups and 1-cycloalkenyl groups and X is a particular leaving group, especially a triflate group. The .alpha.-substituted arylacetamides are useful as intermediates in the preparation (by reduction) of .alpha.-substituted arylethylamines, e.g., 1-substituted-2,3,4,5-tetrahydro-1H-3-benzazepines, having pharmacological activity. Certain benzazepines wherein the 1-substituent R.sup.4 is 1-(1-cycloalkenyl) are novel.

2,3,4,5-tetrahydro-1H-3-benzazepines having anti-psychotic activity

Disclosed herein are novel 1-substituted-2,3,4,5-tetrahydro-1H-3-benzazepines of the general formula I: ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are specified substituents.

Growing community of inventors

Livingston, NJ, United States of America

Wei K Chang