Schering Corporation

Allen Barnett

Joseph A Kozlowski

Sundeep Dugar

Samuel Chackalamannil

Michael J Green

John W Clader

Stuart W McCombie

Wayne D Vaccaro

Joel G Berger

Margaret H Sherlock

Wei K Chang

Wing C Tom

Theodros Asberom

Susan F Vice

Derek B Lowe

Robert D McQuade

Lian-Yong Chen

Margaret E Browne

Jayaram R Tagat

Wang Yuguang

Craig D Boyle

Yuguang Wang

William Billard

Louis Iorio

Martin Steinman

Javaram R Tagat

Gordon Crosby, Jr

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.

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.

The invention describes a method for determining the BZ-1 receptor activity of a test sample or a potential anxiolytic drug.

Method for measuring the BZ-1 receptor binding activity in a test sample

A method, reagents, and kit for determining the levels of D-1 receptor antagonistic activity of neuroleptic drugs. The method correlates competition between analyte and tritiated R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol for binding to D-1 receptors in mammalian brain tissue.

Assay for D-1 antagonistic activity of neuroleptic drugs

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Pine Brook, NJ, United States of America

Allen Barnett