Schering Corporation

Robert D McQuade

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

Allen Barnett

Margaret E Browne

Lian-Yong Chen

Jayaram R Tagat

Wang Yuguang

Craig D Boyle

Yuguang Wang

Javaram R Tagat

Richard Chipkin

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 kit and a method useful for analyzing the plasma concentration of an active neuroleptic drug known to have D-1 receptor antagonist properties utilizing labeled [-]trans 6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo[d]naphtho-[2 ,1-b]-azepine.

Assay kit and methods for neuroleptic drugs

Growing community of inventors

Scotch Plains, NJ, United States of America

Robert D McQuade