Muscarinic antagonists

US5883096A · kind A · utility

Assignee

• SCHERING CORPORATION · US

Inventors

• Derek Lowe · Scotch Plains, US
• Wei K. Chang · Livingston, US
• Joseph A. Kozlowski · Princeton, US
• Joel G. Berger · Cedar Grove, US
• Robert McQuade · Scotch Plains, US
• Allen Barnett · Pine Brook, US
• Margaret H. Sherlock · Bloomfield, US
• Wing C. Tom · Cedar Grove, US
• Sundeep Dugar · Bound Brook, US
• Lian-Yong Chen · Edison, US
• John W. Clader · Cranford, US
• Samuel Chackalamannil · Califon, US
• Wang Yuguang · New Brunswick, US
• Stuart W. McCombie · Caldwell, US
• Jayaram R. Tagat · Westfield, US
• Susan F. Vice · Mountainside, US
• Wayne Vaccaro · Yardley, US
• Michael J. Green · Skillman, US
• Margaret E. Browne · Bloomfield, US
• Theodros Asberom · West Orange, US

Key dates

• Filing date: Feb 16, 1996
• Grant date: Mar 16, 1999
• Expiry date: Feb 16, 2016

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07C2601/14
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

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.