Substituted 2-(R)-methyl piperazines as muscarinic M(2) selective ligands.
A novel series of 2-(R)-methyl-substituted piperazines (e.g., 2) is described. They are potent M(2) selective ligands that have >100-fold selectivity versus the M(1) receptor. In the rat microdialysis assay, compound 14 showed significantly enchanced levels of acetylcholine after oral administration.
Kozlowski
Joseph A
JA
Schering-Plough Research Institute, Kenilworth, NJ 07033-0539, USA. joseph.kozlowski@spcorp.com
Zhou
Guowei
G
Tagat
Jayaram R
JR
Lin
Sue Ing
SI
McCombie
Stuart W
SW
Ruperto
Vilma B
VB
Duffy
Ruth A
RA
McQuade
Robert A
RA
Crosby
Gordon
G
Taylor
Lisa A
LA
Billard
William
W
Binch
Herbert
H
Lachowicz
Jean E
JE
D000109:Acetylcholine / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001665:Binding Sites; D008024:Ligands; D017551:Microdialysis; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000378:metabolism*
D008024:Ligands; D010879:Piperazines; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D000109:Acetylcholine