Design and synthesis of piperidinyl piperidine analogues as potent and selective M2 muscarinic receptor antagonists.
Identification of a number of highly potent M2 receptor antagonists with >100-fold selectivity against the M1 and M3 receptor subtypes is described. In the rat microdialysis assay, this series of compounds showed pronounced enhancement of brain acetylcholine release after oral administration.
Wang
Y
Y
Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. yuguang.wang@spcorp.com
Chackalamannil
S
S
Hu
Z
Z
Clader
J W
JW
Greenlee
W
W
Billard
W
W
Binch
H
H
Crosby
G
G
Ruperto
V
V
Duffy
R A
RA
McQuade
R
R
Lachowicz
J E
JE
D000109:Acetylcholine / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D015195:Drug Design; D017551:Microdialysis; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship
D018727:Muscarinic Antagonists; D010880:Piperidines; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D000109:Acetylcholine