Benzylidene ketal derivatives as M2 muscarinic receptor antagonists.
Benzylidene ketal derivatives were investigated as selective M2 receptor antagonists for the treatment of Alzheimer's disease. Compound 10 was discovered to have subnanomolar M2 receptor affinity and 100-fold selectivity against other muscarinic receptors. Also, 10 demonstrated in vivo efficacy in rodent models of muscarinic activity and cognition.
Boyle
C D
CD
Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. craig.boyle@spcorp.com
Chackalamannil
S
S
Chen
L Y
LY
Dugar
S
S
Pushpavanam
P
P
Billard
W
W
Binch
H
H
Crosby
G
G
Cohen-Williams
M
M
Coffin
V L
VL
Duffy
R A
RA
Ruperto
V
V
Lachowicz
J E
JE
D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D001597:Benzylidene Compounds / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism; D018679:Cholinergic Agonists / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics; D003071:Cognition / Q000187:drug effects; D004355:Drug Stability; D006801:Humans; D008568:Memory / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics; D011485:Protein Binding; D051381:Rats; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013329:Structure-Activity Relationship
D001597:Benzylidene Compounds; D018679:Cholinergic Agonists; D018727:Muscarinic Antagonists; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D000109:Acetylcholine