title: Benzylidene ketal derivatives as M2 muscarinic receptor antagonists.
abstract: 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.
authors.affiliation: Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. craig.boyle@spcorp.com
authors.forename: C D
authors.initials: CD
authors.lastname: Boyle
authors.forename: S
authors.initials: S
authors.lastname: Chackalamannil
authors.forename: L Y
authors.initials: LY
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Dugar
authors.forename: P
authors.initials: P
authors.lastname: Pushpavanam
authors.forename: W
authors.initials: W
authors.lastname: Billard
authors.forename: H
authors.initials: H
authors.lastname: Binch
authors.forename: G
authors.initials: G
authors.lastname: Crosby
authors.forename: M
authors.initials: M
authors.lastname: Cohen-Williams
authors.forename: V L
authors.initials: VL
authors.lastname: Coffin
authors.forename: R A
authors.initials: RA
authors.lastname: Duffy
authors.forename: V
authors.initials: V
authors.lastname: Ruperto
authors.forename: J E
authors.initials: JE
authors.lastname: Lachowicz
mesh_terms: 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
chemical_list: D001597:Benzylidene Compounds; D018679:Cholinergic Agonists; D018727:Muscarinic Antagonists; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D000109:Acetylcholine