title: Design and synthesis of ether analogues as potent and selective M2 muscarinic receptor antagonists.
abstract: Novel, selective M2 muscarinic antagonists, which replace the metabolically labile styrenyl moiety of the prototypical M2 antagonist 1 with an ether linkage, were synthesized. A detailed SAR study in this class of compounds has yielded highly active compounds that showed M2 Ki values of < 1.0 nM and >100-fold selectivity against M1, M3, and M5 receptors.
authors: Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. yuguang.wang@spcorp.com
authors: Y
authors: Y
authors: Wang
authors: S
authors: S
authors: Chackalamannil
authors: W
authors: W
authors: Chang
authors: W
authors: W
authors: Greenlee
authors: V
authors: V
authors: Ruperto
authors: R A
authors: RA
authors: Duffy
authors: R
authors: R
authors: McQuade
authors: J E
authors: JE
authors: Lachowicz
mesh_terms: D000109:Acetylcholine / Q000819:agonists*; D000475:Alkenes / Q000138:chemical synthesis; D015195:Drug Design; D004986:Ether / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D018727:Muscarinic Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D011485:Protein Binding; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D043642:Receptor, Muscarinic M5; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000475:Alkenes; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D043642:Receptor, Muscarinic M5; D011976:Receptors, Muscarinic; D004986:Ether; D000109:Acetylcholine