Sulfide analogues as potent and selective M(2) muscarinic receptor antagonists.
We have discovered highly potent, selective sulfide M(2) receptor antagonists with low molecular weight and different structural features compared with our phase I clinical candidate Sch 211803. Analogue 30 showed superior M(2) receptor selectivity profile over Sch 211803. More importantly, this study provided new leads for the discovery of M(2) receptor antagonists as potential drug candidates.
Wang
Yuguang
Y
Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. yuguang.wang@spcorp.com
Chackalamannil
Samuel
S
Hu
Zhiyong
Z
McKittrick
Brian A
BA
Greenlee
William
W
Ruperto
Vilma
V
Duffy
Ruth A
RA
Lachowicz
Jean E
JE
D001665:Binding Sites; D001667:Binding, Competitive; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D013440:Sulfides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic; D013440:Sulfides