Sulfide analogues as potent and selective M(2) muscarinic receptor antagonists

Yuguang Wang; Samuel Chackalamannil; Zhiyong Hu; Brian A McKittrick; William Greenlee; Vilma Ruperto; Ruth A Duffy; Jean E Lachowicz

doi:10.1016/s0960-894x(02)00096-3

Sulfide analogues as potent and selective M(2) muscarinic receptor antagonists

Bioorg Med Chem Lett. 2002 Apr 8;12(7):1087-91. doi: 10.1016/s0960-894x(02)00096-3.

Authors

Yuguang Wang¹, Samuel Chackalamannil, Zhiyong Hu, Brian A McKittrick, William Greenlee, Vilma Ruperto, Ruth A Duffy, Jean E Lachowicz

Affiliation

¹ Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. [email protected]

PMID: 11909724
DOI: 10.1016/s0960-894x(02)00096-3

Abstract

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.

MeSH terms

Binding Sites
Binding, Competitive
Muscarinic Antagonists / chemical synthesis*
Muscarinic Antagonists / chemistry
Muscarinic Antagonists / pharmacology*
Receptor, Muscarinic M1
Receptor, Muscarinic M2
Receptor, Muscarinic M3
Receptor, Muscarinic M4
Receptors, Muscarinic / drug effects*
Receptors, Muscarinic / metabolism
Sulfides / chemical synthesis*
Sulfides / chemistry
Sulfides / pharmacology*

Substances

Muscarinic Antagonists
Receptor, Muscarinic M1
Receptor, Muscarinic M2
Receptor, Muscarinic M3
Receptor, Muscarinic M4
Receptors, Muscarinic
Sulfides