2. Academic Validation
  3. Discovery of (3-endo)-3-(2-cyano-2,2-diphenylethyl)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octane bromide as an efficacious inhaled muscarinic acetylcholine receptor antagonist for the treatment of COPD

Discovery of (3-endo)-3-(2-cyano-2,2-diphenylethyl)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octane bromide as an efficacious inhaled muscarinic acetylcholine receptor antagonist for the treatment of COPD

  • Bioorg Med Chem Lett. 2009 Aug 15;19(16):4560-2. doi: 10.1016/j.bmcl.2009.07.006.
Zehong Wan 1,  Dramane I Laine,  Hongxing Yan,  Chongjie Zhu,  Katherine L Widdowson,  Peter T Buckley,  Miriam Burman,  James J Foley,  Henry M Sarau,  Dulcie B Schmidt,  Edward F Webb,  Kristen E Belmonte,  Michael Palovich
Affiliations

Affiliation

  • 1 Respiratory Centre of Excellence for Drug Discovery, Research and Development, GlaxoSmithKline Pharmaceuticals, King of Prussia, PA 19406, USA. Zehong.2.Wan@gsk.com
PMID: 19616944 DOI: 10.1016/j.bmcl.2009.07.006
Abstract

Design and syntheses of a novel series of muscarinic antagonists are reported. These efforts have culminated in the discovery of (3-endo)-3-(2-cyano-2,2-diphenylethyl)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octane bromide (4a) as a potent and pan-active muscarinic antagonist as well as a functionally active compound in a murine model of bronchoconstriction. The compound has also displayed pharmacokinetic characteristics suitable for inhaled delivery.

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