Design, synthesis, and structure-activity relationship of tropane muscarinic acetylcholine receptor antagonists

  • J Med Chem. 2009 Aug 27;52(16):5241-52. doi: 10.1021/jm900736e.
Dramane I Lainé  1 ,  Zehong Wan ,  Hongxing Yan ,  Chongjie Zhu ,  Haibo Xie ,  Wei Fu ,  Jakob Busch-Petersen ,  Christopher Neipp ,  Roderick Davis ,  Katherine L Widdowson ,  Frank E Blaney ,  James Foley ,  Alicia M Bacon ,  Edward F Webb ,  Mark A Luttmann ,  Miriam Burman ,  Henry M Sarau ,  Michael Salmon ,  Michael R Palovich ,  Kristen Belmonte
Affiliations
  • 1. Respiratory CEDD, GlaxoSmithKline, 709 Swedeland Road, P.O. Box 1539, King of Prussia, PA 19406-0939, USA. [email protected]
PMID: 19630384 DOI: 10.1021/jm900736e
Abstract

Novel tropane derivatives were characterized as Muscarinic Acetylcholine Receptor antagonists (mAChRs). Through optimization of the structure-activity relationship around the tropane scaffold, the quaternary ammonium salt 34 was identified as a very potent M(3) mAChR antagonist. The compound was functionally active and displayed greater than 24 h duration of action in a mouse model of bronchoconstriction.