2. Academic Validation
  3. Design, synthesis, and structure-activity relationship of tropane muscarinic acetylcholine receptor antagonists

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

Affiliation

  • 1 Respiratory CEDD, GlaxoSmithKline, 709 Swedeland Road, P.O. Box 1539, King of Prussia, PA 19406-0939, USA. dramane.i.laine@gsk.com
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.

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