Novel quinuclidinyl heteroarylcarbamate derivatives as muscarinic receptor antagonists

  • Bioorg Med Chem. 2014 Jul 1;22(13):3478-87. doi: 10.1016/j.bmc.2014.04.031.
Shinya Nagashima  1 ,  Yuji Matsushima  2 ,  Hisao Hamaguchi  2 ,  Hiroshi Nagata  2 ,  Toru Kontani  2 ,  Ayako Moritomo  2 ,  Tadatsura Koshika  2 ,  Makoto Takeuchi  2
Affiliations
  • 1. Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. Electronic address: [email protected].
  • 2. Drug Discovery Research, Astellas Pharma Inc, 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
PMID: 24837158 DOI: 10.1016/j.bmc.2014.04.031
Abstract

Herein, we describe the synthesis and pharmacological profiles of novel quinuclidinyl heteroarylcarbamate derivatives. Among them, the quinuclidin-4-yl thiazolylcarbamate derivative ASP9133 was identified as a promising long-acting muscarinic antagonist (LAMA) showing more selective inhibition of bronchoconstriction against salivation and more rapid onset of action in a rat model than tiotropium bromide.

Keywords
ASP9133; COPD; In vivo selectivity; Long acting muscarinic receptor antagonist.
Products