| Literature DB >> 18272363 |
Michael J Costanzo1, Stephen C Yabut, Han-Cheng Zhang, Kimberley B White, Lawrence de Garavilla, Yuanping Wang, Lisa K Minor, Brett A Tounge, Alexander N Barnakov, Frank Lewandowski, Cynthia Milligan, John C Spurlino, William M Abraham, Victoria Boswell-Smith, Clive P Page, Bruce E Maryanoff.
Abstract
We have explored a series of spirocyclic piperidine amide derivatives (5) as tryptase inhibitors. Thus, 4 (JNJ-27390467) was identified as a potent, selective tryptase inhibitor with oral efficacy in two animal models of airway inflammation (sheep and guinea pig asthma models). An X-ray co-crystal structure of 4 x tryptase revealed a hydrophobic pocket in the enzyme's active site, which is induced by the phenylethynyl group and is comprised of amino acid residues from two different monomers of the tetrameric protein.Entities:
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Year: 2008 PMID： 18272363 DOI： 10.1016/j.bmcl.2008.01.093
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823