2. Academic Validation
  3. Structure-based design of TACE selective inhibitors: manipulations in the S1'-S3' pocket

Structure-based design of TACE selective inhibitors: manipulations in the S1'-S3' pocket

  • Bioorg Med Chem. 2007 Sep 15;15(18):6170-81. doi: 10.1016/j.bmc.2007.06.031.
Adrian Huang 1,  Diane Joseph-McCarthy,  Frank Lovering,  Linhong Sun,  Weiheng Wang,  Weixin Xu,  Yi Zhu,  Junqing Cui,  Yuhua Zhang,  Jeremy I Levin
Affiliations

Affiliation

  • 1 Chemical and Screening Sciences, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, USA. ahuang@wyeth.com
PMID: 17606376 DOI: 10.1016/j.bmc.2007.06.031
Abstract

A series of beta-sulfonyl hydroxamate TACE inhibitors, bearing a butynylamino or a butynyloxy P1' group, was designed and synthesized. Of the compounds investigated, 22 has excellent potency against isolated TACE Enzyme, shows good selectivity over MMP-2 and MMP-13, and oral activity in an in vivo mouse model of TNF-alpha production.

Figures