Structure-based design of TACE selective inhibitors: Manipulations in the S1′–S3′ pocket

A Huang, D Joseph-McCarthy, F Lovering, L Sun…

Index: Huang, Adrian; Joseph-McCarthy, Diane; Lovering, Frank; Sun, Linhong; Wang, Weiheng; Xu, Weixin; Zhu, Yi; Cui, Junqing; Zhang, Yuhua; Levin, Jeremy I. Bioorganic and Medicinal Chemistry, 2007 , vol. 15, # 18 p. 6170 - 6181

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Citation Number: 24

Abstract

A series of β-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-α production.