Novel bis-(arylsulfonamide) hydroxamate-based selective MMP inhibitors

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:18

Article

Subramaniam, Rajesh²  Haldar, Manas K.²  Tobwala, Shakila¹  Ganguly, Bratati¹  Srivastava, D. K.¹  Mallik, Sanku² 

[1] N Dakota State Univ, Dept Chem Biochem & Mol Biol, Fargo, ND 58105 USA

[2] N Dakota State Univ, Dept Pharmaceut Sci, Fargo, ND 58105 USA

关键词: MMP inhibitors;    bis-(arylsulfonamide);    hydroxamate;   

DOI  :  10.1016/j.bmcl.2008.04.035

来源: Elsevier

【 摘 要 】

A series of bis-(arylsulfonamide) hydroxamate inhibitors were synthesized. These compounds exhibit good potency against MMP-7 and MMP-9 depending on the nature, steric bulk, and substitution pattern of the substituents in the benzene ring. In general, the preliminary structure-activity relationships (SAR) suggest that among the DAPA hydroxamates (i) electron-rich benzene rings of the sulfonamides may produce better inhibitors than electron-poor analogs. However, potential H-bond acceptors can reverse the trend depending on the isozyme; (ii) isozyme selectivity between MMP-7 and-9 can be conferred through steric bulk and substitution pattern of the substituents in the benzene ring, and (iii) the MMP-10 inhibition pattern of the compounds paralleled that for MMP-9. (C) 2008 Elsevier Ltd. All rights reserved.

【 授权许可】

Free