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Discovery of macrocyclic hydroxamic acids containing biphenylmethyl derivatives at P1', a series of selective TNF-alpha converting enzyme inhibitors with potent cellular activity in the inhibition of TNF-alpha release.

Abstract：

:SAR exploration at P1' using an anti-succinate-based macrocyclic hydroxamic acid as a template led to the identification of several bulky biphenylmethyl P1' derivatives which confer potent porcine TACE and anti-TNF-alpha cellular activities with high selectivity versus most of the MMPs screened. Our studies demonstrate for the first time that TACE has a larger S1' pocket in comparison to MMPs and that potent and selective TACE inhibitors can be achieved by incorporation of sterically bulky P1' residues.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Xue CB,He X,Corbett RL,Roderick J,Wasserman ZR,Liu RQ,Jaffee BD,Covington MB,Qian M,Trzaskos JM,Newton RC,Magolda RL,Wexler RR,Decicco CP

doi

10.1021/jm0155502

keywords:

subject

Has Abstract

pub_date

2001-10-11 00:00:00

pages

3351-4

issue

21

eissn

0022-2623

issn

1520-4804

pii

jm0155502

journal_volume

44

pub_type

杂志文章

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