377088-77-2Relevant academic research and scientific papers
Discovery of macrocyclic hydroxamic acids containing biphenylmethyl derivatives at P1′, a series of selective TNF-α converting enzyme inhibitors with potent cellular activity in the inhibition of TNF-α release
Xue,He,Corbett,Roderick,Wasserman,Liu,Jaffee,Covington,Qian,Trzaskos,Newton,Magolda,Wexler,Decicco
, p. 3351 - 3354 (2007/10/03)
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-α 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.
