A new 4-(2-methylquinolin-4-ylmethyl) phenyl P1′ group for the β-amino hydroxamic acid derived TACE inhibitors

…, KD Hartman, MD Ribadeneira, JM Trzaskos…

Index: Chen, Xiao-Tao; Ghavimi, Bahman; Corbett, Ronald L.; Xue, Chu-Biao; Liu, Rui-Qin; Covington, Maryanne B.; Qian, Mingxin; Vaddi, Krishna G.; Christ, David D.; Hartman, Karl D.; Ribadeneira, Maria D.; Trzaskos, James M.; Newton, Robert C.; Decicco, Carl P.; Duan, James J.-W. Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 7 p. 1865 - 1870

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Citation Number: 14

Abstract

A new P1′ group for TACE inhibitors was identified by eliminating the oxygen atom in the linker of the original 4-(2-methylquinolin-4-ylmethoxy) phenyl P1′ group. Incorporation of this 4-(2-methylquinolin-4-ylmethyl) phenyl group onto different β-aminohydroxamic acid cores provided compound 18, which demonstrated potent porcine TACE (p-TACE) and human whole blood activity, excellent PK properties, and good selectivity against a variety ...