Author/Authors :
Xiao-Tao Chen، نويسنده , , Bahman Ghavimi، نويسنده , , Ronald L. Corbett، نويسنده , , Chu-Biao Xue، نويسنده , , Ruiqin Liu، نويسنده , , Maryanne B. Covington، نويسنده , , Mingxin Qian، نويسنده , , Krishna G. Vaddi، نويسنده , , David D. Christ، نويسنده , , Karl D. Hartman، نويسنده , , Maria D. Ribadeneira، نويسنده , , James M. Trzaskos، نويسنده , , Robert C. Newton، نويسنده , , Carl P. Decicco، نويسنده , , James J. -W. Duan، نويسنده ,
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 of MMPs.
Keywords :
?-Amino hydroxamic acid , Anti-inflammatory agent , TACE inhibitor , matrix metalloproteinase inhibitor
