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Discovery of beta-benzamido hydroxamic acids as potent, selective, and orally bioavailable TACE inhibitors |
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| Authors: | Duan James J-W Chen Lihua Lu Zhonghui Xue Chu-Biao Liu Rui-Qin Covington Maryanne B Qian Mingxin Wasserman Zelda R Vaddi Krishna Christ David D Trzaskos James M Newton Robert C Decicco Carl P |
| Affiliation: | Research and Development, Bristol-Myers Squibb Company, Princeton, NJ 08543-4000, USA. james.duan@bms.com |
| Abstract: | Beta-benzamido hydroxamic acids were discovered as potent TACE inhibitors. A computer model was constructed to help understanding the binding activities and guiding SAR study. SAR optimization led to the discovery of compound 30 which met all in vitro and in vivo criteria for the program and was selected for further evaluation. |
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