title: Discovery of beta-benzamido hydroxamic acids as potent, selective, and orally bioavailable TACE inhibitors.
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.
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, Princeton, NJ 08543-4000, USA. james.duan@bms.com
authors.forename: James J-W
authors.initials: JJ
authors.lastname: Duan
authors.forename: Lihua
authors.initials: L
authors.lastname: Chen
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Lu
authors.forename: Chu-Biao
authors.initials: CB
authors.lastname: Xue
authors.forename: Rui-Qin
authors.initials: RQ
authors.lastname: Liu
authors.forename: Maryanne B
authors.initials: MB
authors.lastname: Covington
authors.forename: Mingxin
authors.initials: M
authors.lastname: Qian
authors.forename: Zelda R
authors.initials: ZR
authors.lastname: Wasserman
authors.forename: Krishna
authors.initials: K
authors.lastname: Vaddi
authors.forename: David D
authors.initials: DD
authors.lastname: Christ
authors.forename: James M
authors.initials: JM
authors.lastname: Trzaskos
authors.forename: Robert C
authors.initials: RC
authors.lastname: Newton
authors.forename: Carl P
authors.initials: CP
authors.lastname: Decicco
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000072198:ADAM17 Protein; D000284:Administration, Oral; D000818:Animals; D001549:Benzamides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001665:Binding Sites; D001682:Biological Availability; D004285:Dogs; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D001549:Benzamides; D006877:Hydroxamic Acids; D011480:Protease Inhibitors; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606464:Adam17 protein, rat