title: Design and synthesis of procollagen C-proteinase inhibitors.
abstract: Non-peptidic inhibitors of procollagen C-proteinase (PCP) were designed from substrate leads. Compounds were optimized for potency and selectivity, with N-substituted aryl sulfonamide hydroxamates having the best combination of these properties. Compounds 89 and 60 have IC(50) values of 10 and 80 nM, respectively, against PCP; excellent selectivity over MMP's 1, 2, and 9; and activity in cell-based collagen deposition assays.
authors.affiliation: FibroGen Inc., 409 Illinois St, SF, CA 94158, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Turtle
authors.forename: Nicholas
authors.initials: N
authors.lastname: Chow
authors.forename: Charles
authors.initials: C
authors.lastname: Yang
authors.forename: Sergio
authors.initials: S
authors.lastname: Sosa
authors.forename: Udo
authors.initials: U
authors.lastname: Bauer
authors.forename: Mitch
authors.initials: M
authors.lastname: Brenner
authors.forename: David
authors.initials: D
authors.lastname: Solow-Cordero
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Ho
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D055395:Bone Morphogenetic Protein 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D011480:Protease Inhibitors; C525705:BMP1 protein, human; D055395:Bone Morphogenetic Protein 1