title: Biaryl substituted hydantoin compounds as TACE inhibitors.
abstract: We disclose further optimization of hydantoin TNF-alpha convertase enzyme (TACE) inhibitors. SAR with respect to the non-prime region of TACE active site was explored. A series of biaryl substituted hydantoin compounds was shown to have sub-nanomolar K(i), good rat PK, and good selectivity versus MMP-1, -2, -3, -7, -9, and -13.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Kenilworth, NJ 07033, USA. wensheng.yu@merck.com
authors.forename: Wensheng
authors.initials: W
authors.lastname: Yu
authors.forename: Ling
authors.initials: L
authors.lastname: Tong
authors.forename: Seong Heon
authors.initials: SH
authors.lastname: Kim
authors.forename: Michael K C
authors.initials: MK
authors.lastname: Wong
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: De-Yi
authors.initials: DY
authors.lastname: Yang
authors.forename: Bandarpalle B
authors.initials: BB
authors.lastname: Shankar
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lavey
authors.forename: Guowei
authors.initials: G
authors.lastname: Zhou
authors.forename: Aneta
authors.initials: A
authors.lastname: Kosinski
authors.forename: Razia
authors.initials: R
authors.lastname: Rizvi
authors.forename: Dansu
authors.initials: D
authors.lastname: Li
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Feltz
authors.forename: John J
authors.initials: JJ
authors.lastname: Piwinski
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Rosner
authors.forename: Neng-Yang
authors.initials: NY
authors.lastname: Shih
authors.forename: M Arshad
authors.initials: MA
authors.lastname: Siddiqui
authors.forename: Zhuyan
authors.initials: Z
authors.lastname: Guo
authors.forename: Peter
authors.initials: P
authors.lastname: Orth
authors.forename: Himanshu
authors.initials: H
authors.lastname: Shah
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Shelby
authors.initials: S
authors.lastname: Umland
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lundell
authors.forename: Xiaoda
authors.initials: X
authors.lastname: Niu
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kozlowski
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors*; D000072198:ADAM17 Protein; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606464:Adam17 protein, rat