title: Novel TNF-α converting enzyme (TACE) inhibitors as potential treatment for inflammatory diseases.
abstract: Our research on hydantoin based TNF-α converting enzyme (TACE) inhibitors has led to an acetylene containing series that demonstrates sub-nanomolar potency (K(i)) as well as excellent activity in human whole blood. These studies led to the discovery of highly potent TACE inhibitors with good DMPK profiles.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Kenilworth, NJ 07033, USA. vinay.girijavallabhan@spcorp.com
authors.forename: Vinay M
authors.initials: VM
authors.lastname: Girijavallabhan
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Dai
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Feltz
authors.forename: Luke
authors.initials: L
authors.lastname: Firmansjah
authors.forename: Dansu
authors.initials: D
authors.lastname: Li
authors.forename: Seong Heon
authors.initials: SH
authors.lastname: Kim
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kozlowski
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lavey
authors.forename: Aneta
authors.initials: A
authors.lastname: Kosinski
authors.forename: John J
authors.initials: JJ
authors.lastname: Piwinski
authors.forename: Janeta
authors.initials: J
authors.lastname: Popovici-Muller
authors.forename: Razia
authors.initials: R
authors.lastname: Rizvi
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Rosner
authors.forename: Banderpalle B
authors.initials: BB
authors.lastname: Shankar
authors.forename: Neng-Yang
authors.initials: NY
authors.lastname: Shih
authors.forename: M Arshad
authors.initials: MA
authors.lastname: Siddiqui
authors.forename: Ling
authors.initials: L
authors.lastname: Tong
authors.forename: Michael K C
authors.initials: MK
authors.lastname: Wong
authors.forename: De-yi
authors.initials: DY
authors.lastname: Yang
authors.forename: Liping
authors.initials: L
authors.lastname: Yang
authors.forename: Wensheng
authors.initials: W
authors.lastname: Yu
authors.forename: Guowei
authors.initials: G
authors.lastname: Zhou
authors.forename: Zhuyan
authors.initials: Z
authors.lastname: Guo
authors.forename: Peter
authors.initials: P
authors.lastname: Orth
authors.forename: Vincent
authors.initials: V
authors.lastname: Madison
authors.forename: Hong
authors.initials: H
authors.lastname: Bian
authors.forename: Daniel
authors.initials: D
authors.lastname: Lundell
authors.forename: Xiaoda
authors.initials: X
authors.lastname: Niu
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
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000072198:ADAM17 Protein; D000114:Acetylene / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004285:Dogs; D000882:Haplorhini; D006801:Humans; D011480:Protease Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats
chemical_list: D000893:Anti-Inflammatory Agents; D011480:Protease Inhibitors; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606464:Adam17 protein, rat; D000114:Acetylene