title: Novel N-substituted 2-phenyl-1-sulfonylamino-cyclopropane carboxylates as selective ADAMTS-5 (Aggrecanase-2) inhibitors.
abstract: A series of N-substituted sulfonylamino-alkanecarboxylate ADAMTS-5 (Aggrecanase-2) inhibitors has been synthesized and the in vitro enzyme SAR is discussed. This report is the first example of carboxylate-based ADAMTS-5 inhibitors which show strong potency of IC(50)<0.1muM with excellent selectivity over MMP-1 and TACE.
authors.affiliation: Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Shiozaki
authors.forename: Katsuya
authors.initials: K
authors.lastname: Maeda
authors.forename: Tomoya
authors.initials: T
authors.lastname: Miura
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ogoshi
authors.forename: Julia
authors.initials: J
authors.lastname: Haas
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Fryer
authors.forename: Ellen R
authors.initials: ER
authors.lastname: Laird
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Littmann
authors.forename: Steven W
authors.initials: SW
authors.lastname: Andrews
authors.forename: John A
authors.initials: JA
authors.lastname: Josey
authors.forename: Takayuki
authors.initials: T
authors.lastname: Mimura
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Shinozaki
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yoshiuchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Inaba
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors*; D000071116:ADAMTS5 Protein; D002264:Carboxylic Acids / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D010003:Osteoarthritis / Q000188:drug therapy; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D002264:Carboxylic Acids; D011480:Protease Inhibitors; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human