title: Design, synthesis and SAR investigation of thienosultam derivatives as ADAMTS-5 (aggrecanase-2) inhibitors.
abstract: A series of 1,1-dioxothieno[2,3-d]isothiazole (thienosultam) derivatives were designed and synthesized as novel ADAMTS-5 inhibitors for an investigation into a side chain of thienosultam for the S1' pocket. The resulting compounds (19 and 24) show high ADAMTS-5 inhibition and other MMP selectivity, and these compounds show good oral bioavailability.
authors: Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Shizuoka 410-2321, Japan. atobe.mb@om.asahi-kasei.co.jp
authors: Masakazu
authors: M
authors: Atobe
authors: Naomi
authors: N
authors: Maekawara
authors: Masashi
authors: M
authors: Kawanishi
authors: Hiroko
authors: H
authors: Suzuki
authors: Eiichi
authors: E
authors: Tanaka
authors: Shiro
authors: S
authors: Miyoshi
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071116:ADAMTS5 Protein; D000818:Animals; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008297:Male; D015394:Molecular Structure; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D013449:Sulfonamides; D013876:Thiophenes; C480101:beta-sultam; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human