title: Structure-activity study on a series of α-glutamic acid scaffold based compounds as new ADAMTS inhibitors.
abstract: A series of α-glutamic acid scaffold based 4-(benzamido)-4-(1,3,4-oxadiazol-2-yl) butanoic acids were designed and synthesized as new ADAMTS inhibitors. The compounds dose-dependently inhibited the enzymatic activities of ADAMTS-4 and ADAMTS-5. One of the most active compound 2h potently inhibited ADAMTS-4 and ADAMTS-5 with IC(50) values of 1.2 and 0.8 μM, respectively. These inhibitors may serve as new lead compounds for further development of therapeutics to treat osteoarthritis.
authors: Key Laboratory of Regenerative Biology, Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors: Lijie
authors: L
authors: Peng
authors: Lei
authors: L
authors: Duan
authors: Xiaofeng
authors: X
authors: Liu
authors: Mengjie
authors: M
authors: Shen
authors: Yingjun
authors: Y
authors: Li
authors: Jiajie
authors: J
authors: Yan
authors: Honglin
authors: H
authors: Li
authors: Ke
authors: K
authors: Ding
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071121:ADAMTS4 Protein; D000071116:ADAMTS5 Protein; D001665:Binding Sites; D003198:Computer Simulation; D018698:Glutamic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011348:Procollagen N-Endopeptidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D010069:Oxadiazoles; D011480:Protease Inhibitors; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human