title: Design, synthesis and inhibitory activity against human dihydroorotate dehydrogenase (hDHODH) of 1,3-benzoazole derivatives bearing amide units.
abstract: A series of 1,3-benzoazole derivatives possessing amide moieties were designed, synthesized and evaluated as inhibitors against human dihydroorotate dehydrogenase (hDHODH). Compounds A11, A14 and A26 exhibited good to excellent activities against hDHODH at the concentration of 10μM. In particular, compound A14 displayed an IC50 value of 0.178μM with 2-fold preference over A771726. The result implied that a proper degree of steric size and electron density of the C-6 amide moiety was necessary to retain the inhibitory activity of the synthesized compounds.
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Jiling
authors.initials: J
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Dang
authors.initials: D
authors.lastname: Wu
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Xu
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: shaoxusheng@ecust.edu.cn.
authors.forename: Xusheng
authors.initials: X
authors.lastname: Shao
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; Shanghai Collaborative Innovation Center for Biomanufacturing Technology, 130 Meilong Road, Shanghai 200237, China. Electronic address: lizhong@ecust.edu.cn.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry*; D000814:Aniline Compounds / Q000737:chemistry; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry*; D003437:Crotonates; D000090722:Dihydroorotate Dehydrogenase; D015195:Drug Design; D006801:Humans; D006885:Hydroxybutyrates / Q000737:chemistry; D009570:Nitriles; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014052:Toluidines
chemical_list: C000621109:2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-N-(2-fluorophenyl)-1H-benzo(d)imidazole-7-carboxamide; D000577:Amides; D000814:Aniline Compounds; D001562:Benzimidazoles; D003437:Crotonates; D000090722:Dihydroorotate Dehydrogenase; D006885:Hydroxybutyrates; D009570:Nitriles; D011720:Pyrazoles; D014052:Toluidines; C527525:teriflunomide; D044925:Oxidoreductases Acting on CH-CH Group Donors
keywords: 1,3-Benzoazole; Activity; Amide; Scaffold hopping; hDHODH