title: Identification of 1, 4-Dihydrothieno [3', 2':5, 6]thiopyrano[4, 3-c] pyrazole derivatives as human 5-Lipo-oxygenase inhibitors.
abstract: A series of novel 1,4-dihydrothieno[3',2':5,6]thiopyrano[4,3-c]-pyrazole-3-carboxamide derivatives were synthesized and evaluated for their inhibitory activity to human 5-lipo-oxygenase (5-LOX). Compound 7c was found to exhibit significant inhibition to human 5-LOX with IC50 value of 5.7 ± 0.9 μm. Compound 7c was further studied using molecular docking in order to delineate its structure-activity relationship and to gain insight into the design of effective 5-LOX inhibitors.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
authors.forename: Jianshu
authors.initials: J
authors.lastname: Hu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Hu
authors.initials: H
authors.lastname: Meng
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Chun
authors.initials: C
authors.lastname: Hu
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D016859:Lipoxygenase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D062105:Molecular Docking Simulation; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C000599301:1-(7-bromo-1,4-dihydrothieno(3',2'-5,6)thiopyrano(4,3-c)pyrazole-3-carbonyl)-4-(2-fluorophenyl)piperazine; D006575:Heterocyclic Compounds, 3-Ring; D016859:Lipoxygenase Inhibitors; D010879:Piperazines; D011720:Pyrazoles; C031280:pyrazole; D001094:Arachidonate 5-Lipoxygenase
keywords: bioassay; cross-reactivity; human 5-lipo-oxygenase inhibitors; molecular docking; synthesis