title: A reverse method for diversity introduction of benzimidazole to synthesize H(+)/K(+)-ATP enzyme inhibitors.
abstract: A series of 2-[(2-pyridylmethyl)sulfinyl]benzimidazole derivatives were synthesized via a solution phase synthetic route using a reversal method of diversity introduction. Using this synthetic strategy, we obtained two key intermediates (4-A and 4-B) simultaneously, which allows us to introduce diversity points onto the benzimidazole part of the final product under reliable reaction conditions to identify potent H(+)/K(+)-ATP enzyme inhibitors. Compound 14l (IC(50)=1.6×10(-5)M) was comparable with H(+)/K(+)-ATP enzyme inhibitor in vitro.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 2 Nanwei Rd., Xicheng Dist., Beijing 100050, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yan
authors.forename: Zijie
authors.initials: Z
authors.lastname: Liu
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhang
authors.forename: Ruiming
authors.initials: R
authors.lastname: Xu
authors.forename: Xiao
authors.initials: X
authors.lastname: Hu
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D054328:Proton Pump Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013454:Sulfoxides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D001562:Benzimidazoles; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; C031000:benzimidazole; D017506:H(+)-K(+)-Exchanging ATPase