title: Design and synthesis of N-aryl isothioureas as a novel class of gastric H(+) /K(+) -ATPase inhibitors.
abstract: To find new H(+) /K(+) -ATPase inhibitors for the treatment of peptic ulcer disease, a series of novel N-aryl isothiourea derivatives were synthesized and their structures were identified by (1) H NMR and GC-MS. The effects of these compounds on inhibiting gastric acid secretion were evaluated by the guinea pig stomach mucous membrane study with pantoprazole magnesium as a positive control. The results showed that, of the 37 N-aryl isothiourea compounds synthesized, 20 compounds have comparable or stronger gastric acid inhibitory activities than that of pantoprazole magnesium. The quantitative structure-activity relationships (QSARs) of the N-aryl isothiourea compounds were also studied by comparative molecular field analysis (CoMFA) computation, and the model structure that was supposed to give more powerful bioactivities was finally predicted.
authors.affiliation: Key Laboratory of Structure-Based Drugs Design and Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, P. R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.forename: Anhui
authors.initials: A
authors.lastname: Wu
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Wu
authors.forename: Xuhong
authors.initials: X
authors.lastname: Ren
authors.forename: Maosheng
authors.initials: M
authors.lastname: Cheng
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology; D000818:Animals; D003198:Computer Simulation; D017076:Computer-Aided Design; D015195:Drug Design; D008401:Gas Chromatography-Mass Spectrometry; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006168:Guinea Pigs; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008956:Models, Chemical; D015394:Molecular Structure; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D054328:Proton Pump Inhibitors; D000077402:Pantoprazole; D013890:Thiourea
keywords: H+/K+-ATPase; N-Aryl isothiourea; Synthesis