Design and synthesis of N-aryl isothioureas as a novel class of gastric H(+) /K(+) -ATPase inhibitors

Arch Pharm (Weinheim). 2013 Dec;346(12):891-900. doi: 10.1002/ardp.201300276. Epub 2013 Oct 30.

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.

Keywords: H+/K+-ATPase; N-Aryl isothiourea; Synthesis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / pharmacology
  • Animals
  • Computer Simulation
  • Computer-Aided Design
  • Drug Design*
  • Gas Chromatography-Mass Spectrometry
  • Gastric Acid / metabolism
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / enzymology
  • Gastric Mucosa / metabolism
  • Guinea Pigs
  • Magnetic Resonance Spectroscopy
  • Male
  • Models, Chemical
  • Molecular Structure
  • Pantoprazole
  • Proton Pump Inhibitors / chemical synthesis*
  • Proton Pump Inhibitors / pharmacology*
  • Quantitative Structure-Activity Relationship
  • Thiourea / analogs & derivatives
  • Thiourea / chemical synthesis*
  • Thiourea / pharmacology*

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Proton Pump Inhibitors
  • Pantoprazole
  • Thiourea