title: Design, synthesis and pharmacological evaluation of omeprazole-like agents with anti-inflammatory activity.
abstract: A new series of novel benzimidazole derivatives containing substituted pyrid-2-yl moiety and polyhydroxy sugar conjugated to the N-benzimidazole moiety has been synthesized and evaluated as orally bioavailable anti-inflammatory agents with anti-ulcerogenic activity. The anti-inflammatory and anti-ulcerogenic activities of these compounds were compared to diclofenac and omeprazole, respectively. In carrageenan-induced paw oedema assay, 2-methyl-N-((3,4-dimethoxypyridin-2-yl)methyl)-1H-benzimidazol-5-amine (12d) and 1-(1,2,3,5-tetrahydroxy-α-D-mannofuranose)-5-(((3,4-dimethoxypyridin-2yl)methyl)amino)-2-methyl-1H-benzimidazole (15d) displayed dose-dependent anti-inflammatory activities by decreasing the inflammation by 62% and 72%, respectively which is comparable to that of diclofenac (73%). In contrast to diclofenac, the anti-inflammatory activity of these compounds was not only free from any side effects on the gastric mucosa but also showed significant anti-ulcerogenic activity in rat pyloric ligation and ethanol-induced gastric ulcer models similar to that of omeprazole. Together, these findings suggest that 12d and 15d are potent anti-inflammatory agents with concurrent anti-ulcerogenic activity and support its clinical promise as a component of therapeutic strategies for inflammation, for which the gastric side effects are always a major limitation.
authors: Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, Saudi Arabia. elnezhawy@yahoo.com
authors: Ahmed O H
authors: AO
authors: El-Nezhawy
authors: Ayman R
authors: AR
authors: Biuomy
authors: Fatma S
authors: FS
authors: Hassan
authors: Ayman K
authors: AK
authors: Ismaiel
authors: Hany A
authors: HA
authors: Omar
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D002351:Carrageenan; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000188:drug therapy
chemical_list: D000893:Anti-Inflammatory Agents; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D002351:Carrageenan; D009853:Omeprazole; C109865:2-methylbenzimidazole