Lamie Phoebe F, Philoppes John N, Azouz Amany A, Safwat Nesreen M
a Department of Pharmaceutical Organic Chemistry , Beni Suef University , Beni Suef , Egypt.
b Department of Pharmacology and Toxicology, Faculty of Pharmacy , Beni Suef University , Beni Suef , Egypt.
J Enzyme Inhib Med Chem. 2017 Dec;32(1):805-820. doi: 10.1080/14756366.2017.1326110.
Nineteen new compounds containing tetrazole and/or cyanamide moiety have been designed and synthesised. Their structures were confirmed using spectroscopic methods and elemental analyses. Anti-inflammatory activity for all the synthesised compounds was evaluated in vivo. The most active compounds 4c, 5a, 5d-f, 8a and b and 9a and b were further investigated for their ulcerogenic liability and analgesic activity. Pyrazoline derivatives 9b and 8b bearing trimethoxyphenyl part and SONH or SOMe pharmacophore showed equal or nearly the same ulcerogenic liability (UI: 0.5, 0.75, respectively), to celecoxib (UI: 0.50). Most of tested compounds showed potent central and/or peripheral analgesic activities. Histopathological investigations were done to evaluate test compounds effect on rat's gastric tissue. The obtained results were in consistent with the in vitro data on COX evaluation. Docking study was also done for all the target compounds inside COX-2-active site.
已设计并合成了19种含四唑和/或氰胺部分的新化合物。通过光谱方法和元素分析确认了它们的结构。对所有合成化合物的抗炎活性进行了体内评估。对活性最高的化合物4c、5a、5d - f、8a和b以及9a和b进一步研究了它们的致溃疡倾向和镇痛活性。带有三甲氧基苯基部分以及SONH或SOMe药效基团的吡唑啉衍生物9b和8b显示出与塞来昔布（溃疡指数：0.50）相同或几乎相同的致溃疡倾向（溃疡指数分别为0.5、0.75）。大多数测试化合物显示出强效的中枢和/或外周镇痛活性。进行了组织病理学研究以评估受试化合物对大鼠胃组织的影响。所得结果与COX评估的体外数据一致。还对COX - 2活性位点内的所有目标化合物进行了对接研究。
