30770-21-9Relevant academic research and scientific papers
Design, synthesis, and enzyme kinetics of novel benzimidazole and quinoxaline derivatives as methionine synthase inhibitors
Elshihawy, Hosam,Helal, Mohamed A.,Said, Mohamed,Hammad, Mohamed A.
, p. 550 - 558 (2014/01/17)
Methionine synthase catalyzes the transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine, producing methionine and tetrahydrofolate. Benzimidazole and deazatetrahydrofolates derivatives have been shown to inhibit methionine synthase by competing with the substrate 5-methyltetrahydrofolate. In this study, a novel series of substituted benzimidazoles and quinoxalines were designed and assessed for inhibitory activity against purified rat liver methionine synthase using a radiometric enzyme assay. Compounds 3g, 3j, and 5c showed the highest activity against methionine synthase (IC50: 20 μM, 18 μM, 9 μM, respectively). Kinetic analysis of these compounds using Lineweaver-Burk plots revealed characteristics of mixed inhibition for 3g and 5c; and uncompetitive inhibition for 3j. Docking study into a homology model of the rat methionine synthase gave insights into the molecular determinants of the activity of this class of compounds. The identification of these drug-like inhibitors could lead the design of the next generation modulators of methionine synthase.
Benzimidazole, benzoxazole and benzothiazole derivatives as 5HT 2B receptor ligands. Synthesis and preliminary pharmacological evaluation
Giorgioni,Accorroni,Di Stefano,Marucci,Siniscalchi,Claudi
, p. 57 - 73 (2007/10/03)
2-Phenethylbenzimidazole, 2-phenethylbenzoxazole and 2- phenethylbenzothiazole derivatives were synthesized to explore the structural features of the serotonin 5-HT2B receptor antagonists. Those molecules were designed to recognize the 5-HT2B receptor and to discriminate it from the 5-HT2A and 5-HT2c subtypes. All compounds were characterized by binding affinity determination for 5-HT 2A and 5-HT2c subtypes and antagonistic activity for 5-HT2B receptor in rat stomach fundus. None of the new compounds showed affinity for 5-HT2A and 5-HT2c subtypes, but some of them displayed antagonistic activity in rat stomach fundus at micromolar concentrations. Birkhaeuser Boston 2005.
