Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835 215, India.
Eur J Med Chem. 2013 Nov;69:762-7. doi: 10.1016/j.ejmech.2013.09.010. Epub 2013 Sep 18.
Ethyl and phenyl carbamate derivatives of pyrazoline (3a-3h) were synthesized and tested for their MAO inhibitory activity. All the compounds were found to be selective towards MAO-A. Phenyl carbamates (3e-3h) were better than ethyl carbamates (3a-3d) and displayed the best selectivity index. Compound 3f (KiMAO-A; 4.96 ± 0.21 nM) was found to be equally potent as that of standard drug, Moclobemide (KiMAO-A; 5.01 ± 0.13 nM) but with best selectivity index (8.86 × 10(-5)). Molecular docking studies with R &S conformer of 3f revealed S-enantiomer is better than R-enantiomer as reported earlier by other groups. It is proposed that VdW's radii of the substitution (bulkiness) in ring B determine the potency of phenyl carbamates.
吡唑啉（3a-3h）的乙酯和苯氨基甲酸酯衍生物被合成并测试其 MAO 抑制活性。所有化合物均被发现对 MAO-A 具有选择性。苯氨基甲酸酯（3e-3h）优于乙酯（3a-3d），并显示出最佳的选择性指数。化合物 3f（KiMAO-A；4.96 ± 0.21 nM）与标准药物吗氯贝胺（KiMAO-A；5.01 ± 0.13 nM）同样有效，但具有最佳的选择性指数（8.86×10（-5））。与 3f 的 R 和 S 构象的分子对接研究表明，正如其他小组早些时候报道的那样，S-对映体优于 R-对映体。据推测，环 B 中取代基（体积）的 VdW 半径决定了苯氨基甲酸酯的效力。
