Kumar Ashwani, Jain Sandeep, Parle Milind, Jain Neelam, Kumar Parvin
Drug Discovery and Research Laboratory, Department of Pharmaceutical Sciences,Guru Jambheshwar University of Science and Technology, Hisar -125 001, Haryana, India.
Department of Pharmaceutical Education and Research, BPSMV, Khanpur kalan, Sonepat, Haryana, India.
EXCLI J. 2013 Dec 13;12:1030-42. eCollection 2013.
A series of 3-aryl-1-phenyl-1H-pyrazole derivatives was synthesized in good yield and assayed in vitro as inhibitors of the mice acetylcholinesterase (AChE) and two goat liver monoamine oxidase (MAO) isoforms, MAO-A and MAO-B. Most of the compounds demonstrated a good AChE and selective MAO-B inhibitory activities in the nanomolar or low micromolar range. N-((3-(4-chlorophenyl)-1-phenyl-1H-pyrazole-4-yl) methylene) benzenamine (3e, pIC50 = 4.2) and N-((4-fluorophenyl)-1-phenyl-1H-pyrazole-4-yl) methylene) methanamine (3f, pIC50 = 3.47) were the most potent AChE and highly selective MAO-B inhibitors respectively. Structure activity relationships showed that chloro derivatives were more effective AChE inhibitors as compared to fluoro derivatives while reverse trend was observed in MAO-B inhibitory activity. With the aid of modeling studies, potential binding orientations as well as interactions of the compounds in the AChE and MAO-B active sites were examined.
合成了一系列3-芳基-1-苯基-1H-吡唑衍生物，产率良好，并作为小鼠乙酰胆碱酯酶（AChE）和两种山羊肝脏单胺氧化酶（MAO）同工型MAO-A和MAO-B的抑制剂进行了体外测定。大多数化合物在纳摩尔或低微摩尔范围内表现出良好的AChE和选择性MAO-B抑制活性。N-((3-(4-氯苯基)-1-苯基-1H-吡唑-4-基)亚甲基)苯胺（3e，pIC50 = 4.2）和N-((4-氟苯基)-1-苯基-1H-吡唑-4-基)亚甲基)甲胺（3f，pIC50 = 3.47）分别是最有效的AChE和高选择性MAO-B抑制剂。构效关系表明，与氟代衍生物相比，氯代衍生物是更有效的AChE抑制剂，而在MAO-B抑制活性方面观察到相反的趋势。借助建模研究，研究了化合物在AChE和MAO-B活性位点的潜在结合取向以及相互作用。
