Puratchikody A, Doble Mukesh
Department of Pharmaceutical Engineering and Technology, Bharathidasan Institute of Technology, Bharathidasan University, Tiruchirappalli 620024, India.
Bioorg Med Chem. 2007 Jan 15;15(2):1083-90. doi: 10.1016/j.bmc.2006.10.025. Epub 2006 Oct 18.
This paper describes the pharmacological evaluation pertaining to antinociceptive (hot plate and tail flick) and antiinflammatory (based on Carrageenan-induced paw oedema) activities, and QSAR studies on 2-substituted-4,5-diphenyl-1H-imidazoles. Compounds with phenyl substitution with -F, -Cl, -NH(2), -N(CH(3))(2), -OH and -OCH(3) at the p-position showed higher activity than the other substitutions in all the three studies. QSARs developed for the 60 and 120s hot plate data indicate that the models for both the cases not only fit the data very well (R(2)>0.9, R(adj)(2)>0.86), but also have very good predictive capability (q(2)>0.81). The descriptors used in the model relate to surface area, volume, dipole moment and ADME properties of the molecule. Good QSARs for the 60 and 120s tail flick data are developed. The models fit the data well (R(2)>0.8, R(adj)(2)>0.74), and in addition have good predictive capability (q(2)>0.66). Surface area, specifically polar surface area, HOMO and molecular connectivity index appear in the models. Very good QSAR model is developed for the antiinflammatory data (R(2)=0.86, R(adj)(2)=0.822 and q(2)=0.64) with aqueous solubility, number of hydrogen bond donor groups, surface area and principal moment of inertia as the molecular descriptors.
本文描述了关于2-取代-4,5-二苯基-1H-咪唑的抗伤害感受（热板法和甩尾法）及抗炎（基于角叉菜胶诱导的爪肿胀）活性的药理学评价，以及定量构效关系（QSAR）研究。在对位带有-F、-Cl、-NH₂、-N(CH₃)₂、-OH和-OCH₃的苯基取代化合物在所有这三项研究中均显示出比其他取代更高的活性。针对60秒和120秒热板数据建立的QSAR表明，这两种情况下的模型不仅与数据拟合得非常好（R²>0.9，Radj²>0.86），而且具有非常好的预测能力（q²>0.81）。模型中使用的描述符与分子的表面积、体积、偶极矩和药物代谢动力学性质相关。针对60秒和120秒甩尾数据建立了良好的QSAR。模型与数据拟合良好（R²>0.8，Radj²>0.74），并且此外还具有良好的预测能力（q²>0.66）。模型中出现了表面积，特别是极性表面积、最高占据分子轨道（HOMO）和分子连接性指数。针对抗炎数据建立了非常好的QSAR模型（R² = 0.86，Radj² = 0.822，q² = 0.64），其分子描述符为水溶性、氢键供体基团数量、表面积和惯性矩。
