CONACYT-Centro de Investigaciones Químicas-IICBA, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Cuernavaca 62209, Mexico.
Centro de Investigaciones Químicas-IICBA, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Cuernavaca 62209, Mexico.
Bioorg Med Chem. 2019 Jun 15;27(12):2376-2386. doi: 10.1016/j.bmc.2018.12.041. Epub 2018 Dec 31.
In this paper, we report the synthesis of a new series of α-aminophosphonates derivatives based in an efficient three-component reaction. All compounds prepared showed significant anti-inflammatory activity, being the compounds 1a, 1c, 1d, 1f, 2b and 2c the most promising ones, in terms of maximal efficacy (over 95%), potency (ED range between 0.7 and 10.1 mg/ear) and relative potency (range from 0.04 to 0.67). Compounds 1a, 1c, 1d and 1f significantly decrease the number of neutrophils (range from 46.7 to 63.0%) and monocytes (18.9-34.1%) in blood samples from the orbital sinus. Additionally, QSAR model revealed that the spherical molecular shape and the location of the HOMO on the phenyl ring improves the anti-inflammatory activity of the compounds. The values of R, Q, s and F statistical parameters and the QUIK, asymptotic Q and Overfitting rules validate the descriptive and predictive ability of the QSAR model. Altogether these results suggest that these new α-aminophosphonates are potential agents for the treatment of inflammation.
在本文中，我们报告了一系列基于高效三组分反应的新型α-氨基膦酸酯衍生物的合成。所有制备的化合物均表现出显著的抗炎活性，其中化合物 1a、1c、1d、1f、2b 和 2c 的效果最佳（超过 95%），效力（ED 范围在 0.7 到 10.1 mg/耳之间）和相对效力（范围在 0.04 到 0.67 之间）。化合物 1a、1c、1d 和 1f 显著降低了眼眶窦血液样本中的中性粒细胞（46.7-63.0%）和单核细胞（18.9-34.1%）的数量。此外，QSAR 模型表明，球形分子形状和 HOMO 在苯基环上的位置提高了化合物的抗炎活性。R、Q、s 和 F 统计参数值以及 QUIK、渐近 Q 和过拟合规则验证了 QSAR 模型的描述和预测能力。总之，这些结果表明，这些新型的α-氨基膦酸酯可能是治疗炎症的潜在药物。
