000Synthesis of new α-aminophosphonates: Evaluation as anti-inflammatory agents and QSAR studies

In this paper, we report the synthesis of a new series of alpha-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 (ED50 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-2, Q(2), s and F statistical parameters and the QUIK, asymptotic Q(2) and Overfitting rules validate the descriptive and predictive ability of the QSAR model. Altogether these results suggest that these new a-aminophosphonates are potential agents for the treatment of inflammation.