RESUMEN
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 (ED50 range between 0.7 and 10.1â¯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 R2, Q2, s and F statistical parameters and the QUIK, asymptotic Q2 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.
Asunto(s)
Antiinflamatorios/uso terapéutico , Etanolaminas/uso terapéutico , Inflamación/tratamiento farmacológico , Organofosfonatos/uso terapéutico , Relación Estructura-Actividad Cuantitativa , Animales , Antiinflamatorios/síntesis química , Antiinflamatorios/química , Etanolaminas/síntesis química , Etanolaminas/química , Ratones , Estructura Molecular , Monocitos/metabolismo , Neutrófilos/metabolismo , Organofosfonatos/síntesis química , Organofosfonatos/químicaRESUMEN
The reduction of gamma-N-benzylamino-beta-ketophosphonates derived from readily available amino acids can be carried out stereoselectively with Zn(BH(4))(2) at -78 degrees C to produce the anti-gamma-amino-beta-hydroxyphosphonates.