Autori: Zamora, Ismael; Oprea, Tudor I.; Ungell, Anna-Lena

Editorial: Hoeltje, Hans-Dieter; Sippl, Wolfgang, Prous Science, Barcelona, Spain, Rational Approaches to Drug Design, Proceedings of the 13th European Symposium on Quantitative Structure-Activity Relationships, p.271-280, 2001.

Rezumat:

No high quality QSAR model was achievable for oral availability because this physiol. process is multifactorial and difficult to describe using linear models. A strategy was proposed to break down the complexity of oral availability into simpler, more fundamental processes. For the permeability process, a model based on 20 compds. and Caco-2 measurements is presented. The ghost erhytrocytes diffusion rate, as measured by NMR for 12 compds., that is believed to represent passive diffusion through a membrane, was successfully modeled using VolSurf. Two models to predict and explain the inhibition of cephalexine uptake that represents a measure of the dipeptide carrier system were developed and shown. From this 3D quant. structure absorption relationship, a pharmacophoric model can be achieved. The applicability of this model to predict active transport via the peptide carrier in general is limited, since the present study data set is too homogeneous. However, it suggests that modeling of active transport is possible, indicating possible new applications of mol. modeling in drug discovery.

Cuvinte cheie: Computer program; Molecular Structure-Property Relationships; Oral drug delivery permeability model