Insight into the Bioactivity and Metabolism of Human Glucagon Receptor Antagonists from 3D‐QSAR Analyses
Haifeng Chen, Xiaojun Yao, Michel Petitjean, Hairong Xia, Jian-Hua Yao, Annick Doucet Panaye, Jean Pierre Doucet, Botao Fan · QSAR & Combinatorial Science · 2004
Abstract Descriptors, such as logP, the number of hydrogen bond donors, the number of hydrogen bond acceptors, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) combined with fields of CoMFA and CoMSIA to construct models for hyperglycemia decrease activity and metabolism of human glucagon receptor antagonists. The results reveal that including logP, HOMO and LUMO energies is meaningful for QSAR/QSMR model. The models were validated by using a test set of structural diverse compounds that had not been included in the CoMFA and CoMSIA models. Support Vector Machines (SVM) have been used to select the suitable additional descriptors to construct 3D‐QSAR/QSMR models. A key factor to mention is that activity and metabolism models simultaneously. These in silico ADME models are helpful in making quantitative prediction of inhibitory activities and rates of metabolism before resorting in vitro and in vivo experimentation.