3-D-QSAR analysis of N-(3-acyloxy-2-benzylpropyl)-N'-dihydroxytetrahydrobenzazepine and tetrahydroisoquinoline and N-(3-acyloxy-2-benzylpropyl)-N'-(4-hydroxy-3-methoxybenzyl) thioureas analogues as potent vanilloid receptor ligands.

ABSTRACT

3-D-Quantitative structure--activity relationships of N-(3-acyloxy-2-benzylpropyl)-N'-dihydroxytetrahydro-benzazepine and tetrahydroisoquinoline and N-(3-acyloxy-2-benzylpropyl)-N'-(4-hydroxy-3-methoxybenzyl) thiourea analogues as potent vanilloid receptor ligands were investigated using the CoMFA and the COMSIA methods. The best CoMFA model obtained in this study from 29 substituted thiourea analogues is a two-component model with the following statistics. R(2)((cv))=0.407 and RMSE((cv))=0.532 for the cross-validation, and R(2)=0.705 and RMSE=0.375 for the fitted. The best COMSIA model obtained from the same 29 compounds is a two-component model with the following statistics R(2)((cv))=0.336 and RMSE((cv))=0.563 for the cross-validation, and R(2)=0.693 and RMSE=0.382 for the fitted.