Lipophilicity prediction of WB-4101 analogues using the ILM approach

The hydropathicity of a series of WB-4101 derivatives active as alpha(1) ad renergic antagonists was studied. The compounds were submitted to a detaile d conformational search in vacuo with a Monte-Carlo method, followed by a m olecular dynamics simulation. The lowest energy conformation was inserted i nto a water cluster and the system was again subjected to a detailed molecu lar dynamics procedure (300 ps). The hydropathicity molecular index (ILM) w as then calculated by the water positions in the cluster and the 3D profile was projected on the molecular surface. The results were compared with the experimental logP values and with the values predicted by other computatio nal methods. An analysis of the relationships between conformational and lo cal hydropathicity properties was also performed.