J. Chem. Inf. Computer Sci., 36, 872-878 (1996)

DOI: 10.1021/ci950066r

Molecular lipophilic potential on van der Waals surfaces as a tool in the study of 4-alkylpyrazoles

A new method for the calculation and analysis of lipophilic properties on molecular surfaces is presented. In this method, both, the concept of molecular lipophilic potential developed by Audry and co-workers and the approach of Ghose and Crippen implying that the hydrophobicity of a molecule can be obtained as the sum of certain atomic contributions, are combined. Then, shape analysis methodology is applied to characterize the interrelation between this molecular lipophilic potential and the van der Waals surfaces of a family of pyrazoles, which are known inhibitors of the enzyme liver alcohol dehydrogenase. In this study graphical representations and analytical methods are used. The mentioned topological analysis provides certain codes which combine lipophilic and steric information and are unique and characteristic of each pyrazole. These three-dimensional codes were correlated with the inhibitory activity of this series of pyrazoles. The inhibitory power of 4-isopentylpyrazole was not known experimentally before this study was carried out. Thus, by using these combined codes, the inhibitory activity of the isopentyl derivative was suggested to be lower than that of its linear isomer. This hypothesis was confirmed after the synthesis of 4-isopentylpyrazole and its enzymatic evaluation.