I. Rozas et M. Martin, MOLECULAR LIPOPHILIC POTENTIAL ON VAN-DER-WAALS SURFACES AS A TOOL INTHE STUDY OF 4-ALKYLPYRAZOLES, Journal of chemical information and computer sciences, 36(4), 1996, pp. 872-878
Citations number
38
Categorie Soggetti
Information Science & Library Science","Computer Application, Chemistry & Engineering","Computer Science Interdisciplinary Applications",Chemistry,"Computer Science Information Systems
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 a
nd the approach of Ghose and Crippen implying that the hydrophobicity
of a molecule can be obtained as the sum of certain atomic contributio
ns, are combined. Then, shape analysis methodology is applied to chara
cterize the interrelation between this molecular lipophilic potential
and the van der Waals surfaces of a family of pyrazoles, which are kno
wn inhibitors of the enzyme liver alcohol dehydrogenase. In this study
graphical representations and analytical methods are used. The mentio
ned topological analysis provides certain codes which combine lipophil
ic and steric information and are unique and characteristic of each py
razole. These three-dimensional codes were correlated with the inhibit
ory activity of this series of pyrazoles. The inhibitory power of 4-is
opentylpyrazole was not known experimentally before this study was car
ried out. Thus, by using these combined codes, the inhibitory activity
of the isopentyl derivative was suggested to be lower than that of it
s linear isomer. This hypothesis was confirmed after the synthesis of
4-isopentylpyrazole and its enzymatic evaluation.