The interrelation of physicochemical parameters and topological descriptors for a series of beta-blocking agents.
The intercorrelation between a series of physicochemical parameters and topological indices for a set of beta-blockers is investigated. Partition coefficients are calculated using the ClogP program, and the results are compared with previous data, both experimental and theoretical. These data are complemented by hydrophilicity and solubility calculations, together with the determination of molecular area and volume. Connectivity indices, of order 1 and 2, including simple, valence, and differential terms, are evaluated. The derivation of a recently proposed topological descriptor, the eccentric adjacency index, from the adjacency and distance matrices, is presented. The corresponding valence term, a novel descriptor, is developed, and other indices related to the distance matrix, the Wiener and Hyper-Wiener terms, are included. A high degree of linear correlation between the connectivity indices is noted. The correlations for first-order terms are slightly superior to the corresponding second-order values. This is particularly true when considering the valence terms compared with the nonvalence terms. The relationship between these terms and reported pharmacological properties are investigated. A decrease in the eccentric adjacency index resulted in an increase in the pharmacological property.
Department of Pharmaceutical Chemistry, Trinity College, Dublin 2, Ireland. jquigley@tcd.ie
John M
JM
Quigley
Sarah M
SM
Naughton
D000319:Adrenergic beta-Antagonists / Q000737:chemistry* / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D057927:Hydrophobic and Hydrophilic Interactions; D021281:Quantitative Structure-Activity Relationship; D012984:Software; D012995:Solubility
D000319:Adrenergic beta-Antagonists