Quantitative structure-activity relationship (QSAR) represents an attempt to relate structural descriptors of compounds with their physicochemical properties and biological activities. It is widely used for the prediction of physicochemical properties in chemical, environmental, and pharmaceutical areas.1,2) The main steps involved in this method include the following: data collection, molecular descriptor selection and procurement, correlation model development and finally model evaluation. At present, many types of molecular descriptors have been proposed to describe the structural features of the molecules. [3][4][5] The main focus of these studies is to search for regularity in the manner in which molecular properties change as molecular structure changes. 6,7) One such property is the hydrolysis of drug molecules. Double ester prodrugs of penicillins are more susceptible to enzymatic hydrolysis than their simple alkyl esters but have the problem of poor aqueous solubility. This problem of carboxylic acid prodrugs was overcome by the synthesis of benzoglycolamide esters.8) The literature reveals many reports on QSRR (quantitative structure reactivity relationship).9-15) Chung et al. 16) has shown structure reactivity relationships in chemical hydrolysis of prodrugs of nicotinic acid. Similar studies on QSRR were found in literature. [17][18][19] In such studies the reactivity, in terms of rate constants, is determined and then correlated with structural parameters by use of suitable statistical techniques. The aim of this study was to establish quantitative relationship(s) between structure of benzogylcolamide esters 8) and their basic hydrolytic rate constants. Bundgaard et al. 8) synthesized benzoglycolamide esters and studied their physicochemical properties and stability, which were based on qualitative observations, which can be fortuitous also. But the correlation of benzoglycolamide ester structure with hydrolytic rate constant has not yet been investigated.In view of above and in continuation of our studies on correlation of molecular properties with activity, [20][21][22] we decided to study the usefulness of QSAR in the prediction of the basic hydrolytic rate constant of benzoglycolamide esters synthesized by Bundgaard et al.8) The multiple linear regression (MLR) model has been developed as a calibration model for predicting the Ϫlog kc of compounds belonging to test set and investigating their linear characteristics. The present results are important from a point of accurate prediction of Ϫlog kc. Our model can predict the basic hydrolytic rate constant of variety of a benzoglycolamide esters and it reduces the need for different time consuming experiments. MethodologyThe main aim of the present work was development of a quantitative model to predict the basic hydrolytic rate constant of different benzoglycolamide esters. In the present work, the hydrolytic rate constants of 44 benzoglycolamide esters synthesized 8) were subjected to MLR with their physicochemical properties. The best MLR mod...