A NEW QUANTUM-CHEMICAL APPROACH IN QSAR-ANALYSIS - PARAMETRIZATION OFCONFORMATIONAL ENERGIES INTO MOLECULAR DESCRIPTORS JMN (STERIC) AND JSN (ELECTRONIC)

Two new types of structure-related molecular descriptors, JMn and JSn, have been developed using conformational energies from quantum chemic al calculations. For this purpose propipocaine (CAS 3670-68-6) was cho sen as a model and 42 analogues were studied. The quantum chemical cal culations were performed applying AM1 and PCILO approximation methods. Appropriate mathematical models were designed to calculate steric par ameter log JM1 and electronic parameters JS1 to JS6. The values obtain ed for these parameters were used in multiple linear regression analys is for the evaluation of the structure-activity relationship. Furtherm ore, a comparison between electronic parameters JSn and sigma (Hammett ) was made. The results show, that these parameters can be used succes sfully in predicting the biological activity of compounds in this mode l. Although, JS5 values are comparable to sigma-Hammett, the electroni c parameter JS2 gives a better correlation in QSAR-analysis involving two parameters JS2 and log JM1.