Quantitative Structure Activity Relationship Study of Anti-Mycobacterium Avium Agents and the Calculation of Some Physico-Chemical Properties of Organic Compounds

The extreme importance of the partition coefficient between n-octanol and water (log P) in QSAR studies and in rational drug design requires one to have access to a reliable log P estimation method. To fulfill this need, a computer automated structure evaluation (CASE) approach to the calculation of the partition coefficient was developed. Besides the partition coefficient, the water solubility of a drug is also a key factor in determining its biological activity. Therefore, we developed a group contribution approach and a computer program to calculate the aqueous solubility for organic compounds. It was applied to a study of the relationships between the water solubility and biodegradability of organic compounds of environmental interest. Another useful physico-chemical property in many fields chemistry is the normal boiling point. A novel method that combines a group contribution approach and graph theory for the calculation of the normal boiling point of organic compounds was developed. A computer program was also developed to automate this approach. To assist the development of new anti-M. avium agents, we have successfully applied the Computer Automated Structure Evaluation (CASE) and the Comparative Molecular Field Analysis (CoMFA) programs to the study of quantitative structure anti- M. avium activity relationships of 2-acylamino-2-alkythiobenzothiazoles. Advisors/Committee Members: Klopman, Gilles.