Quantitative Structure-Activity Relationships and Molecular Orbitals in Medicinal Chemistry
Seeking to attain the ultimate goal of rational drug design and to aid in the postulation of drug-action mechani sms at the molecular level , investigators have emp loyed two distinctly different techniques of particular interest to us. in the first techni que, statistical methods have been applied to the corre lati on of biological activity data with either the arbitrary parameters of the mathematical mode ls such as that reported by Free and Wilson  or linear free-energy-re lated physi cochemical properties ascribed to portions of the molecule, such as the wide lyapplied model of Hansch [2,3,4]. Although gradual changes in chemical structure and correspond ing changes in biological activity have intrigued sci ent ists for about 100 years , signifi cant progress in quantitative correlation techniques has developed only in the past fifteen years or so [6,7,8].
KeywordsInhibitory Potency Molecular Orbital Calculation Molecular Orbital Method Substituent Position Quantum Biology
Unable to display preview. Download preview PDF.
- Hansch, C., pp . 141–167 in Proceedings of the Third International Congress on Pharmacology, Sao Paulo, 1966, Vol . 7, Pergamon Press, New York (1968).Google Scholar
- Hansch, C., p Drug Design, Vol . 1, (E. J . Ariëns, ed .) Academic Press, New York (in press).Google Scholar
- Brown, A. C., and Fraser, T., Trans. Roy. Soc. Edinburgh, 25, 151 (1869)Google Scholar
- [5a]through Ariëns, E. J ., Simonis, A. M., and Van Rossum, J. M.,“Drug-Receptor Interacti on: Interacti on of One or More Drugs with One Receptor System”, Mol. Pharmacol., (E. J. Ari ëns, ed .) Academic Press, New York (1964) , p . 126.Google Scholar
- Purcell, W. P., Singer, J . A., Sundaram, K., and Parks, G. L., Chapter 10 in Medicinal Chemistry, 3rd Edition, (A. Burger, ed.) John Wiley and Sons, Inc., New York (in press) , p. 164.Google Scholar
- Purcell, W. P., and Clayton, J. M., Chapter 28 in Annual Reports in Medicinal. Chemistry, 1968, (C. K. Cain, ed.) Academic Press, New York (1969) , p. 314.Google Scholar
- Pullman, B., and Pullman, A., Quantum Biochemistry, Intersci ence Publishers, New York (1963).Google Scholar
- Taft, R. W., Jr., Chapter 13 in Steric Effects in Organic Chemistry, (M. S. Newman, ed.) John Wi ley and Sons, Inc., New York (1956).Google Scholar
- Tigertt, W. D., Military Med., Suppl., 131, 853 (1966).Google Scholar
- Williams, R. T., p . 652 in Detoxication Mechanisms, 2nd Edition, John Wiley and Sons, Inc., New York (1959).Google Scholar