Physicochemical properties in structure-activity analysis
Prominent among the methods of relating structure to biological activity, in order to rationalise drug activity and to predict novel analogues for synthesis, is the quantitative approach popularly known as Hansch Analysis (Hansch et al., 1963; Hansch, 1981). In Hansch Analysis, the biological activities of a parent molecule and a series of simple derivatives are subjected to regression analysis to find an equation relating activity to some combination of parameters representing changes in hydrophobic, electronic, and steric effects within the series. This enables conclusions to be drawn regarding the influence of physicochemical properties on drug transport or on drug binding.
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- CHEUNG, H.S., WANG, F.L., ONDETTI, M.A., SABO, E.F. & CUSHMAN, D.W. (1980). Binding of peptide substrates and inhibitors of angiotensin-converting enzyme. J. biol. Chem., 255, 401–407.Google Scholar
- KIM, D.H., GUINOSSO, C.J., BUZBY, G.C., HERBST, D.R., McCAULLY, R.J., WICKS, T.C. & WENDT, R.L. (1983). Mercaptopropanoyl-indoline-2-carboxylic acids and related compounds as potent angiotensin converting enzyme inhibitors and antihypertensive agents. J. med. Chem., 26, 394–403.CrossRefGoogle Scholar
- LIPSCOMB, W.N., REEKE, G.N., HARTSUCK, J. A., QUIOCHO, F.A. & BETHGE, P.H. (1970). The structure of carboxypeptidase A. VIII: Atomic interpretation at 0.2nm resolution, a new study of the complex of glycyl-L-tyrosine with CPA, and mechanistic deductions. Phil. Trans. R. Soc, B257, 177–214.CrossRefGoogle Scholar
- NORTH, A.C.T. (1982). Use of interactive computer graphics in studying molecular structures and interactions. Chem. and Ind., 221–225.Google Scholar
- OSAWA, E. & MUSSO, H. (1982). Application of molecular mechanics calculations to organic chemistry. Top. Stereochem., 13, 117–193.Google Scholar
- SUTTON, L.E. (1958,1965). Tables of interatomic distances and configuration in molecules and ions. Special publication nos. 11,18. The Chemical Society, London.Google Scholar