A multivariate approach to QSAR

Sammanfattning: Quantitative structure-activity relationships (OSAR) constitute empirical analogy models connecting chemical structure and biological activity. The analogy approach to QSAR assume that the factors important in the biological system also are contained in chemical model systems.The development of a QSAR can be divided into subproblems:1. to quantify chemical structure in terms of latent variables expressing analogy,2. to design test series of compounds,3. to measure biological activity and4. to construct a mathematical model connecting chemical structure and biological activity.In this thesis it is proposed that many possibly relevant descriptors should be considered simultaneously in order to efficiently capture the unknown factors inherent in the descriptors. The importance of multivariately and multipositionally varied test series is discussed. Multivariate projection methods such as PCA and PLS are shown to be appropriate far QSAR and to closely correspond to the analogy assumption.The multivariate analogy approach is applied to a beta- adrenergic agents, b haloalkanes, c halogenated ethyl methyl ethers and d four different families of peptides.