Design and Quantitative Structure-Activity Relationships

MOLECULAR DESIGN AND QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS 

Ariens, Medicinal Chemistry, A Series of Monographs Vol. 11 Drug Design, Vol. 5, Academic Press, New York, 1975. 

Nauta and R. F. Rekker, The Hydrophobic Fragment Constant, Elsevier, Amsterdam, The Netherlands, 1977. 

---

Even with combinatorial chemistry and HTS, lead generation can be extremely laborious because of the vast number of different molecules possible (framework and biofunctional group combinations). To ease this burden, some rational drug design and quantitative structure activity relationships (QSARs) are often introduced to direct the programme and utilise a company s finite screening resource as efficiently as possible. 

H. Matter, E. Defossa, U. Heinelt, P.-M. Blohm, D. Schneider et al., Design and quantitative structure-activity relationship of 3-amidinobenzyl-l H-indole-2-carboxamides as potent, nonchiral, and selective inhibitors of blood coagulation factor Xa, J. Med. Chem. 2002, 45, 2749-2769. 

C. D. Selassie, Z. Fang, R. Li, C. Hansch, G. Debnath, T. E. Klein, R. Langridge, and B. T. Kaufman. On the structure selectivity problem in drug design. A comperative study of benzylpyrimidine inhibition of vertebrate and bacterial dihydrofolate reductase via molecular graphics and quantitative structure-activity relationships. Journal of Medicinal Chemistry, 32 1895-1905, 1989. 

O. Ivanciuc, Chemical graphs, molecular matrices and topological indices in chemoin-formatics and quantitative structure-activity relationships, Curr. Comput. Aided Drug Design 9 (2013) 153-163. 

Closely related to multivariate calibration are the applications of multivariate methods for investigations of structure-property or stmcture-activity relationships (see Quantitative Structure-Activity Relationships in Drug Design and Quantitative Structure-Property Relationships (QSPR)). 

The mapping of properties to surface features in SPERM can be regarded as a limiting case of the last class of local similarity measures to be discussed here, these being measures that are based upon electrostatic, steric, and hydrophobic fields analogous to those that underlie current approaches to 3D QSAR (see Comparative Molecular Field Analysis (CoMFA) and Quantitative Structure-Activity Relationships in Drug Design). 

---