Lead optimization: quantitative structure-activity relations

Abstract

The optimization of bioactivity in a series is one of the aims in the design of crop protection chemicals. The approach of Hansch is the most developed model in this area. Here electronic, hydrophobic, and steric substituent constants are used for a quantitative analysis of the possible ways in which substitution may modulate bio- activity in a congeneric series (quantitative structure-activity relations; q.s.a.r.). An essential prerequisite of this approach is the availability of reliable substituent constants. The present state of the art is reviewed, with emphasis on steric parameters where several new approaches have been developed recently, and based upon recent q.s.a.r. studies from the literature as well as from our own laboratories. Q.s.a.r. may lead to significant regression equations, which can be used in different ways: the correlation between pesticidal activity and substituent properties provides the possibility of predicting the most favourable member of the class concerned. The resulting equations can also be given a physical interpretation in terms of the mode of action of the series studied. The scope and limitations of these applications are discussed.