Selecting the right compounds for screening: does Lipinski's Rule of 5 for pharmaceuticals apply to agrochemicals?
Large numbers of compounds are now available through combinatorial chemistry and from compound vendors to screen for lead-level agrochemical activity. The likelihood that compounds with whole-organism activity will be discovered can be increased if compounds with physicochemical parameters consistent with transport to the target site are selected for screening. Certain ranges of simple parameters (molecular mass, log P, hydrogen-bond donors and acceptors, rotatable bonds) have been correlated with oral bioavailability of drugs. The distribution of these parameters for commercial insecticides and post-emergence herbicides was examined and ranges consistent with whole-organism activity are proposed for the two classes of agrochemical. The most significant difference identified between drugs and these two classes of agrochemicals was the lower numbers of hydrogen-bond donors allowed in the latter cases. The frequency with which certain functional groups occur in drugs and agrochemicals was also compared.
Tice
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Rohm and Haas Company, 727 Norristown Road, Spring House, PA 19477-0904, USA. colin_tice@rohmhaas.com
D016573:Agrochemicals / Q000737:chemistry*; D000465:Algorithms; D001682:Biological Availability; D020650:Combinatorial Chemistry Techniques / Q000706:statistics & numerical data; D016208:Databases, Factual; D005069:Evaluation Studies as Topic; D006540:Herbicides / Q000737:chemistry* / Q000493:pharmacokinetics; D006860:Hydrogen Bonding; D007306:Insecticides / Q000737:chemistry* / Q000493:pharmacokinetics; D015394:Molecular Structure; D008970:Molecular Weight; D000442:Octanols / Q000737:chemistry; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
D016573:Agrochemicals; D006540:Herbicides; D007306:Insecticides; D000442:Octanols; D014867:Water