“Utilization of Operational Schemes for Analog Synthesis in Drug Design“

Picture BLP 18 100

Although Hansch and Leo had demonstrated the value of analysing compound potency using steric and electronic descriptors, it took John Topliss to reframe the approach as a decision tree that chemists could rapidly apply to explore chemical series. Beyond the well remembered ‘aryl substitution tree’ there is also an alkyl side chain tree and 3 example series.

It is interesting to note Topliss’s reflection on the use of statistical methods by chemists:

“Another problem in the utilization of the standard Hansch method is the reluctance on the part of some medicinal chemists to become involved with mathematics, statistical procedures, and computers. For these individuals a nonmathematical utilization of the Hansch approach might be of considerable interest.“

Topliss: J. Med. Chem. 1972, 15, 1006 – 1011

Almost all chemists use computers now, but still many remain resistant to applying mathematics or statistics to their design process

For a recent review see: http://dx.doi.org/10.1021/acs.jcim.7b00195

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