Acidic, basic and neutral compounds from large pharmaceutical company patents published during 2000-9 were compared with oral drugs launched worldwide.  These compound groups occupy distinctly different molecular weight, lipophilicity, and aromatic/aliphatic chemical space.  'Molecular inflation,' and concomitant increased ADMET risk, is occurring in most target classes in patent compounds versus oral drugs and is largely caused by increases in lipophilicity and aromaticity.  Independently of lipophilicity, molecular weight or ion class, oral drugs have lower aromatic - aliphatic atom differences than patent compounds.  A target-unbiased analysis of the patents in the major target classes from ten pharmaceutical companies was performed by pairwise comparisons of the molecular properties of compounds in all specific targets shared between the companies. The results show that corporate strategy plays a dominant role in determining relative patent molecular properties. Medicinal design practice and behaviour can therefore help alleviate the current disastrously high pipeline attrition rates.

Molecular properties and drug attrition: Are we responding to the challenge?

241st National Meeting (2011)

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