Drug-like and lead-like concepts were established in the late 1990s and are widely acknowledged.  A large volume of data shows that compounds occupying less drug-like space have poorer drug metabolism, increased toxicity risks, and increased clinical pipeline attrition.  Despite these observations, drug design outcomes over the past decade, as assessed by the compounds in patent applications from major pharmaceutical Companies, show significantly inflated drug-like properties relative to recently approved oral drugs.  Overall compound quality - an amalgamation of lipophilicity, size, shape, polarity, chirality and aromaticity - can be quantified.  A comparison of 18 different companies' patents, taking into account the targets pursued, shows that inter-company variation in compound quality is comparable to the physicochemical differences between the major drug target classes.  There is considerable scope in the pharmaceutical industry for improving small molecule drug design capabilities and drug-like compound quality, thereby minimising risks of compound-related clinical pipeline attrition.

Current medicinal chemistry: Is there room for improvement in compound quality?

243rd National Meeting (2012)

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