A Comparison of Physiochemical Property Profiles of Development and Marketed Oral Drugs
Mark C. Wenlock, Rupert P. Austin, Patrick Barton, Andrew M. Davis, and Paul
D. Leeson; J Medicinal Chemistry, 46, pp 1250 - 1256 (2003).

Abstract:

The process of drug discovery applies rigorous selection pressures. Marketed
oral drugs will generally possess favorable physiochemical properties with
respect to absorption, metabolism, distribution, and clearance. This paper
describes a study in which the distributions of physiochemical properties of
oral drugs in different phases of clinical development are compared to those
already marketed. The aim is to identify the trends in physiochemical
properties that favor a drug's successful passage through clinical
development and on to the market. Two libraries were created, one of current
development oral drugs and one of marketed oral drugs. Statistical analysis
of the two showed that the mean molecular weight of orally administered
drugs in development decreases on passing through each of the different
clinical phases and gradually converges toward the mean molecular weight of
marketed oral drugs. It is also clear that the most lipophilic compounds are
being discontinued from development.