The Importance of Molecular Design Principles in Delivering High Quality Pharmaceutical Candidates

  • Thomas E. PrisinzanoEmail author
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 15)


High throughput screening of large chemical libraries of compounds is a proven way to identify novel chemical entities that target a biological system of interest. This technology is being used by industry and a growing number of academic screening centers for drug discovery campaigns. Unfortunately, many of the components of screening libraries have poor drug-like properties and require optimization. Typical components of a screening hit that need to be optimized include water solubility, reduced potential for toxicity, and metabolic stability. Presently, methods to alter individual molecular properties are not well elucidated. This chapter will discuss the molecular design principles that have been used successfully to alter the physiochemical properties of molecules through medicinal chemistry. Insights will be provided into the differences in approaches needed for optimization of a biological probe for target validation versus that of a hit to lead campaign, the design of more drug-like libraries, and the over-reliance of potency in optimization campaigns.


Chemical Probe Furan Ring Biological Target Kappa Opioid Receptor Trifluoromethyl Group 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This chapter is based in part on a short course in Contemporary Medicinal Chemistry given by Professors Lester A. Mitscher and Thomas E. Prisinzano provided by the International Organization for Chemical Sciences in Development (IOCD). The author wishes to thank the National Institute on Drug Abuse (DA018151) for financial support of the medicinal chemistry described in the case study. The content is the sole responsibility of the author and does not necessarily represent the official views of the National Institute on Drug Abuse, National Institutes of Health.


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Copyright information

© American Association of Pharmaceutical Scientists 2015

Authors and Affiliations

  1. 1.Department of Medicinal ChemistryUniversity of Kansas School of PharmacyLawrenceUSA

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