Chapter 2 - Advantages of Good Drug-like Properties

Abstract

Drug discovery is continuously advancing as new fundamental knowledge, methods, technologies, and strategies are introduced. These new capabilities result in changes in the discovery process. Drug-like property optimization is another area of drug discovery advancement. It offers significant opportunities for enhancing discovery success. Much of the early history of drug discovery focused on finding active compounds. Issues such as PK, toxicity, solubility, and stability were addressed during the development phase. This great need for enhancement was actively addressed by adding resources to assess biopharmaceutical properties during late discovery. This chapter focuses on the fundamental knowledge, methods, and strategies of absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) and how structures can be optimized. It describes how optimization of ADME/Tox has progressed. Drug-like properties are an integral element of drug discovery projects. The chapter briefly reviews the process of drug discovery and development. A new strategy introduced into discovery is structure-property relationships (SPRs). This is complementary to SAR. The structures of compounds are correlated to their property performance. Exploration of SAR by synthesis of analogs having systematic modifications of the core structural scaffold has allowed optimization of binding by orders of magnitude.