A Medicinal Chemistry Perspective on Structure-Based Drug Design and Development

The application of X-ray crystallography and molecular modeling can provide valuable insight into the optimization of the molecular interactions of a drug–protein complex to achieve potency and selectivity of a drug candidate. For the successful application of SBDD in a drug development program, the impact of these structural modifications required to improve potency and selectivity must be considered in the context of balancing of a multitude of drug properties and other considerations that include solubility, bioavailability, metabolism, distribution, toxicology, chemical stability, and intellectual property space. The utility of structure-based design from the medicinal chemist’s perspective is described in this chapter.