Drug candidates fail for many reasons: poor therapeutic index, poor pharmacokinetics, inadequate physicochemical properties, drug-drug interactions, metabolic inactivation, and poor cost-benefits ratio. Sometimes, there is little a medicinal chemist can do. On the other hand, however, medicinal chemists can improve some key features of drug-like molecules. Herein we highlight the potential of orthogonally functionalized pyridines and relevant heterocycles in medicinal chemistry optimization initiatives.
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