With four imidazopyridine-containing drugs and one pyrazolopyridine-containing drug on the market, bicyclic pyridines containing ring-junction nitrogen are privileged structures in medicinal chemistry. With two nitrogen atoms with potential to serve as hydrogen bond acceptors, imidazopyridines and pyrazolopyridines may boost binding to target proteins and elevate potency. In addition, these structures have found utility in FBDD, covalent inhibitors, reducing metabolic liabilities, and creating novel chemical space and intellectual properties. With many of the advanced intermediates now commercially available, they will find more and more applications in drug discovery.
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Cyclopropane is the smallest cyclic compound with unique structural features and physicochemical properties, which is widely used in the design of small molecule drugs. In drug design, it is often used to increase activity, fix conformation and improve PK and water solubility. The introduction of cyclopropyl groups into drugs can change various properties of molecules, such as improving metabolic stability; increasing biological activity; enhancing drug efficacy; limiting polypeptide conformation and slowing down its hydrolysis; reducing plasma clearance; improving drug dissociation and many more. Cyclopropane rings are widely found in marketed drugs, including cardiovascular drugs, central nervous system (CNS) drugs, anticancer drugs, autoimmune and anti-inflammatory drugs.
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