Role of Pyridines in Medicinal Chemistry and Design of BACE1 Inhibitors Possessing a Pyridine Scaffold

Pyridine is a unique aromatic ring. Although pyridines are used industrially, pyridine moieties are present in many natural products, such as vitamins, coenzymes, and alkaloids, and also in many drugs and pesticides. Pyridine moieties are often used in drugs because of their characteristics such as basicity, water solubility, stability, and hydrogen bond-forming ability, and their small molecular size. Because pyridine rings are able to act as the bioisosteres of amines, amides, heterocyclic rings containing nitrogen atoms, and benzene rings, their replacement by pyridine moieties is important in drug discovery. Recently, we synthesized a series of BACE1 inhibitors by in silico conformational structure-based drug design and found an important role of pyridine moiety as a scaffold. In this chapter, we describe the important role of pyridines in medicinal chemistry and the development of β-secretase inhibitors possessing a pyridine scaffold for the treatment of Alzheimer’s disease.