Recent Advances in the Chemistry of Pyrimido[5,4-c] Isoquinoline Derivatives: Part I

Isoquinoline and pyrimidine, as heterocyclic compounds, offer significant advantages as fundamental building blocks in the development of novel drug entities. Their combination in isoquinoline- pyrimidine-inspired hybrids has demonstrated a wide range of promising biological characteristics. In recent years, numerous studies have focused on the synthesis and medicinal chemistry applications of pyrimido[5,4-c] isoquinoline ring systems (Py-isoQs5,4-c). This review provides a comprehensive overview of the synthesis of Py-isoQs5,4-c, utilizing barbituric acid, thiobarbituric acid, pyrimidine, isoquinoline, and their derivatives. The preparation of these compounds is achieved through various chemical reactions, including the Pictet–Spengler, Suzuki–Miyaura, Stille cross-coupling, Bischler-Napieralski-like, and one-pot three-component reactions. These synthetic approaches enable the efficient construction of Py-isoQs5,4-c, facilitating further exploration and investigation of their medicinal potential.