Pyrido[2,3-d]pyrimidin-7(8H)-ones: Synthesis and Biomedical Applications

Abstract

Pyrido[2,3-d]pyrimidines (1) are a type of privileged heterocyclic scaffolds capable of providing ligands for several receptors in the body. Among such structures, our group and others have been particularly interested in pyrido[2,3-d]pyrimidine-7(8H)-ones (2) due to the similitude with nitrogen bases present in DNA and RNA. Currently there are more than 20,000 structures 2 described which correspond to around 2900 references (half of them being patents). Furthermore, the number of references containing compounds of general structure 2 have increased almost exponentially in the last 10 years. The present review covers the synthetic methods used for the synthesis of pyrido[2,3-d]pyrimidine-7(8H)-ones (2), both starting from a preformed pyrimidine ring or a pyridine ring, and the biomedical applications of such compounds.

The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design

“…3 A plethora of synthetic compounds with heterocyclic structural frameworks have been identified -with privileged six-membered N-containing pyridine and dihydropyridine ringslinked to a diverse range of bioactivity. [4][5][6][7] In the realm of six-membered heterocyclic structures, they have unique and interesting characteristics. Owing to their therapeutic potential, medicinal chemists have recently become drawn toward scaffolds in order to synthesize a wide range of novel bioactive molecules.…”

1,6-Naphthyridin-2(1H)-ones: Synthesis and Biomedical Applications

“…Then, we carried out searches with a C3-C4 double bond 13 (12,047 structures) and a C3-C4 single bond 14 (7067 structures) (Figure 2). It has already been described [3] that a single-bond search may include some double-bonded structures. Therefore, the resulting search was curated using the Substract command of the Combine Answer Sets tool in SciFinder to obtain the final set of 5318 molecules with a C3-C4 single bond (Figure 2).…”

“…Such privileged structures are usually heterocyclic compounds such as quinoline, benzimidazole, pyrazole, indole, piperazine, and others, that are present in many drugs developed throughout the history of medicinal chemistry. Another example of such privileged heterocycles are pyrido [2,3-d]pyrimidine structures and, more particularly, pyrido [2,3d]pyrimidin-7(8H)-ones [3] that have allowed our group to describe compounds with nM activities as breakpoint-cluster-region protein (BCR) kinase inhibitors for B lymphoid malignancies [4], discoidin domain-containing receptor 2 (DDR2) inhibitors for treatment of lung cancer [5], such as hepatitis C virus (HCV) inhibitors [6], and other biological activities.…”

Microwave Assisted Reactions of Azaheterocycles Formedicinal Chemistry Applications

“…Compounds containing pyridine, pyridazine, pyrimidine, pyrazine, -and their fused derivatives-, are described to possess a wide range of biological activities, with these including antiviral, anti-HIV, antituberculosis, antimalarial, antileishmanial, antibacterial, antifungal, anti-inflammatory, anticancer, antihypertensive, diuretics, antiaggregative, antiplatelet, cardiotonics, antineurodegenerative, antidepressant, anxiolytics, anticonvulsivant, analgesic, sedatives, antiallergic, etc. [16,21,[40][41][42][43][44][45][46][47][48][49][50][51][52][53]. A large variety of syntheses are described for these compounds, with some of them using MW technology.…”