Ersitat Ramon Llull, By way of Augusta 390, E-08017 Barcelona, Spain; [email protected] (J.M.O.); [email protected] (R.P.d.l.B.); [email protected] (R.E.-T.); [email protected] (J.T.) Correspondence: [email protected]; Tel.: 34-660-921-Abstract: Naphthyridines, also referred to as diazanaphthalenes, are a group of heterocyclic compounds that consist of six isomeric bicyclic GNF6702 Epigenetics systems containing two pyridine rings. 1,6-Naphthyridines are a single from the members of such a household capable of giving ligands for numerous receptors in the physique. Among such structures, 1,6-naphthyridin-2(1H)-ones (7) are a subfamily that consists of greater than 17,000 compounds (using a single or double bond among C3 and C4) integrated in more than 1000 references (most of them patents). This overview will cover the evaluation of the diversity on the substituents present at positions N1, C3, C4, C5, C7, and C8 of 1,6-naphthyridin-2(1H)-ones, the synthetic methods utilised for their synthesis (both starting from a preformed pyridine or pyridone ring), along with the biomedical applications of such compounds.Citation: Oliveras, J.M.; Puig de la Bellacasa, R.; Estrada-Tejedor, R.; Teixid J.; Borrell, J.I. 1,6-Naphthyridin-2(1H)-ones: Synthesis and Biomedical Applications. Pharmaceuticals 2021, 14, 1029. https://doi.org/10.3390/ ph14101029 Academic Editors: Thierry Besson and Pascal Marchand Received: 12 September 2021 Accepted: 4 October 2021 Published: 9 OctoberKeywords: 1,6-naphthyridin-2(1H)-one; substitution pattern; synthesis; biological activity1. Introduction At the beginning of any analysis project aimed in the improvement of new prospective drug candidates for the remedy of a certain illness, one in the most important choices to become taken is the choice of the central molecular structure (scaffold) on which to introduce the substituents needed to interact together with the corresponding biological receptor. Such scaffolds can be chosen primarily based on the all-natural ligands of the receptor, the synthetic background with the analysis group, or, regularly, employing the so-called privileged heterocyclic structures, a notion introduced by Evans within the late 1980s [1,2]. Such privileged structures are usually heterocyclic compounds including quinoline, benzimidazole, pyrazole, indole, piperazine, and others, which can be present in numerous drugs created all through the history of medicinal chemistry. A different instance of such privileged heterocycles are pyrido[2,3-d]pyrimidine structures and, more especially, pyrido[2,3d]pyrimidin-7(8H)-ones [3] that have permitted 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 two (DDR2) inhibitors for therapy of lung cancer [5], which include hepatitis C virus (HCV) inhibitors [6], and also other biological activities. Equivalent structures are naphthyridines, also named pyridopyridines and benzodiacins, a group of Benidipine MedChemExpress diazanaphthalene compounds composed of six isomeric heterocyclic systems containing two pyridine rings. They can be divided into two smaller groups: the 1,Xnaphthyridines (X = five, 6, 7, 8) along with the 2,X-naphthyridines (X = 6, 7) (Figure 1) [7]. Because the synthesis by Reissert in 1893 in the 1st naphthyridine, who proposed the offered name, we had to wait until 1927 when the unsubstituted 1,5-naphthyridine (1) and 1, eight naphthyridine (four) have been synthesized. Lastly, the household was completed together with the synthesis in 1958 of 1,6-(2).