Ersitat Ramon Llull, Via 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 systems containing two pyridine rings. 1,6-Naphthyridines are 1 with the members of such a loved ones capable of offering ligands for numerous receptors inside the physique. Among such structures, 1,6-naphthyridin-2(1H)-ones (7) are a subfamily that contains more than 17,000 compounds (with a single or double bond between C3 and C4) included in more than 1000 references (the majority of them patents). This review will cover the analysis from the diversity in the substituents present at positions N1, C3, C4, C5, C7, and C8 of 1,6-naphthyridin-2(1H)-ones, the synthetic strategies made use of for their synthesis (both beginning from a preformed pyridine or pyridone ring), plus the biomedical applications of such compounds.Citation: YC-001 site 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 particular disease, a single from the most important decisions to become taken could be the collection of the central molecular structure (scaffold) on which to introduce the substituents necessary to interact with the corresponding biological receptor. Such scaffolds could be selected based around the organic ligands of the receptor, the synthetic background with the investigation group, or, frequently, utilizing the so-called privileged heterocyclic structures, a idea introduced by Evans inside the late 1980s [1,2]. Such privileged structures are often heterocyclic compounds including quinoline, benzimidazole, pyrazole, indole, piperazine, and other folks, which are present in numerous drugs created throughout the history of medicinal chemistry. A different instance of such privileged heterocycles are pyrido[2,3-d]pyrimidine structures and, far more particularly, pyrido[2,3d]pyrimidin-7(8H)-ones [3] which 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 treatment of lung cancer [5], such as hepatitis C virus (HCV) inhibitors [6], as well as other biological activities. Related structures are naphthyridines, also known as pyridopyridines and benzodiacins, a group of diazanaphthalene compounds composed of six isomeric heterocyclic systems containing two pyridine rings. They are able to be divided into two small groups: the 1,Xnaphthyridines (X = 5, six, 7, eight) and also the 2,X-naphthyridines (X = 6, 7) (GSK2646264 Formula Figure 1) [7]. Because the synthesis by Reissert in 1893 with the initial naphthyridine, who proposed the given name, we had to wait till 1927 when the unsubstituted 1,5-naphthyridine (1) and 1, 8 naphthyridine (4) had been synthesized. Lastly, the household was completed with the synthesis in 1958 of 1,6-(2).