Synthesis and Biological Activity of 2,7-Naphthyridine Derivatives: An Overview

Abstract

: 2,7-Naphthyridine is one of the six structural isomers of pyridopyridine. Biological investigations have shown that these compounds have a broad spectrum of activity. They have been found to have antitumor, antimicrobial, analgesic and anticonvulsant effects. The broad spectrum of biological activity of 2,7-naphthyridine derivatives is the main reason for the preparation of new compounds containing this scaffold. This review aims to present various methods of obtaining 2,7-naphthyridine analogs. Compounds containing a 2,7-naphthyridine moiety can be synthesized from a variety of substrates and may be classified into four main categories: those derived from acyclic compounds, from quinoline derivatives, from pyridine derivatives, and from other compounds. Most of them were obtained by the cyclocondensation or intramolecular cyclization of pyridine derivatives. Cyclocondensations of non-cyclic substrates also produced 2,7-naphthyridine derivatives. Tricyclic benzo[2,7]naphthyridines were prepared from quinolines. The 2,7-naphthyridine scaffold has also been synthesized by the rearrangement of pyrrolo[3,4-c]pyridines, pyrano[3,4-c]pyridines or thiopyrano[3,4-c]pyridines.

Synthesis of new pentaheterocyclic systems based on the triazolo[3,4-a]-2,7-naphthyridine core

“…In an our previous work, 20 we synthesized pyrazolo [3,4c]tetrazolo [5,1-a]-2,7-naphthyridine 8, and it was found that in the solid state and in solution, it existed exclusively in the tetrazole form. As expected, heating compound 1 with hydrazine hydrate in ethanol at reflux afforded the corresponding 10-benzyl-8,9,10,11-tetrahydro-5H-pyrazolo [3,4-c][1,2,4]triazolo [3,4-a]-2,7naphthyridin-7-amine (7). Compounds 7 and 8 were then heated at reflux (5 h) with acetylacetone to obtain the 5-benzyl-9,11-dimethyl-4,5,6,7-tetrahydropyrimido[1',2': (10), respectively, via the well known Knorr synthesis of pyrazoles (Scheme 3).…”

“…9-Benzyl-5-chloro-7,8,9,10-tatrahydro [1,2,4]triazolo [3,4-a]-2,7-naphthyridin-6-carbonitrile (1) 24 was used as starting compound for the synthesis. Its reaction with ethyl mercaptoacetate led to the cyclization of a thiophene ring with formation of ethyl 7-amino-10-benzyl-8,9,10,11-tetrahydrothieno[2,3c] [1,2,4]triazolo [3,4-a]-2,7-naphthyridin-6-carboxylate (2).…”

“…In fact, they have an exceptionally broad spectrum of biological activities and are used in medicine, industry, agriculture and other fields. [1][2][3] Among all naphthyridines, 2,7-isomer derivatives are amongst the only compounds whose synthesis and properties have not yet been thoroughly investigated. 3 Over the last several decades, the interest in derivatives of 2,7-naphthyridine has been growing due to their wide spectrum of biological activity.…”

“…[1][2][3] Among all naphthyridines, 2,7-isomer derivatives are amongst the only compounds whose synthesis and properties have not yet been thoroughly investigated. 3 Over the last several decades, the interest in derivatives of 2,7-naphthyridine has been growing due to their wide spectrum of biological activity. It has been reported that they possess antitumor, 4 antiproliferative 5 and antimalarial 6 activities.…”

Synthesis of 1-Amino-3-oxo-2,7-naphthyridines via Smiles Rearrangement: A New Approach in the Field of Chemistry of Heterocyclic Compounds

“…2,7-Naphthyridine derivatives are interesting compounds in the field of heterocyclic chemistry due to some of their interesting biological activities, as evidenced by recent reviews [ 1 , 2 , 3 ]. Literature data shows that some 2,7-naphthyridine derivatives are potent and selective 3-phosphoinositide-dependent Kinase-1 [ 4 ], PDE5 [ 5 ], c-Kit/VEGFR-2 Kinase [ 6 ] inhibitors, while pyrazolo[3,4- c ]-2,7-naphthyridines are bombesin receptor subtype-(3BRS-3) agonists [ 7 ].…”