Fused 1,5-Naphthyridines: Synthetic Tools and Applications

Carme Masdeu,Endika Martin-Encinas,Francisco Palacios,Concepcion Alonso,Maria Fuertes,Gloria Rubiales,Asier Selas

doi:10.3390/molecules25153508

Carme Masdeu, Endika Martin-Encinas + Show 5 more

Open Access

https://doi.org/10.3390/molecules25153508

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Journal: Molecules	Publication Date: Jul 31, 2020
Citations: 13	License type: CC BY 4.0

Affiliation: University of the Basque Country

Abstract

Heterocyclic nitrogen compounds, including fused 1,5-naphthyridines, have versatile applications in the fields of synthetic organic chemistry and play an important role in the field of medicinal chemistry, as many of them have a wide range of biological activities. In this review, a wide range of synthetic protocols for the construction of this scaffold are presented. For example, Friedländer, Skraup, Semmlere-Wolff, and hetero-Diels-Alder, among others, are well known classical synthetic protocols used for the construction of the main 1,5-naphthyridine scaffold. These syntheses are classified according to the nature of the cycle fused to the 1,5-naphthyridine ring: carbocycles, nitrogen heterocycles, oxygen heterocycles, and sulphur heterocycles. In addition, taking into account the aforementioned versatility of these heterocycles, their reactivity is presented as well as their use as a ligand for metal complexes formation. Finally, those fused 1,5-naphthyridines that present biological activity and optical applications, among others, are indicated.

Highlights

Several reviews have appeared in the area of naphthyridines [1,2,3,4] including some references to fused 1,5-naphthyridines
To avoid overlapping with previous contributions, our wish in this review is coverage since 2003. Heterocyclic compounds, such as fused 1,5-naphthyridines, are significantly important in the field of medicinal chemistry, because many of them present a wide variety of biological activities
It was reported that pyronaridine I (Figure 1) has a high activity against Plasmodium falciparum and Plasmodium vivax [6,7]

Summary

Introduction

Several reviews have appeared in the area of naphthyridines [1,2,3,4] including some references to fused 1,5-naphthyridines. During reaction, ethylene dichloride (EDC) was used as solvent and short reaction times were applied to the process (Scheme 6, route b) Following this improved manufacturing process, 9-chloroacridine 20 was synthesized in a high purity, increased yield and lower production cost. In order to reduce undesired impurities produced during reaction, ethylene dichloride (EDC) was used as solvent and short reaction times were applied to the process (Scheme 6, route b) A sseerriies ooff eeiigghhtt eetthhyyll 66--ooxxoo--66HH--iinnddoolloo[[33,,22,,11--ddee]] [[11,,55]]nnaapphhtthhyyrriiddiinnee--11--ccaarrbbooxxyyllaatteess 8800 wwaass prepaarreedd bearriinngg various substituents in the aarromatic rriinngg,, ttooggeetthheerr wwiitthh tthhee 88--aazzaa aanndd 99--aazzaa aannaalloogguueess ((SScchheemmee 2211)).

Conclusions

47. For excellent recent review see