Synthesis of 1,6‐Naphthyridine and Its Derivatives: A Systematic Review

Abstract

The naturally and synthetically obtained 1,6-naphthyridine derivatives possess a wide range of pharmacological properties. This factor inspired the medicinal chemists and organic chemists to develop new methods for the synthesis of 1,6-naphthyridine derivatives. This review will discuss the synthesis of 1,6-naphthyridine and its derivatives from diverse starting materials or key intermediates in a systematic manner with appropriate mechanisms.

Oxidative Cyclization of 5H-Chromeno[2,3-b]pyridines to Benzo[b]chromeno[4,3,2-de][1,6]naphthyridines, Their NMR Study and Computer Evaluation as Material for LED

“…The structures of 2a-f were optimized and the required energies were calculated using the Hartree-Fock theory method with the 6-311G(d) basic set. (25), 330 (58), 304 (13), 267 (18), 204 (6), 177 (4), 164 (4), 83 (7), 41 (9) (15), 330 (13), 257 (14), 222 (19), 178 (14), 153 (11), 90 (11) (8), 237 (6), 216 (5), 189 (10), 164 (10), 136 (5), 28 (26)…”

“…Due to their unique structural features, highly condensed polycyclic compounds are increasingly crucial in polymer chemistry, materials science, and pharmaceutical chemistry. Naphthyridines are nitrogen-containing heterocyclic analogs of naphthalenes [10]. They contain a nitrogen atom in each of their benzene rings.…”

Microwave-assisted one-pot two-step imine formation–hetero-Diels–Alder–detosylation/aromatization sequence: direct access to dibenzo[b,h][1,6]naphthyridines

“…14 Consequently, developing efficient and straightforward synthetic methodologies for the synthesis of [1,6]naphthyridines remains an essential task. 15…”

Synthesis, In Vitro Cytotoxicity, and DFT Studies of Novel 2‐Amino Substituted Benzonaphthyridines as PDK1 Inhibitors

“…[30] Recently significant attention focused on procedures for the modification of 1,6-naphthyridine derivatives with the aim of looking for new biological active compounds. [31,32] It is a small wonder therefore that significant efforts were made to discover and optimize new reactions that facilitate the construction of [1,6]naphthyridine derivatives. The significant role of PDK-1 in naphthyridine analogues plays a key signaling pathways involved in the evolution of cancer prompted us to investigate the use of PDK-1 inhibitors as anticancer agents.…”

“…A series of novel 1,6‐naphthyridine derivatives have been prepared as potential inhibitors of human topoisomerase I, [23] antiproliferative, antitumor, [24,25] anticonvulsive agents, [26] p38 mitogen‐activated protein kinase inhibitors, [27] JAK2 inhibitors, [28,29] and spleen tyrosine kinase inhibitors [30] . Recently significant attention focused on procedures for the modification of 1,6‐naphthyridine derivatives with the aim of looking for new biological active compounds [31,32] . It is a small wonder therefore that significant efforts were made to discover and optimize new reactions that facilitate the construction of [1,6]naphthyridine derivatives.…”