2.6- Naphthyridine structure

Tetracyclic /3-carboline alkaloids, known as canthines, have a peri-fused indolo[3,2,Tbroad range of pharmacological effects (antimicrobial, cytotoxic, antibacterial, anticancer). 

A completely aromatic naphthyridine structure has been proposed by Houtz [121] ... 

Grassie and co-workers (1958) [146] proposed that the hydrogenated naphthyridine structure was formed by the nitrile polymerization reaction alone. 

Quinolones is the name given to a broad family of synthetic chemotherapeutic antibacterials chemically based on the 4-quinolone and 1,8-naphthyridine structures. The structures of these two quinolone nuclei and an example of a drug from each of these groups are shown in Fig. 6.17a, b. Cinoxacin is an example of a... 

Shortly after Gabriel and Colman reported cinchomeronylacetic ester, Pels reported a similar quinolinimidoacetic ester (40) to provide a 1,6-naphthyridine (41).The structure of the isolated compound was not unambiguously determined for more than 30 years.More recently, the reaction has been shown to produce both 41 and 42 in a 3 1 ratio... 

A methiodide of 6-chloro-2-methyl-l,5-naphthyridine has been 2irepared no structure was assigned, but it is probably the 1-salt (142). The 5-N atom of 1,6-dimethyl-2-naphthyridone undergoes... 

The amination of 2-bromo-l,5-naphthyridine also proceeds without rearrangement to yield 2-amino-1,5-naphthyridine (up to 80%) together with 1,5-naphthyridine (10%) and a substance (CgH8N4,10% yield) of unknown structure as by-products. Thus, here also it remains uncertain whether a 2,3-aryne is an intermediate. 

Tlie pKa values of 3-iiitro-l,6-iiaphthyridiiie (pAT = 2.32) and 8-iiitro-l,6-iiaphthyridiiie (pAT = 2.59) were reported (63JCS4237). In contrast to 3-nitro-l,5-naphthyridine cation (166a), the cations of 3-nitro-l,6-naphthyri-dine and 8-nitro-l,6-naphthyridine form in aqueous solution covalent hydrates. Tire most likely structures for the hydrated cations are presented as 167A/167B and 168A/168B, respectively (63JCS4237). 

Structures considered are quinolizinium (187), and 1,5- (188), 1,6- (189), 1,7- (190), 1,8- (191), and 2,7- (192) naphthyridines. In the naphthyridines the 10 7r-electrons are delocalized in five bonding molecular orbitals, which are distorted by the annular nitrogens in such a way that positions ortho and para to those nitrogens are less likely to be electrophilically haloge-nated than meta carbons. Compounds with a nitrogen at the ring junction carry a positive charge and will be naturally resistant to electrophilic attack. 

Naphthylamine, 1-phcnylazo-metal complexes structure, 6,44 1,8-Naphthyridine metal complexes, 2, 92, 93 Neel temperature, 1, 258 Neocupferron... 

Two-dimensional planar interpenetrating networks have been formed using the spacer ligand 2,2 -bis-l,6-naphthyridine with a zinc salt.274 Helicate structures have been synthesized which rely heavily on non-covalent interactions in the metal-assisted self-assembly process in solution.275... 

Structural characterization of [Ru(bpy)2(napy-V)(MeCN)][PF6]2 has confirmed that the 1,8-naphthyridine (napy) ligand is monodentate the two monodentate ligands are mutually cw." ... 

RUj(0H)Cl(H20) (napy)2](C10 ) (napy=l, 8-naphthyridine) is made from Ru3(napy)2Cl and AgClO in acetone [794,795], The X-ray crystal structure shows the two Ru atoms to be bridged by the chloro and hydroxo ligands, with two bridging naphthyridine ligands (Fig. 1.35). 

In terms of structural classes, Mitscher described seven cores that fall under the quinolonefamily, as shown below in Figure 4.1 (Mitscher, 2005). Of these cores, three templates have produced the most commercially successful drugs. They include the 4-0X0-1,4-dihydroquinolone (5), 7-oxo-2,3-dihydro-7H-pyrido-[l,2,3-d,e]-l,4-benzo-xazine (6), and the 4-oxo-l,4-dUiydro-[l,8]-naphthyridine cores (7). 

Comparison of the bond lengths with those of benzene, naphthalene and pyridine suggests that whilst there is certainly aromatic character some bond fixation occurs in the naphthyridines. It is probable that canonical structure (1) (of, for example, 1,5-naphthyridine) and to a lesser extent structures (7) and (8) are the major contributors to the ground state, but the charged structures (9) and (10) must also be included in order to account for the chemical properties of the naphthyridines. 

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