Naphthyridinones, structure

In this chapter, an attempt has been made to present a total number of 20 QSAR models (12 QSAR models for topo I inhibitors and eight QSAR models for topo II inhibitors) on 11 different heterocyclic compound series (an-thrapyrazoles, benzimidazoles, benzonaphthofurandiones, camptothecins, desoxypodophyllotoxins, isoaurostatins, naphthyridinones, phenanthridines, quinolines, quinolones, and terpenes) as well as on some miscellaneous heterocyclic compounds for their inhibition against topo I and II. They have been found to be well-correlated with a number of physicochemical and structural parameters. The conclusion, from the analysis of these 20 QSAR, has been drawn that the inhibition of topo I is largely dependent on the hydrophobicity of the compounds/substituents. On the other hand, steric parameters (molar refractivity, molar volume, and Verloop s sterimol parameters) are important for topo II inhibition. 

Another structurally related series is the 2-ary 1-1,8-naphthyridin-4-ones (37 to 48, see Table 6.7), which contain a second nitrogen in the aromatic A ring. Compounds with meta-substituted phenyls (methoxy-, chloro-, or fluoro-) or a-naphthyl groups at the C-2 position showed potent cytotoxicity in the NCI 60 human tumor cell line panel with GI50 values in the low micromolar to nanomolar range (Tables 6.7 and 6.8).51 The tumor cell line selectivity varies with the various substituents. 2-(3 -Methoxyphenyl)-naphthyridinone (37) was significantly more cytotoxic in several cancer cell lines than the corresponding 2-(3 -meth-oxyphenyl)-quinolone (36). Both compound classes were potent inhibitors of tubulin polymerization the 2-ary 1-1,8-naphthyridin-4-ones had activity nearly comparable with those... 

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