2,7-Naphthyridinones , from

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. 

The adducts from the Diels-Alder reaction of 2(17/)-pyrazinones with 3-butynylaminomethyl side chains undergo thermolysis to give either [l,7]naphthyridinones or [2,7]naphthyridines <1996T9161>. The intramolecular... 

From an overwhelming mass of data on 7t-deficient nitrogenous heterocycles, it is usually considered axiomatic that (wherever possible) hydroxy-1,5-naphthyridines will exist predominantly as their respective 1,5-naphthyridinone tautomers for example, l,5-naphthyridin-2-ol (2) will exist as l,5-naphthyridin-2( 1 //)-one (3). This postulate has been strengthened by ionization constant, infrared spectral, and ultraviolet spectral measurements on simple 1,5-naphthyridinones 887,1026,1027,1035,1040 calculations have been less meaningful.1295... 

Nitro-1,6-naphthyridin-2( 1 //)-one gave 2-chloro-3-nitro-1,6-naphthyridine (10) (POCl3, reflux, 3 h 44%) 819 4-chloro-8-nitro-l,6-naphthyridine (75 min 68%)48 and 5-chloro-8-iodo-l,6-naphthyridine (likewise 64%)1042 were made similarly from the corresponding 1,6-naphthyridinones. 

A new and efficient annulation of acylamino and carboxylate ester groups offers a convenient synthetic route to naphthyridinones and 2-quinoIinone. The intermediate (7.2) is obtained in two stages from 2-pivaIoylaminopyridine very good yields are obtained at each of the three stages. 

Much later, an alternate synthesis of naphthyridinones and quinoli-nones was discovered. Palladium-catalyzed amidation of halo aromatic rings with an ortho carbonyl group with primary or secondary amides to from substituted naphthyridinones and quinolinones (Scheme 97) (04OL2433). 

Naphthyridines have been prepared by means of a Niementowski synthesis from ethyl 2-amino-6-phenylnicotinate and by means of Friedlander synthesis from 2-aminonicotinaldehydes. Ethyl 2-amino-6-phenylnicotinate (IX lll), which is readily prepared from ethyl a-ethoxycarbonyl acetimidate and benzoylacetaldehyde, condenses with the simple esters (DC-122 R = H, CH3, CfiHs) in the presence of sodium to give good yields of 1,8-naphthyridinones (IX-113). 

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