2.4- Diamino-6- quinazolines

Amino- and hydrazino-quinazolines exhibited antibacterial ac-tivity and a patent claim on the in vitro action of 2,4-diamino-quinazolines was rnade. The preparation of thiopegan derivatives as potential antimalarials and antibacterials deserves mention. Complete inhibition of influenza virus in vitro but not in vivo was shown by. 6,8-dichloro-2,4-dihydroxyquinazoline and other cyclic ureas. Activity against trachoma virus was also displayed by several 2-trichloromethylquinazolines. ... 

A particularly interesting example of this method of synthesis is the cy-clrzation of the 4-amino-3-(2-aminophyenyl)-l,2,4-triazoloes 73 with cyanogen bromide. Primarily, this reaction was applied to synthesize the 6-amino-l,2,4-triazolo[4,3-d]benzodiazepine hydrobromides 74 the obtained products, however, were found to be the l,5-diamino-l,2,4-triazolo-[l,5-c]quinazolin-ium bromides 77. Structure elucidation of 77 was accomplished by direct... 

Rastelli, G., Fanelli, F., Menziani, M.C., Cocchi, M. and De Benedetti, P.G. (1991) Conformational analysis, molecular modeling and quantitative structure-activity relationships studies of 2,4-diamino-6,7-dimethoxy-2-substituted quinazoline al-adrenergic antagonists. Journal of Molecular Structure (Theochem), 251, 307—318. 

Hu et al. (91MI1) report the Dimroth rearrangement of 2-hydrazino- to 2,3-diamino quinazolin-4-ones under catalysis of carboxylic acid derivatives this reaction is followed by an in situ cyclization in which the same carboxylic acid derivatives serve as C,-synthons. l-Acylamino-2-alkylthiopyrimidines are hydrazinolyzed and cyclized to 3-amino-1,2,4-triazolofl, 5-a]pyrimidinium salts (89EGP270711). 

Reaction of 2,3-diamino-l 17/-pyrido[2,l -h]quinazolin-l 1-ones (162) with sodium nitrite in aqueous acetic acid at 40°C for 1 h, or with diphenylni-trosamine in acetic acid in the presence of sodium acetate at 75-85°C gave linear tetracyclic derivatives (163) (84GEP3300477). 

A very recent synthesis of 2,4-diamino-5-substituted quinazolines (261) has been described. Elaboration of these compounds into precursors for the preparation of isoFA and isoAP analogues is in progress [146]. 

Diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline Glucuronic acid... 

Four different QSAR were derived for the inhibition of DHFR from rat liver, human leukemia, mouse L1210, and bovine liver by 2,4-diamino, 5-Y, 6-Z-quinazolines (Fig. 1.3) (202, 213-215). A comparison of their QSAR presents an interesting study on the importance of spanned space in delineating enz37me-recep-tor interactions. 

Inhibition of Human Liver DHFR by 2,4-Diamino, 5-Y, 6-Z-quinazolines (214)... 

To a stirred, ice-cooled suspension of NaCl (1 g) in CISO3H (30 mL) was added in portions quinazolme-2,4-diamine sulfate (13.85 g, 0.05 mol). The resulting mixture was heated at 150-160 °C for 3 h, cooled, and then poured onto ice. The resulting precipitate was collected and washed with H O to afford 2,4-diamino-quinazoline-6-sulfonyl chloride as the sulfate salt yield 19.1 g (99%) mp >300°C,... 

Marelius J, GraffnerNordberg M, Hansson T, Hallberg A, Aqvist J. 1998. Computation of affinity and selectivity binding of 2,4-diaminopteridine and 2,4-diamino-quinazoline inhibitors to dihydrofolate reductases. J. Comput.-AidedMolec. Des. 12 119-31... 

In view of their structural similarity to quinolines and pyrimidines quinazoli-nes have been extensively explored for antiprotozoal activities. A large number of 2,4-diamino-6-substituted quinazolines (43) and 2,4-diamino-7-(arylmethylamino)-pyrido[3,2-d] pyrimidines (44) were found to exhibit potent activity against P. bcrghei, P. gallinaceum and P. falciparum in experimental animals [8]. One compound of this class, WR-158122 (43, R=2-naphthalenesulphonyl) has been evaluated in humans infected with the Uganda I strain of P. falciparum the compound caused only temporary elimination of parasitaemia and recrudescence was observed just after 9-16 days post- treatment [8]. 

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