Quinazolin-4-ones, 2,3-diamino

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). 

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]. 

As part of the major effort undertaken at the Chester Beatty Research Institute in the area of quinazoline antifolates, Jones [42] synthesized 5,8-dideazafolate (III.156), 5-methyl-5,8-dideazafolate (III.160), and 5-chloro-5,8-dideazafolate (III. 161) by a synthesis which basically followed the Davoll scheme, except for one important modification 2,4-diamino-quinazoline-6-carbonitriles were converted into 2-amino-4(3//)-oxoquinazohne-6-carboni-triles in boiling 2 M HCl rather than in alkali. Hydrolysis of the 4-amino group under these conditions was more than 99% complete, thus ensuring the purity of the final products. 

Amino- and hydrazino-quinazolines exhibited antibacterial activity and a patent claim on the in vitro action of 2,4-diamino-quinazolines was made. " 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. 7-Chloro-6-sulfonamido-4(37I)quinazolinones are more effective than the mercury diuretics and can be administered orally. The 1 -dihydro derivatives are even more effective and one (59) has been marketed under the name Quinethazone. ... 

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