3346-23-4Relevant articles and documents
Inhibition of human O6-alkylguanine-DNA alkyltransferase and potentiation of the cytotoxicity of chloroethylnitrosourea by 4(6)- (benzyloxy)-2,6(4)-diamino-5-(nitro or nitroso)pyrimidine derivatives and analogues
Terashima, Isamu,Kohda, Kohfuku
, p. 503 - 508 (1998)
A series of 4(6)-(benzyloxy)-2,6(4)-diamino-5-(nitro or nitroso)pyrimidine derivatives and analogues of which 4(6)-benzyloxy groups were replaced with a (2-, 3-, or 4-fluorobenzyl)oxy or (2-, 3-, or 4- pyridylmethyl)oxy group, was synthesized. The abilities of these compounds to inhibit human O6-alkylguanine-DNA alkyltransferase (AGAT) in vitro and to potentiate the cytotoxicity of 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3- (2-chloroethyl)-3-nitrosourea (ACNU) toward HeLa S3 cells were evaluated. 2,4-Diamino-6-[(2-fluorobenzyl)oxy]-5-nitropyrimidine (3) and 2,4-diamino-5- nitro-6-(2-pyridylmethoxy)pyrimidine (6), whose ortho positions of the 6- substituent are modified, were much weaker in terms of these abilities than the corresponding meta- or para-modified compounds. These results are consistent with those of our previous study using a series of O6- benzylguanine derivatives. All 5-nitrosopyrimidine derivatives examined exerted both stronger AGAT-inhibition and ACNU-enhancement abilities than the corresponding 5-nitro derivatives. Among a variety of compounds that we have examined to date, 2,4-diamino-6-[(4-fluorobenzyl)oxy]-5-nitrosopyrimidine (10) exhibited the strongest ability to inhibit AGAT, and its magnitude was 2.5 and 50 times those of 4-(benzyloxy)-2,6-diamino-5-nitrosopyrimidine (9) and O6-benzylguanine (1), respectively. A strong positive correlation was observed between the ability to inhibit AGAT and to potentiate the cytotoxicity of ACNU. This strongly indicates that 4(6)-(benzyloxy)pyrimidine derivatives and their analogues potentiate ACNU cytotoxicity by inhibiting AGAT activity. To characterize the reactivity of test compounds, alkyl- transfer reactions were also carried out using the biomimetic alkyl-transfer system.
A 2, 4 - diamino - 5 - nitro - 6 - hydroxy pyrimidine preparation method and application thereof (by machine translation)
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Paragraph 0039-0050, (2018/05/01)
The present invention provides a 2, 4 - diamino - 5 - nitro - 6 - hydroxy pyrimidine preparation method, comprises the following steps: in a sulfuric acid solution, 2, 4 - diamino - 6 - hydroxy pyrimidine with nitric acid nitration; after the reaction is complete, the cooling crystallization, filtering, washing, drying, to obtain 2, 4 - diamino - 5 - nitro - 6 - hydroxy pyrimidine; the invention also provides a method for preparing nitro pyrimidine 2, 4, 5 - c amino - 6 - hydroxy pyrimidine method, comprises the following steps: N in the catalyst under the action of the, nitro pyrimidine in the lye A with C1 - C4 alcohol in the mixed solution, react with hydrogen; the method of the invention preparation of guanine, not the production of the inorganic salt as a by-product, waste water generation and emissions is lowered to that of the existing technology 1/6 - 1/8. (by machine translation)
