唐慰慈, J.Schmid, HHFiebig, GEisenbrand. 含硫亚硝基脲衍生物J. 药学学报, 1986, 21(7): 502-509.
引用本文: 唐慰慈, J.Schmid, HHFiebig, GEisenbrand. 含硫亚硝基脲衍生物J. 药学学报, 1986, 21(7): 502-509.
TANG WEI-CI, J SCHMID, H.H FIEBIG , G EISENBRAND, . SUIFUR CONTAINING NITROSOUREASJ. Acta Pharmaceutica Sinica, 1986, 21(7): 502-509.
Citation: TANG WEI-CI, J SCHMID, H.H FIEBIG , G EISENBRAND, . SUIFUR CONTAINING NITROSOUREASJ. Acta Pharmaceutica Sinica, 1986, 21(7): 502-509.

含硫亚硝基脲衍生物

SUIFUR CONTAINING NITROSOUREAS

  • 摘要: 本文报道一系列含硫亚硝基脲衍生物的合成、光谱学特征及对小鼠白血病L1210的作用。这些化合物都是CNC-半胱胺的衍生物,包括二硫化合物、2-氯乙基氨甲酸酯衍生物以及与羰基化合物环合而成的2,2-二取代的CNC-四氢噻唑。CNC-半胱胺及其二硫化合物、CNC-胱胺甲酰叠氮均有良好的抗L1210的作用;相应的氨甲酸酯衍生物和四氢噻唑衍生物的作用不明显。值得注意的是,2-甲基-2-乙氧羰甲基-3-CNC-四氢噻唑(15b)是一个例外,它对L1210有显著的抑制作用。

     

    Abstract: N′-N-(2-chloroethyl)-N-nitroso carbamoyl cysteamine (CNC-cysteamine) and several related compounds as well as 2,2-disubstituted CNC-thiazolidines, the condensation products with ketones, have been synthesized and tested against L 1210 leukemia in mice.Reaction of CNC-azide with cysteamine yielded CNC-cysteamine and bis (CNC) cystamine. Reaction of CNC-azide with cystamine in the presence of triethylamine gave bis-(CNC) cystamine, unexpectedly, formation of CNC-cystamine carboxylazide as a minor reaction product was also observed. Because the presence of triethylamine was necessary, an intermediate azidocarboxyl triethylammonium cation was supposed as the azidocarboxylating agent.N-(2-Chloroethyl) carbamoyl cysteamine 2-chloroethylcarbamate was formed when 2-chloroethyl isocyanate was reacted with cysteamine. Nitrosation of this cysteamine N,S-dicarbamoyl derivative or of CNC-cysteamine 2-chloroethylcarbamate, formed by reaction of CNC-cysteamine with 2-cyloroethyl isocyanate, led to formation of a mixture of two dinitroso isomers.The 2,2-disubstituted 3-CNC-thiazolidine derivatives were synthesized by nitrosation of corresponding 2,2-disubstituted 3-N-(2-chlorpethyl) carbamoyl thiazolidines, which could be obtained by carbamoylating of thiazolidine derivatives with 2-chloroethyl isocyanate. The 2-monosubstituted 3-N-(2-chloroethyl) carbamoyl thiazolidines decomposed by nitrosation under ring cleavage.Preliminary test of the newly synthesized CNC-derivatives in L1210 leukemia in mice revealed that the CNC-cysteamnie and its disulfide, as well as the CNC-cystamine carboxylazide are highly active against L1210 laukemia in mice, whereas the 2-chloroethylearbamate and the thiazolidine derivatives are ineffective except one compound, namely the (±) 2-methyl-2-ethoxycarbonylmethyl-3-CNC-thiazolidine, the high activity excited great attention.

     

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