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 L
1210 leukemia in mice revealed that the CNC-cysteamnie and its disulfide, as well as the CNC-cystamine carboxylazide are highly active against L
1210 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.