• Archives of Pharmacal Research
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• v.17 no.6
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• pp.420-423
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• 1994

Various N'-substituted anilino-N-methyl-N'-nitrosoureas(2a-n) were easily prepared from the reaction of substituted phenylhydraines $(3, 4-CH_3, {\;} 3-, {\;} 4-OCH_3, {\;} 3-, {\;} 4-F, {\;} 3, {\;} 4-Cl, {\;} 4-Br, {\;} 2-, {\;} 3-, {\;} 4-NO_2, 4-(NO_2)_2)$ with methyl isocyanate, followed by the nitrosation with 99% HCOOH and dry sodium lnitrite powder. Surprisingly, of these series of analogus, the anilino-nitrocosureas substituted with eletron-withdrawing nitro groups (2k-a) showed significantly low $ED_{30}$ values of $1.4-3.4 {\mu}g/ml.$ In addition, none of these copounds subtituted with electron-donating groups exhibited cytotoxicities.

• YAKHAK HOEJI
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• v.29 no.2
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• pp.62-69
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• 1985

The isomeric intermediates, $3{\alpha}$and $3{\beta}-amino-5{\alpha}-cholestane required for the synthesis of N-nitrosoureas, N-(2-chloroethyl)-N-nitrosocarbamoyl-$3{\alpha}-amino-5{\alpha}$-cholestane (9), N-methyl-N-nitrosocarbamoyl-3${\alpha}-amino-5{\alpha}-cholestane$ (10), N-(2-chloroethyl)-N-nitrosocarbamoyl-$3{\beta}-amino-5{\alpha}-cholestane$: (7), and N-methyl-N-nitrosocarbamoyl-$3{\beta}-amino-5{\alpha}-cholestane$ (8) were obtained through the $LiAlH_{4}$ reduction of $5{\alpha}$-cholestan-3-one oxime, followed by the chromatographic separation: the assignment of the stereochemistry of both isomers were based on the shape and chemical shift of $C_{3}$-proton resonances on their NMR spectra and on the elution mobility on the TLC. The urea intermediates, N-(2-chloroethyl) carbamoyl-3.alpha.-amino-5.alpha.-cholestane (13), N-methylcarbamoyl-$3{\alpha}-amino-5{\alpha}-cholestane$ (14), N-(2-chloroethyl) carbamoyl-$3{\beta}-amino-5{\alpha}-cholestane (11) and N-methyl-$3{\beta}-amino-5{\alpha}$-cholestane (12) were prepared by the treatment of each isomers ($3{\alpha}$-amino-and $3{\beta}-amino-5{\alpha}$-cholestane) with alkyl isocyanates in anhydrous $CHCl_{3}$, and the corresponding nitrosoureas, 7-10 were obtained by the nitrosation of the ureas, 11-14, with AcOH (or HCOOH)/$NaNO_{2}$ in ice-cold condition. The inhibitory activity of the nitrosoureas, 7-10, and their intermediates, 12-14 towards the growth of L1210 murine leukemia cells, were examined. Among them, the compounds 9 and 10 exhibited high activity having $ED_{50}$ to be 5.5g/ml and 6.1g/ml, respectively.