Antimitotic, antigenic, and structural relationships of nitrogen mustard and its homologues

Abstract

Of the three degradation products of nitrogen mustard (mechlorethamine, HN2) only N methyl 2 chloroethyl 2 hydroxyethylamine was antimitotically active and crossreactive to HN2 in tests for delayed hypersensitivity. The other two degradation products, N,N dimethyl N,N' bis (2 chloroethyl piperazinium and N methyldiethanolamine, were neither antimitotically active nor antigenically crossreactive to HN2. Thirteen of 17 HN2 homologues tested were found to be antimitotically active, but only 5 of them were crossreactive to HN2 in regard to delayed hypersensitivity. From structure function analysis it is concluded that with open chain derivatives crossreactivity to HN2 requires only a 2 chloroethylamino group as one determinant unit; a substituent with 2 carbon atoms such as ethyl, ethanol, and ethoxy at the nitrogen atom determined a specificity for crossreactivity to HN2. With cyclic derivatives, however, the ring size determines specificity: 6 and 7 but not 5 membered ring compounds were crossreactive to HN2. These results are potentially applicable to the therapy of cutaneous disease.