TUMOUR CHEMOTHERAPY Ⅻ.SYNTHESIS OF NITROGEN MUSTARD RELATED TO ANTIARTHRITICS

A number of nitrogen mustards related to antiarthritics——antipyrin, butazolidine and others—have been prepared in continuation of the work reported in part Ⅱ of this series of research. It was hoped that these compounds could be useful in the sense that they contained characteristic nitrogen mustard group on the one hand, and analgetic part on the other. 4-Aminoantipyrin (Ⅰ) on treatment with ethylene oxide formed 4-bis-(β-hydroxyethyl) aminoantipyrin (Ⅱ). The latter compound was then chlorinated with phosphorous oxychloride to give antipyrin mustard (Ⅲ). Two 1, 2-diphenyl-3,5-diketopyrazolidines. (Ⅳ and Ⅴ ) were treated with halogen giving the corresponding halogeno derivatives (Ⅵ and Ⅶ). Condensation of the latter with bis-(β-chloroethyl) amine gave the expected nitrogen mustards (Ⅷ and Ⅸ). Both Ⅳ and Ⅷ gave the corresponding nitrogen mustards Ⅺ and ⅩⅣ. On treatment with p-bis-(β-chloroethyl) aminobenzaldehyde, (Ⅺ), upon catalytic hydrogenation gave Ⅻ. Preliminary pharmacologic test revealed that these compounds do not show any significant inhibitory activity against tumour cells in vivo.