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Journal of Pharmacology And Experimental Therapeutics, Vol. 100, Issue 4, 398-407, 1950
Copyright © 1950 by American Society for Pharmacology and Experimental Therapeutics

THE NITROGEN MUSTARD-LIKE ACTIONS OF 2,4,6-TRIS(ETHYLENIMINO)-S-TRIAZINE AND OTHER BIS(ETHYLENIMINES)

Frederick S. Philips 1 and John B. Thiersch 1

1 Pharmacology Section, Division of Experimental Chemotherapy, Sloan-Kettering Institute for Cancer Research, New York, New York

1. The toxicity of 2,4,6-tris(ethylenimino)-s-triazine (V) and three other bis(ethylenimines) was studied in mice, rats, cats and dogs. Their toxicological activity was compared with and found similar to that of a group of nitrogen mustards including bis(2-chloroethyl)-methylamine (HN2). However, close structural analogs of the bis(ethyleminines), containing no ethylenimine constitutents, proved to be relatively inactive agents.

2. When given in doses near the LD50, the bis(ethylenimines) and the nitrogen mustards evoked a similar delayed lethal syndrome and identical alterations in all hematopoietic organs and intestinal epithelium. On the other hand, doses of compound V near the LD50 were found to elicit fewer signs of acute intoxication than comparable doses of HN2. It was suggested that this difference might be associated with the valence of constituent imine N atoms which is, respectively, tertiary in V but quaternary in ethylenimonium transformation products of HN2.

3. The advantages of V in therapy of those clinical lymphomas which respond to treatment with HN2 were discussed in the light of the above observation.

4. Finally, the common pharmacological properties of bis(ethylenimines) and nitrogen mustards were considered to be related to the presence of chemically reactive 3-membered heterocyclic constituents, namely, tertiary ethylenimine groups in the former agents and quaternary ethylenimonium groups in the in vivo transformation products of the latter agents.

Submitted on August 4, 1950




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Copyright © 1950 by the American Society for Pharmacology and Experimental Therapeutics.