Summary
The synthesis of new analogs of the anticancer agent BCNU is described. It involves the preparation of N-(2-chloroethyl)-N-nitrosocarbamoylazide and its reaction with aliphatic diamines and aminoalcohols to yield 1,1′-polymethylenebis 3-(2-chloroethyl)-3-nitrosoureas and 1-(ω-hydroxyalkyl)-3-(2-chloroethyl)-3-nitrosoureas. Screening for chemotherapeutic activities of the newly synthesized nitrosoureas against rat leukemia L 5222 and s.c. Walker carcinosarcoma 256 revealed remarkable differences between individual compounds. The water soluble 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea was the most active compound of this series, effecting 90% cures in i.p. inoculated L 5222 leukemia.
Zusammenfassung
Die Synthese neuer Analoge von BCNU wird beschrieben. Sie beruht auf der Herstellung von N-(2-Chloräthyl)-N-nitrosocarbamoyl Azid und dessen Umsetzung mit aliphatischen Diaminen und Aminoalkoholen zu den entsprechenden 1,1′-Polymethylenbis-3-(2-chloräthyl)-3-nitrosoharnstoffen, sowie 1-(ω-Hydroxyalkyl)-3-(2-chloräthyl) 3-nitrosoharnstoffen. Die Prüfung der chemotherapeutischen Wirksamkeit der neu synthetisierten Nitrosoharnstoffe gegen die Rattenleukämie L 5222 und gegen das s.c. Walker Carcinosarkom 256 ergab bemerkenswerte Unterschiede zwischen den einzelnen Verbindungen. Der wasserlösliche 1-(2-Hydroxyäthyl)-3-(2-chloräthyl)-3-nitrosoharnstoff war die wirksamste Verbindung dieser Reihe; er ergab 90% Heilungen bei der Rattenleukämie L 5222.
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Dedicated to Prof. J. Eisenbrand, on the occasion of his 75th birthday.
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Eisenbrand, G., Fiebig, H.H. & Zeller, W.J. Some new congeners of the anticancer agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) synthesis of bifunctional analogs and water soluble derivatives and preliminary evaluation of their chemotherapeutic potential. Z. Krebsforsch. 86, 279–286 (1976). https://doi.org/10.1007/BF00286946
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DOI: https://doi.org/10.1007/BF00286946