A New Class of Nitrosoureas. I. Synthesis and Antitumor Activity of 1-(2-Chloroethyl)-3, 3-disubstituted-1-nitrosoureas having a Hydroxyl Group at the β-Position of the Substituents

• Published in: Chemical & pharmaceutical bulletin Vol. 29; no. 9; pp. 2509 - 2515
• Main Authors: TSUJIHARA, KENJI, OZEKI, MASAKATSU, MORIKAWA, TAMIO, ARAI, YOSHIHISA
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 1981
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Male; Mice; Nitrosourea Compounds - chemical synthesis; Nitrosourea Compounds - pharmacology; oxazolidinones
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.29.2509

1-(2-Chloroethyl)-3, 3-disubstituted-1-nitrosoureas (5a-m), a new class of nitrosoureas, were synthesized and tested for antitumor activities against leukemia L1210 and Ehrlich ascites carcinoma. The nitrosoureas (5e-k) having a hydroxyl group at the β-position of the substituents showed remarkable antitumor activities. In particular, 1-(2-chloroethyl)-3, 3-bis (2-hydroxyethyl)-1-nitrosourea (5k) had excellent activities and showed 5 and 16 times greater therapeutic ratios than 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea against leukemia L1210 and Ehrlich ascites carcinoma, respectively. These nitrosoureas (5e-k) appear to be activated nonenzymatically by attack of the hydroxyl group on the carbonyl group to give the oxazolidinones (6) and chloroethyl diazohydroxide (7) without generation of the isocyanates (8).