Cyclohexyl chloroethyl nitrosourea

Chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU) [13010-47-4] (Vol. 26, Suppl. 7 1 (NB Overall evaluation upgraded from 2B to 2A with supporting evidence from other carcinogenicity and its mechanisms)... 

Although N-methyl-N-nitrosourea can induce cancer in human beings, its derivatives were found to be potent antitumor agents. l,3-Bis(2-chloroethyl)-l-nitrosourea (BCNU), l-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU) and l-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl-l-nitrosourea (PCNU) l-(2-Choroethyl)-3-(4-methylcyclo-hexyl)-l-nitrosourea and l-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea showed antitumor activity by alkylating with DNA [82-84]. N-Nitrosourea-based prodrugs designed to become activated by tumor-associated proteases were found to provide enhanced... 

Two TV-nitrosoureas, Bischloroethyl-nitrosourea (BCNU) and l-chloroethyl-3-cyclohexyl-1-nitrosourea (CCNU), have been used as anticancer agents in clinics but their mechanism and their toxicities have yet to be determined78. 

Lomustine Lomustine, l-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (30.2.4.3), is made by reacting ethanolamine with cyclohexylisocyanate, which forms l-(2-hydroxyethyl)-3-cyclohexylurea (30.2.4.1). Upon reaction with thionyl chloride, the hydroxyl gronp in it is replaced with a chlorine atom, giving l-(2-chloroethyl)-3-cyclohexylurea (30.2.4.2). This is nitrated in non-aqueons conditions with formic acid and sodinm nitrite to give lomustine (30.2.4.3) [67,68]. 

SYNS BELUSTINE CCNU CECENU CEENU CHLOROETHYLCYCLOHEXYLNITROSOUREA N-(2-CHLOROETHYL)-N -CYCLOHEXYL-N-NITROSOUREA (CHLORO-2-ETHYL)-l-CYCLOHEXYL-3-NITROSOUREA CINU (CLORO-2-ETIL)-l-CICLOESIi 3-NITROSO-UREA (ITALIAN) ICIG 1109 LOMUSTINE NCI-C04740 NSC-79037 RB 1509 SRI 2200... 

SYNS N-(2-CHLOROETHYL)-N -(tratis-4-METHYL-CYCLOHEXYL)-N-NITROSOUREA l-(2-CHLORO-ETHYL)-3-(trans-4-METHYLCYCLOHEXYL)-l-NITROSOUREA ICIG 1110 ME-CCNU METHYL-CCNU trans-METHYL-CCNU METHYL-LOMUSTINE NCI-C04955 NSC-95441 SEMUSTINE... 

CHLOROETHYL)-3-CYCLOHEXYL-l-NITROSOUREA see CGV250 N-(2-CHLOROETHYL)-N -CYCLOHEXYL-N-NITROSOUREA see CGV250... 

One further development is worth mentioning. A slight chemical modification to the nitrogen mustards provides the nitrosourea mustards like car-mustine (6zs-chloroethyl nitrosourea, BCNU), lomustine (chloroethyl, cyclohexyl nitrosourea, CCNU), semustine and streptozocin. The first three of these penetrate the brain well and are thus useful for eradicating deposits of cancer cells there. Unlike the other nitrosoureas, streptozocin is a natural product, isolated from the microorganism Streptomyces acromogenes, and has selectivity for tumours of the pancreas. 

AG Borel, FS Abbott. Identification of carbamoylated thiol conjugates as metabolites of the antineoplastic l-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea, in rats and humans. Drug Metab Dispos 21 889, 1993. 

The nitrosoureas, which include compounds, such as 1, 3- iT-(2-chloroethyl)-l-nitrosourea (carmustine BCNU), l-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (lomustine CCNU), and its methyl derivative (semustine methyl-CCNU), as well as the antibiotic streptozocin (streptozoto-cin), exert their cytotoxicity throngh the spontaneous breakdown to an alkylating intermediate, the 2-chloroethyl diazonium ion (see Fignre 15). 

Chang, T.K..H., H. Chen, and D.J. Waxman (1994). l-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) modulates rat liver microsomal cyclophosphamide and ifosphamide activation by suppressing cytochrome P450 2C11 messenger RNA levels. Drug Metab. Dispos. 22,... 

Some nitrosoamines have other biological effects than carcinogenic action. A/-(2-Chloroethyl)-A -cyclohexyl-A/-nitrosourea (4.15) has a cytostatic effect (Ferguson, 1975) and another A/-nitrosourea derivative, streptozotocin (4.16), is an antibiotic (Herr et al., 1967). 

Shapiro WR. Studies on the chemotherapy of experimental brain tumors evaluation of l-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, vincristine, and 5-fluorouracil. J Natl Cancer Inst 1971 46 359-368. 

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