Urea 1-methyl-1-nitroso

NG = N-Methyl-N -NitrO N Nitrosoguanidine, MNU = N-Methyl-Nitroso-urea,EMS = Ethyl methanesulphonate, AcDMN =Acetoxydimethylnitros-amine, NM = Nitrosomorpholine, NP = Nitrosopyrrolidine. 

Enol ether additives were used to probe the protonation of 3-cyclopen-tenylidene (127). Treatment of A-nitroso-A-(2-vinylcyclopropyl)urea (124) with sodium methoxide generates 2-vinylcyclopropylidene (126) by way of the labile diazo compound 125 (Scheme 25). For simplicity, products derived directly from 126 (allene, ether, cycloadduct) are not shown in Scheme 25. The Skat-tebpl rearrangement of 126 generates 127 whose protonation leads to the 3-cyclopentenyl cation (128). In the presence of methanol, cyclopentadiene (130) and 3-methoxycyclopentene (132) were obtained.53 With an equimolar mixture of methyl vinyl ether and methanol, cycloaddition of 127 (—> 131)... 

Experimental studies showed antitumoral effects of raloxifene in different in vitro preparations and animal models. Raloxifene has been able to inhibit the mitogenic effect induced by estrogens on ZR-75-1 cells, an estrogen responsive human breast cancer cell line (Poulin et al. 1989). In a well-accepted rat model of breast cancer induced by nitroso-methyl urea (NMU) raloxifene significantly suppressed the development of breast tumors and acted synergistically with 9 cis-retinoic acid (Anzano et al. 1996). 

Fig. 1.25. Regulation of alkylation repair in E. coK by methylation of the Ada protein. The effect of methylating agents, such as N-nitroso-N-methyl urea lead to the formation of methyl phospho-triesters (P-Me) of DNA, as well as various base adducts. The Ada protein possesses an N-termi-nal and a C-terminal domain. In one of the first steps of alkylation repair the methyl groups of the phosphotriester is transferred to the Ada protein. The Ada protein is methylated on a Cys residue at its N-terminal domain and thereby transformed into an active transcription activator. In its methylated form the Ada protein binds to the control region of various genes to stimulate their transcription. Among the genes under the control of the Ada protein are its own gene, as well others required for DNA repair (alkB, alkA). After Lindahl et al., 1988.

Groups of female Fischer 344 rats, six to eight weeks old, were either left untreated (group A) or received a single intravesicular instillation of 0.3 mg A-methyl-A-nitroso-urea (group B), six intravesicular instillations of 2.5 mg methyl methanesulfonate at 14-day intervals (group C) or sequential treaments with 0.3 mg A-methyl-A-nitrosourea followed by six intravesicular instillations of 2.5 mg methyl methanesulfonate at 14-day intervals (group D). The numbers of rats with bladder tumours were (A) 0/25, (B) 7/29 (24%), (C) 2/27 (7%) and (D) 19/33 (58%) (Tudor et al., 1984). 

The exchange procedure described was developed in the submitter s laboratories for the preparation of dideuteriodia-zomethane for labeling studies. It is basically a modification of a procedure that has been used extensively in the literature.7 However, the literature procedures give relatively little detail. This modified procedure permits the synthesis of fairly large amounts of high-purity dideuteriodiazomethane. Dideuterio-diazomethane has also been prepared from N-nitroso methyl-dg-urea and related trideuterated diazomethane precursors.8 Deuterated chloroform and hydrazine hydrate have also been used to prepare dideuteriodiazomethane.9... 

Chemical Name l-(2-Chloroethyl)-l-nitroso-3-[(2-methyl-4-aminopyrimidin-5-yl)-methyl]urea... 

SYNS METHYLNITROSO-HARNSTOFF (GERMAN) N-METHYL-N-NITROSO-HARNSTOFF (GERMAN) METHYLNITROSOUREA 1-METHYL-l-NITROSO-UREA METHYLNITROSOUREE (FRENCH) MNU N-NITROSO-N-METHYLCARBAMIDE N-NITROSO-N-METHYI HARNSTOFF (GERMAN) NITROSO-METHYLUREA N-NITROSO-N-METHYLUREA 1-NITROSO-l-METFtYLUREA NMH NMU NSC-23909 Q RCRA WASTE NUMBER U177 SKI 24464 SRI 859... 

C8H8CIN302 1-methyl-1-nitroso-3- p-chlorophenyl)urea 25355-61-7 310.15 25.990 1,2 13425 C8H802 2-hydroxy-5-methylbenzaldehyde 613-84-3 490.65 42.986 1,2... 

The best known and most widely used diazoalkane is diazomethane (95 equation 39). Preparative methods for diazomethane involve, in general, the nitrosation of a methylamine derivative (93), followed by cleavage under alkaline conditions. Methylamine derivatives used have included the urethanes, ureas,carboxamides, sulfonamides, guanidines and even the methylamine adducts of unsaturated ketones and sulfones. N-nitroso-N-methyl p-toluenesulfonamide (Diazald, Aldrich) is currently the most commonly used diazomethane precursor. Diazomethane is both toxic and explosive. Although in the past it has been purified by codistillation with ether, it is now usually generated, stored and used as an ether solution without distillation. 

Synonyms Methyl-CCNU Iraws-Methyl-CCNU Lomustine, methyl Methyl CCNU MeCCNU Me CCNU Me-CCNU NSC-95441 NSC 95441 NCI-C04955 Urea, N-(2-chloroethyl)-N -(4-me-thylcyclohexyl)-N-nitroso-, /ra s-(9CI) Urea, 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-l-nitroso-, /ra s-(8CI) l-(2-Chloroethyl)-3-(/ra s-4-methyl-... 

Several different methods have been employed for the preparation of diazo(trimethylsilyl)meth-ane (1). At present, the best synthetic method seems to be the diazo transfer reaction between diphenylphosphoryl azide and (trimethylsilyl)methylmagnesium chloride.However, the product often contains (chloromethyl)trimethylsilane and hexamethyldisiloxane as impurities. This method can also be employed for the synthesis of diazo(triethylsilyl)methane and diazo(di-ethylmethylsilyl)methane. The diazo transfer reaction can also be carried out with (trimethyl-silyl)methyllithium and tosyl azide. Other methods are the silylation of diazomethane with (trimethylsilyl)trifluoromethanesulfonate or chloro(trimethyl)silane and the base-induced cleavage of A-nitroso-A-[(trimethylsilyl)methyl]urea or the related carbamate or acet-amide.2° =... 

However, from a synthetic point of view the method has a limited potential because a large number of products is usually formed. Thus, when 7V-nitroso-A-(exo-tricyclo[3.2.1.0 ]oct-6-en-n ti-3-yl)urea (1) was reacted with a mixture of sodium methoxide and sodium borohydride in methanol, the reaction mixture obtained consisted of six polycycloalkyl methyl ethers (total yield 54%) and exo-tricyclo[3.2.1.0 ]oct-6-ene (2), bicyclo[3.2.1]octa-2,6-diene (3), tricyclo[3.2.1.0 ]oct-3-ene (4), and cndo-6-ethynylbicyclo[3.1.0]hex-2-ene (5). " Less complex is the reaction involving the tricyclo[3.2.1.0 ]octane-2-diazonium ion (6), which yielded a mixture of 2-methoxytricyclo[3.2.1.0 ]octane (7) and tricyclo[3.2.1.0 ]octane (8) in a 56 44 ratio, but in unknown yield. ... 

Cesarone CF, Bolognesi C, Santi L. 1979. DNA repair synthesis in mice spermatids after treatment with N-methyl-N-nitroso urea and N-N-dimethylnitrosamine. 

A-Methyl-m-nitroaniline A-Methyl-A-nitroso-ra-nitroaniline (20 g) is added to a warm (50°) solution of urea (15 g) in water (75 ml) and sulfuric acid (75 ml), whereupon nitrogen, carbon dioxide, and nitric oxide are at once evolved. The mixture is then heated for a further 15 min at 100°, and finally allowed to cool. The secondary amine is precipitated by ammonia and recrystallized from light petroleum. The yield is 15.5 g, and the m.p. 67.5°. 

Methyl-l-nitroso urea may be used in place of the carbamate (2-17) and for many years probably presented the most popular method for preparing diazomethane solutions. 

Following Arndt (1943), 1-methyl-l-nitroso urea is added to aqueous potassium hydroxide and ether at 5 °C in a flask fitted with a condenser set for distillation. On heating the mixture to the boiling point of ether, the yellow diazomethane is codistilled with the ether and collected in ice-cooled ether contained in another flask. On completion of the reaction, the distillate becomes colorless. 

Methyl-l-nitroso urea was subsequently shown to be a potent carcinogen (see Sect. 4.2), and its use is now discouraged. For the synthesis of diazoalkanes, for which no other route is described in the literature, N-alkyl-N-nitroso ureas may still be the reagent of choice. This is the case, for example, for diazo acetaldehyde (2.48), which was obtained (2-18) by Abdallah et al. (1983) by cleavage of A-(2,2-dimethoxy-ethyl)-AT-nitroso urea (2.47). The corresponding iV-nitroso urea was also used successfully for the preparation of 4-(2-diazoethyl)-2,3,3-trimethylcyclopentene (2.49) by Adam et al. (1985). Various other methods failed to lead to this diazoalkane. 

Tn 1961 Skipper and coworkers originally demonstrated that adminis-tration of 1-methyl-1-nitrosourea increased the lifespan of mice intra-cerebrally inoculated with L1210 leukemic cells (I). This demonstration launched extensive research into the synthesis and testing of N-nitroso-ureas for antitumor activity (2), a line of research that continues to the... 

Methods for synthesizing anisomycin and pentenomycin, ° and the chemistry and biological transformations of bleomycin and phleomycin have been reviewed.D-Ribo-furanosyl and -pyranosyl derivatives of iV-methyl-iV-nitroso-urea have been prepared as analogues of streptozotocin [2-deoxy-2-(JV-methyl-A -nitrosoureido)-D-glucose] they were reported to be more active against LI 210 leukaemia in mice and less toxic than the parent antibiotic. Likewise N- 2-chloroethyl)-iV-nitrosoureido derivatives of cyclopentane tetrols (35) and cyclohexane tetrols (36) have been synthesized for comparison with streptozotocin. ... 

See N-Nitroso-N-methylurea N-Nitroso-N-methylurea CAS 684-93-5 EINECS/ELINCS 211-678-4 Synonyms MethyInitrosourea 1-Methyl-1-nitrosourea N-Methyl-N-nitrosourea MNU N-Nitroso-N-methylcarbamide Nitrosomethylurea 1-Nitroso-1-methylurea NMU Urea, N-methyl-N-nitroso-Empirical C2H5N3O2 Formula CH3N(N0)C(0)NH2 Properties Pale yel. cryst. sol. in water (< 0.1 g/100 ml, 18 C), polar org. soivs. insol. in nonpolar org. soivs. m.w. 103.10 m.p. 124 C Toxicology May cause eye/skin irritation, dermatitis, skin allergy if allergy develops, very low future exposure can cause itching, skin rash high exposure may cause headache,... 

Urea, N-methyl-N-nitroso-. See N-Nitroso-N-methylurea Urea peroxide... 

Skidmore CJ, Davies MI, Goodwin PM, Halldorsson H, Lewis PJ, Shall S, Zia ee A-A (1979) The involvement of poly(ADP-ribose) polymerase in the degradation of NAD caused by 7-radiation and N-methyl-N-nitroso-urea. Eur J Biochem 101 135-142... 

Gray DA, Durkacz BW, Shall S (1981) Inhibitors of nuclear ADP-ribosyl transferase retard DNA repair after N-methyl-N-nitroso-urea. FEBS Lett 131 173-177... 

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