The n-oxidation of methylhydrazine catalyzed by purified mouse liver microsomal mixed function amine oxidase is shown. At pH 7.7 and 25 °C, methylhydrazine has nearly the same maximal n-oxidation rate as dimethylaniline. Although methane can be detected as a product of n-oxidation of methylhydrazine, it may represent the chemical decomposition product of a n-oxidized intermediate.
Isolated hepatocytes and liver microsomes incubated with monomethylhydrazine, 1,1-dimethylhydrazine and 1,2-dimethylhydrazine produced free radical intermediates which were detected by ESR spectroscopy by using 4-pyridyl-1-oxide-t-butyl nitrone as spin trapping agent. The spectral features of the spin adducts derived from all three hydrazine derivatives corresponded to the values reported for the methyl free radical adduct of 4-pyridyl-1-oxide-t-butyl nitrone. In the microsomal preparations, inhibitors of the mixed function oxidase system and the destruction of cytochrome P450 by pretreating the rats with cobalt chloride all decreased the free radical formation. Methimazole, an inhibitor of FAD-containing monoxygenase system, similarly decreased the activation of 1,1-dimethylhydrazine, but not that of monomethylhydrazine and 1,2-dimethylhydrazine. The addition to liver microsomes of physiological concentrations of glutathione (GSH) lowered by approx 80% the intensities of the ESR signals. Consistently, incubation of isolated hepatocytes with methylhydrazine decreased the intracellular GSH content, suggesting that GSH can effectively scavenge the methyl free radicals. The results obtained suggest that methyl free radicals could be the alkylating species responsible for the toxic and/or carcinogenic effect of methylhydrazines.
Methylhydrazine can be metabolized to carbon dioxide by rat liver slices. Reactive metabolites that were capable of binding covalently to nucleic acids were detected. Biotransformation of methylhydrazine might not be a detoxification process but may produce metabolites that are themselves active. No liver DNA guanine could be methylated in hamsters given the highest feasible doses of methylhydrazine. This does not appear to be an important intermediate in the methylation of DNA guanine seen in hydrazine-treated animals. Monoalkylhydrazines, including methylhydrazine, were converted to the corresponding hydrocarbons in the presence of liver microsomes, oxygen, and energy-producing co-factors. Mixed-function aminooxidases in the liver can oxidize alkylhydrazines in the presence of oxygen and NADPH. The formation of methane from methylhydrazine may be due to the decomposition of an N-oxidation intermediate. ...Methylhydrazine is oxidized by neutrophils (from rat peritoneal exudates) leading to the formation of alkyl radicals. Azide could inhibit this step.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A3; 已确认的动物致癌物，对人类的相关性未知。
A3; Confirmed animal carcinogen with unknown relevance to humans.
At request of the Minister of Social Affairs and Employment, the Health Council of the Netherlands evaluates the carcinogenic properties of substances at the workplace and proposes a classification with reference to the EU-directive. This evaluation is performed by the Dutch Expert Committee on Occupational Standards. The present report contains an evaluation by the committee on the carcinogenicity of N-methylhydrazine. The Committee concludes that N-methylhydrazine should be considered as carcinogenic to humans (comparable with EU-category 2). N-methylhydrazine is genotoxic. Evaluation. No data on humans are available. There is sufficient evidence for the carcinogenicity of N-methylhydrazine in experimental animals. Inhalation of N-methylhydrazine induced benign and malignant tumors in mice and hamsters and oral (drinking water) exposure caused benign tumors in mice and malignant tumors in hamsters in one experiment. No tumors were found in rats and dogs following inhalation, but the exposure time in rats may have been too short, that is 1 year instead of 2 years as recommended in OECD guideline 451. There is some evidence for mutagenic activity in in vitro bacterial systems. No mutations were induced in mammalian cell systems, but chromosome and DNA damage have been found. In vivo, N-methylhydrazine was negative in a dominant lethal assay in rats and mice and in a micronucleus test in dogs. Conflicting results were obtained with respect to DNA damage in liver in vivo assessed with the alkaline elution technique. Recommendation for classification. The committee is of the opinion that N-methylhydrazine should be considered as carcinogenic to humans. It is classified as a genotoxic carcinogen (classification comparable with EU category 2).
来源:Hazardous Substances Data Bank (HSDB)
毒理性
暴露途径
该物质可以通过吸入其蒸汽、通过皮肤接触以及摄入进入人体。
The substance can be absorbed into the body by inhalation of its vapour, through the skin and by ingestion.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
(14)C labeled methylhydrazine was administered to mice, dogs, and monkeys. All species excreted 25-40% of the dose in urine within 24 hr. In mice ... approx the same amount was excreted in respired air. Both carbon dioxide and radioactive methane were found.
The respiratory and urinary excretion of ip administered monomethylhydrazine (MMH) by rats was studied by means of radiotracer technique. Rats given 0.12 mM/kg respired approx 45% of the labeled carbon during the following 24 hr. Of the respired radioactivity, 20-25% was (14)C labeled carbon dioxide and the remainder was (14)C-methane. At the subconvulsive dose, 40% of the administered radioactivity was excreted in the urine. The percentage of urinary excretion of (14)C from higher doses was less, but the net amount excreted was slightly higher.
Nitrogenase Model Complexes [Cp*Fe(μ-SR1)2(μ-η2-R2N═NH)FeCp*] (R1 = Me, Et; R2 = Me, Ph; Cp* = η5-C5Me5): Synthesis, Structure, and Catalytic N−N Bond Cleavage of Hydrazines on Diiron Centers
摘要：
The reactions of [Cp*Fe(mu-SR1)(3)FeCp*] (Cp* = eta(5)-C5Me5; R-1 = Et, Me) with 1.5 equiv (RNHNH2)-N-2 (R-2 = Ph, Me) give the mu-eta(2)-diazene diiron thiolate-bridged complexes [Cp*Fe(mu-SR1)(2)(mu-eta(2)-(RN)-N-2 NH)FeCp*], along with the formation of PhNH2 and NH3. These mu-eta(2)-diazene diiron thiolate-bridged complexes exhibit excellent catalytic N-N bond cleavage of hydrazines under ambient conditions.
Plant Growth Regulator Daminozide Is a Selective Inhibitor of Human KDM2/7 Histone Demethylases
作者：Nathan R. Rose、Esther C. Y. Woon、Anthony Tumber、Louise J. Walport、Rasheduzzaman Chowdhury、Xuan Shirley Li、Oliver N. F. King、Clarisse Lejeune、Stanley S. Ng、Tobias Krojer、Mun Chiang Chan、Anna M. Rydzik、Richard J. Hopkinson、Ka Hing Che、Michelle Daniel、Claire Strain-Damerell、Carina Gileadi、Grazyna Kochan、Ivanhoe K. H. Leung、James Dunford、Kar Kheng Yeoh、Peter J. Ratcliffe、Nicola Burgess-Brown、Frank von Delft、Susanne Muller、Brian Marsden、Paul E. Brennan、Michael A. McDonough、Udo Oppermann、Robert J. Klose、Christopher J. Schofield、Akane Kawamura
DOI：10.1021/jm300677j
日期：2012.7.26
N-demethylation of Nε-methyl lysine residues in histones and are current therapeutic targets. A set of human 2-oxoglutarate analogues were screened using a unified assay platform for JmjC demethylases and related oxygenases. Results led to the finding that daminozide (N-(dimethylamino)succinamic acid, 160 Da), a plant growth regulator, selectivelyinhibits the KDM2/7 JmjC subfamily. Kinetic and crystallographic
[EN] CRBN LIGANDS AND USES THEREOF<br/>[FR] LIGANDS CRBN ET LEURS UTILISATIONS
申请人：KYMERA THERAPEUTICS INC
公开号：WO2019140387A1
公开（公告）日：2019-07-18
The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of CRBN, and the treatment of CRBN-mediated disorders.
本发明提供了化合物、其组合物以及使用这些化合物抑制CRBN并治疗CRBN介导的疾病的方法。
Rh(i) and Ir(i) catalysed intermolecular hydroamination with substituted hydrazines
作者：Serin L. Dabb、Barbara A. Messerle
DOI：10.1039/b814591a
日期：——
The catalysed intermolecular hydroamination of a series of terminal alkynes with substituted hydrazines was achieved using Rh(I) and Ir(I) complexes.
Synthesis of 4-Substituted Chlorophthalazines, Dihydrobenzoazepinediones, 2-Pyrazolylbenzoic Acid, and 2-Pyrazolylbenzohydrazide via 3-Substituted 3-Hydroxyisoindolin-1-ones
作者：Hanh Nho Nguyen、Victor J. Cee、Holly L. Deak、Bingfan Du、Kathleen Panter Faber、Hakan Gunaydin、Brian L. Hodous、Steven L. Hollis、Paul H. Krolikowski、Philip R. Olivieri、Vinod F. Patel、Karina Romero、Laurie B. Schenkel、Stephanie D. Geuns-Meyer
DOI：10.1021/jo3000628
日期：2012.4.20
hydrazine, followed by chlorination with POCl3. We have also discovered twonovel transformations of 3-vinyl- and 3-alkynyl-3-hydroxyisoindolinones. Addition of vinyl organometallic reagents to N,N-dimethylaminophthalimide (8a) provided dihydrobenzoazepinediones 15a–15c via the proposed ringexpansion of 3-vinyl-3-hydroxyisoindolinone intermediates. 3-Alkynyl-3-hydroxyisoindolinones react with hydrazine and
Studying Products of Hydrazine Interaction with Isothiocyanates by Means of Chromatography and Mass Spectrometry
作者：A. V. Ul’yanov、K. E. Polunin、I. A. Polunina、A. K. Buryak
DOI：10.1134/s0036024421050290
日期：2021.5
compounds in real-time and delayed modes are optimized. The physicochemical characteristics of the sorption of thiosemicarbazides are determined. The decomposition and fragmentation of their metastable protonated molecules are studied. Schemes are proposed for the formation of fragmented and characteristic thiosemicarbazide ions in different modes of ionization.
