Nitromethane is apparently metabolized by different mechanism than nitroethane and nitropropane in that negligible amt of nitrites are found in blood following iv injection of 1 mmol in rabbits.
Liver microsomes from phenobarbital pretreated rats convert nitromethane to acetone and nitrate in presence of the reduced form of nicotinamide-adenine dinucleotide phosphate and oxygen. Addition of nitromethane to oxidized rat liver microsomal suspension gave rise to substrate binding difference spectrum with peak at 437 nm, interpreted as formation of cytochrome p450 no complex. Parallel to complex formation, oxidized rat liver microsomes catalyzed prodn of formaldehyde from nitromethane in the reduced form of nicotinamide-adenine dinucleotide phosphate-dependent reaction.
Formaldehyde generated from nitromethane was found only in trace amounts after incubation with microsomes from from Fischer 344 rat liver, but none was found after incubation with rat nasal microsomes. Nitromethane inhibited rabbit liver cytochrome P450 activity, apparently competing for the same ferrohaemochrome- binding sites as carbon monoxide.
IDENTIFICATION AND USE: Nitromethane is a colorless oily liquid. It is used as solvent for cellulosic compounds, polymers, waxes, fats; chemical synthesis; model rocket fuel; gasoline additive. HUMAN EXPOSURE AND TOXICITY: Symptoms of inhalation include cough, drowsiness, headache, nausea, sore throat, unconsciousness, and vomiting. Allergic contact hand dermatitis was documented in 4 coworkers who similarly handled an adhesive solvent containing nitromethane. All 4 cases were confirmed by patch testing and resolved after allergen avoidance. One case of human poisoning has been reported. In that case, a handyman was exposed to high concentrations of nitrocellulose and nitromethane resulting in a 67% conversion of his hemoglobin to methemoglobin and sulfhemoglobin. Treatment with hyperbaric oxygen, transfusion, peritoneal dialysis and then 6 sessions of hemodialysis resulted in recovery. Nitromethane is confirmed animal carcinogen with unknown relevance to humans. ANIMAL STUDIES: The most common signs of toxicity in acute animal studies were central nervous system (CNS) depression and slight irritation of the respiratory tract. Histopathologic changes were mainly in the liver and kidneys with the liver showing the most prominent injury, ie subcapsular damage, focal necrosis, fatty infiltration, congestion, and edema. The sulfhemoglobinemia and methemoglobinemia formation activities of similar drugs were studied in mice after administration of one or three ip doses. After administration of a single dose, nitromethane did not produce methemoglobinemia. Nitromethane produced sulfhemoglobinemia only after administration of three consecutive doses. Under the conditions of 2 yr inhalation studies conducted by NTP, there was no evidence of carcinogenic activity of nitromethane in male rats. There was clear evidence of carcinogenic activity of nitromethane in female rats based on increased incidences of mammary gland fibroadenomas and carcinomas. There was clear evidence of carcinogenic activity of nitromethane in male mice based on increased incidences of harderian gland adenomas and carcinomas. There was clear evidence of carcinogenic activity in female mice, based on increased incidences of liver neoplasms (primarily adenomas) and harderian gland adenomas and carcinomas. Increased incidences of alveolar/bronchiolar adenomas and carcinomas in male and female mice exposed to nitromethane were also considered to be related to chemical administration. Reproductive effects were investigated in female rats. No differences were found between treated and control rats in percentages of successful matings, litter size, pup mortality, birth weight, or maternal behavior. Pups were tested at 2.5 months of age in a maze-learning apparatus; the offspring of treated rats showed impaired maze learning when compared to controls. In another developmental study male rats had decreased caudal, epididymal, and testicular weights and decreased sperm counts. There was a dose-response decrease in epididymal sperm motility. Female mice showed a dose-related increase in the average estrous cycle length. Nitromethane was not mutagenic in Salmonella typhimurium strains TA 98 and TA 100 with and without activation. Nitromethane was further tested for mutagenicity of using the Salmonella assay, Drosophila melanogaster and an in vivo micronucleus test. Nitromethane was inactive in each of the three mutagenic test systems.
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.
Nitroparaffins are absorbed through lung and from GI tract. Applications to skin give no evidence of sufficient absorption to result in systemic injury. /nitroparaffins/
[EN] PYRAZOLE DERIVATIVES USEFUL AS INHIBITORS OF FAAH<br/>[FR] DÉRIVÉS DE PYRAZOLE UTILES COMME INHIBITEURS DE FAAH
申请人：MERCK & CO INC
公开号：WO2009151991A1
公开（公告）日：2009-12-17
The present invention is directed to certain imidazole derivatives which are useful as inhibitors of Fatty Acid Amide Hydrolase (FAAH). The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzheimer disease, and Parkinson's disease
The present invention relates to azoline compounds of formula (I) wherein A, B1, B2, B3, G1, G2, X1, R1, R3a, R3b, Rg1 and Rg2 are as defined in the claims and the description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.
[EN] SUBSTITUTED BENZYLAMINE COMPOUNDS, THEIR USE IN MEDICINE, AND IN PARTICULAR THE TREATMENT OF HEPATITIS C VIRUS (HCV) INFECTION<br/>[FR] COMPOSÉS DE BENZYLAMINE SUBSTITUÉS, LEUR UTILISATION EN MÉDECINE, EN PARTICULIER DANS LE TRAITEMENT D'UNE INFECTION PAR LE VIRUS DE L'HÉPATITE C (VHC)
申请人：ASTEX THERAPEUTICS LTD
公开号：WO2013064538A1
公开（公告）日：2013-05-10
The invention provides compounds of the formula (I): or a salt, N-oxide or tautomer thereof, wherein A is CH, CF or nitrogen; E is CH, CF or nitrogen; and R0 is hydrogen or C1-2 alkyl; R1a is selected from CONH2; CO2H; an optionally substituted acyclic C1-8 hydrocarbon group; and an optionally substituted monocyclic carbocyclic or heterocyclic group of 3 to 7 ring members, of which 0, 1, 2, 3 or 4 are heteroatom ring members selected from O, N and S; R2 is selected from hydrogen and a group R2a; R2a is selected from an optionally substituted acyclic d-8 hydrocarbon group; an optionally substituted monocyclic carbocyclic or heterocyclic group of 3 to 7 ring members, of which 0, 1 or 2 ring members are heteroatom ring members selected from O, N and S; and an optionally substituted bicyclic heterocyclic group of 9 or 10 ring members, of which 1 or 2 ring members are nitrogen atoms; wherein at least one of R1 and R2 is other than hydrogen; R3 is an optionally substituted 3- to 10-membered monocyclic or bicyclic carbocyclic or heterocyclic ring containing 0, 1, 2 or 3 heteroatom ring members selected from N, O and S; R4a is selected from halogen; cyano; C1-4 alkyl optionally substituted with one or more fluorine atoms; C1-4 alkoxy optionally substituted with one or more fluorine atoms; hydroxy-C1-4 alkyl; and C1-2 alkoxy-C1-4 alkyl; R5 is selected from hydrogen and a substituent R5a; and R5a is selected from C1-2 alkyl optionally substituted with one or more fluorine atoms; C1-3 alkoxy optionally substituted with one or more fluorine atoms; halogen; cyclopropyl; cyano; and amino, The compounds have activity against hepatitis C virus and can be used in the prevention or treatment of hepatitis C viral infections.
construction of carbon–sulfur bonds has been achieved via halogen-free Cs2CO3-promoted cross dehydrogenative coupling (CDC) of thiophenols with acetonitrile. This transformation provides a straightforward route to the synthesis of sulfenylated acetonitriles in up to 80% yield.
通过无卤的Cs 2 CO 3促进的硫酚与乙腈的交叉脱氢偶联（CDC），实现了构建碳-硫键的新方法。这种转化为亚磺酰化乙腈的合成提供了一条简单的途径，产率高达80％。
Synthesis of [3-<sup>13</sup>C]-, [4-<sup>13</sup>C]- and [11-<sup>13</sup>C]-porphobilinogen
作者：Prativa B. S. Dawadi、Els A. M. Schulten、Johan Lugtenburg
