Nitrobenzene appears as a pale yellow to dark brown liquid. Flash point 190°F. Very slightly soluble in water. Toxic by inhalation and by skin absorption. Combustion give toxic oxides of nitrogen. Density 10.0 lb /gal.
颜色/状态：
Greenish-yellow crystals or yellow, oily liquid
气味：
Odor of volatile oil almond
味道：
Aqueous solutions are sweet tasting
蒸汽密度：
4.3 (EPA, 1998) (Relative to Air)
蒸汽压力：
0.245 mm Hg at 25 °C (est)
亨利常数：
2.40e-05 atm-m3/mole
大气OH速率常数：
1.40e-13 cm3/molecule*sec
自燃温度：
900 °F (482 °C)
分解：
When heated to decomposition it emits toxic fumes of /nitrogen oxides/.
粘度：
1.863 mPa-s at 25 °C
燃烧热：
-10,420 BTU/LB= -5,791 CAL/G= -242.5X10+5 J/KG
汽化热：
55.01 kJ/mol at 25 °C
表面张力：
46.34 mN/m at 20 °C
电离电位：
9.92 eV
气味阈值：
Odor detection in air: 1.46x10-2 mg/l /vapor/, purity not specified.
Metabolism of nitrobenzene in mammals involves both oxidation and reduction reactions. Evidence for this has come from the identification of potential products of nitrobenzene oxidation and reduction reactions in the urine of humans and animals that had been exposed to the compound. Oxidation products of nitrobenzene include o-, m-, and p-nitrophenol; reduction products of nitrobenzene include nitrosobenzene, phenylhydroxylamine, and aniline. The metabolites from aniline include the following oxidative metabolites: o-, m-, and p-aminophenol, nitrocatechols, and aniline. For all metabolites, involvement in phase II reactions is likely, and the formation and appearance of sulfated or glucuronidated conjugates has been demonstrated
The processes driving the metabolism of nitrobenzene in mammals display tissue specificity. Three primary mechanisms have been identified: reduction to aniline by intestinal microflora, reduction by hepatic microsomes and in erythrocytes, and oxidative metabolism by hepatic microsomes. First, nitrobenzene has been shown to undergo a three-step, two-electronsper-step transfer reduction to aniline in intestinal microflora. The intermediates in this process are nitrosobenzene and phenylhydroxylamine. Second, nitrobenzene undergoes a six-step, one-electron-per-step transfer reduction to aniline that takes place in hepatic microsomes and erythrocytes ... intermediates in the latter process include a nitro anion free radical, nitrosobenzene, an hydronitroxide free radical, phenylhydroxylamine, and a theoretical amino-cation free radical. The reductive intermediates have been shown to reverse chemically (ie, aniline can oxidize back towards nitrobenzene or any step in between), with the direction of flow depending on local redox potentials. .
The appearance of conjugated derivatives of nitrophenols in the urine of female giant chinchilla rabbits having received an oral dose of nitrobenzene (0.5 g in 25 mL water by stomach tube) implied that the compound can undergo oxidation reactions in addition to the more extensively characterized reduction reactions.
The action of bacteria normally present in the small intestine of the rat is an important element in the formation of methemoglobin resulting from nitrobenzene exposure. Germ-free rats do not develop methemoglobinemia when intraperitoneally dosed with nitrobenzene ... When nitrobenzene (200 mg/kg bw in sesame oil) was intraperitoneally administered to normal Sprague-Dawley rats, 30-40% of the hemoglobin in the blood was converted to methemoglobin within 1-2 hr. When the same dose was administered to germ-free or antibiotic-pretreated rats, there was no measurable methemoglobin formation, even when measured up to 7 hr after treatment. The nitroreductase activities of various tissues (liver, kidney, gut wall) were not significantly different in germ-free and control rats, but the activity was negligible in gut contents from germ-free rats and high in control rats. This led the authors to suggest that a nitrobenzene metabolite such as aniline (which is formed by the bacterial reduction of nitrobenzene in the intestines of rats) is involved in methemoglobin formation. In addition, diet has been shown to play a role in the production of methemoglobin by influencing the intestinal microflora; the presence of pectin in the diets of rats was shown to increase the ability of orally administered nitrobenzene to induce methemoglobinemia. This was correlated with the increased in vitro reductive metabolism of (14C)nitrobenzene by the cecal contents of rats fed purified diets containing increasing amounts of pectin.
IDENTIFICATION: Nitrobenzene is a colorless to pale yellow oily liquid with an odor similar to bitter almonds or shoe polish. It is soluble in water and it represents a fire hazard. Nitrobenzene is a synthetic chemical. It does not occur naturally. Its main use is in the synthesis of aniline and is used as a chemical intermediate to produce polyurethane. It is used as a solvent during petroleum refining and in the manufacture of cellulose ethers and acetates. It is used to produce dinitrobenzenes, dichloroanilines and in the synthesis of other compounds including acetominophen. HUMAN EXPOSURE: Nitrobenzene can be inhaled or by skin penetration. Nitrobenzene has been detected in ambient air and water and in finished water supplies. Nitrobenzene is found in fish. Occupational exposure occurs in petroleum plants and other facilities that produce nitrobenzene. The spleen is the target organ in humans occupationally exposed to this chemical. The spleen in tender and enlarged. Liver effects including hepatic enlargement and tenderness and altered serum chemistries have been reported in a woman exposed to nitrobenzene by inhalation. Headache, confusion, vertigo and nausea were reported. Orally exposed persons have included symptoms of apnea and coma. ANIMAL/PLANT/BACTERIAL STUDIES: Nitrobenzene causes toxicity in multiple organs by all routes of exposure, This solvent causes methemoglobinemia based on all routes of administration. All exposure routes are associated with hemolytic anemia, splenic conjestion, liver, bone marrow and spleen hematopoiesis. In rats, nitrobenzene caused splenic capsular lesions via gavage or dermal application. Effects on the liver were noted in rats and mice after both gavage and dermal application of nitrobenzene with centrilobular hepatocyte necrosis, hepatocellular nucleolar enlargement, severe hydroscopic degeneration and pigment accumulation in Kupfer cells. Incleased vacuolation of the X zone of the adrenal gland was noted in female mice after oral administration and dermal dosing. In subchronic oral and dermal studies in rats and mice, central nervous system lesions in the cerebellum and brainstem was life threatening. These lesions included petechial hemorrhages and hepatic toxicity. Dose dependent neurological effects included ataxia, head tilt, arching, loss of righting reflex, tremors, coma and consulsions were noted. Other target organs included kidney (increased kidney weight, glomerular and tubular epithelial swelling, pigmentation of tubular epithelial cells), nasal epithellium (glandularization of respiratory epithelium, pigment disposition and degeneration of olfactory epithellium), thyroid (follicular cell hyperplasia), thymus (involution) and pancreas (mononuclear cell infiltration) while lung pathology (emphysema, atelectasis and bronchiolization of alveolar celll walls) was reported in rabbits. In an inhalation study using male and female B6C3F1 mice and male and female Fischer 344 rats and male Sprague Dawley rats, survival was not adversely affected at the concentrations tested for mice; but nitrobenzene was toxic and carcinogenic in both species and both rat strains including a spectrum of benign and malignant (lung, thyroid, mammary gland, liver and kidney) neoplasms. Nitrobenzene was not genotoxic in bacteria and mammalian ceells in vitro and mammalian cells in vivo. Studies reported DNA damage in repair assays, genetic mutation assays, chromosomal effects assays and cell transformation assays. Nitrobenzene was a testicular toxicant. Nitrobenzene appears to be toxic to bacteria and may adversely affect sewage facilities. The toxicity of nitrobenzene to fresh water invertebrates, Daphnia, marine invertebrates and fish indicate high acute toxicity.[
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
癌症分类：D组 不可归入人类致癌性类别
Cancer Classification: Group D Not Classifiable as to Human Carcinogenicity
Under the Guidelines for Carcinogen Risk Assessment (U.S. EPA, 2005), nitrobenzene is classified as "likely to be carcinogenic to humans" by any route of exposure. While there are no human carcinogenicity data on nitrobenzene, the cancer characterization is based on evidence of the compound's tumorigenicity in a single well-conducted study in two animal species.
CLASSIFICATION: D; not classifiable as to human carcinogenicity. BASIS FOR CLASSIFICATION: Based on no data concerning carcinogenicity in humans or animals. HUMAN CARCINOGENICITY DATA: None. ANIMAL CARCINOGENICITY DATA: None. /Based on former classification system/
Classification of carcinogenicity: 1) evidence in humans: inadequate; 2) evidence in animals: sufficient. Overall summary evaluation of carcinogenic risk to humans is Group 2B: The agent is possibly carcinogenic to humans.
Extensive intestinal absorption of nitrobenzene has been demonstrated in experimental animals. For example, a total of six rabbits (sex and strain not stated) were administered (14C)nitrobenzene and unlabeled nitrobenzene at total doses of 200 mg/kg (two animals) and 250 mg/kg (three animals) by stomach tube. One animal was exposed to 400 mg/kg; however, it died after 2 days. Animals were kept in metabolic cages for 30 hours after dosing to permit the collection of feces, urine, and expired air. Exhaled derivatives were trapped in ethanol and/or CO2 absorbers. Thereafter, the animals were housed in open cages so that their urine and feces could be collected up to 10 days. By 4-5 days after dosing animals, the author found that nearly 70% of the radioactivity had been eliminated from the body. This included 1% of the radioactivity expired as CO2, 0.6% expired as nitrobenzene (up to 30 hours), 58% excreted as metabolites in the urine (up to 4-5 days), and 9% eliminated in the feces (up to 4-5 days).
Single oral doses of 22.5 or 225 mg/kg (14C)-labeled nitrobenzene were administered to male F344 (CDF[F344]/CrlBR), CD (Crl:CD[SD]BR), and axenic CDF(F344)/CrlGN rats and to male B6C3F1 (B6C3F1/Crl/BR) mice (225 mg/kg only). Animals were housed in metabolic cages for 72 hours after dosing to collect urine, feces, and expired air. In the conventional rats, 56-65% of the administered dose was recovered in the urine, with a maximum of 21.4% recovered in the feces. Six metabolites were found in the bile of conventional rats. Since the metabolites were absent from the bile of axenic rats, the authors concluded that the reduction of nitrobenzene at the nitro group that produced metabolites in conventional rats must have been initiated in the intestines. When corrected for overall recovery, these data provide intestinal absorption estimates of 62-69% in conventional rats. The estimate from the mouse data was lower (43%).
Data from a number of sources point to the capacity of nitrobenzene to penetrate the dermal barrier in humans. For example, human research subjects were placed in an exposure chamber containing nitrobenzene vapor for 6 hours, while receiving fresh air through a breathing tube and mask . The absorption rate per unit of concentration of nitrobenzene was highly variable (0.23 to 0.30 mg/hour per ug/L), depending on the nitrobenzene concentration in the chamber (5 to 30 ug/L) and whether the subject was dressed or naked. In naked subjects exposed to a chamber concentration of 10 ug/L nitrobenzene, the absorbed dose ranged from 10 to 19 mg compared with 8 to 16 mg in clothed subjects. Depending on the air concentration (5 to 30 ug/L), normal working clothes reduced the overall absorption of nitrobenzene by 20 to 30%.
(14C)-labeled /nitrobenzene/ in acetone (4 ug/sq cm) /was applied/ to a 13 sq cm circular area of the ventral forearm surface of six subjects. The skin site was not protected and the subjects were asked not to wash the area for 24 hours. The authors also examined the elimination of nitrobenzene following intravenous administration as a comparison with the dermal absorption and elimination studies. For the skin absorption studies, the cumulative amounts of radiolabel measured in urine over 5 days amounted to approximately 1.53 + or - 0.84% of the load. The highest rate of absorption was monitored in the first 24-hour period after application, but excretion in the urine was still measurable between 96 and 120 hours after application. The absorption rate (percent dose per hour) over the 120-hour period was as follows: 0.022%/hour: 0 to 12 hours; 0.022%/hour: 12 to 24 hours; 0.013%/hour: 24 to 48 hours; 0.013%/hour: 48 to 72 hours; 0.011%/hour: 72 to 96 hours; and 0.006%/hour: 96 to 120 hours. Continued excretion of (14C)-label at the later time points may have represented redistribution of nitrobenzene or its metabolites from adipose tissue rather than continued absorption. Following intravenous administration of (14C)-nitrobenzene, 60.5% of the radioactive label was detected in the urine by 20 hours after administration. When corrected for the appearance of nitrobenzene in urine following an intravenous injection, an overall dermal absorption factor of approximately 2.6% was determined for nitrobenzene.
Novel processes for the preparation of adenosine compounds and intermediates thereto
申请人：——
公开号：US20030069423A1
公开（公告）日：2003-04-10
Novel processes for the preparation of adenosine compounds and intermediates thereto. The adenosine compounds prepared by the present processes may be useful as cardiovascular agents, more particularly as antihypertensive and anti-ischemic agents, as cardioprotective agents which ameliorate ischemic injury or myocardial infarct size consequent to myocardial ischemia, and as an antilipolytic agents which reduce plasma lipid levels, serum triglyceride levels, and plasma cholesterol levels. The present processes may offer improved yields, purity, ease of preparation and/or isolation of intermediates and final product, and more industrially useful reaction conditions and workability.
Cell adhesion-inhibiting antiinflammatory and immune-suppressive compounds
申请人：Abbott Laboratories
公开号：US20040116518A1
公开（公告）日：2004-06-17
The present invention relates to novel cinnamide compounds that are useful for treating inflammatory and immune diseases and cerebral vasospasm, to pharmaceutical compositions containing these compounds, and to methods of inhibiting inflammation or suppressing immune response in a mammal.
Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
申请人：Vertex Pharmaceuticals Incorporated
公开号：US20150231142A1
公开（公告）日：2015-08-20
The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
[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.
[EN] THIENOPYRIDONE DERIVATIVES AS AMP-ACTIVATED PROTEIN KINASE (AMPK) ACTIVATORS<br/>[FR] DÉRIVÉS DE THÉNOPYRIDONE COMME ACTIVATEURS DE LA PROTÉINE KINASE DÉPENDANTE DE L'AMP (AMPK)
申请人：MERCK PATENT GMBH
公开号：WO2009124636A1
公开（公告）日：2009-10-15
The present invention relates to compounds of formula (I) wherein R1, R2 and R3 are as defined in claim 1, including pharmaceutical compositions thereof and for their use in the treatment and/or prevention of diseases and disorders modulated by AMP agonists. The invention is also directed to intermediates and to a method of preparation of compounds of formula (I).
