NIOSH REL: TWA 1 ppm, 15-min C 1 ppm, IDLH 85 ppm; OSHA
PEL: TWA 2 ppm, 15-min C 10 ppm; ACGIH TLV: TWA 2 ppm.
LogP：
0.017 at 21℃
物理描述：
Acrylonitrile, stabilized appears as a clear colorless liquid with a strong pungent odor. Flash point 32°F. Prolonged exposure to the vapors or skin contact harmful. Density 6.7 lb / gal. Vapors heavier than air. Combustion produces toxic oxides of nitrogen. Requires storage and handling in closed systems. Used in insecticides and to make plastics, fibers and other chemicals. Rate of onset: Immediate Persistence: Minutes to hours Odor threshold: 17 ppm Source/use/other hazard: Plastics, coatings, adhesives industries; dyes; pharmaceuticals; flam gas.
颜色/状态：
Clear, colorless liquid at room temperature
气味：
Practically odorless, or with a very slight odor of peach kernels
PYROLYSIS OF ORLON @ 600 °C IN NITROGEN ATMOSPHERE GIVES RELATIVELY LARGE AMT OF HYDROGEN CYANIDE, AMMONIA, HYDROGEN, & METHANE ... .
粘度：
0.34 sq mm/s at 25 °C
腐蚀性：
Attacks copper and copper alloys ... attacks aluminum in high concentration
燃烧热：
1761.8 kJ/mol at 25 °C (liquid)
汽化热：
32.6 kJ/mol at 25 °C
表面张力：
27.76 dyn/cm at 15.1 °C; 27.54 mN/m at 17.8 °C
电离电位：
10.91 eV
聚合：
Hazardous polymerization may occur. Polymerization may be caused by elevated temperature or alkalies. Uninhibited monomer vapor may form polymer in vents and other confined spaces.
气味阈值：
Detection of acrylonitrile in water is 1.86x10+1 ppm; chemically pure
The metabolism of acrylonitrile to the epoxide, 2-cyanoethylene oxide (ANO) was examined in rat liver microsomes, lung microsomes, and isolated enriched lung cell preparations. GC/high resolution MS was used to quantitate ANO in microsomal and cellular extracts by monitoring the fragment ion C2H3N (m/z 41.0265). The limit of detection was 0.05 pmol of ANO/0.5 microliter of standard solution, microsomal extract, or cellular extract injected onto the column, and the linear range of analysis was 0.05 to 12.5 pmol of ANO. Kinetic parameters of Vmax, V/K, and Km were calculated for microsomal ANO formation. Liver microsomes were quantitatively more active than lung microsomes on a mg of protein basis. The Vmax (pmol of ANO formed/min/mg of protein) was 666.61 for liver and 45.07 for lung microsomes. The V/K (pmol of ANO/min/mg of protein/microM) was 12.83 for liver and 0.02 for lung microsomes. The apparent Km was 51.93 uM and 1853.83 uM for liver and lung microsomes, respectively. When calculated as nmol of ANO formed/min/nmol of microsomal P-450, the Vmax for lung was equivalent to the Vmax for liver. ANO formation in the rat lung was cell specific. The rates of metabolism in the Clara cell-enriched fraction, the alveolar type II cell-enriched fraction, and the cell suspension were 2.55, 0.38, and 0.67 pmol of ANO formed/min/mg of protein, respectively. No metabolism was observed in the endothelial (small) cell-enriched fraction or in the alveolar macrophages. The results suggest that the lung contributes to the metabolism and disposition of inhaled acrylonitrile.
... Acrylonitrile was administered by gavage at 0, 2.5, 10, or 20 mg/kg/day, 5 days per week, for 2 years. Urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine were measured as markers of exposure to acrylonitrile. In general, there were dose-related increases in urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine concentrations in all dosed groups of mice and at all time points. ...
Acrylonitrile is metabolized to cyanide. Interestingly, the overall amount of acrylonitrile metabolism is substantially less in humans than in rodents, and the amount of cyanide produced as a result is greater in rodents than humans.
In liver fractions from Sprague-Dawley rats, the metabolism of acrylonitrile (VCN) to cyanide (CN-) was localized the microsomal fraction and required NADPH and O2 for maximal activity. The biotransformation of VCN to CN- was characterized with respect to time, microsomal protein concentration, pH, and temperature. Metabolism of VCN was increased in microsomes obtained from phenobarbital-, Aroclor 1254-, or 3-methylcholanthrene-treated rats (479%, 414%, and 142% of control, respectively) and decreased with CoCl2 treatment (54% of control). The KM estimated for VCN with the phenobarbital (54.8 +/- 9.5 mM) or Aroclor 1254 (40.9 +/- 4.1 mM) preparation was lower than the control (190.7 +/- 19.7 mM). Addition of SKF 525-A or CO to incubation mixtures inhibited VCN metabolism. Addition of the epoxide hydratase inhibitor, 1,1,1-trichloropropane 2,3-oxide, decreased the formation of CN- from VCN. Addition of glutathione, cysteine, D-penicillamine, or 2-mercaptoethanol enhanced the release of CN- from VCN. These findings indicate that VCN is metabolized to CN- via a cytochrome P-450-dependent mixed-function oxidase system.
来源:Hazardous Substances Data Bank (HSDB)
代谢
丙烯腈已知的人类代谢物包括环氧化丙烯腈。
Acrylonitrile has known human metabolites that include Cyanoethylene oxide.
IDENTIFICATION AND USE: Acrylonitrile is a clear, colorless liquid at room temperature. Acrylonitrile is used as a monomer for acrylic and modacrylic fibers and whiskers, in copolymers with styrene and butadiene (ABS resins), in the manufacture of adiponitrile, and in nitrile rubbers. Acrylonitrile is no longer used as a fumigant and nitrile resins made with acrylonitrile are no longer used to make beverage bottles. HUMAN STUDIES: Dermal exposure to acrylonitrile causes irritation, burns, and blisters. Additionally, dermal exposure to acrylonitrile can lead to systemic toxicity and lethality. Chronic effects can also occur after exposure to acrylonitrile vapors or liquid. 576 Japanese workers exposed to 5-20 ppm acrylonitrile over 10 yr showed headache, fatigue, nausea, and weakness with symptoms of anemia, jaundice, conjunctivitis, and abnormal whole blood and serum specific gravity, cholinesterase, urobilinogen, bilirubin, urinary protein, and sugar values, indicative of liver injury and a general toxic effect. In cultured human bronchial epithelial cells acrylonitrile induced cytotoxicity, sister chromatid exchanges and DNA single strand breaks. Acrylonitrile affected semen quality among exposed workers. Acrylonitrile or its metabolites could induce reproductive defects as an in vivo multipotent genotoxic agent by inducing DNA strand breakage and sex chromosome non-disjunction in spermatogenesis. Exposure to acrylonitrile in pregnant workers caused increasing risk of preterm delivery and birth defects. ANIMAL STUDIES: After a single oral dose of 46.5 mg/kg bw acrylonitrile, moderate to marked hyperplasia of the Clara cells lining the bronchioles was observed in male rats. A 10% aqueous solution administered to the eyes of a rabbit caused a trace of pain and slight conjunctival irritation immediately following contact. There was no corneal injury at any time. The conjunctiva was completely normal within 24 hours. Intraperitoneal injection of 50 mg/kg bw acrylonitrile daily for three weeks to adult rats resulted in loss of body weight, leukocytosis, functional disturbances in the liver and kidneys, slight damage to the neuronal cells of the brain stem and cortex and parenchymal degeneration of the liver and kidneys. A single intravenous dose of 150 mg/kg bw (15 mg/animal) acrylonitrile administered to rats produced bilateral adrenocortical hemorrhage and necrosis. Acrylonitrile was administered in the drinking water to rats for 2 yr at dose levels of 35, 100, and 300 ppm. A statistically significant incidence of tumors was observed in the brain (astrocytomas), ear canal (Zymbal gland), stomach (nonglandular portion), mammary gland (females only), tongue, pituitary gland, pancreas (males only), and uterus. Rats exposed by inhalation to 40 or 80 ppm of acrylonitrile had no statistically significant changes in reproductive success or fetal development. Only the pups of rats administered acrylonitrile per os (65 mg/kg) for days 6 to 15 of gestation had an increase in malformations. At the high dose level there was a significant increase in acaudate or short-tailed fetuses. The majority of other abnormalities including short trunk, anteriorly displaced ovaries, missing ribs, and imperforate anus were observed in the acaudate and short-tailed fetuses whether these animals were from the control or experimental group. The only anomaly that occurred solely in treated animals was a right-sided aortic arch, which appeared in one fetus from the 25 mg/kg/day group and one fetus from the 65 mg/kg/day group. Acrylonitrile, in aqueous or gas phases, induced reverse mutations in Salmonella typhimurium TA1530, TA1535, TA1950, TA100, TA1538, TA98 and TA1978 in the presence of metabolic activation.
Organic nitriles decompose into cyanide ions both in vivo and in vitro. Consequently the primary mechanism of toxicity for organic nitriles is their production of toxic cyanide ions or hydrogen cyanide. Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin. (L97)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌性证据
丙烯腈基于在实验动物研究中充分的致癌性证据，合理预期为人类致癌物。
Acrylonitrile is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
癌症分类：B1组可能的人类致癌物
Cancer Classification: Group B1 Probable Human Carcinogen
CLASSIFICATION: B1; probable human carcinogen. BASIS FOR CLASSIFICATION: The observation of a statistically statistically significant increase in the incidence of lung cancer in exposed workers and observation of tumors, generally astrocytomas in the brain, in studies in two rat strains exposed by various routes (drinking water, gavage, and inhalation) forms the basis for this classification.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
丙烯腈可以通过呼吸道、消化道和完好无损的皮肤轻易被吸收。
Acrylonitrile is readily absorbed from the respiratory and gastrointestinal tracts and through the intact skin.
Fat tissue accumulation of acrylonitrile may also occur. While the high solubility of acrylonitrile in water (7.35 percent at 20 °C) would permit the excretion of the unchanged compound in the urine, the urinary detection 72 hours after exposure in the rabbit strongly suggests either fat storage or reversible protein binding.
After intravenous injection of a lethal dose of acrylonitrile (75 mg/kg bw) in rabbits, the hydrogen cyanide concentration in the blood rose steadily until the death of the animals; the thiocyanate concentration in the blood increased slightly during this period. After a single intravenous injection of 15 mg/kg bw, about 3% of the dose was expired for about 1 hr, and approximately 10% of the total dose was gradually excreted in the urine for more than 48 hr after its injection. The total amount of thiocyanate (formed from hydrogen cyanide) excreted in the urine over 24 hr after the injection of acrylonitrite was equivalent to about 14% of the dose.
In guinea pigs, elimination of acrylonitrile in urine was demonstrated within 24 hr and 30 hr after oral and sc admin, respectively. ... In rats given doses of 26-40 mg/kg body wt, elimination of thiocyanate in urine was over 20% of dose after oral admin, 2-5% after ip or sc injection and 1% after iv admin. Greater amt of acrylonitrile is transformed into thiocyanate after oral than after ip admin in hamsters and mice.
Nickel(II) N‐Heterocyclic Carbene Complexes: Versatile Catalysts for C–C, C–S and C–N Coupling Reactions
作者：Lourdes Benítez Junquera、Francys E. Fernández、M. Carmen Puerta、Pedro Valerga
DOI：10.1002/ejic.201700057
日期：2017.5.18
A variety of Ni(II) complexes with a wide range of electronic and steric properties, bearing picolyl-imidazolidene ligands (a-g) and Cp (2a-f) or Cp* (3a,c,g) groups, have been synthesised and characterised using NMR and single crystal X-ray crystallography. The complexes have been used as precatalysts for a wide range of catalytic transformations most likely involving a Ni0/NiII catalytic cycle. In
demonstrated efficacy in rheumatoid arthritis, inflammatory bowel disease, and psoriasis with the approval of several drugs. Aiming to develop potent JAK1/2 inhibitors, two series of triazolo [1,5-a] pyridine derivatives were designed and synthesized by various strategies. The pharmacological results identified the optimized compounds J-4 and J-6, which exerted high potency against JAK1/2, and selectivity
[EN] INHIBITORS OF BRUTON'S TYROSINE KINASE<br/>[FR] INHIBITEURS DE TYROSINE KINASE DE BRUTON
申请人：BIOCAD JOINT STOCK CO
公开号：WO2018092047A1
公开（公告）日：2018-05-24
The present invention relates to a new compound of formula I: or pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: V1 is C or N, V2 is C(R2) or N, whereby if V1 is C then V2 is N, if V1 is C then V2 is C(R2), or if V1 is N then V2 is C(R2); each n, k is independently 0, 1; each R2, R11 is independently H, D, Hal, CN, NR'R", C(O)NR'R", C1-C6 alkoxy; R3 is H, D, hydroxy, C(O)C1-C6 alkyl, C(O)C2-C6 alkenyl, C(O)C2-C6 alkynyl, C1-C6 alkyl; R4 is H, Hal, CN, CONR'R", hydroxy, C1-C6 alkyl, C1-C6 alkoxy; L is CH2, NH, O or chemical bond; R1 is selected from the group of the fragments, comprising: Fragment 1, Fragment 2, Fragment 3 each A1, A2, A3, A4 is independently CH, N, CHal; each A5, A6, A7, A8, A9 is independently C, CH or N; R5 is H, CN, Hal, CONR'R", C1-C6 alkyl, non-substituted or substituted by one or more halogens; each R' and R" is independently selected from the group, comprising H, C1-C6 alkyl, C1-C6 cycloalkyl, aryl; R6 is selected from the group: [formula II] each R7, R8, R9, R10 is independently vinyl, methylacetylenyl; Hal is CI, Br, I, F, which have properties of inhibitor of Bruton's tyrosine kinase (Btk), to pharmaceutical compositions containing such compounds, and their use as pharmaceuticals for treatment of diseases and disorder.
Synthesis and biological activity of substituted 2,4-diaminopyrimidines that inhibit Bacillus anthracis
作者：Baskar Nammalwar、Richard A. Bunce、K. Darrell Berlin、Christina R. Bourne、Philip C. Bourne、Esther W. Barrow、William W. Barrow
DOI：10.1016/j.ejmech.2012.05.018
日期：2012.8
the lowest MICs with values of 0.5 μg/mL and 0.375–1.5 μg/mL, respectively. It is likely that the S isomers of 1 will bind the substrate-binding pocket of dihydrofolate reductase (DHFR) as in B. anthracis was found for (S)-1a. The final step in the convergent synthesis of target systems 1 from (±)-1-(1-substituted-2(1H)-phthalazinyl)-2-propen-1-ones 6 with 2,4-diamino-5-(5-iodo-3,4-dimethoxybenzyl)pyrimidine
制备了一系列取代的 2,4-二氨基嘧啶1 ，并使用先前报道的 (±)-3-5-[(2,4-二氨基-5-嘧啶基)甲基]-2,3 评估了其抗炭疽杆菌的活性-二甲氧基苯基}-1-(1-丙基-2( 1H )-酞嗪基)-2-丙烯-1-酮( 1a )，最低抑菌浓度(MIC)值为1-3μg/mL，作为标准。在目前的工作中，相应的异丁烯基 ( 1e ) 和苯基 ( 1h ) 衍生物在最低 MIC 方面表现出最显着的活性，分别为 0.5 μg/mL 和 0.375–1.5 μg/mL。 1的S异构体很可能会结合二氢叶酸还原酶 (DHFR) 的底物结合袋，就像在炭疽芽孢杆菌中发现的 ( S ) -1a一样。由 (±)-1-(1-取代-2(1 H )-酞嗪基)-2-丙烯-1-酮6与 2,4-二氨基-5-( 收敛合成目标系统1的最后一步5-碘-3,4-二甲氧基苯甲基)嘧啶( 13 )是在密封管条件下通过新型Heck偶联反应完成的。
Melanocortin-4 receptor binding compounds and methods of use thereof
申请人：Millennium Pharmaceuticals, Inc.
公开号：US20040082779A1
公开（公告）日：2004-04-29
Provided are MC4-R binding compounds of the formula XVII:
1
wherein L
2
is a linker group, and P
1
, P
2
, P
3
, P
4
, Z
1
, Z
2
, Z
3
, Z
4
, Z
5
, t, s, and R are as described in the specification. Methods of using the compounds to treat MC4-R associated disorders, such as disorders associated with weight loss, are also provided.
