丙烯酸 | 59913-86-9

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物 - 无环羧酸
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 丙烯酸
• 中文别名: 丙烯酸（HPAA）；败脂酸；乙烯基甲酸；2-丙烯酸；败酯酸；AA
• 英文名称: acrylic acid
• 英文别名: 2-propenoic acid；prop-2-enoic acid；propenoic acid；Hydron;prop-2-enoate
• CAS: 59913-86-9；79-10-7
• 化学式: C₃H₄O₂
• mdl: MFCD00004367
• 分子量: 72.0636
• InChiKey: NIXOWILDQLNWCW-UHFFFAOYSA-N

物化性质

• 熔点：
  13 °C (lit.)
• 沸点：
  139 °C (lit.)
• 密度：
  1.051 g/mL at 25 °C (lit.)
• 蒸气密度：
  2.5 (vs air)
• 闪点：
  130 °F
• 溶解度：
  1000克/升
• 最大波长(λmax)：
  231nm(lit.)
• 暴露限值：
  TLV-TWA 10 ppm (30 mg/m3) (ACGIH).
• LogP：
  0.46 at 25℃
• 物理描述：
  Liquid
• 颜色/状态：
  Acrid liquid
• 气味：
  Acrid odor and fumes
• 蒸汽密度：
  2.5 (NTP, 1992) (Relative to Air)
• 蒸汽压力：
  3.97 mm Hg at 25 °C
• 亨利常数：
  Henry's Law constant = 3.7X10-7 atm-cu m/mol at 25 °C (est)
• 稳定性/保质期：
  Stable under recommended storage conditions. Contains the following stabilizer(s): Mequinol (>/=0.018 - </=0.02%)
• 自燃温度：
  395 °C
• 分解：
  Acrylic acid rapidly decomposes in the atmosphere by photochemical attack on the double bond.
• 腐蚀性：
  Corrosive to metals
• 燃烧热：
  -1368.4 kJ/mole
• 汽化热：
  10,955.1 gcal/gmole
• 表面张力：
  28.1 dynes/cm at 30 °C
• 聚合：
  May undergo exothermic polymerization at room temperature.
• 气味阈值：
  Odor Threshold Low: 0.09 [mmHg]; Odor Threshold High: 1.0 [mmHg]; Detection odor threshold from AIHA (mean = 0.092 ppm)
• 折光率：
  Index of refraction: 1.4224 at 20 °C/D
• 解离常数：
  4.26 (at 25 °C)
• 保留指数：
  1659.7 ;1638.8 ;1625.7

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  5
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

丙烯酸通过氧化途径迅速代谢成二氧化碳。丙烯酸的主要代谢途径似乎是一种次要的、非维生素B12依赖的丙酸代谢途径，包括与脂肪酸β-氧化类似的反应。在尿液中可以检测到比丙烯酸极性更高的、特性不明的物质。尿液中未检测到未代谢的丙烯酸，但发现了少量的3-羟基丙酸。没有检测到环氧化中间体。在体外（胃组织）和体内，丙烯酸与谷胱甘肽和非蛋白巯基的亲和力非常低。导致组织损伤的高剂量丙烯酸会引起少量巯基尿酸衍生物的形成。

Acrylic acid is rapidly metabolized by oxidative pathways to CO2. The main metabolic pathway of acrylic acid seems to be a secondary, non-vitamin-B12 dependent pathway of propionic acid metabolism consisting in reactions similar to fatty acid beta-oxidation. In urine poorly characterized substances of a higher polarity than those of acrylic acid are detected. Unmetabolized acrylic acid could not be detected in urine, however small amounts of 3-hydroxypropionic acid were found. Epoxide intermediates were not detected. In vitro (stomach tissue) and in vivo acrylic acid reacts with glutathione and non-protein sulfhydryls to a very low extent. High dosages of acrylic acid leading to tissue damage cause the formation of small amounts of mercapturic acid derivates.

来源:Hazardous Substances Data Bank (HSDB)

代谢

口服给予大鼠4、40或400 mg/kg bw [2,3-(14)C]-丙烯酸（溶于0.5%的水性甲基纤维素溶液中），在72小时内，44-65%的放射性通过呼出的空气被消除，2.9-4.3%的放射性残留在尿液中。大鼠尿液中代谢物的HPLC图谱显示有两种主要代谢物。其中一个主要代谢物是3-羟基丙酸。在保留时间对应于2,3-环氧丙酸或N-乙酰-S-(2-羧基-2-羟基乙基)胱氨酸的地方没有检测到放射性。在大鼠口服丙烯酸（4、40、400或1,000 mg/kg）后1小时，据报道，在4 mg/kg以上的剂量下，腺胃中的非蛋白巯基（NPSH）显著减少。在1,000 mg/kg的剂量下，前胃中的NPSH减少。丙烯酸对血液或肝脏中的NPSH没有显著影响。

After oral administration of 4, 40, or 400 mg/kg bw [2,3-(14)C]-acrylic acid in a 0.5% aqueous methylcellulose solution to rats, within 72 hr 44-65% of the radioactivity had been eliminated via expired air and 2.9-4.3% remained in the urine. The HPLC profile of metabolites observed in the urine of rats indicated two major metabolites. One of the major metabolites co-eluted was 3-hydroxypropionic acid. Radioactivity could not be detected at the retention times corresponding to that of 2,3-epoxypropionic acid or N-acetyl-S-(2-carboxy-2-hydroxyethyl)cysteine. One hour following an oral dose of acrylic acid (4, 40, 400, or 1,000 mg/kg) in rats a significant depletion of /Non-protein sulfhydryls/ (NPSH) in the glandular stomach was reported at doses above 4 mg/kg. In the forestomach NPSH depletion occurred at a dose of 1,000 mg/kg. No significant effect of acrylic acid on NPSH in the blood or liver was observed

来源:Hazardous Substances Data Bank (HSDB)

代谢

丙烯酸和丙酸代谢物通过给大鼠单次灌胃单一剂量（400 mg/kg bw）后，使用（13）C-NMR分析尿液进行比较。确定了3-羟基丙酸、N-乙酰-S-(2-羧基乙基)半胱氨酸和N-乙酰-S-(2-羧基乙基)半胱氨酸-S-氧化物作为丙烯酸的代谢物。没有检测到未改变的丙烯酸。相比之下，丙酸处理的大鼠尿液的谱图只显示了一些归因于甲基丙二酸的小的（13）C富集信号。这些代谢物（CO2和甲基丙二酸）与哺乳动物丙酸代谢的已知主要维生素B12依赖途径一致。一个替代途径涉及β-氧化。丙烯酰辅酶A形成3-羟基丙酸，然后可以被氧化成丙二半醛。进一步的分解产生乙酰辅酶A和CO2。可以想象，在这种实验中使用的高剂量导致了对巯基尿酸的排泄和检测。

... The metabolites of acrylic acid and propionic acid /were compared/ using (13)C-NMR analysis of the urine of rats after gavage of single doses (400 mg/kg bw). 3-Hydroxypropionic acid, N-acetyl-S-(2-carboxyethyl)cysteine and N-acetyl-S-(2-carboxyethyl)cysteine-S-oxide were identified as metabolites of acrylic acid. No unchanged acrylic acid was detected. In contrast, the spectra of urine from a propionic acid-treated rat revealed only a few minor (13)C-enriched signals that were assigned to methylmalonic acid. These metabolites (CO2 and methylmalonic acid) are consistent with the known major vitamin B12-dependent pathway of propionate metabolism in mammals. An alternative pathway involves beta-oxidation. Acrylyl-CoA forms 3-hydroxypropionic acid that can then be oxidized to malonic semialdehyde. Further catabolism yields acetyl-CoA and CO2. It is conceivable that excretion and detection of the mercapturates are a consequence of the high dose used in this experiment.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠口服或皮肤给药后，对尿代谢物和组织进行了HPLC分析。一个主要极性代谢物无法被识别，占剂量的约2%至3%。还检测到了与3-羟基丙酸共同洗脱的代谢物。还检测到了少量其他代谢物。对口服给药的大鼠血浆和肝脏也进行了HPLC分析，以寻找丙烯酸和代谢物。给药后1小时，血浆中与3-羟基丙酸共同洗脱的代谢物占40毫克/千克体重剂量的约0.5%。在应用更高剂量后，在血浆中也检测到了这种代谢物。在1小时后的任何时间点，血浆或肝脏中均未检测到丙烯酸或其代谢物。在给药后的任何时间点，肾脏中均未检测到它们……在其他实验中，对按照类似给药方案口服给药的小鼠肝脏进行了HPLC分析，以寻找丙烯酸和代谢物。给药后1小时，检测到了几种比丙烯酸极性更高的代谢物，包括3-羟基丙酸，但在1小时后的时间点未检测到。在任何时间点，经皮肤给药后的小鼠肝脏中均未检测到丙烯酸。在大鼠皮肤给药后，尿液中检测到了一个与丙烯酸共同洗脱的峰，以及口服给药后发现的的主要代谢物。在40毫克/千克体重皮肤给药组的尿液中检测到了少量另一种代谢物，但在10毫克/千克体重给药后未检测到。

Following single doses (40 or 150 mg/kg) of [1-(14)C]-acrylic acid to rats urinary metabolites and tissues were analyzed by HPLC. A major polar metabolite which could not be identified accounted for approximately 2 to 3% of the dose. A metabolite that coeluted with 3-hydroxypropionic acid was also detected. Small amounts of several other metabolites were detected. Plasma and liver from orally dosed rats were also analyzed for acrylic acid and metabolites by HPLC. One hour after dosing, a metabolite in plasma that co-eluted with 3-hydroxypropionic acid accounted for about 0.5% of the dose after 40 mg/kg bw. This metabolite was also detected in plasma after application of the higher dose. Neither acrylic acid nor metabolites were detected in plasma or liver at times later than 1 hr. They were not detected in kidney at any time after administration ... In other experiments, livers from mice dosed by gavage following a similar dosing regime were analyzed for acrylic acid and metabolites by HPLC. Several metabolites of higher polarity than those of acrylic acid including 3-hydroxypropionic acid were detected 1 hr after administration, but not at times later than 1 hr. Acrylic acid was not detected in livers from mice at any time after cutaneous administration of 40 mg/kg bw. After cutaneous dosing in rats, a peak that coeluted with acrylic acid was detected in urine along with the major metabolite found after oral dosing. A trace amount of another metabolite was detected in urine from the 40 mg/kg bw cutaneous dose group but not after dosing 10 mg/kg bw.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：丙烯酸是一种挥发性的无色液体。它用于制造塑料、标志用模具粉、建筑单元、装饰徽章和标志、涂料应用的聚合物溶液、乳液聚合物、油漆配方、皮革加工和纸张涂层；也用于医学和牙科，用于牙托、人造牙齿和矫形水泥。商业级的冰丙烯酸含有聚合物形成抑制剂对甲氧基苯酚（200 ppm）。人体研究：无论暴露途径如何，丙烯酸都能迅速被吸收和代谢。由于其代谢和消除迅速，丙烯酸的半衰期很短（几分钟），因此不具有生物累积的潜力。该物质对眼睛、皮肤和呼吸道具有腐蚀性，摄入后也会如此。吸入该物质可能导致肺水肿。肺水肿的症状通常在几小时后才会显现，并且会在身体努力时加重。动物研究：尽管已报告了广泛的LD50值，但大多数数据表明，丙烯酸通过口服途径具有低到中等急性毒性，通过吸入或皮肤途径具有中等急性毒性。丙烯酸对皮肤和眼睛具有腐蚀性或刺激性，对呼吸道有强烈刺激性。已报告皮肤致敏现象。现有的生殖研究表明，丙烯酸不具有致畸性，对生殖没有影响。体外遗传毒性测试已获得阳性和阴性结果。没有关于丙烯酸致癌性的实验数据。生态毒性研究：丙烯酸对细菌和土壤微生物的毒性较低。藻类是水生生物中最敏感的群体。丙烯酸会减少或消除接受饮食暴露的企鹅的细菌种群。

IDENTIFICATION AND USE: Acrylic acid is a volatile colorless liquid. It is used in the manufacture of plastics, molding powder for signs, construction units, decorative emblems and insignias, polymer solutions for coatings applications, emulsion polymers, paints formulations, leather finishing, and paper coatings; also used in medicine and dentistry for dental plates, artificial teeth, and orthopedic cement. Commercial glacial acrylic acid contains polymer formation inhibitor hydroquinone monomethyl ether (200 ppm). HUMAN STUDIES: Regardless of the route of exposure, acrylic acid is rapidly absorbed and metabolized. Owing to its rapid metabolism and elimination, the half-life of acrylic acid is short (minutes) and therefore it has no potential for bioaccumulation. The substance is corrosive to the eyes, skin and respiratory tract, and also upon ingestion. Inhalation of the substance may cause lung edema. The symptoms of lung edema often do not become manifest until a few hours have passed, and they are aggravated by physical effort. ANIMAL STUDIES: Although a wide range of LD50 values has been reported, most data indicate that acrylic acid is of low to moderate acute toxicity by the oral route and moderate acute toxicity by the inhalation or dermal route. Acrylic acid is corrosive or irritating to skin and eyes, and is a strong irritant to the respiratory tract. Skin sensitization have been reported. Available reproduction studies indicate that acrylic acid is not teratogenic and has no effect on reproduction. Both positive and negative results have been obtained in in vitro genotoxicity tests. No experimental data relevant to the carcinogenicity of acrylic acid were available. ECOTOXICITY STUDIES: The toxicity of acrylic acid to bacteria and soil microorganisms is low. Algae are the most sensitive group of aquatic organisms. Acrylic acid reduces or eliminates bacterial populations in penguins receiving dietary exposure.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：没有关于丙烯酸致癌性的相关流行病学数据。没有关于丙烯酸致癌性的相关实验数据。总体评估：丙烯酸的致癌性在人类中无法分类（第3组）。

Evaluation: No epidemiological data relevant to the carcinogenicity of acrylic acid were available. No experimental data relevant to the carcinogenicity of acrylic acid were available. Overall evaluation: Acrylic acid is not classifiable as to its carcinogenicity in humans (Group 3).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

A4；不可归类为人类致癌物。

A4; Not classifiable as a human carcinogen.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：丙烯酸

IARC Carcinogenic Agent:Acrylic acid

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：第3组：无法归类其对人类致癌性

IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

三只雄性Sprague-Dawley大鼠为一组，单次口服剂量为4、40或400 mg/kg的2,3-(14)C-丙烯酸或2、20或200 mg/kg的2,3-(14)C-丙烯酸乙酯，载体为0.5%水溶液甲基纤维素（每千克25微居里），体积为每千克10毫升……在给药后不同时间点收集尿液、粪便和呼出的二氧化碳，直至72小时后处死动物。丙烯酸和丙烯酸乙酯迅速消除，主要在呼出的二氧化碳中（占44%至65%）。大约35%至60%的丙烯酸和大约60%的丙烯酸乙酯在8小时内消除。丙烯酸乙酯的放射性代谢物在尿液中的排泄量更大。在72小时内，从给予4和400 mg/kg丙烯酸的动物中回收了90%至76%的放射性物质；19%至25%在组织中回收，大部分在脂肪组织中（占9%至15%）。对于丙烯酸乙酯，从给予2至200 mg/kg的剂量中回收了108%至73%的剂量；13%至10%在组织中找到，大部分通常在肌肉组织中（占5.6%至5%），28%至8%通过尿液排出。

Groups of three male Sprague-Dawley rats were given a single oral dose of 4, 40, or 400 mg/kg of 2,3-(14)C-acrylic acid or 2, 20, or 200 mg/kg 2,3-(14)C-ethyl acrylate in 0.5% aqueous methylcellulose (25 uCi/kg) at a volume of 10 mL/kg ... Urine, feces, and expired carbon dioxide were collected at various intervals up to 72 hours after dosing, and the animals were then killed. Acrylic acid and ethyl acrylate were eliminated rapidly, primarily in expired carbon dioxide (44% to 65%). 35% to 60% of the acrylic acid and approximately 60% of the ethyl acrylate was eliminated within 8 hours. Urinary excretion of radioactive metabolites was greater with ethyl acrylate. Within 72 hours, 90% to 76% of the radioactivity was recovered from the animals dosed with 4 and 400 mg/kg acrylic acid; 19% to 25% was recovered in the tissues, with most being found in adipose tissue, (9% to 15%). With ethyl acrylate, 108% to 73% of the dose was recovered with 2 to 200 mg/kg; 13% to 10% was found in the tissues, with the most generally being found in muscle tissue (5.6% to 5%), and 28% to 8% was excreted in the urine.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

三只雄性Sprague-Dawley大鼠在禁食后通过灌胃给予400 mg/kg的1,2,3-(13)C3-丙烯酸，并与2,3-(14)C-丙烯酸（40至46 uCi/kg）共同给药……收集72小时内的尿液、粪便和呼出气体，然后处死动物。总回收率为98%。大部分放射性物质，78%，在呼出的二氧化碳中回收。大约13%的放射性物质在组织中回收，其中近5%的剂量在肌肉中，3%在肝脏中，2%在皮肤中，1%在脂肪组织中。组织与血液的放射性浓度比分别为肝脏11.1、肾脏3.2、脂肪组织2.6、胃2.4、脾2.1和大肠2.0。大约6%的剂量通过尿液排出，1%通过粪便排出。核磁共振光谱未在尿液中检测到未改变的丙烯酸。

Three fasted male Sprague-Dawley rats were given 400 mg/kg 1,2,3-(13)C3-acrylic acid coadministered with 2,3-(14)C-acrylic acid (40 to 46 uCi/kg) in distilled water by gavage ... Urine, feces, and expired air were collected for 72 hours, and the animals were then killed. Total recovery was 98%. The majority of the radioactivity, 78%, was recovered in expired carbon dioxide. Approximately 13% of the radioactivity was recovered in the tissues, with almost 5% of the dose found in the muscle, 3% found in the liver, 2% found in the skin, and 1% found in adipose tissue. The tissue-to-blood radioactivity concentration ratios were 11.1, 3.2, 2.6, 2.4, 2.1, and 2.0 for the liver, kidneys, adipose tissue, stomach, spleen, and large intestine, respectively. Approximately 6% of the dose was eliminated in the urine and 1% was eliminated in the feces. Nuclear magnetic resonance spectroscopy did not detect unchanged acrylic acid in the urine.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

(14)C-丙烯酸的处置是通过使用雄性大鼠剪下的背部皮肤在体外确定的……向暴露的表皮表面（1.77平方厘米）涂抹了1%（体积/体积）的(14)C-丙烯酸，95微升，并在皮肤上安装了一个蒸发陷阱。在6小时内，剂量中有23.9% +/- 5.4%被吸收到流出物中或发现于皮肤中，至少有60%的剂量被蒸发。所施加剂量的总回收率大约为85%。

The disposition of (14)C-acrylic acid was determined in vitro using clipped dorsal skin from male rats ... One percent (v/v) (14)C-Acrylic Acid, 95 uL, was applied to the exposed epidermal surface (1.77 sq cm), and an evaporation trap was fitted over the skin. Over a 6-hour period, 23.9% +/- 5.4% of the dose was absorbed in the effluent or was found in the skin and at least 60% of the dose was evaporated. Total recovery of the applied dose was approximately 85%.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

丙烯酸在大鼠和小鼠口服或吸入给药后迅速吸收。构建了一个杂交的计算流体动力学和基于生理学的药代动力学吸入剂量的模型，用于在鼻腔嗅区进行丙烯酸组织剂量的种间（大鼠-人类）外推。模型模拟表明，在相似暴露条件下，人类嗅上皮暴露于丙烯酸的量比大鼠嗅上皮低2-3倍。经皮给药后，部分丙烯酸蒸发，其余的在这些动物体内迅速吸收。经皮吸收强烈依赖于载体和溶液的pH值。

Acrylic acid is rapidly absorbed in rats and mice after oral or inhalation administration. A hybrid computational fluid dynamics and physiologically-based pharmacokinetics inhalation dosimetry model was constructed for interspecies (rat-human) extrapolation of acrylic acid tissue dose in the olfactory region of the nasal cavity. The model simulations indicate that under similar exposure conditions human olfactory epithelium is exposed with acrylic acid to 2-3 fold lower than rat olfactory epithelium. After dermal administration some acrylic acid is evaporated, the remainder undergoes rapid absorption in these animals. Dermal absorption is strongly dependent on the vehicle and the pH value of the solution.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 职业暴露等级：
  B
• 职业暴露限值：
  TWA: 2 ppm (6 mg/m3) [skin]
• TSCA：
  Yes
• 危险等级：
  8

制备方法与用途

这篇文章主要介绍了丙烯酸的相关信息，包括其性质、用途、生产方法和安全储存运输注意事项。以下是文章的主要内容总结：

1. 性质：

   • 易燃液体。
   • 中等毒性物质。
   • 遇空气混合可爆，高温下易聚合发热引起爆炸。

2. 用途：

   • 制胶粘剂（如静电植绒、植毛的胶粘剂）。
   • 制造铜版纸涂饰剂。
   • 用于生产各种聚丙烯酸盐类产品（如铵盐、钠盐等），作为凝集剂、水质处理剂、分散剂、增稠剂等多种高分子助剂。

3. 生产方法：

   • 氰乙醇法：以氯乙醇和氰化钠为原料，反应生成丙烯酸。
   • 丙烯腈水解法：利用硫酸水解丙烯腈制得丙烯酸。
   • 高压雷佩法：将乙炔与一氧化碳、水在催化剂存在下反应生成丙烯酸。
   • 丙烯氧化法：丙烯在钼-铋等复合催化剂存在下，常压氧化生成丙烯醛；再进一步氧化得到丙烯酸。

4. 安全储存运输：

   • 库房需通风低温干燥，并与氧化剂分开存放。
   • 灭火时使用雾状水、二氧化碳、泡沫或干粉灭火器。

这篇文章详细介绍了丙烯酸的化学性质和应用范围，同时也提醒了在生产和使用过程中应注意的安全事项。

反应信息

• 作为反应物：
  描述：

  丙烯酸 在 bromine chloride 作用下， 以 水 为溶剂， 生成 2-Brom-3-chlor-propionsaeure
  参考文献：
  名称：

  Groszkowski,S.; Sienkiewicz,G., Roczniki Chemii, 1971, vol. 45, p. 1779 - 1782

  摘要：

  DOI：
• 作为产物：
  描述：

  丙烯醛 在 C₄H₁₁FeMo₆NO₂₄^(3-)*3C₁₆H₃₆N⁽¹⁺⁾ 、 水 、 氧气 、 sodium carbonate 作用下， 50.0 ℃ 、101.33 kPa 条件下， 反应 8.0h， 以98%的产率得到丙烯酸
  参考文献：
  名称：

  高效铁（III）催化水中的醛的好氧氧化，用于绿色制备羧酸

  摘要：

  开发了第一个非均质铁（III）催化水中醛的需氧氧化的例子。该方法利用1个大气压的氧气作为唯一的氧化剂，在极其温和的水性条件下进行，并涵盖了各种功能化的醛类。色谱法通常对于产品纯化不是必需的。它的操作简便性，克级氧化性以及连续重复使用催化剂的能力，使这种新方法在环境方面无害且具有成本效益。这种方法的通用性使其有可能在工业规模上使用。

  DOI：

  10.1002/anie.201612225
• 作为试剂：
  描述：

  甲氧基乙腈 在 iron(II) nitrate 、 氧气 、 copper(II) nitrate 、 丙烯酸 作用下， 生成 氰基甲酸甲酯
  参考文献：
  名称：

  DE728834

  摘要：

  公开号：

文献信息

• [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。
• Discovery of triazolo [1,5-a] pyridine derivatives as novel JAK1/2 inhibitors
  作者：Kuan Lu、Weibin Wu、Cunlong Zhang、Zijian Liu、Boren Xiao、Zigao Yuan、Anqi Li、Dawei Chen、Xin Zhai、Yuyang Jiang

  DOI：10.1016/j.bmcl.2020.127225

  日期：2020.7

  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

  在多种药物的批准下，小分子JAK抑制剂已被证明在类风湿性关节炎，炎症性肠病和牛皮癣中有效。为了开发有效的JAK1 / 2抑制剂，通过各种策略设计并合成了两个系列的三唑并[1,5- a ]吡啶衍生物。药理结果确定了优化的化合物J-4和J-6，它们对JAK1 / 2具有很高的效力，并且在酶法测定中具有优于JAK3的选择性。此外，J-4和J-6可有效抑制JAK1 / 2高表达BaF3细胞的增殖，并具有可接受的肝微粒体代谢稳定性。因此，J-4和J-6 可能作为有希望的JAK1 / 2抑制剂有待进一步研究。
• [EN] DUAL PHARMACOPHORES - PDE4-MUSCARINIC ANTAGONISTICS<br/>[FR] PHARMACOPHORES DUALS, ANTAGONISTES DES RÉCEPTEURS MUSCARINIQUES ET INHIBITEURS DE L'ACTIVITÉ PDE4
  申请人：GLAXO GROUP LTD

  公开号：WO2009100169A1

  公开（公告）日：2009-08-13

  The present invention is directed to novel compounds of Formula's (I) - (VI), and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use in therapy, for example as inhibitors of phosphodiesterase type IV (PDE4) and as antagonists of muscarinic acetylcholine receptors (mAChRs), in the treatment of and/or prophylaxis of respiratory diseases, including inflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis (e.g. allergic rhinitis), atopic dermatitis or psoriasis.

  本发明涉及式(I) - (VI)的新化合物，以及其药学上可接受的盐、药物组合物及其在治疗中的应用，例如作为磷酸二酯酶IV (PDE4)的抑制剂和肌碱乙酰胆碱受体 (mAChRs)的拮抗剂，用于治疗和/或预防呼吸道疾病，包括炎症性和/或过敏性疾病，如慢性阻塞性肺病（COPD）、哮喘、鼻炎（例如过敏性鼻炎）、特应性皮炎或银屑病。
• [EN] BRUTON'S TYROSINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA TYROSINE KINASE DE BRUTON
  申请人：PFIZER

  公开号：WO2014068527A1

  公开（公告）日：2014-05-08

  Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (BTK). Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the BTK inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions. (Formula I)

  本文披露了一种与Bruton's酪氨酸激酶（BTK）形成共价键的化合物。公开了制备这些化合物的方法。还披露了包括这些化合物的药物组合物。公开了使用BTK抑制剂的方法，单独或与其他治疗剂联合治疗自身免疫疾病或症状、异源免疫疾病或症状、癌症，包括淋巴瘤，以及炎症性疾病或症状的方法。 (化学式I)
• [EN] PROCESS FOR THE PREPARATION OF 1-[(3R)-3-[4-AMINO-3-(4-PHENOXYPHENVL)-1H- PVRAZOLO[3,4-D]PYRINIIDIN-1-Y1]-1-PIPERIDINVL]-2-PROPEN-1-ONE AND ITS POLYMORPHS THEREOF<br/>[FR] PROCÉDÉ DE PRÉPARATION DE 1-[(3R)-3-[4-AMINO-3-(4-PHÉNOXYPHÉNYL)-1H- PYRAZOLO[3,4-D]PYRINIIDIN-1-Y1]-1-PIPÉRIDINYL]-2-PROPÈN-1-ONE ET DE SES POLYMORPHES
  申请人：MSN LABORATORIES PRIVATE LTD

  公开号：WO2016170545A1

  公开（公告）日：2016-10-27

  The present invention relates to an improved process for the preparation of 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)- 1 H-pyrazolo[3,4-d]pyrimidin- 1 -yl]- 1 -piperidin yl]-2-propen-1-one compound of formula- 1 and its polymorphs thereof, which is represented by the following structural formula:

  本发明涉及一种改进的制备1-[(3R)-3-[4-氨基-3-(4-苯氧基苯基)-1H-吡唑并[3,4-d]嘧啶-1-基]-1-哌啶基]-2-丙烯-1-酮化合物及其多晶形式的方法，其由以下结构式表示：

表征谱图