氰基乙酰邻三氟甲基苯胺 | 419534-37-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 氰基乙酰邻三氟甲基苯胺
• 中文别名: 2-氰基-N-[2-(三氟甲基)苯基]乙酰胺
• 英文名称: 2-cyano-N-(2-(trifluoromethyl)phenyl)acetamide
• 英文别名: 2-cyano-N-[2-(trifluoromethyl)phenyl]acetamide
• CAS: 419534-37-5
• 化学式: C₁₀H₇F₃N₂O
• mdl: MFCD03946384
• 分子量: 228.174
• InChiKey: QRMBMSKLEQIKLX-UHFFFAOYSA-N

物化性质

• 沸点：
  383.7±42.0 °C(Predicted)
• 密度：
  1.375±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2926909090

反应信息

• 作为反应物：
  描述：

  氰基乙酰邻三氟甲基苯胺 在 盐酸羟胺 、 sodium carbonate 作用下， 以 甲醇 、 水 为溶剂， 反应 2.0h， 以67%的产率得到3-amino-3-(hydroxyimino)-N-[2-(trifluoromethyl)phenyl]propanamide
  参考文献：
  名称：

  Low Molecular Weight Amidoximes that Act as Potent Inhibitors of Lysine-Specific Demethylase 1

  摘要：

  The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 dysregulation is thought to contribute to the development of cancer. We reported that (bis)guanidines, (bis)biguanides, and their urea- and thiourea isosteres are potent inhibitors of LSD1 and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a series of small molecule amidoximes that are moderate inhibitors of recombinant LSD1 but that produce dramatic changes in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target of LSD1, in Calu-6 lung carcinoma cells. In addition, these analogues increase cellular levels of secreted frizzle-related protein (SFRP) 2, H-cadherin (HCAD), and the transcription factor GATA4. These compounds represent leads for an important new series of drug-like epigenetic modulators with the potential for use as antitumor agents.

  DOI：

  10.1021/jm3002845
• 作为产物：
  描述：

  1-氰基乙酰-3,5-二甲基吡唑 、 邻氨基三氟甲苯 生成 氰基乙酰邻三氟甲基苯胺
  参考文献：
  名称：

  咪唑并[1,2-b]吡唑-7-甲酰胺的合成、细胞毒性表征和合成孔径雷达研究

  摘要：

  研究了新型咪唑并[1,2-b]吡唑-7-甲酰胺的合成和体外细胞毒特性。在利用 MCF-7 人乳腺、4T1 乳腺和 HL-60 人早幼粒细胞白血病癌细胞系的 2D 和 3D 培养物进行先导优化后，构建了一个 67 元文库，并构建了构效关系（SAR ) 确定。七个合成的类似物表现出亚微摩尔活性，其中化合物 63 发挥最显着的效力，具有显着的 HL-60 敏感性（IC50 = 0.183 μM）。

  DOI：

  10.1002/ardp.201800062

文献信息

• Development of Novel AKR1C3 Inhibitors as New Potential Treatment for Castration-Resistant Prostate Cancer
  作者：Satoshi Endo、Hiroaki Oguri、Jin Segawa、Mina Kawai、Dawei Hu、Shuang Xia、Takuya Okada、Katsumasa Irie、Shinya Fujii、Hiroaki Gouda、Kazuhiro Iguchi、Takuo Matsukawa、Naohiro Fujimoto、Toshiyuki Nakayama、Naoki Toyooka、Toshiyuki Matsunaga、Akira Ikari

  DOI：10.1021/acs.jmedchem.0c00939

  日期：2020.9.24

  crystallographic study of AKR1C3 complexes with 2j and 2l. The inhibitors suppressed proliferation of prostate cancer 22Rv1 and PC3 cells through both androgen-dependent and androgen-independent mechanisms. Additionally, 2j and 2l prevented prostate tumor growth in a xenograft mouse model. Furthermore, the inhibitors significantly augmented apoptotic cell death induced by anti-CRPC drugs (abiraterone or enzalutamide)

  醛基酮还原酶（AKR）1C3催化活性雄激素的合成，从而促进前列腺癌的发展。AKR1C3还通过前列腺素和反应性醛的代谢促进非雄激素依赖性细胞增殖和存活。由于其在去势抵抗性前列腺癌（CRPC）组织中的升高，AKR1C3是CRPC的有希望的治疗靶标。在这项研究中，我们发现了一种新型的强效AKR1C3抑制剂N-（4-氟苯基）-8-羟基-2-亚氨基-2 H-色烯-3-羧酰胺（2d），并用IC 50合成了其衍生物值比其他AKR（1C1、1C2和1C4）高25-56 nM，选择性> 220倍。通过结晶研究AKR1C3与2j和2l的复合物阐明了抑制效力的结构因素。所述抑制剂通过雄激素依赖性和雄激素依赖性机制抑制前列腺癌22Rv1和PC3细胞的增殖。另外，2j和2l阻止了异种移植小鼠模型中前列腺肿瘤的生长。此外，这些抑制剂显着增加了由抗CRPC药物（阿比特龙或enzalutamide）诱导的凋亡细胞死亡。
• Synthesis, Structure−Activity Relationships, and Pharmacokinetic Properties of Dihydroorotate Dehydrogenase Inhibitors:  2-Cyano-3-cyclopropyl-3-hydroxy- <i>N</i>-[3‘-methyl-4‘-(trifluoromethyl)phenyl]propenamide and Related Compounds
  作者：Elizabeth A. Kuo、Philip T. Hambleton、David P. Kay、Phillip L. Evans、Saroop S. Matharu、Edward Little、Neil McDowall、C. Beth Jones、Charles J. R. Hedgecock、Christopher M. Yea、A. W. Edith Chan、Peter W. Hairsine、Ian R. Ager、W. Roger Tully、Richard A. Williamson、Robert Westwood

  DOI：10.1021/jm9604437

  日期：1996.1.1

  been synthesized. Their in vivo biological activity determined in rat and mouse delayed type hypersensitivity has been found to correlate well with their in vitro DHODH potency. The most promising compound (3) has shown activity in rat and mouse collagen (II)-induced arthritis models (ED50 = 2 and 31 mg/kg, respectively) and has shown a shorter half-life in man when compared with leflunomide. Clinical

  新型免疫抑制剂来氟米特（1）的活性代谢物（2）已显示出抑制二氢乳清酸脱氢酶（DHODH）的作用。该酶催化从头进行嘧啶生物合成的第四步。已经合成了一系列活性代谢物2的类似物。已经发现它们在大鼠和小鼠迟发型超敏反应中的体内生物学活性与其体外DHODH效力密切相关。最有希望的化合物（3）在大鼠和小鼠胶原（II）诱导的关节炎模型中显示出活性（分别为ED50 = 2和31 mg / kg），与来氟米特相比，在人中的半衰期更短。类风湿关节炎的临床研究正在进行中。
• Synthesis and biological activity of a series of diaryl-substituted .alpha.-cyano-.beta.-hydroxypropenamides, a new class of anthelmintic agents
  作者：Eric B. Sjogren、Michael A. Rider、Peter H. Nelson、Stanford Bingham、Anthony L. Poulton、Mark A. Emanuel、Richard Komuniecki

  DOI：10.1021/jm00115a020

  日期：1991.11

  A series of alpha-cyano-beta-hydroxypropenamides was prepared and tested for anthelmintic activity. Alpha-cyano-beta-hydroxy hydroxy-N-[4-(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)phenyl]propenamide (1) showed good activity against the nematode Nematospirodes dubius in a mixed parasite infection in mice; several of the analogues were also effective against the cestode Hymenolepis nana. In sheep trials, 1 caused 100% reduction of the hematophagous nematode Haemonchus contortus after a single dose of 20 mg/kg but did not show satisfactory control of Trichostrongylus colubriformis or Ostertagia circumcincta. Against the liver fluke Fasciola hepatica, 1 suppressed egg production but only temporarily, suggesting that the adult flukes were not eliminated. Mechanism of action studies on 1 using Ascaris mitochondria showed it to be an uncoupler of oxidative phosphorylation.
• [EN] PHARMACEUTICAL COMPOSITIONS OF TERIFLUNOMIDE<br/>[FR] COMPOSITIONS PHARMACEUTIQUES DE TÉRIFLUNOMIDE
  申请人：EMCURE PHARMACEUTICALS LTD

  公开号：WO2017125841A1

  公开（公告）日：2017-07-27

  The present invention relates to pharmaceutical compositions of Teriflunomide or pharmaceutically acceptable salts thereof and method of preparation of such compositions. Typically, the composition according to present invention comprises about 1% w/w to about 30% w/w Teriflunomide, or a pharmaceutically acceptable salt thereof, about 0.1% w/w to about 0.8% w/w colloidal silicon dioxide, about 5% w/w to about 20% w/w disintegrant, about 0% w/w to about 40% w/w binder, about 0.1% w/w to about 2% w/w lubricant and the remaining percentage comprising diluents and optionally suitable agents to adjust the pH of the composition in the range of about 4.5 to 7.0.
• Preparation and Characterization of Impurities of Teriflunomide—An Immunomodulatory Agent
  作者：C. Suresh、D. R. Devi、K. Basavaiah、A. S. K. Reddy、K. V. V. Prasada Rao、G. A. Kumar

  DOI：10.1134/s1070363224040212

  日期：2024.4