N-(2-氯苯基)-2-氰基乙酰胺 | 50982-66-6

• 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: N-(2-氯苯基)-2-氰基乙酰胺
• 中文别名: 2-氰基-N-(2-氯苯基)-乙酰胺
• 英文名称: N-(2-chlorophenyl)-2-cyanoacetamide
• 英文别名: 2-cyano-N-[2-(chloro)phenyl]acetamide；N-(2-chlorophenyl)cyanoacetamide；cyano-acetic acid-(2-chloro-anilide)；Malonsaeure-(2-chlor-anilid)-nitril；Cyan-essigsaeure-(2-chlor-anilid)
• CAS: 50982-66-6
• 化学式: C₉H₇ClN₂O
• mdl: MFCD00463630
• 分子量: 194.62
• InChiKey: QNLTWNKEBOCLPE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.111
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  2

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：

  N-(2-氯苯基)-2-氰基乙酰胺 在 盐酸羟胺 、 sodium carbonate 作用下， 以 甲醇 、 水 为溶剂， 反应 2.0h， 以69%的产率得到3-amino-3-(hydroxyimino)-N-[2-(chloro)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：

  氰乙酸 、 邻氯苯胺 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 N-(2-氯苯基)-2-氰基乙酰胺
  参考文献：
  名称：

  Synthesis of 8-hydroxy-2-iminochromene derivatives as selective and potent inhibitors of human carbonyl reductase 1

  摘要：

  人类酮醛还原酶1（CBR1）是短链脱氢酶/还原酶超家族的成员，它将蒽环类抗癌药物还原为它们较不具有抗癌作用的C-13羟基代谢物，这些代谢物与心脏毒性的发病机制有关，这是药物的副作用。

  DOI：

  10.1039/c5ob00847f

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。
• Syntheses and biological evaluation of 2-amino-3-acyl-tetrahydrobenzothiophene derivatives; antibacterial agents with antivirulence activity
  作者：Hung The Dang、Erik Chorell、Hanna Uvell、Jerome S. Pinkner、Scott J. Hultgren、Fredrik Almqvist

  DOI：10.1039/c3ob42478b

  日期：——

  by pilicides) is a promising approach to combating bacterial infection. A high-throughput screening campaign of a library of 17 500 small molecules identified 2-amino-3-acyl-tetrahydrobenzothiophene derivatives (hits 2 and 3) as novel inhibitors of pili-dependent biofilm formation in a uropathogenic Escherichia coli strain UTI89. Based on compounds 2 and 3 as the starting point, we designed and synthesized

  开发针对毒力因子的新化合物（例如，通过pilicides 抑制菌毛组装）是对抗细菌感染的一种有前途的方法。一个由 17500 个小分子组成的文库的高通量筛选活动将 2-氨基-3-酰基-四氢苯并噻吩衍生物（命中2和3）鉴定为泌尿致病性大肠杆菌菌株 UTI89中菌毛依赖性生物膜形成的新型抑制剂。以化合物2和3为出发点，我们设计合成了一系列结构相关的类似物，并研究了它们对大肠杆菌生物膜形成的活性UTI89。初始命中的系统结构修改为其 SAR 提供了有价值的信息，以供进一步优化。此外，母体分子的小结构变化导致大肠杆菌生物膜发育的低微摩尔抑制剂 ( 20-23 )，而对细菌生长没有影响。在血凝 (HA) 滴度测定和电子显微镜 (EM) 测量中证实命中化合物3及其类似物20可防止菌毛形成。这些发现表明，2-氨基-3-酰基-四氢苯并噻吩可以作为一类新的化合物，进一步作为具有抗毒力活性的抗菌剂。
• 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。
• Nickel-promoted oxidative domino C_sp3–H/N–H bond double-isocyanide insertion reaction to construct pyrrolin-2-ones
  作者：Li-Rong Wen、Ning-Ning Wang、Wu-Bo Du、Qiang Ma、Lin-Bao Zhang、Ming Li

  DOI：10.1039/d1ob00139f

  日期：——

  double isocyanide insertion reaction of acetamides with isocyanides has been developed for the synthesis of pyrrolin-2-one derivatives. A wide range of acetamides bearing various functional groups are compatible with this reaction system by utilizing Ni(acac)2 as a catalyst. In this transformation, isocyanide could serve as a C1 connector and insert into the inactive Csp3–H bond, representing an effective

  乙酰胺与异氰酸酯的第一个镍催化的氧化多米诺骨牌C sp3 -H / N-H双异氰酸酯插入反应已被开发用于吡咯烷-2-酮衍生物的合成。通过利用Ni（acac）2作为催化剂，各种带有各种官能团的乙酰胺与该反应体系相容。在此转化过程中，异氰酸酯可以用作C1连接器，并插入无活性的C sp3- H键，代表构建杂环的有效方法。
• The synthesis and biological evaluation of some caffeic acid amide derivatives: E-2-Cyano-(3-substituted phenyl)acrylamides
  作者：Wei Zhou、Hai-bo Li、Chun-nian Xia、Xian-ming Zheng、Wei-xiao Hu

  DOI：10.1016/j.bmcl.2009.02.081

  日期：2009.4

  A series of caffeic acid amide derivatives 2-cyano-(3-substituted phenyl)acrylamides were synthesized via Knoevenogal condensation of substituted benzaldehydes with cyanoacetamides. The structure of compound 1f was determined as E-isomer by X-ray diffractive analysis. The biological screening tests in vitro showed that compound 1b has obvious inhibitory activities against human gastric carcinoma cell

  通过取代苯甲醛与氰基乙酰胺的Knoevenogal缩合反应，合成了一系列咖啡酸酰胺衍生物2-氰基-（3-取代的苯基）丙烯酰胺。通过X射线衍射分析确定化合物1f的结构为E-异构体。体外生物筛选试验表明，化合物1b对人胃癌细胞系BGC-823，人鼻咽癌细胞系KB和人肝癌细胞系BEL-7402具有明显的抑制活性，IC 50值为5.6μg/ mL，13.1μg。 / mL和12.5μg/ mL。还提出了一些初步的构效关系（SAR），这可能为进一步研究提供指导。