2-氰基-N-间甲苯乙酰胺 | 54153-19-4

• 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: 2-氰基-N-间甲苯乙酰胺
• 中文别名: 氟醚卡酰胺；氟卡尼；2-氰基-N-(3-甲基苯基)乙酰胺
• 英文名称: 2-cyano-N-m-tolylacetamide
• 英文别名: 2-cyano-N-(3-methylphenyl)acetamide
• CAS: 54153-19-4
• 化学式: C₁₀H₁₀N₂O
• mdl: MFCD01342353
• 分子量: 174.202
• InChiKey: OTQOVOMLCZXTDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 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：

  2-氰基-N-间甲苯乙酰胺 在 乙酸铵 、 sulfur 、 溶剂黄146 、 二乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 苯 为溶剂， 反应 16.0h， 生成 2-(Chloromethyl)-3-(3-methylphenyl)-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-one
  参考文献：
  名称：

  Manjunath, Kadthala Shekar; Mohan, Shamanna; Naragund, Laxmi Venkatesh Gurachar, Arzneimittel-Forschung/Drug Research, 1997, vol. 47, # 9, p. 1005 - 1008

  摘要：

  DOI：
• 作为产物：
  描述：

  氰乙酸甲酯 生成 2-氰基-N-间甲苯乙酰胺
  参考文献：
  名称：

  TAKIGUCHI, KAZUO;YAMADA, KUNIHIKO;SUZUKI, MAMORU;NUNAMI, KEN-ICHI;HAYASHI+, AGR. AND BIOL. CHEM., 53,(1989) N, C. 69-76

  摘要：

  DOI：

文献信息

• Optimization of 2-Acylaminocycloalkylthiophene Derivatives for Activity against Staphylococcus aureus RnpA
  作者：Michaelle Chojnacki、Xufeng Cao、Daniel P. Flaherty、Paul M. Dunman

  DOI：10.3390/antibiotics10040369

  日期：——

  Staphylococcus aureus is well-recognized to cause debilitating bacterial infections that are difficult to treat due to the emergence of antibiotic resistance. As such, there is a need to develop new antimicrobials for the therapeutic intervention of S. aureus disease. To that end, S. aureus RnpA is an essential enzyme that is hypothesized to participate in two required cellular processes, precursor tRNA (ptRNA) maturation and mRNA degradation. Corresponding high throughput screening campaigns have identified the phenylcarbamoyl cyclic thiopenes as a chemical class of RnpA inhibitors that display promising antibacterial effects by reducing RnpA ptRNA and mRNA degradation activities and low human cell toxicity. Herein, we perform a structure activity relationship study of the chemical scaffold. Results revealed that the cycloalkane ring size and trifluoroacetamide moiety are required for antibacterial activity, whereas modifications of the para and/or meta positions of the pharmacophore’s phenyl group allowed tuning of the scaffold’s antimicrobial performance and RnpA inhibitory activity. The top performing compounds with respect to antimicrobial activity also did not exhibit cytotoxicity to human cell lines at concentrations up to 100 µM, greater than 100-fold the minimum inhibitory concentration (MIC). Focused studies of one analog, RNP0012, which exhibited the most potent antimicrobial and inhibition of cellular RnpA activities revealed that the compound reduced bacterial burden in a murine model of S. aureus disease. Taken together, the results presented are expected to provide an early framework for optimization of next-generation of RnpA inhibitor analogues that may represent progenitors of a new class of antimicrobials.

  金黄色葡萄球菌被广泛认为会引起难以治疗的细菌感染，因为抗生素耐药性的出现。因此，有必要开发新的抗菌药物来治疗金黄色葡萄球菌疾病。为此，金黄色葡萄球菌RnpA是一种必不可少的酶，据推测参与两个必需的细胞过程，前体tRNA（ptRNA）成熟和mRNA降解。相应的高通量筛选活动已经确定苯基氨基环硫烯为一种RnpA抑制剂的化学类，通过降低RnpA ptRNA和mRNA降解活性以及低人类细胞毒性显示出有希望的抗菌效果。在这里，我们进行了化学骨架的结构活性关系研究。结果显示，环烷烃环大小和三氟乙酰胺基团对抗菌活性是必需的，而对药效团苯基的对位和/或间位的修饰允许调节骨架的抗微生物性能和RnpA抑制活性。在抗微生物活性方面表现最佳的化合物在浓度高达100 µM时也没有对人类细胞系表现出细胞毒性，这比最低抑菌浓度（MIC）高出100倍。对一种类似物RNP0012的重点研究显示，该化合物减少了在金黄色葡萄球菌疾病小鼠模型中的细菌负担。综合而言，所呈现的结果预计将为优化下一代RnpA抑制剂类似物的早期框架提供基础，这些类似物可能代表新一类抗菌药物的前体。
• 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。
• Reactions of diethyl 2-(ethoxymethylene)malonate with 2-cyanoacetanilides: unexpected transfer of the ethoxymethylene moiety
  作者：Nikolay Yu. Gorobets、Valeriya P. Tkachova、Roman P. Tkachov、Oleksandr D. Dyachenko、Eduard B. Rusanov、Vladimir D. Dyachenko

  DOI：10.3998/ark.5550190.0011.b21

  日期：——

  A sodium ethoxide catalyzed reaction of N-substituted cyanoacetanilides 1a-f with diethyl 2-(ethoxymethylene)malonate 2 unexpectedly leads to the corresponding 2-amino-5-cyano-6oxo-N,1-diaryl-1,6-dihydropyridine-3-carboxamides 3a-f, while the expected 5-cyano-2hydroxy-6-oxo-1-aryl-1,6-dihydropyridine-3-carboxylates 4a-f were observed only as minor products.

  N-取代的氰基乙酰苯胺 1a-f 与 2-(乙氧基亚甲基)丙二酸二乙酯 2 的乙醇钠催化反应出人意料地生成了相应的 2-amino-5-cyano-6oxo-N,1-diaryl-1,6-dihydropyridine-3 -carboxamides 3a-f，而预期的 5-cyano-2hydroxy-6-oxo-1-aryl-1,6-dihydropyridine-3-carboxylates 4a-f 仅作为次要产物被观察到。
• Synthesis of novel pyrido[2,1-b]benzothiazole and N-substituted 2-pyridylbenzothiazole derivatives showing remarkable fluorescence and biological activities
  作者：Rasha A. Azzam、Galal H. Elgemeie、Rokia R. Osman

  DOI：10.1016/j.molstruc.2019.127194

  日期：2020.2

  Abstract The synthesis of novel pyrido[2,1-b]benzothiazole and pyrido[2,1-b]benzoimidazole derivatives was achieved via the reaction of N-aryl-2-cyano-3,3-bis(methylthio)acrylamide with benzothiazoleylacetonitrile and benzoimidazoleylacetonitrile, respectively, while N-substituted 2-pyridylbenzothiazole derivatives were synthesized by reacting 2-(benzo[d]thiazol-2-yl)-3-(dimethylamino)acrylonitrile

  摘要 通过 N-芳基-2-氰基-3,3-双（甲硫基）丙烯酰胺与苯并噻唑乙腈反应，合成了新型吡啶并[2,1-b]苯并噻唑和吡啶并[2,1-b]苯并咪唑衍生物。和苯并咪唑基乙腈，而 N-取代的 2-吡啶基苯并噻唑衍生物是通过 2-(苯并[d]噻唑-2-基)-3-(二甲氨基)丙烯腈与氰基乙酰胺、芳基氰基乙酰胺或 2-氰基-N'反应合成的-(4-取代的亚苄基)乙酰肼。基于稳态荧光测量，新合成的 N-取代 2-吡啶基苯并噻唑衍生物表现出显着的荧光特性，具有相当高的量子产率（0.25-0.29）。此外，还评估了所有新合成衍生物的抗微生物和抗病毒活性。
• A versatile new synthesis of quinolines and related fused pyridines. Part 8. Conversion of anilides into 3-substituted quinolines and into quinoxalines
  作者：Otto Meth-Cohn、Salah Rhouati、Brian Tarnowski、Andrew Robinson

  DOI：10.1039/p19810001537

  日期：——

  3-substituted quinolines (7). When N-nitrosodialkylamines are used in place of dimethylformamide as the Vilsmeier agent, the anilides are converted into 2-chloroquinoxalines in low yields. Several by-products are formed and the mechanisms have been explored. Thus, the formation of ethyl N-arylcabamate from the corresponding propionanilide is shown to involve an C→O alkyl migration related to a Wolff rearrangement

  苯胺（4）（ArNHCOCH 2 R）在Vilsmeier条件下很容易转化为2-氯-3-R-喹啉（5），可以用锌和乙酸除去2-氯基团，生成3-取代的喹啉（7 ）。当使用N-亚硝基二烷基胺代替二甲基甲酰胺作为Vilsmeier剂时，该苯胺化物以低收率转化成2-氯喹喔啉。形成了几种副产物，并研究了其机理。因此，由相应的丙酰苯胺形成的N-芳基氨基甲酸乙酯乙酯显示出与沃尔夫夫重排有关的C→O烷基迁移，而N-芳基甲酰亚胺基二氯化物（18），腈和异氰化物是从被取代的侧链的C-C裂解中衍生而来的。尽管使用磷酰溴而不是氯化物导致苯胺以低收率转化为氯，但Vilsmeier试剂或溶剂的酰氯组分的变化通常是无用的。