5-amino-4-cyano-3-methyl-N-phenylthiophene-2-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-amino-4-cyano-3-methyl-N-phenylthiophene-2-carboxamide
• 化学式: C₁₃H₁₁N₃OS
• mdl: MFCD00100996
• 分子量: 257.316
• InChiKey: GYCMLVIJRXMKNW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-amino-4-cyano-3-methyl-N-phenylthiophene-2-carboxamide 在 1,2,3,4,5,6,7,8-八硫杂环辛烷 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以70%的产率得到3-amino-4,6-dihydro-4-imino-N-phenylthieno[3,4-c]thiophene-1-carboxamide
  参考文献：
  名称：

  乙酰乙酰苯胺用于合成具有细胞毒活性的噻吩衍生物的用途

  摘要：

  乙酰乙酰苯胺1与元素硫和丙二腈2的反应生成噻吩衍生物3。后者是通过与氯化芳基重氮，苯甲醛和乙酸酐反应而合成不同噻吩和稠合衍生物的关键原料。此外，与苯基异硫氰酸酯的反应产生了稠合衍生物。化合物3与元素硫的反应产生二噻吩衍生物。另外，化合物3与氰基乙酸乙酯的反应产生了N-氰基乙酰胺衍生物，该N-氰基乙酰胺衍生物能够通过与不同试剂反应而进一步杂环化。针对三种癌细胞系MCF-7（乳腺癌），NCI-H460（非小细胞肺癌），和SF-268（CNS癌症），其中某些化合物显示出最佳的细胞毒性。结果表明，化合物5a，5b，8、22和23显示出对癌细胞系的最佳细胞毒性作用。关键词：噻吩，噻吩并[2,3-d]嘧啶，香豆素，细胞毒性公牛。化学 Soc。埃塞俄比亚。2017，31（3），519-534。DOI：http：//dx.doi.org/10.4314/bcse.v31i3.16

  DOI：

  10.4314/bcse.v31i3.16
• 作为产物：
  描述：

  苯胺 在 1,2,3,4,5,6,7,8-八硫杂环辛烷 、 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 17.0h， 生成 5-amino-4-cyano-3-methyl-N-phenylthiophene-2-carboxamide
  参考文献：
  名称：

  EFFECTIVE MICROWAVE SYNTHESIS OF BIOACTIVE THIENO[2,3-d]PYRTMIDINES

  摘要：

  A series of novel 2-amino-3-cyanothiophenes (2a-2j) were synthesized using heterogeneous base (K2CO3) supported Gewald reaction. Cyclization of 2a-j with formamide and urea in conventional heating as well as microwave irradiation gave thieno[2,3-d]pyrimidines (3a-3j) and thieno[2,3-d]pyrimidin-2(1H)-ones(4a-4j) respectively. The reaction rates were faster and yields were higher in the microwave conditions. The structures of the compounds were confirmed with elemental analysis, mass spectral analysis, FTIR, H-1 NMR and C-13 NMR techniques. All the synthesized compounds were subjected to antimicrobial activity (MIC) in vitro by broth dilution method and exhibited a moderate antimicrobial activity.

  DOI：

  10.4067/s0717-97072017000100010

文献信息

• Design, Synthesis and Fungicidal Activity of N-(thiophen-2-yl) Nicotinamide Derivatives
  作者：Hongfei Wu、Xingxing Lu、Jingbo Xu、Xiaoming Zhang、Zhinian Li、Xinling Yang、Yun Ling

  DOI：10.3390/molecules27248700

  日期：——

  Based on the modification of natural products and the active substructure splicing method, a series of new N-(thiophen-2-yl) nicotinamide derivatives were designed and synthesized by splicing the nitrogen-containing heterocycle natural molecule nicotinic acid and the sulfur-containing heterocycle thiophene. The structures of the target compounds were identified through 1H NMR, 13C NMR and HRMS spectra

  基于天然产物的修饰和活性亚结构拼接方法，将含氮杂环天然分子烟酸和含硫杂环拼接设计合成了一系列新型N-(噻吩-2-基)烟酰胺衍生物噻吩。目标化合物的结构通过1H NMR、13C NMR和HRMS谱进行了鉴定。所有化合物在温室中对黄瓜霜霉病（CDM，Pseudoperonospora cubensis (Berk.et Curt.) Rostov.）的体内生物测定结果表明，化合物 4a (EC50 = 4.69 mg/L) 和 4f (EC50 = 1.96 mg /L) 表现出优异的杀菌活性，高于双氟草胺 (EC50 = 21.44 mg/L) 和氟吗啉 (EC50 = 7.55 mg/L)。针对 CDM 的田间试验的生物测定结果表明，化合物 4f 的 10% EC 制剂显示出优异的功效（分别为 70% 和 79% 的控制效果，分别为 100 mg/L 和 200 mg/L），优于那些两种商业杀真菌剂
• Inhibitors of hepatitis B virus targeting capsid assembly
  申请人：THE CURATORS OF THE UNIVERSITY OF MISSOURI

  公开号：US10759774B2

  公开（公告）日：2020-09-01

  The present invention provides novel compounds and methods for treating, preventing or inhibiting hepatitis B virus (HBV).

  本发明提供了用于治疗、预防或抑制乙型肝炎病毒（HBV）的新型化合物和方法。
• EFFECTIVE MICROWAVE SYNTHESIS OF BIOACTIVE THIENO[2,3-d]PYRTMIDINES
  作者：TASLIMAHEMAD T KHATRI、VIRESH H SHAH

  DOI：10.4067/s0717-97072017000100010

  日期：——

  A series of novel 2-amino-3-cyanothiophenes (2a-2j) were synthesized using heterogeneous base (K2CO3) supported Gewald reaction. Cyclization of 2a-j with formamide and urea in conventional heating as well as microwave irradiation gave thieno[2,3-d]pyrimidines (3a-3j) and thieno[2,3-d]pyrimidin-2(1H)-ones(4a-4j) respectively. The reaction rates were faster and yields were higher in the microwave conditions. The structures of the compounds were confirmed with elemental analysis, mass spectral analysis, FTIR, H-1 NMR and C-13 NMR techniques. All the synthesized compounds were subjected to antimicrobial activity (MIC) in vitro by broth dilution method and exhibited a moderate antimicrobial activity.
• Mohareb, R. M.; Elkholy, Y. M.; Sayed, N. I. Abdel, Phosphorus, Sulfur and Silicon and the Related Elements, 1995, vol. 106, # 1-4, p. 193 - 202
  作者：Mohareb, R. M.、Elkholy, Y. M.、Sayed, N. I. Abdel

  DOI：——

  日期：——
• 5-Aminothiophene-2,4-dicarboxamide analogues as hepatitis B virus capsid assembly effectors
  作者：Jing Tang、Andrew D. Huber、Dallas L. Pineda、Kelsey N. Boschert、Jennifer J. Wolf、Jayakanth Kankanala、Jiashu Xie、Stefan G. Sarafianos、Zhengqiang Wang

  DOI：10.1016/j.ejmech.2018.12.047

  日期：2019.2

  Chronic hepatitis B virus (HBV) infection represents a major health threat. Current FDA-approved drugs do not cure HBV. Targeting HBV core protein (Cp) provides an attractive approach toward HBV inhibition and possibly infection cure. We have previously identified and characterized a 5-amino-3-methylthiophene-2,4-dicarboxamide (ATDC) compound as a structurally novel hit for capsid assembly effectors (CAEs). We report herein hit validation through studies on absorption, distribution, metabolism and excretion (ADME) properties and pharmacokinetics (PK), and hit optimization via analogue synthesis aiming to probe the structure-activity relationship (SAR) and structure-property relationship (SPR). In the end, these medicinal chemistry efforts led to the identification of multiple analogues strongly binding to Cp, potently inhibiting HBV replication in nanomolar range without cytotoxicity, and exhibiting good oral bioavailability (F). Two of our analogues, 19o (EC50 = 0.11 mu M, CC50 > 100 mu M = 25%) and 19k (EC50 = 0.31 mu M, CC50 > 100 mu M, F = 46%), displayed overall lead profiles superior to reported CAEs 7-10 used in our studies. (C) 2018 Elsevier Masson SAS. All rights reserved.