methyl 2-amino-6-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: methyl 2-amino-6-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate
• 英文别名: Methyl 2-amino-6-methyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate
• 化学式: C₁₁H₁₅NO₂S
• mdl: MFCD01114962
• 分子量: 225.312
• InChiKey: YHYBWJHQHFHSSW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.545
• 拓扑面积：
  80.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-amino-6-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 反应 8.0h， 生成 methyl 6-methyl-2-(4-methylpiperazine-1-carboxamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate
  参考文献：
  名称：

  Synthesis of urea analogues bearing N-alkyl-N'-(thiophen-2-yl) scaffold and evaluation of their innate immune response to toll-like receptors

  摘要：

  Previous high throughput virtual screening of 10 million-compound and following cell based validation led to the discovery of a novel, nonlipopeptide-like chemotype ZINC 6662436, as toll-like receptor 2 (TLR2) agonists. In this report, compounds belonging to four areas of structural modification of ZINC6662436 were evaluated for biological activity using human HEK-Blue TLR2 reporter cells, and human THP-1 monocytic cells, yield SMU-C13 as an optimized, direct and high potent (EC50 = 160 nM) agonist of human TLR2. Moreover, preliminary mechanism studies indicated that SMU-C13 through activates TLR1 and TLR2 then stimulates the NF-kappa B activation to trigger the downstream cytokines, such as TNF-alpha and secreted alkaline phosphatase (SEAP). (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.02.067
• 作为产物：
  描述：

  4-甲基环己酮 、 氰乙酸甲酯 在 sulfur 、 三乙胺 作用下， 以35 %的产率得到methyl 2-amino-6-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate
  参考文献：
  名称：

  4,5,6,7-四氢苯并噻吩 2,3 衍生物的发现、合成和体外表征作为视黄酸受体相关孤儿受体 γt 的有效调节剂

  摘要：

  视黄酸受体相关孤儿受体γt（RORγt）是一种在多种组织中表达的核受体，是治疗炎症和自身免疫性疾病、代谢性疾病和耐药癌症类型的潜在药物靶点。我们在此报告了 RORγt 4,5,6,7-四氢苯并噻吩调节剂的 2,3 衍生物的发现。我们还报告了一组这些衍生物在酸性/中性 pH 下的溶解度、小鼠/人/狗/大鼠微粒体稳定性、Caco-2 和 MDR1-MDCKII 渗透性。对于这组调节剂，与激动剂锁水合相比，空间冲突和推拉机制引起的反向激动会导致蛋白质构象更大的不稳定性。独立于这两种机制，我们观察到由于与 Cys320-Glu326 和 Arg364-Phe377 亲水区域的相互作用，所测试的 4,5,6,7-四氢苯并噻吩的 2,3 衍生物对 RORγt 具有基础调节活性。当前研究中报告的药物发现方法可用于发现核受体和其他球状蛋白靶点的调节剂。

  DOI：

  10.1021/acs.jmedchem.3c00021

文献信息

• Synthesis and Biological Evaluation of New Antitubulin Agents Containing 2-(3′,4′,5′-trimethoxyanilino)-3,6-disubstituted-4,5,6,7-tetrahydrothieno[2,3-c]pyridine Scaffold
  作者：Romeo Romagnoli、Filippo Prencipe、Paola Oliva、Barbara Cacciari、Jan Balzarini、Sandra Liekens、Ernest Hamel、Andrea Brancale、Salvatore Ferla、Stefano Manfredini、Matteo Zurlo、Alessia Finotti、Roberto Gambari

  DOI：10.3390/molecules25071690

  日期：——

  characterized by the presence of a 3′,4′,5′-trimethoxyanilino moiety and a cyano or an alkoxycarbonyl group at its 2- or 3-position, respectively, were designed, synthesized, and evaluated for antiproliferative activity on a panel of cancer cell lines and for selected highly active compounds, inhibition of tubulin polymerization, and cell cycle effects. We have identified the 2-(3′,4′,5′-trimethoxyanilino)-3-

  基于 4,5,6,7-四氢噻吩并[2,3-c]吡啶和4,5,6,7-四氢苯并[b]噻吩分子骨架的两个新系列化合物，其特征在于存在3' ,4',5'-三甲氧基苯胺基部分和其 2-或 3-位的氰基或烷氧基羰基分别被设计、合成和评估对一组癌细胞系和选定的高活性化合物的抗增殖活性、抑制微管蛋白聚合和细胞周期效应。我们已经鉴定了 2-(3',4',5'-trimethoxyanilino)-3-cyano-6-methoxycarbonyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine 衍生物 3a 及其 6-乙氧羰基同系物 3b 作为新型抗增殖剂，可抑制癌细胞生长，对一组三种癌细胞系的 IC50 值范围为 1.1 至 4.7 μM。它们在微摩尔水平与微管蛋白的相互作用导致细胞在细胞周期的 G2/M 期积累并导致细胞凋亡。细胞凋亡研究发现，化合物3a和3b以剂量依赖
• Methyl N-(carbazolyl)acetyl-2-aminotetrahydrobenzothiophene-3-carboxylates as modulators of NMDA receptors
  作者：V. B. Sokolov、A. Yu. Aksinenko、A. V. Gabrel’yan、V. V. Grigoriev

  DOI：10.1007/s11172-019-2602-4

  日期：2019.8

  Methyl N-(carbazolyl)acetyl-2-aminotetrahydrothiophene-3-carboxylates were synthesized by alkylation of carbazoles with the corresponding chloroacetylamides of 2-aminotiophenes. The radioligand binding method showed the presence of the modulating effect of the synthesized compounds on the neuronal NMDA receptors.

  通过咔唑与 2-氨基噻吩的相应氯乙酰酰胺的烷基化，合成了 N-(咔唑基)乙酰基-2-氨基四氢噻吩-3-羧酸甲酯。放射性配体结合法表明，合成的化合物对神经元 NMDA 受体有调节作用。
• Methyl esters of 2-aminotetrahydrobenzothiophene-3-carboxylic acids decorated with trifluoromethyl-containing heterocycles
  作者：V. B. Sokolov、A. Yu. Aksinenko、O. A. Dranyi、V. V. Grigoriev

  DOI：10.1007/s11172-018-2365-3

  日期：2018.12

  Methyl 2-aminothiophene-3-carboxylates were modified with trifluoromethyl-containing five-membered heterocycles by cyclocondensation of methyl trifluoropyruvate N-thiophen-2-ylimines with 1,3-N,N-binucleophiles (2-aminothiazoline and benzamidines) to obtain the corresponding 5-oxo-6-trifluoromethyl-2,3,5,6-tetrahydroimidazoles and 5-oxo-2-phenyl-4-trifluoromethyl-4,5-dihydro-1H-imidazoles. Radioligand

  通过三氟丙酮酸甲酯 N-噻吩-2-亚胺与 1,3-N,N-双亲核试剂（2-氨基噻唑啉和苯甲脒）的环缩合，用含三氟甲基的五元杂环修饰 2-氨基噻吩-3-羧酸甲酯，得到相应的 5-oxo-6-trifluoromethyl-2,3,5,6-四氢咪唑和 5-oxo-2-phenyl-4-trifluoromethyl-4,5-dihydro-1H-imidazoles。放射性配体结合用于研究合成化合物对神经元 NMDA 受体的影响。
• A Simple Synthesis of Alkyl 2-Aminobenzo[b]thiophene-3-carboxylates via an Unexpected Dehydrogenation of Alkyl 2-Amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylates
  作者：Mehdi Adib、Maryam Bayanati、Mehdi Soheilizad、Helia Ghazvini、Mahmood Tajbakhsh、Massoud Amanlou

  DOI：10.1055/s-0034-1379475

  日期：——

  A simple method for the preparation of alkyl 2-aminobenzo[b]thiophene-3-carboxylates is described. Alkyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylates, generated from the Gewald three-component reaction between cyclohexanones, alkyl cyanoacetates and sulfur, undergo dehydrogenation in benzonitrile under an air atmosphere to afford alkyl 2-aminobenzo[b]thiophene-3-carboxylates in good to excellent yields.