methyl 3-amino-6-methyl-1-benzo[b]thiophene-2-carboxylate | 1427420-06-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: methyl 3-amino-6-methyl-1-benzo[b]thiophene-2-carboxylate
• 英文别名: methyl 3-amino-6-methylbenzo[b]thiophene-2-carboxylate；Methyl 3-amino-6-methyl-1-benzothiophene-2-carboxylate
• CAS: 1427420-06-1
• 化学式: C₁₁H₁₁NO₂S
• 分子量: 221.28
• InChiKey: WAXJPGUKZXMRQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 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 3-amino-6-methyl-1-benzo[b]thiophene-2-carboxylate 在 亚硝酸特丁酯 、 cesium bicarbonate 、 palladium diacetate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 copper(ll) bromide 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 20.0h， 生成 Methyl 6-methyl-3-(3,4,5-trimethoxyanilino)-1-benzothiophene-2-carboxylate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 2-(Alkoxycarbonyl)-3-Anilinobenzo[b]thiophenes and Thieno[2,3-b]pyridines as New Potent Anticancer Agents

  摘要：

  Two new series of inhibitors of tubulin polymerization based on the 2-(alkoxycarbonyl)-3-(3',4',5'-trimethoxyanilino)benzo[b]thiophene and thieno[2,3-b]pyridine molecular skeletons were synthesized and evaluated for antiproliferative activity on a panel of cancer cell lines, inhibition of tubulin polymerization, cell cycle effects, and in vivo potency. Antiproliferative activity was strongly dependent on the position of the methyl group on the benzene portion of the benzo[b]thiophene nucleus, with the greatest activity observed when the methyl was located at the C-6 position. Also, in the smaller thieno[2,3-b]pyridine series, the introduction of the methyl group at the C-6 position resulted in improvement of antiproliferative activity to the nanomolar level. The most active compounds (4i and 4n) did not induce cell death in normal human lymphocytes, suggesting that the compounds may be selective against cancer cells. Compound 4i significantly inhibited in vivo the growth of a syngeneic hepatocellular carcinoma in Balb/c mice.

  DOI：

  10.1021/jm400043d
• 作为产物：
  描述：

  4-甲基-2-硝基苯腈 、 巯基乙酸甲酯 在 水 、 potassium hydroxide 作用下， 以 乙二醇二甲醚 为溶剂， 反应 1.0h， 以48%的产率得到methyl 3-amino-6-methyl-1-benzo[b]thiophene-2-carboxylate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 2-(Alkoxycarbonyl)-3-Anilinobenzo[b]thiophenes and Thieno[2,3-b]pyridines as New Potent Anticancer Agents

  摘要：

  Two new series of inhibitors of tubulin polymerization based on the 2-(alkoxycarbonyl)-3-(3',4',5'-trimethoxyanilino)benzo[b]thiophene and thieno[2,3-b]pyridine molecular skeletons were synthesized and evaluated for antiproliferative activity on a panel of cancer cell lines, inhibition of tubulin polymerization, cell cycle effects, and in vivo potency. Antiproliferative activity was strongly dependent on the position of the methyl group on the benzene portion of the benzo[b]thiophene nucleus, with the greatest activity observed when the methyl was located at the C-6 position. Also, in the smaller thieno[2,3-b]pyridine series, the introduction of the methyl group at the C-6 position resulted in improvement of antiproliferative activity to the nanomolar level. The most active compounds (4i and 4n) did not induce cell death in normal human lymphocytes, suggesting that the compounds may be selective against cancer cells. Compound 4i significantly inhibited in vivo the growth of a syngeneic hepatocellular carcinoma in Balb/c mice.

  DOI：

  10.1021/jm400043d

文献信息

• 2-Amino-4-aryl thiazole: a promising scaffold identified as a potent 5-LOX inhibitor
  作者：Shweta Sinha、T. V. Sravanthi、S. Yuvaraj、S. L. Manju、Mukesh Doble

  DOI：10.1039/c5ra28187c

  日期：——

  (1d), p-fluoro substituted 2-amino-4-aryl thiazole, with an IC50 of ∼10 μM. Another lead compound identified is (4a), a thiazolopyrazole acid derivative (IC50 ∼ 40 μM). All the compounds exhibit poor DPPH radical scavenging activity which suggests that their action occurs not due to the disruption of the redox cycle of iron present in the enzyme (unlike zileuton) but through competitive inhibition, since

  人5-脂氧合酶（5-LOX）是白三烯生物合成中的重要酶，并且是哮喘和变态反应治疗的靶标。齐留通是目前市售的该目标的这种酶（IC的唯一药物50〜1μM）。因此，非常需要开发新的先导化合物。一系列2-芳基吲哚，噻唑并吡唑酸，恶二唑并苯并噻吩，1,4-二取代-1,2,3-三唑，2-氨基-4-芳基噻唑和4,4'-（1,4-亚苯基）双（当针对此酶进行测试时，发现1,3,3-噻唑）衍生物可鉴定出有效的化合物（1d），即对氟取代的2-氨基-4-芳基噻唑，IC 50约为10μM。鉴定出的另一种铅化合物是（4a）噻唑并吡唑酸衍生物（IC50〜40微米）。所有化合物均表现出差的DPPH自由基清除活性，这表明它们的作用并非由于破坏了酶中存在的铁的氧化还原循环（与齐留通不同），而是由于竞争抑制，因为V max保持恒定，但K m增加随着抑制剂浓度的增加。1d和4a与5-LOX活性位点的分子对接也支持实验数据，并表明
• Cu-Catalyzed Denitrogenative Transannulation of 3-Aminoindazoles To Assemble 1-Aminoisoquinolines and 3-Aminobenzothiophenes
  作者：Yao Zhou、Ya Wang、Yixian Lou、Qiuling Song

  DOI：10.1021/acs.orglett.9b02288

  日期：2019.11.15

  We disclose a novel Cu-catalyzed denitrogenative transannulation of 3-aminoindazoles to afford diverse functionalized 3-aminobenzothiophenes and 1-aminoisoquinolines, in which denitrogenative transannulation of 3-aminoindazoles is reported for the first time. This transformation proceeds via an "extrude-and-sew" strategy with an unprecedented radical reactivity of 3-aminoindazoles.
• Synthesis and Biological Evaluation of 2-(Alkoxycarbonyl)-3-Anilinobenzo[<i>b</i>]thiophenes and Thieno[2,3-<i>b</i>]pyridines as New Potent Anticancer Agents
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Maria Kimatrai Salvador、Delia Preti、Mojgan Aghazadeh Tabrizi、Marcella Bassetto、Andrea Brancale、Ernest Hamel、Ignazio Castagliuolo、Roberta Bortolozzi、Giuseppe Basso、Giampietro Viola

  DOI：10.1021/jm400043d

  日期：2013.3.28

  Two new series of inhibitors of tubulin polymerization based on the 2-(alkoxycarbonyl)-3-(3',4',5'-trimethoxyanilino)benzo[b]thiophene and thieno[2,3-b]pyridine molecular skeletons were synthesized and evaluated for antiproliferative activity on a panel of cancer cell lines, inhibition of tubulin polymerization, cell cycle effects, and in vivo potency. Antiproliferative activity was strongly dependent on the position of the methyl group on the benzene portion of the benzo[b]thiophene nucleus, with the greatest activity observed when the methyl was located at the C-6 position. Also, in the smaller thieno[2,3-b]pyridine series, the introduction of the methyl group at the C-6 position resulted in improvement of antiproliferative activity to the nanomolar level. The most active compounds (4i and 4n) did not induce cell death in normal human lymphocytes, suggesting that the compounds may be selective against cancer cells. Compound 4i significantly inhibited in vivo the growth of a syngeneic hepatocellular carcinoma in Balb/c mice.