3-氨基-6-甲氧基-1-苯并[b]噻吩-2-羧酸甲酯 | 189439-55-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 中文名称: 3-氨基-6-甲氧基-1-苯并[b]噻吩-2-羧酸甲酯
• 英文名称: methyl 3-amino-6-methoxy-1-benzo[b]thiophene-2-carboxylate
• 英文别名: methyl 3-amino-6-methoxybenzo[b]thiophene-2-carboxylate；methyl 3-amino-6-methoxy-1-benzothiophene-2-carboxylate
• CAS: 189439-55-2
• 化学式: C₁₁H₁₁NO₃S
• 分子量: 237.279
• InChiKey: VZWRCBXURPSNIX-UHFFFAOYSA-N

物化性质

• 沸点：
  399.6±37.0 °C(Predicted)
• 密度：
  1.338±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  89.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-氨基-6-甲氧基-1-苯并[b]噻吩-2-羧酸甲酯 在 四丁基氯化铵 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 二乙二醇二甲醚 、 乙腈 为溶剂， 生成 4-chloro-7-methoxybenzo[4,5]thieno[3,2-d]pyrimidin-2-amine
  参考文献：
  名称：

  Tricyclic aminopyrimidine histamine H4 receptor antagonists

  摘要：

  This report discloses the development of a series of tricyclic histamine H-4 receptor antagonists. Starting with a low nanomolar benzofuranopyrimidine HTS hit devoid of pharmaceutically acceptable properties, we navigated issues with metabolism and solubility to furnish a potent, stable and water soluble tricyclic histamine H-4 receptor antagonist with desirable physiochemical parameters which demonstrated efficacy a mouse ova model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.014
• 作为产物：
  描述：

  2-氟-4-甲氧基苯腈 、 巯基乙酸甲酯 在 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-氨基-6-甲氧基-1-苯并[b]噻吩-2-羧酸甲酯
  参考文献：
  名称：

  Tricyclic aminopyrimidine histamine H4 receptor antagonists

  摘要：

  This report discloses the development of a series of tricyclic histamine H-4 receptor antagonists. Starting with a low nanomolar benzofuranopyrimidine HTS hit devoid of pharmaceutically acceptable properties, we navigated issues with metabolism and solubility to furnish a potent, stable and water soluble tricyclic histamine H-4 receptor antagonist with desirable physiochemical parameters which demonstrated efficacy a mouse ova model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.014

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
• Synthesis of [1]benzothieno[3,2-<i>d</i>]pyrimidines substituted with electron donating substituents on the benzene ring
  作者：Alexander J. Bridges、Hairong Zhou

  DOI：10.1002/jhet.5570340412

  日期：1997.7

  2-fluorobenzonitriles were converted to the corresponding 3-amino[1]benzothiophenecarboxylic acid esters, which in turn were annulated with formamidine or various equivalents to produce the desired tricyclic benzothienopyrimidines. Various methoxy and nitro/amino substituents were placed on the phenyl ring, requiring several different strategies to prepare the desired benzothiophenes. Several different pyrimidone annulations

  将各种2-氟苄腈转化为相应的3-氨基[1]苯并噻吩羧酸酯，然后将其与甲am或各种等价物进行环化，生成所需的三环苯并噻吩并嘧啶。将各种甲氧基和硝基/氨基取代基置于苯环上，需要几种不同的策略来制备所需的苯并噻吩。还需要几种不同的嘧啶酮环化。还描述了在四步一锅式低温锂化过程中使用富电子的2-溴苄腈来生产高度富电子的氨基[1]苯并噻吩羧酸酯。7-氨基-8-氟[1]苯并噻吩并[3,2 - d ]嘧啶-4（3 H）的合成）-一种相对简单，但是合成相应的7-氨基-8-protio类似物非常困难，并且需要多种方法才能找到成功的方法。
• Oxazolidin-2-one derivatives, preparation method therefor and
  申请人：Synthelabo

  公开号：US05969146A1

  公开（公告）日：1999-10-19

  Compounds derived from oxazolidin-2-one of formula (I) ##STR1## in which: R.sub.1 represents a hydrogen atom, an alkyl group, a hydroxyalkyl group, a fluoroalkyl group, a hydroxyfluoroalkyl group, a cyanoalkyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted phenylmethyl group or an R.sub.3 A- group in which R.sub.3 is a cycloalklyl or cyclooxyalkyl group which is unsubstituted or substituted by a hydroxyl group and A is a --CH.sub.2 or --CH.sub.2 --CH.sub.2 radical, R.sub.2 represents a hydrogen atom or a methyl group, X represents an oxygen or sulphur atom or an NR.sub.4 group where R.sub.4 is an alkyl group or a hydrogen atom, and Z represents an oxygen atom or a --CH.dbd.CH or --CH.sub.2 --CH.sub.2 group, their process of preparation and their applications in therapeutics.

  从氧唑啉-2-酮衍生的化合物，其化学式为（I）##STR1##其中：R.sub.1代表氢原子、烷基、羟基烷基、氟烷基、羟基氟烷基、氰基烷基、取代或未取代苯基、取代或未取代苯甲基或R.sub.3 A-基团，其中R.sub.3是未取代或取代的环烷基或环氧烷基，A是--CH.sub.2或--CH.sub.2--CH.sub.2基团，R.sub.2代表氢原子或甲基，X代表氧原子、硫原子或NR.sub.4基团，其中R.sub.4是烷基或氢原子，Z代表氧原子或--CH.dbd.CH或--CH.sub.2--CH.sub.2基团，它们的制备过程及在治疗学中的应用。
• 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.
• Synthesis of novel 3-(aryl)benzothieno[2,3-c]pyran-1-ones from Sonogashira products and intramolecular cyclization: Antitumoral activity evaluation
  作者：Maria-João R.P. Queiroz、Ricardo C. Calhelha、Luís A. Vale-Silva、Eugénia Pinto、M. São-José Nascimento

  DOI：10.1016/j.ejmech.2008.11.002

  日期：2009.5

  Several novel 3-(aryl)benzothieno[2,3-c]pyran-1-ones (tricyclic lactones) were prepared either by a tandem one-pot Sonogashira coupling and intramolecular cyclization, reacting the 3-bromobenzo[b]thiophene-2-carboxylic acid with arylacetylenes, or by Sonogashira coupling of the methyl 3-bromobenzo[b]thiophene-2-carboxylate or the methyl 3-bromo-6-methoxybenzo[b]thiophene-2-carboxylate with arylacetylenes followed by an electrophilic intramolecular cyclization using iodine or TFA in two separate steps. The Sonogashira products and the tricyclic lactones obtained were evaluated for their capacity to inhibit the in vitro growth of three human tumor cell lines, MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer). Most of the compounds showed a high growth inhibitory effect on all the tested cell lines, with GI(50) values in the mu M range. A structure-activity relationship was established for the Sonogashira products and for the tricyclic lactones, namely related to the presence and position of substituents (OMe and/or F) in the benzothiophene moiety or in the phenyl ring. (C) 2008 Elsevier Masson SAS. All rights reserved.