1-(furan-2-yl)-3-(1-methyl-1H-indol-3-yl)-3-(methylthio)-prop-2-en-1-one | 1416249-59-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-(furan-2-yl)-3-(1-methyl-1H-indol-3-yl)-3-(methylthio)-prop-2-en-1-one
• 英文别名: 1-(Furan-2-yl)-3-(1-methylindol-3-yl)-3-methylsulfanylprop-2-en-1-one
• CAS: 1416249-59-6
• 化学式: C₁₇H₁₅NO₂S
• 分子量: 297.378
• InChiKey: RQMLHPSQTZGRLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(furan-2-yl)-3-(1-methyl-1H-indol-3-yl)-3-(methylthio)-prop-2-en-1-one 在 盐酸羟胺 、 barium(II) hydroxide 作用下， 以 乙醇 为溶剂， 以74%的产率得到2-[3-(furan-2-yl)isoxazol-5-yl]-1-methyl-1H-indole
  参考文献：
  名称：

  羟胺与 1,3-双（杂）芳基单硫代 1,3-二酮和 1,3-双（杂）芳基-3-（甲硫基）-2-丙烯酮的环缩合反应：合成 3,5-双（杂）芳基异恶唑具有互补区域选择性

  摘要：

  已经开发了区域选择性合成具有互补区域选择性的 3,5-双（杂）芳基异恶唑的有效途径。该方法包括盐酸羟胺与 1,3-双（杂）芳基-单硫代取代的 1,3-二酮 1 或与 3-甲硫基-1,3-双（杂）芳基-2-丙烯酮 2 在各种反应条件。在第一个方案中，在醋酸钠/醋酸（pH 2.2）的存在下，在回流的乙醇/苯中用盐酸羟胺处理二酮 1，得到 3,5-双（杂）芳基异恶唑 5，其中杂（芳基）与单硫代取代的 1,3-二酮的硫代羰基相连的部分位于 3-位。另一方面，盐酸羟胺与3-(甲硫基)-1反应，3-双(杂)芳基-2-丙烯酮2在氢氧化钡存在下在回流乙醇中以高产率得到具有互补区域选择性的3,5-双(杂)芳基异恶唑6。已经提出了由前体 1 和 2 形成区域异构异恶唑 5 和 6 的可能机制。

  DOI：

  10.1002/ejoc.201301667
• 作为产物：
  描述：

  methyl 1-methyl-1H-indole-3-carbodithioate 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 1-(furan-2-yl)-3-(1-methyl-1H-indol-3-yl)-3-(methylthio)-prop-2-en-1-one
  参考文献：
  名称：

  Cyclocondensation of Arylhydrazines with 1,3-Bis(het)arylmonothio-1,3-diketones and 1,3-Bis(het)aryl-3-(methylthio)-2-propenones: Synthesis of 1-Aryl-3,5-bis(het)arylpyrazoles with Complementary Regioselectivity

  摘要：

  Two efficient highly regioselective routes for the synthesis of unsymmetrically substituted 1-aryl-3,5-bis(het)arylpyrazoles with complementary regioselectivity starting from active methylene ketones have been reported. In the first protocol, the newly synthesized 1,3-bis(het)aryl-monothio-1,3-diketone precursors (prepared by condensation of active methylene ketones with het(aryl) dithioesters in the presence of sodium hydride) were reacted with arylhydrazines in refluxing ethanol under neutral conditions, furnishing 1-aryl-3,5-bis(het)arylpyrazoles 7, in which the het(aryl) moiety attached to the thiocarbonyl group of monothio-1,3-diketones is installed at the 3-position. In the second method, the corresponding 3-(methylthio)-1,3-bis(het)aryl-2-propenones (prepared in situ by base-induced alkylation of 1,3-monothiodiketones) were condensed with arylhydrazines in the presence of potassium tert-butoxide in. refluxing tert-butyl alcohol, yielding 1-aryl-3,5-bis(het)arylpyrazoles 9 with complementary regioselectivity (method A). The efficiency of this protocol was further improved by developing a one-pot, three-component procedure for the synthesis of pyrazoles 9, directly from active methylene ketones, by reacting in situ generated 3-(methylthio)-1,3-bis(het)aryl-2-propenones with arylhydrazines in the presence of sodium hydride (instead of potassium tert-butoxide as base). The structures and regiochemistry of newly synthesized pyrazoles were confirmed from their spectral and analytical data along with X-ray crystallographic data of three pairs of regioisomers.

  DOI：

  10.1021/jo400599e

文献信息

• Anti-Cancer Activity of 2,4-Disubstituted Thiophene Derivatives: Dual Inhibitors of Lipoxygenase and Cyclooxygenase
  作者：Kodagahalli Rakesh、Swamy Jagadish、Toreshettahally Swaroop、Chakrabhavi Mohan、Nanjundaswamy Ashwini、Kachigere Harsha、Farhan Zameer、Kesturu Girish、Kanchugarakoppal Rangappa

  DOI：10.2174/1573406411666141210141918

  日期：2015.6.30

  2,4-Disubstituted thiophene derivatives were synthesized and assessed for antiinflammatory and anti-cancer activities by targeting two important enzymes of the arachidonic acid metabolism. Both lipoxygenase and cyclooxygenase enzymes play vital role in chronic inflammation and carcinogenesis. Previous studies have proved that COX-2 and 5-LOX are highly activated in various types of cancers; hence inhibition of these clinically important enzymes constitutes the essential criterion for the suppression of tumor progression and metastasis. Among the tested derivatives, 2d and 2g compounds emerged as potent inhibitors of lipoxygenase and cyclooxygenase enzymes. The potent inhibitor of cyclooxygenase was further tested for in vitro cytotoxicity on cervical cancer (HeLa) cells and in vivo tumor model studies using EAT bearing mice where 2-(3,4,5- trimethoxyphenyl)-4-(N-methylindol-3-yl) thiophene (2g) showed eloquent activity. Further, in silico modeling results confirmed the active catalytic ligand binding pockets, which is evident from higher atomic contact energy values of 2d and 2g than compared to standard drug. Thus, 2g may find better application in management of inflammation and in proapoptotic therapeutic engineering.

  合成了2,4-二取代噻吩衍生物，并针对花生四烯酸代谢中的两个重要酶系评估了其抗炎和抗癌活性。脂氧合酶和环氧合酶在慢性炎症和致癌过程中起着至关重要的作用。先前的研究表明，COX-2和5-LOX在多种癌症类型中高度激活；因此，抑制这些临床重要酶系构成了抑制肿瘤进展和转移的基本标准。在测试的衍生物中，2d和2g化合物作为脂氧合酶和环氧合酶的强效抑制剂脱颖而出。进一步对环氧合酶的强效抑制剂进行了体外细胞毒性测试，针对宫颈癌细胞（HeLa细胞）和使用EAT荷瘤小鼠的体内肿瘤模型研究，其中2-(3,4,5-三甲氧基苯基)-4-(N-甲基吲哚-3-基)噻吩（2g）表现出显著活性。此外，计算模型结果证实了活性催化配体结合口袋的存在，这从2d和2g的高原子接触能值与标准药物相比得到了证实。因此，2g可能在炎症管理和促凋亡治疗工程中得到更好的应用。
• Attempted Simmon–Smith reaction on β-alkylthio-α,β-unsaturated ketones: a regiospecific synthesis of 2,4-disubstituted thiophenes
  作者：Toreshettahally R. Swaroop、Rangaswamy Roopashree、Hiriyakkanavar Ila、Kanchugarakoppal S. Rangappa

  DOI：10.1016/j.tetlet.2012.10.110

  日期：2013.1

  A new regiospecific route to 2,4-disubstituted thiophenes has been developed through Simmon-Smith reaction on beta-methylthio-alpha,beta-unsaturated ketones. Extension of the reaction to beta-ethylibenzylthio-alpha,beta-unsaturated ketones also gave the corresponding 2,4-disubstituted thiophenes in a regiospecific manner. A probable mechanism involving a carbenoid methylene insertion to divalent sulfur followed by intramolecular aldol condensation has been suggested.[GRAPHICS](C) 2012 Elsevier Ltd. All rights reserved.