2-thioxo-2,5,6,7,8,9-hexahydro-1H-cyclohepta[b]pyridine-3-carbonitrile | 123413-84-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-thioxo-2,5,6,7,8,9-hexahydro-1H-cyclohepta[b]pyridine-3-carbonitrile
• 英文别名: 2-sulfanylidene-1,5,6,7,8,9-hexahydrocyclohepta[b]pyridine-3-carbonitrile
• CAS: 123413-84-3
• 化学式: C₁₁H₁₂N₂S
• mdl: MFCD00459741
• 分子量: 204.296
• InChiKey: KIHZYQBHSQBGAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-thioxo-2,5,6,7,8,9-hexahydro-1H-cyclohepta[b]pyridine-3-carbonitrile 在 三乙胺 作用下， 以 乙醇 为溶剂， 生成 propan-2-yl 6-amino-5-cyano-2-[(3-cyano-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-2-yl)sulfanylmethyl]-4-(6-nitro-1,3-benzodioxol-5-yl)-4H-pyran-3-carboxylate
  参考文献：
  名称：

  4-(3-氰基吡啶-2-基硫基)乙酰乙酸酯在杂环合成中的应用

  摘要：

  取代的 2-amino-4-aryl-3-cyano-5-oxo-5,6-dihydro-4H-pyrano[2,3-d]pyrido[3",2":4,5]thieno[3,2 -b]吡啶是通过 4-羟基-1H-噻吩并[2,3-b;4,5-b]二吡啶-2-酮与亚芳基丙二腈的反应或羟基噻吩二吡啶酮与醛和丙二腈的三组分反应合成的在三乙胺存在下的 DMF 中。在4-(3-cyanopyridin-2-)反应的基础上,开发了取代3-烷氧基羰基-6-氨基-4-芳基-2-(3-氰基吡啶-2-基硫甲基)-4H-吡喃的合成方法。硫代)乙酰乙酸酯和亚芳基丙二腈或醛和丙二腈。4-(3-氰基吡啶-2-基硫基)乙酰乙酸乙酯和4-甲氧基亚苄基氰基硫代乙酰胺用于合成6-(吡啶-2-基硫甲基)-3-氰基吡啶-2(1H)-硫酮。

  DOI：

  10.1023/b:rucb.0000011877.60574.34
• 作为产物：
  描述：

  环庚酮 在 sodium methylate 、 哌啶乙酸盐 作用下， 以 甲醇 、 水 为溶剂， 反应 16.0h， 生成 2-thioxo-2,5,6,7,8,9-hexahydro-1H-cyclohepta[b]pyridine-3-carbonitrile
  参考文献：
  名称：

  A synthesis, in silico, in vitro and in vivo study of thieno[2,3-b]pyridine anticancer analogues

  摘要：

  吡啶并噻吩[2,3-b]吡啶与TDP1结合，最佳类似物为9d，IC₅₀为0.5 μM。

  DOI：

  10.1039/c5md00245a
• 作为试剂：
  描述：

  2-(hydroxymethylene)cycloheptanone 、 2-氰基硫代乙酰胺 、 哌啶 、 溶剂黄146 在 2-thioxo-2,5,6,7,8,9-hexahydro-1H-cyclohepta[b]pyridine-3-carbonitrile 、 水 作用下， 以 水 为溶剂， 反应 0.25h， 生成 2-thioxo-2,5,6,7,8,9-hexahydro-1H-cyclohepta[b]pyridine-3-carbonitrile
  参考文献：
  名称：

  Thienopyridine Derivatives for the Treatment and Prevention of Dengue Virus Infections

  摘要：

  本发明揭示了使用某些噻唑吡啶衍生物化合物以治疗病毒感染的方法和制药组合物，通过以治疗有效剂量给药。同时还揭示了使用这些化合物和制药组合物的方法。具体地，揭示了治疗由黄热病毒、日本脑炎病毒、西尼罗河病毒、登革热病毒和蜱媒脑炎病毒等引起的病毒感染的方法。

  公开号：

  US20130129677A1

文献信息

• Substituted 4-(3-Cyanopyridin-2-ylthio)acetoacetates: New Convenient Reagents for the Synthesis of Heterocycles
  作者：Lyudmila Rodinovskaya、Anatoliy Shestopalov、Anna Gromova、Alexander Shestopalov

  DOI：10.1055/s-2006-942433

  日期：——

  Polyfunctional 4-(3-cyanopyridin-2-ylthio)acetoacetates were used in the synthesis of 4-hydroxy-1H-thieno[2,3-b:4,5-b]dipyridin-2-ones. The latter were used in reactions with arylidene-malononitriles or in three-component reactions with aldehydes and malononitrile to give 2-amino-4-aryl-3-cyano-5-oxo-5,6-dihydro-4H-pyrano[2,3-d]pyrido[3',2':4,5]thieno[3,2-b]pyridines. Utilizing 4-(3-cyanopyridin-2

  多官能团 4-(3-cyanopyridin-2-ylthio)acetoacetates 用于合成 4-hydroxy-1H-thieno[2,3-b:4,5-b]dipyridin-2-ones。后者用于与亚芳基-丙二腈的反应或与醛和丙二腈的三组分反应，得到 2-amino-4-aryl-3-cyano-5-oxo-5,6-dihydro-4H-pyrano[2, 3-d]吡啶并[3',2':4,5]噻吩并[3,2-b]吡啶。利用 4-(3-cyanopyridin-2-ylthio)acetoacetates 和亚芳基丙二腈或醛和丙二腈，我们开发了一种合成取代的 3-alkoxycarbonyl-6-amino-4-aryl-2-(3-cyanopyridin-2-基硫甲基）-4H-吡喃。取代的 4-(3-cyanopyridin-2-ylthio)acetoacetates 与水合肼反应生成取代的
• Synthesis and antiproliferative activity of 2-chlorophenyl carboxamide thienopyridines
  作者：Michelle van Rensburg、Euphemia Leung、Natalie A. Haverkate、Chatchakorn Eurtivong、Lisa I. Pilkington、Jóhannes Reynisson、David Barker

  DOI：10.1016/j.bmcl.2016.12.009

  日期：2017.1

  3-Amino-2-arylcarboxamide-thieno[2,3-b]pyridines are a known class of antiproliferative compounds with activity against the phospholipase C enzyme. To further investigate the structure activity relationships of these derivatives a series of analogues were prepared modifying key functional groups. It was determined that modification of the 3-amino and 2-aryl carboxamide functionalities resulted in complete elimination of activity, whilst modification at C-5 allowed compounds of greater activity to be prepared. (C) 2016 Elsevier Ltd. All rights reserved.
• Shestopalov, A. M.; Rodinovskaya, L. A.; Sharanin, Yu. A., Journal of general chemistry of the USSR, 1988, vol. 58, # 4, p. 745 - 752
  作者：Shestopalov, A. M.、Rodinovskaya, L. A.、Sharanin, Yu. A.、Litvinov, V. P.

  DOI：——

  日期：——
• A convenient synthesis of 5-deaza nonclassical antifolates: Reaction of cyanothioacetamide with sodium salts of 2-(hydroxymethylene)-1-cycloalkanones
  作者：Galal E.H. Elgemeie、Badria A.W. Hussain

  DOI：10.1016/s0040-4020(01)80745-6

  日期：1994.4

  Condensation of cyanothioacetamide with sodium salts of 2-(Hydroxymethylene)-1-cycloalkanones afforded the corresponding pyridine-2(1H)-thiones 4. Compounds 4 served as a key intermediates for the synthesis of condensed 2,4-diaminopyrido[2,3-d]pyridines 7. Compounds 7 were of interest as potential inhibitors of dihydrofolate reductase.
• 3-Amino-thieno[2,3-b]pyridines as microtubule-destabilising agents: Molecular modelling and biological evaluation in the sea urchin embryo and human cancer cells
  作者：Chatchakorn Eurtivong、Victor Semenov、Marina Semenova、Leonid Konyushkin、Olga Atamanenko、Jóhannes Reynisson、Alex Kiselyov

  DOI：10.1016/j.bmc.2016.11.041

  日期：2017.1

  A series of 3-amino-thieno[2,3-b]pyridines was prepared and tested in a phenotypic sea urchin embryo assay to identify potent and specific molecules that affect tubulin dynamics. The most active compounds featured a tricyclic core ring system with a fused cycloheptyl or cyclohexyl substituent and unsubstituted or alkyl-substituted phenyl moiety tethered via a carboxamide. Low nano-molar potency was observed in the sea urchin embryos for the most active compounds (1-5) suggestive of a microtubule-destabilising effect. The molecular modelling studies indicated that the tubulin colchicine site is inhibited, which often leads to microtubule-destabilisation in line with the sea urchin embryo results. Finally, the identified hits displayed a robust growth inhibition (GI(50) of 50-250 nM) of multidrug-resistant melanoma MDA-MB-435 and breast MDA-MB-468 human cancer cell lines. This work demonstrates that for the thieno[2,3-b]pyridines the most effective mechanism of action is microtubule-destabilisation initiated by binding to the colchicine pocket. (C) 2016 Elsevier Ltd. All rights reserved.