6-pyridin-4-yl-2-sulfanylidene-1H-pyridine-3-carbonitrile

• 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: 6-pyridin-4-yl-2-sulfanylidene-1H-pyridine-3-carbonitrile
• 化学式: C₁₁H₇N₃S
• 分子量: 213.263
• InChiKey: HSRUWAZUZSWSHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-pyridin-4-yl-2-sulfanylidene-1H-pyridine-3-carbonitrile 在 三乙胺 作用下， 以 乙醇 为溶剂， 生成 ethyl 6-amino-5-cyano-2-[(3-cyano-6-pyridin-4-ylpyridin-2-yl)sulfanylmethyl]-4-pyridin-3-yl-4H-pyran-3-carboxylate
  参考文献：
  名称：

  取代的 4-(3-Cyanopyridin-2-ylthio)acetoacetates：用于合成杂环化合物的新型便捷试剂

  摘要：

  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

  DOI：

  10.1055/s-2006-942433
• 作为产物：
  描述：

  4-乙酰吡啶 、 聚合甲醛 、 2-氰基硫代乙酰胺 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 生成 6-pyridin-4-yl-2-sulfanylidene-1H-pyridine-3-carbonitrile
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2016.11.041

文献信息

• Reactions of N-(2-chloroacetyl)-α-amino acids with 3-cyanopyridine-2(1H)-thiones. New promising route to 3,4-dihydropyrido[3",2":4,5]thieno[3,2-e][1,4]diazepine-2(1H),5-diones
  作者：A. E. Fedorov、A. M. Shestopalov、P. A. Belyakov

  DOI：10.1023/b:rucb.0000011878.52263.c4

  日期：2003.10

  The reactions of N-(2-chloroacetyl)-α-amino acids with 3-cyanopyridine-2(1H)-thiones afforded N-(3-aminothieno[2,3-b]pyridin-2-ylcarbonyl)-α-amino acids. Heating of the latter smoothly produced 3,4-dihydropyrido[3",2":4,5]thieno[3,2-e][1,4]diazepine-2(1H),5-diones in high yields.

  N-(2-氯乙酰基)-α-氨基酸与 3-氰基吡啶-2(1H)-硫酮反应得到 N-(3-氨基噻吩并[2,3-b]吡啶-2-基羰基)-α-氨基酸。后者的加热平稳地以高产率产生 3,4-dihydropyrido[3",2":4,5]thieno[3,2-e][1,4]diazepine-2(1H),5-diones。
• 4-(3-Cyanopyridin-2-ylthio)acetoacetates in synthesis of heterocycles
  作者：L. A. Rodinovskaya、A. M. Shestopalov、A. V. Gromova

  DOI：10.1023/b:rucb.0000011877.60574.34

  日期：2003.10

  Substituted 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 were synthesized by the reactions of 4-hydroxy-1H-thieno[2,3-b;4,5-b]dipyridin-2-ones with arylidenemalononitriles or by the three-component reactions of hydroxythienodipyridinones with aldehydes and malononitrile in DMF in the presence of triethylamine. Methods for syntheses of substituted

  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。
• THIENO[2,3-b]PYRIDINE DERIVATIVE AND QUINOLINE DERIVATIVE, AND USE THEREOF
  申请人：The University of Tokyo

  公开号：US20190177336A1

  公开（公告）日：2019-06-13

  It is an object of the present invention to provide a compound inhibiting the binding between ALS-related mutant SOD1 and Derlin-1, a medicament comprising the compound, and a method for treating ALS by administering the medicament to a patient. More specifically, the aforementioned compound is represented by the following formula (1): wherein X represents a sulfur atom or —CH═CH—; A 1 to A 4 each independently represent a carbon atom or a nitrogen atom, and at least one of A 1 to A 4 is a nitrogen atom; R 1 represents a 1,2,3,4-tetrahydroquinolyl group (or a 3,4-dihydro-1(2H)-quinolyl group), a 3,4-dihydro-4,4-dimethyl-1(2H)-quinolyl group, a 2,3,4,5-tetrahydro-1H-1-benzazepinyl group, or a substituent represented by the following formula (2): wherein R 4 represents an unsubstituted or optionally substituted phenyl group, an unsubstituted or optionally substituted pyridyl group, or an unsubstituted or optionally substituted naphthyl group, and R 5 represents any one of a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group (optionally containing an oxygen atom and/or a double bond), or an unsubstituted or optionally substituted aromatic lower alkyl group; R 2 represents a hydrogen atom, a lower alkyl group, a lower acyl group, or an unsubstituted or optionally substituted aromatic lower alkyl group; and R 3 represents a hydrogen atom, or R 2 and R 3 may bind to each other to form a ring.

  本发明的目的是提供一种抑制ALS相关突变SOD1和Derlin-1结合的化合物，包括该化合物的药物以及通过向患者施用该药物治疗ALS的方法。具体而言，上述化合物由以下公式（1）表示：其中X表示硫原子或-CH═CH-；A1至A4分别独立表示碳原子或氮原子，且至少有一个为氮原子；R1表示1,2,3,4-四氢喹啉基（或3,4-二氢-1（2H）-喹啉基），3,4-二氢-4,4-二甲基-1（2H）-喹啉基，2,3,4,5-四氢-1H-1-苯并氮杂环基或由以下公式（2）表示的取代基：其中R4表示未取代或可选取代的苯基，未取代或可选取代的吡啶基或未取代或可选取代的萘基，而R5表示氢原子，低碳基，低烯基，低炔基（可选含氧原子和/或双键）或未取代或可选取代的芳香基低碳基中的任意一种；R2表示氢原子，低碳基，低酰基或未取代或可选取代的芳香基低碳基；而R3表示氢原子，或R2和R3可结合形成环。
• Thieno[2,3-b]pyridine derivative, quinoline derivative, and use thereof
  申请人：The University of Tokyo

  公开号：US10689394B2

  公开（公告）日：2020-06-23

  A compound represented by the following formula (1) is provided: wherein X represents a sulfur atom or —CH═CH—; A1 to A4 each independently represent a carbon atom or a nitrogen atom, and at least one of A1 to A4 is a nitrogen atom; R1 represents any one of a 1,2,3,4-tetrahydroquinolyl group (or a 3,4-dihydro-1(2H)-quinolyl group), a 3,4-dihydro-4,4-dimethyl-1(2H)-quinolyl group, a 2,3,4,5-tetrahydro-1H-1-benzazepinyl group, or a substituent represented by the following formula (2): wherein R4 represents a 2,3,4-trifluorophenyl group, a 4-iodophenyl group, a 2,3-difluorophenyl group, a 3,5-difluorophenyl group, a 5-fluoro-2-methylphenyl group, a 3-pentafluorosulfanylphenyl group, a 2,6-dimethylphenyl group, a 4-benzyloxyphenyl group, a 3,5-bis(trifluoromethyl)biphenyl group, a 4-tert-butylphenyl group, a 3-methoxyphenyl group, an unsubstituted or substituted pyridyl group, or an unsubstituted or substituted naphthyl group; R5 represents a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group optionally containing an oxygen atom and/or a double bond, or an unsubstituted or substituted aromatic lower alkyl group; R2 represents a hydrogen atom, a lower alkyl group, a lower acyl group, or an unsubstituted or substituted aromatic lower alkyl group; and R3 represents a hydrogen atom, or R2 and R3 may bind to each other to form a ring.

  提供了下式（1）所代表的化合物： 其中X代表硫原子或-CH═CH-；A1至A4各自独立地代表碳原子或氮原子，且A1至A4中至少有一个是氮原子；R1 代表 1，2，3，4-四氢喹啉基（或 3，4-二氢-1(2H)-喹啉基）、3，4-二氢-4，4-二甲基-1(2H)-喹啉基、2，3，4，5-四氢-1H-1-苯并氮杂卓基或下式(2)所代表的取代基中的任一个： 其中 R4 代表 2,3,4-三氟苯基基团、4-碘苯基基团、2,3-二氟苯基基团、3,5-二氟苯基基团、5-氟-2-甲基苯基基团、3-五氟硫代苯基基团、2,6-二甲基苯基基团4-苄氧基苯基、3,5-双（三氟甲基）联苯基、4-叔丁基苯基、3-甲氧基苯基、未取代或取代的吡啶基或未取代或取代的萘基；R5 代表氢原子、低级烷基、低级烯基、任选含有氧原子和/或双键的低级炔基、或未取代或取代的芳香族低级烷基； R2 代表氢原子、低级烷基、低级酰基、或未取代或取代的芳香族低级烷基；以及 R3 代表氢原子，或 R2 和 R3 可相互结合形成一个环。
• Reactions of (S)-N-trifluoroacetyl-5-bromo-4-oxonorvaline methyl ester with vicinal mercaptonitriles. Synthesis of δ-hetaryl-substituted α-amino acids
  作者：A. E. Fedorov、A. M. Shestopalov、P. A. Belyakov

  DOI：10.1023/b:rucb.0000009653.64403.cc

  日期：2003.9

  The reactions of (S)-N-trifluoroacetyl-5-bromo-4-oxonorvaline methyl ester with vicinal mercaptonitriles afforded delta-hetaryl-N-trifluoroacetyl-substituted alpha-amino acids (hetaryl is thiazol-2-yl, 2-thienyl, or thieno[2,3-b]pyridin-6-yl).