5-cyano-6-mercapto-4-methyl-2(1H)-pyridinone | 93272-85-6

• 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: 5-cyano-6-mercapto-4-methyl-2(1H)-pyridinone
• 英文别名: 2-mercapto-4-methyl-6-oxo-1,6-dihydropyridine-3-carbonitrile；1,6-dihydro-2-mercapto-4-methyl-6-oxopyridine-3-carbonitrile；4-methyl-6-oxo-2-sulfanyl-1H-pyridine-3-carbonitrile
• CAS: 93272-85-6
• 化学式: C₇H₆N₂OS
• mdl: MFCD06652478
• 分子量: 166.203
• InChiKey: QNEWVOYCROIYKG-UHFFFAOYSA-N

物化性质

• 熔点：
  270-271 °C (decomp)
• 沸点：
  314.7±42.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  53.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-cyano-6-mercapto-4-methyl-2(1H)-pyridinone 在 lithium hydroxide monohydrate 、 水 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 3-(((3-cyano-4-methyl-6-oxo-1,6-dihydropyridin-2-yl)thio)methyl)benzoic acid
  参考文献：
  名称：

  [EN] OXOPYRIDINE DERIVATIVES USEFUL AS AMINOCARBOXYMUCONATE SEMIALDEHYDE DECARBOXYLASE (ACMSD) INHIBITORS
  [FR] DÉRIVÉS D'OXOPYRIDINE UTILES EN TANT QU'INHIBITEURS DE LA SEMIALDÉHYDE DÉCARBOXYLASE D'AMINOCARBOXYMUCONATE (ACMSD)

  摘要：

  公开号：

  WO2018125983A8
• 作为产物：
  描述：

  morpholinium 3-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-thiolate 在 盐酸 作用下， 以 水 为溶剂， 以6.83 g的产率得到5-cyano-6-mercapto-4-methyl-2(1H)-pyridinone
  参考文献：
  名称：

  Structure–Activity Relationships of Privileged Structures Lead to the Discovery of Novel Biased Ligands at the Dopamine D₂ Receptor

  摘要：

  Biased agonism at GPCRs highlights the potential for the discovery and design of pathway-selective ligands and may confer therapeutic advantages to ligands targeting the dopamine D-2 receptor (D2R). We investigated the determinants of efficacy, affinity, and bias for three privileged structures for the D2R, exploring changes to linker length and incorporation of a heterocyclic unit. Profiling the compounds in two signaling assays (cAMP and pERK1/2) allowed us to identify and quantify determinants of biased agonism at the D2R. Substitution on the phenylpiperazine privileged structures (2-methoxy vs 2,3-dichloro) influenced bias when the thienopyridine heterocycle was absent. Upon inclusion of the thienopyridine unit, the substitution pattern (4,6-dimethyl vs 5-chloro-6-methoxy-4-methyl) had a significant effect on bias that overruled the effect of the phenylpiperazine substitution pattern. This latter observation could be reconciled with an extended binding mode for these compounds, whereby the interaction of the heterocycle with a secondary binding pocket may engender bias.

  DOI：

  10.1021/jm500457x

文献信息

• 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。
• The discovery of thienopyridine analogues as potent IκB kinase β inhibitors. Part II
  作者：Jiang-Ping Wu、Roman Fleck、Janice Brickwood、Alison Capolino、Katrina Catron、Zhidong Chen、Charles Cywin、Jonathan Emeigh、Melissa Foerst、John Ginn、Matt Hrapchak、Eugene Hickey、Ming-Hong Hao、Mohammed Kashem、Jun Li、Weimin Liu、Tina Morwick、Richard Nelson、Daniel Marshall、Leslie Martin、Peter Nemoto、Ian Potocki、Michel Liuzzi、Gregory W. Peet、Erika Scouten、David Stefany、Michael Turner、Steve Weldon、Clare Zimmitti、Denise Spero、Terence A. Kelly

  DOI：10.1016/j.bmcl.2009.08.054

  日期：2009.10

  An SAR study that identified a series of thienopyridine-based potent I kappa B Kinase beta (IKK beta) inhibitors is described. With focuses on the structural optimization at C(4) and C(6) of structure 1 (Fig. 1), the study reveals that small alkyl and certain aromatic groups are preferred at C(4), whereas polar groups with proper orientation at C(6) efficiently enhance compound potency. The most potent analogues inhibit IKKb with IC(50)s as low as 40 nM, suppress LPS-induced TNF-alpha production in vitro and in vivo, display good kinase selectivity profiles, and are active in a HeLa cell NF-kappa B reporter gene assay, demonstrating that they directly interfere with the NF-kappa B signaling pathway. (C) 2009 Elsevier Ltd. All rights reserved.
• Dyachenko, V. D.; Sharanin, Yu. A.; Shestopalov, A. M., Journal of general chemistry of the USSR, 1990, vol. 60, # 10, p. 2131 - 2138
  作者：Dyachenko, V. D.、Sharanin, Yu. A.、Shestopalov, A. M.、Rodinovskaya, L. A.、Turov, A. V.、et al.

  DOI：——

  日期：——
• Wagner; Vieweg; Leistner, Pharmazie, 1990, vol. 45, # 2, p. 102 - 109
  作者：Wagner、Vieweg、Leistner、Bohm、Krasselt、Hanfe ld、Prantz、Grupe

  DOI：——

  日期：——
• New method of synthesis of substituted 2-pyridones
  作者：V. P. Litvinov、Yu. A. Sharanin、B. K. Promonenkov、L. A. Rodinovskaya、A. M. Shestopalov、V. Yu. Mortikov

  DOI：10.1007/bf00959212

  日期：1984.8