(3-amino-4,6-dimethylthieno[2,3-b]pyridin-2-yl)(4-hydroxyphenyl)methanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3-amino-4,6-dimethylthieno[2,3-b]pyridin-2-yl)(4-hydroxyphenyl)methanone
• 英文别名: (3-Amino-4,6-dimethylthieno[2,3-b]pyridin-2-yl)-(4-hydroxyphenyl)methanone
• 化学式: C₁₆H₁₄N₂O₂S
• 分子量: 298.365
• InChiKey: OIZBQYWDYBMWGF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3-amino-4,6-dimethylthieno[2,3-b]pyridin-2-yl)(4-hydroxyphenyl)methanone 在 human hepatocyte 作用下， 生成 4-[(3-Amino-4,6-dimethylthieno[2,3-b]pyridin-2-yl)-hydroxymethyl]phenol
  参考文献：
  名称：

  基于不可烯化的酮核的一系列新型，有效的中枢神经系统渗透剂M 4 PAM的发现和合成孔径雷达：处置方面的挑战

  摘要：

  这封信描述了基于不可烯化酮核的一系列新型M 4 PAM的化学优化，该酮核是从MLPCN功能性高通量筛选中鉴定出来的。HTS命中力强，选择性强且具有CNS渗透性；但是，该化合物在体外和体内均高度清除。SAR提供了维持M 4 PAM效力和CNS暴露的类似物。但是，清除率仍然很高。代谢物鉴定研究表明，该系列产品经历了快速且接近定量的还原代谢，转化为相应的没有M 4 PAM活性的仲醇代谢物。

  DOI：

  10.1016/j.bmcl.2016.07.042
• 作为产物：
  描述：

  2-cyano-2-cyclohexylidenethioacetamide 在 氢氧化钾 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 (3-amino-4,6-dimethylthieno[2,3-b]pyridin-2-yl)(4-hydroxyphenyl)methanone
  参考文献：
  名称：

  Synthesis of Substituted 1,3-Cyclohexadienes, Pyridine-2(1H)-thiones, and Thieno[2,3-d]pyrimidine- 4(3H)-thiones by the Michael Reaction

  摘要：

  Cyclopentylidene- and cyclohexylidene(cyano)acetamides reacted with malononitrile and cyano-(thioacetamide) according to the Michael pattern with exchange of the methylene components to give substituted 1-amino-2,6,6-tricyano-1,3-cyclohexadienes and thieno[2,3-d]pyrimidine-4(3H)-thiones. Condensation of cyclopentylidene- and cyclohexylidene(cyano)acetamide with 1,3-dicarbonyl compounds afforded 4,6-dimethyl-3-cyanopyridine-2(1H)-thione and morpholinium 4-methyl-6-oxo-3-cyano-1,6-dihydropyridine-2-thiolate which were converted into substituted 2-alkylsulfanylpyridines, thieno[2,3-b]pyridines, thiazolo[3,2-a]pyridine, and 2H-[1,3]thiazino[3,2-a]pyridine.

  DOI：

  10.1023/b:rujo.0000034978.81993.bd

文献信息

• An expedient synthesis of novel bis[thienopyridines] linked to arene or heteroarene core as novel hybrid molecules
  作者：Mostafa E. Salem、Ahmed H. M. Elwahy、Ahmed F. Darweesh

  DOI：10.24820/ark.5550190.p011.297

  日期：——

  A series of novel bis(thieno[2,3-b]pyridines) based arenes or heteroarenes have been synthesized from the appropriate bisbromoacetyl derivatives upon treatment with the corresponding 2-mercaptonicotinonitrile derivatives in ethanolic sodium ethoxide at reflux. Attempts to synthesize these compounds via bis-alkylation of the appropriate phenol derivative with the corresponding dibromo compounds using

  在回流的乙醇钠中，用相应的 2-巯基烟腈衍生物处理合适的双溴乙酰衍生物，合成了一系列新型双（噻吩并 [2,3-b] 吡啶）基芳烃或杂芳烃。使用弱碱通过适当的苯酚衍生物与相应的二溴化合物的双烷基化来合成这些化合物的尝试没有成功。
• Synthesis of Substituted 1,3-Cyclohexadienes, Pyridine-2(1H)-thiones, and Thieno[2,3-d]pyrimidine- 4(3H)-thiones by the Michael Reaction
  作者：V. D. Dyachenko、A. D. Dyachenko、A. N. Chernega

  DOI：10.1023/b:rujo.0000034978.81993.bd

  日期：2004.3

  Cyclopentylidene- and cyclohexylidene(cyano)acetamides reacted with malononitrile and cyano-(thioacetamide) according to the Michael pattern with exchange of the methylene components to give substituted 1-amino-2,6,6-tricyano-1,3-cyclohexadienes and thieno[2,3-d]pyrimidine-4(3H)-thiones. Condensation of cyclopentylidene- and cyclohexylidene(cyano)acetamide with 1,3-dicarbonyl compounds afforded 4,6-dimethyl-3-cyanopyridine-2(1H)-thione and morpholinium 4-methyl-6-oxo-3-cyano-1,6-dihydropyridine-2-thiolate which were converted into substituted 2-alkylsulfanylpyridines, thieno[2,3-b]pyridines, thiazolo[3,2-a]pyridine, and 2H-[1,3]thiazino[3,2-a]pyridine.
• Discovery and SAR of a novel series of potent, CNS penetrant M4 PAMs based on a non-enolizable ketone core: Challenges in disposition
  作者：Michael R. Wood、Meredith J. Noetzel、James C. Tarr、Alice L. Rodriguez、Atin Lamsal、Sichen Chang、Jarrett J. Foster、Emery Smith、Peter Chase、Peter S. Hodder、Darren W. Engers、Colleen M. Niswender、Nicholas J. Brandon、Michael W. Wood、Mark E. Duggan、P. Jeffrey Conn、Thomas M. Bridges、Craig W. Lindsley

  DOI：10.1016/j.bmcl.2016.07.042

  日期：2016.9

  This Letter describes the chemical optimization of a novel series of M4 PAMs based on a non-enolizable ketone core, identified from an MLPCN functional high-throughput screen. The HTS hit was potent, selective and CNS penetrant; however, the compound was highly cleared in vitro and in vivo. SAR provided analogs for which M4 PAM potency and CNS exposure were maintained; yet, clearance remained high

  这封信描述了基于不可烯化酮核的一系列新型M 4 PAM的化学优化，该酮核是从MLPCN功能性高通量筛选中鉴定出来的。HTS命中力强，选择性强且具有CNS渗透性；但是，该化合物在体外和体内均高度清除。SAR提供了维持M 4 PAM效力和CNS暴露的类似物。但是，清除率仍然很高。代谢物鉴定研究表明，该系列产品经历了快速且接近定量的还原代谢，转化为相应的没有M 4 PAM活性的仲醇代谢物。