N-cyclohexyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: N-cyclohexyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine
• 英文别名: N-cyclohexyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-amine；N-cyclohexyl-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-amine
• 化学式: C₁₆H₂₁N₃S
• 分子量: 287.429
• InChiKey: PVIRULZHKLRIFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5,6,7,8-四氢-[1]-苯并噻吩[2,3-d]嘧啶-4(1h)-酮 在 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 异丙醇 、 甲苯 为溶剂， 反应 4.0h， 生成 N-cyclohexyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine
  参考文献：
  名称：

  Subtle modifications to a thieno[2,3-d]pyrimidine scaffold yield negative allosteric modulators and agonists of the dopamine D2 receptor

  摘要：

  We recently described a structurally novel series of negative allosteric modulators (NAMs) of the dopamine D-2 receptor (D2R) based on thieno[2,3-d]pyrimidine 1, showing it can be structurally simplified to reveal low molecular weight, fragment-like NAMs that retain robust negative cooperativity, such as 3. Herein, we report the synthesis and functional profiling of analogues of 3, placing specific emphasis on examining secondary and tertiary amino substituents at the 4-position, combined with a range of substituents at the 5/6-positions (e.g. aromatic/aliphatic carbocycles). We identify analogues with diverse pharmacology at the D2R including NAMs with sub-mu M affinity (9h) and, surprisingly, low efficacy partial agonists (9d and 9i). (C) 2019 Published by Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.01.061

文献信息

• Green catalyst access to thieno [2, 3‐b] pyridines derivatives
  作者：Nawel Mehaoui、Souheyla Boudjema、Zahira Kibou、Noureddine Choukchou‐Braham、Abderrahim Choukchou‐Braham

  DOI：10.1002/jhet.4635

  日期：——

  benefits including a quicker reaction time, an easy set-up, and high yields. Spectroscopic data (IR, +H and 13C NMR spectra) have revealed the structural details of all target compounds. The catalyst was characterized by X-ray diffraction, BET and Fourier-transformed infrared spectroscopy. X-ray diffraction showed that PVW was correctly incorporated on an acid activated clays support. In comparison

  目前的研究重点是使用具有 Keggin 结构并负载在酸活化 (PVW/AAM) 上的钨钒磷酸杂多酸 H 4 PW 11 VO 40 ·8 H 2 O (PVW) 合成新取代的 Thieno [2, 3- b] 吡啶衍生物。建议的协议是一种简单、环保的方法，用于在无溶剂反应条件下合成从 3-cyano-2-aminothiopene 获得的 thieno [2,3-b] 嘧啶衍生物作为构建块。使用合成的 PVW/AAM 催化剂实现了取代的 Thieno [2, 3-b] 吡啶衍生物的优异产率 (60%–97%)。目前的工艺提供的好处包括更快的反应时间、简单的设置和高产率。光谱数据（IR，+ H 和13 C NMR 光谱）揭示了所有目标化合物的结构细节。通过X射线衍射、BET和傅里叶变换红外光谱对催化剂进行了表征。X 射线衍射表明 PVW 正确地结合在酸活化粘土载体上。与母体钨钒磷酸相比，PVW
• IRAK INHIBITORS AND USES THEREOF
  申请人：Nimbus Iris, Inc.

  公开号：EP2663312B1

  公开（公告）日：2017-10-11
• Subtle modifications to a thieno[2,3-d]pyrimidine scaffold yield negative allosteric modulators and agonists of the dopamine D2 receptor
  作者：Tim J. Fyfe、Barrie Kellam、Shailesh N. Mistry、Peter J. Scammells、J. Robert Lane、Ben Capuano

  DOI：10.1016/j.ejmech.2019.01.061

  日期：2019.4

  We recently described a structurally novel series of negative allosteric modulators (NAMs) of the dopamine D-2 receptor (D2R) based on thieno[2,3-d]pyrimidine 1, showing it can be structurally simplified to reveal low molecular weight, fragment-like NAMs that retain robust negative cooperativity, such as 3. Herein, we report the synthesis and functional profiling of analogues of 3, placing specific emphasis on examining secondary and tertiary amino substituents at the 4-position, combined with a range of substituents at the 5/6-positions (e.g. aromatic/aliphatic carbocycles). We identify analogues with diverse pharmacology at the D2R including NAMs with sub-mu M affinity (9h) and, surprisingly, low efficacy partial agonists (9d and 9i). (C) 2019 Published by Elsevier Masson SAS. All rights reserved.