2-{[(thiophen-2-ylmethyl)-amino]-methyl}-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one | 1418131-87-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃嘧啶类
• 英文名称: 2-{[(thiophen-2-ylmethyl)-amino]-methyl}-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one
• 英文别名: 2-((Thiophen-2-ylmethylamino)methyl)-7,8-dihydro-3H-pyrano[4,3-d]pyrimidin-4(5H)-one；2-[(thiophen-2-ylmethylamino)methyl]-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-4-one
• CAS: 1418131-87-9
• 化学式: C₁₃H₁₅N₃O₂S
• 分子量: 277.347
• InChiKey: OCWZKGMPXYUVNX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  91
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  对羟基苯丙酸 、 2-{[(thiophen-2-ylmethyl)-amino]-methyl}-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以9%的产率得到3-(4-hydroxyphenyl)-N-((4-oxo-4,5,7,8-tetrahydro-3H-pyrano[4,3-d]pyrimidin-2-yl)methyl)-N-(thiophen-2-ylmethyl)propanamide
  参考文献：
  名称：

  Identification of NVP-TNKS656: The Use of Structure–Efficiency Relationships To Generate a Highly Potent, Selective, and Orally Active Tankyrase Inhibitor

  摘要：

  Tankyrase 1 and 2 have been shown to be redundant, druggable nodes in the Wnt pathway. As such, there has been intense interest in developing agents suitable for modulating the Wnt pathway in vivo by targeting this enzyme pair. By utilizing a combination of structure-based design and LipE-based structure efficiency relationships, the core of XAV939 was optimized into a more stable, more efficient, but less potent dihydropyran motif 7. This core was combined with elements of screening hits 2, 19, and 33 and resulted in highly potent, selective tankyrase inhibitors that are novel three pocket binders. NVP-TNKS656 (43) was identified as an orally active antagonist of Wnt pathway activity in the MMTV-Wnt1 mouse xenograft model. With an enthalpy-driven thermodynamic signature of binding, highly favorable physicochemical properties, and high lipophilic efficiency, NVP-TNKS656 is a novel tankyrase inhibitor that is well suited for further in vivo validation studies.

  DOI：

  10.1021/jm400807n
• 作为产物：
  描述：

  2-chloromethyl-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one 在 sodium azide 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 、 水 、 丙酮 为溶剂， 反应 37.75h， 生成 2-{[(thiophen-2-ylmethyl)-amino]-methyl}-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one
  参考文献：
  名称：

  Identification of NVP-TNKS656: The Use of Structure–Efficiency Relationships To Generate a Highly Potent, Selective, and Orally Active Tankyrase Inhibitor

  摘要：

  Tankyrase 1 and 2 have been shown to be redundant, druggable nodes in the Wnt pathway. As such, there has been intense interest in developing agents suitable for modulating the Wnt pathway in vivo by targeting this enzyme pair. By utilizing a combination of structure-based design and LipE-based structure efficiency relationships, the core of XAV939 was optimized into a more stable, more efficient, but less potent dihydropyran motif 7. This core was combined with elements of screening hits 2, 19, and 33 and resulted in highly potent, selective tankyrase inhibitors that are novel three pocket binders. NVP-TNKS656 (43) was identified as an orally active antagonist of Wnt pathway activity in the MMTV-Wnt1 mouse xenograft model. With an enthalpy-driven thermodynamic signature of binding, highly favorable physicochemical properties, and high lipophilic efficiency, NVP-TNKS656 is a novel tankyrase inhibitor that is well suited for further in vivo validation studies.

  DOI：

  10.1021/jm400807n

文献信息

• [EN] NOVEL 2-PIPERIDIN-1-YL-ACETAMIDE COMPOUNDS FOR USE AS TANKYRASE INHIBITORS<br/>[FR] NOUVEAUX COMPOSÉS 2-PIPERIDIN-1-YL-ACETAMIDE UTILISABLES EN TANT QU'INHIBITEURS DE TANKYRASE
  申请人：NOVARTIS AG

  公开号：WO2013012723A1

  公开（公告）日：2013-01-24

  The present invention provides for compounds of formula (I), wherein R1-R5 and L are defined herein. The present invention also provides for pharmaceutical compositions and combinations comprising a compound of formula (I) as well as for the use of such compounds as tankyrase inhibitors and in the treatment of Wnt signaling and tankyrase 1 and 2 signaling related disorders which include, but are not limited to, cancer.

  本发明提供了式(I)的化合物，其中R1-R5和L在此处定义。本发明还提供了包含式(I)化合物的药物组合物和组合物，以及将这些化合物用作坦基酶抑制剂以及用于治疗Wnt信号和坦基酶1和2信号相关疾病的用途，包括但不限于癌症。
• [EN] 4-OXO-3,5,7,8-TETRAHYDRO-4H-PYRANO {4,3-D} PYRMINIDINYL COMPOUNDS FOR USE AS TANKYRASE INHIBITORS<br/>[FR] COMPOSÉS DE 4-OXO-3,5,7,8-TÉTRAHYDRO-4H-PYRANO{4,3-D}PYRIMINIDINYLE UTILISABLES À TITRE D'INHIBITEURS DE TANKYRASES
  申请人：NOVARTIS AG

  公开号：WO2013010092A1

  公开（公告）日：2013-01-17

  The present invention provides for compounds of formula (I) wherein R1 and R2 are defined herein. The present invention also provides for pharmaceutical compositions and combinations comprising a compound of formula (I) as well as for the use of such compounds as tankyrase inhibitors and in the treatment of Wnt signaling and tankyrase 1 and 2 signaling related disorders which include, but are not limited to, cancer.

  本发明提供了以下式（I）中R1和R2被定义的化合物。本发明还提供了含有式（I）化合物的药物组合物和配方，以及将这些化合物用作坦基酶抑制剂以及用于治疗Wnt信号和坦基酶1和2信号相关疾病的用途，包括但不限于癌症。
• NOVEL 2-PIPERIDIN-1-YL-ACETAMIDE COMPOUNDS FOR USE AS TANKYRASE INHIBITORS
  申请人：Cheung Atwood Kim

  公开号：US20150025070A1

  公开（公告）日：2015-01-22

  The present invention provides for compounds of formula (I): wherein R 1 -R 5 and L are defined herein. The present invention also provides for pharmaceutical compositions and combinations comprising a compound of formula (I) as well as for the use of such compounds as tankyrase inhibitors and in the treatment of Wnt signaling and tankyrase 1 and 2 signaling related disorders which include, but are not limited to, cancer.

  本发明提供了公式（I）的化合物：其中R1-R5和L在此定义。本发明还提供了含有公式（I）化合物的药物组合物和组合物，以及将这些化合物用作坦克酶抑制剂和治疗与Wnt信号和坦克酶1和2信号相关的疾病的用途，包括但不限于癌症。
• 4-OXO-3,5,7,8-TETRAHYDRO-4H-PYRANO[4,3-D]PYRMINIDINYL COMPOUNDS FOR USE AS TANKYRASE INHIBITORS
  申请人：Novartis AG

  公开号：US20150210709A1

  公开（公告）日：2015-07-30

  The present invention provides for compounds of formula (I) wherein R 1 and R 2 are defined herein. The present invention also provides for pharmaceutical compositions and combinations comprising a compound of formula (I) as well as for the use of such compounds as tankyrase inhibitors and in the treatment of Wnt signaling and tankyrase 1 and 2 signaling related disorders which include, but are not limited to, cancer.

  本发明提供了公式（I）中R1和R2被定义的化合物。本发明还提供了包含公式（I）化合物的制药组合物和组合物，以及将这些化合物用作坦克酶抑制剂和治疗Wnt信号和坦克酶1和2信号相关疾病的用途，其中包括但不限于癌症。
• 2-piperidin-1-yl-acetamide compounds for use as tankyrase inhibitors
  申请人：Cheung Atwood Kim

  公开号：US09181266B2

  公开（公告）日：2015-11-10

  The present invention provides for compounds of formula (I): wherein R1-R5 and L are defined herein. The present invention also provides for pharmaceutical compositions and combinations comprising a compound of formula (I) as well as for the use of such compounds as tankyrase inhibitors and in the treatment of Wnt signaling and tankyrase 1 and 2 signaling related disorders which include, but are not limited to, cancer.

  本发明提供了式(I)的化合物，其中R1-R5和L如本文所定义。本发明还提供了包含式(I)化合物的药物组合物和制剂，以及将这些化合物用作坦克酶抑制剂和治疗Wnt信号和与坦克酶1和2信号相关的疾病的用途，包括但不限于癌症。