4-chlorothieno[3,2-d]pyrimidine-6-carbonyl chloride | 875339-14-3

• 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: 4-chlorothieno[3,2-d]pyrimidine-6-carbonyl chloride
• CAS: 875339-14-3
• 化学式: C₇H₂Cl₂N₂OS
• 分子量: 233.078
• InChiKey: VLKFTMFLJYWQNK-UHFFFAOYSA-N

物化性质

• 沸点：
  367.7±37.0 °C(Predicted)
• 密度：
  1.690±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  13
• 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：
  71.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-chlorothieno[3,2-d]pyrimidine-6-carbonyl chloride 在 氨 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 18.67h， 生成 4-(4-(2-hydroxyethyl)piperazin-1-yl)thieno[3,2-d]pyrimidine-6-carboxamide
  参考文献：
  名称：

  Discovery of Thieno[3,2-d]pyrimidine-6-carboxamides as Potent Inhibitors of SIRT1, SIRT2, and SIRT3

  摘要：

  The sirtuins SIRT1, SIRT2, and SIRT3 are NAD(+) dependent deacetylases that are considered potential targets for metabolic, inflammatory, oncologic, and neurodegenerative disorders. Encoded library technology (ELT) was used to affinity screen a 1.2 million heterocycle enriched library of DNA encoded small molecules, which identified pan-inhibitors of SIRT1/2/3 with nanomolar potency (e.g., 11c: IC50 = 3.6, 2.7, and 4.0 nM for SIRT1, SIRT2, and SIRT3, respectively). Subsequent SAR studies to improve physiochemical properties identified the potent drug like analogues 28 and 31. Crystallographic studies of 11c, 28, and 31 bound in the SIRT3 active site revealed that the common carboxamide binds in the nicotinamide C-pocket and the aliphatic portions of the inhibitors extend through the substrate channel, explaining the observable SAR. These pan SIRT1/2/3 inhibitors, representing a novel chemotype, are significantly more potent than currently available inhibitors, which makes them valuable tools for sirtuin research.

  DOI：

  10.1021/jm400204k
• 作为产物：
  描述：

  4-氯噻吩并[3,2-d]嘧啶 在 2,2,6,6-四甲基哌啶 、 正丁基锂 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 7.0h， 生成 4-chlorothieno[3,2-d]pyrimidine-6-carbonyl chloride
  参考文献：
  名称：

  Discovery of Thieno[3,2-d]pyrimidine-6-carboxamides as Potent Inhibitors of SIRT1, SIRT2, and SIRT3

  摘要：

  The sirtuins SIRT1, SIRT2, and SIRT3 are NAD(+) dependent deacetylases that are considered potential targets for metabolic, inflammatory, oncologic, and neurodegenerative disorders. Encoded library technology (ELT) was used to affinity screen a 1.2 million heterocycle enriched library of DNA encoded small molecules, which identified pan-inhibitors of SIRT1/2/3 with nanomolar potency (e.g., 11c: IC50 = 3.6, 2.7, and 4.0 nM for SIRT1, SIRT2, and SIRT3, respectively). Subsequent SAR studies to improve physiochemical properties identified the potent drug like analogues 28 and 31. Crystallographic studies of 11c, 28, and 31 bound in the SIRT3 active site revealed that the common carboxamide binds in the nicotinamide C-pocket and the aliphatic portions of the inhibitors extend through the substrate channel, explaining the observable SAR. These pan SIRT1/2/3 inhibitors, representing a novel chemotype, are significantly more potent than currently available inhibitors, which makes them valuable tools for sirtuin research.

  DOI：

  10.1021/jm400204k

文献信息

• [EN] INHIBITORS OF VEGF RECEPTOR AND HGF RECEPTOR SIGNALING<br/>[FR] INHIBITEURS DE SIGNALISATION DE RECEPTEUR DU FACTEUR DE CROISSANCE ENDOTHELIALE (VEGF) ET DE RECEPTEUR DE FACTEUR DE CROISSANCE DES HEPATOCYTES (HGF)
  申请人：METHYLGENE INC

  公开号：WO2006010264A1

  公开（公告）日：2006-02-02

  The invention relates to the inhibition of vascular endothelial growth factor (VEGF) receptor signaling and hepatocyte growth factor (HGF) receptor signaling. The invention provides compounds and methods for inhibiting VEGF receptor signaling and HGF receptor signaling. The invention also provides compositions and methods for treating cell proliferative diseases and conditions

  该发明涉及抑制血管内皮生长因子（VEGF）受体信号和肝细胞生长因子（HGF）受体信号的方法。该发明提供了抑制VEGF受体信号和HGF受体信号的化合物和方法。该发明还提供了治疗细胞增殖性疾病和症状的组合物和方法。
• INHIBITORS OF VEGF RECEPTOR AND HGF RECEPTOR SIGNALING
  申请人：Saavedra Mario Oscar

  公开号：US20060287343A1

  公开（公告）日：2006-12-21

  The invention relates to the inhibition of VEGF receptor signaling and HGF receptor signaling. The invention provides compounds and methods for inhibiting VEGF receptor signaling and HGF receptor signaling. The invention also provides compositions and methods for treating cell proliferative diseases and conditions

  本发明涉及抑制VEGF受体信号和HGF受体信号的方法。本发明提供了抑制VEGF受体信号和HGF受体信号的化合物和方法。本发明还提供了用于治疗细胞增殖性疾病和病状的组合物和方法。
• Inhibitors of VEGF receptor and HGF receptor signaling
  申请人：Vaisburg Arkadii

  公开号：US20060074056A1

  公开（公告）日：2006-04-06

  The invention relates to the inhibition of VEGF receptor signaling and HGF receptor signaling. The invention provides compounds and methods for inhibiting VEGF receptor signaling and HGF receptor signaling. The invention also provides compositions and methods for treating cell proliferative diseases and conditions

  本发明涉及抑制VEGF受体信号和HGF受体信号的方法。本发明提供了抑制VEGF受体信号和HGF受体信号的化合物和方法。本发明还提供了治疗细胞增殖性疾病和病状的组合物和方法。
• Inhibitors of VEGF Receptor and HGF Receptor Signalling
  申请人：Vaisburg Arkadii

  公开号：US20100216766A1

  公开（公告）日：2010-08-26

  The invention relates to the inhibition of VEGF receptor signaling and HGF receptor signaling. The invention provides compounds and methods for inhibiting VEGF receptor signaling and HGF receptor signaling. The invention also provides compositions and methods for treating cell proliferative diseases and conditions

  本发明涉及抑制VEGF受体信号和HGF受体信号的方法。本发明提供了抑制VEGF受体信号和HGF受体信号的化合物和方法。本发明还提供了治疗细胞增殖性疾病和病症的组合物和方法。
• Substituted thieno[3,2-d]pyridines as inhibitors of the VEGF receptor and HGF receptor
  申请人：Methylgene Inc.

  公开号：US07772247B2

  公开（公告）日：2010-08-10

  The invention relates to the inhibition of VEGF receptor signaling and HGF receptor signaling. The invention provides compounds and methods for inhibiting VEGF receptor signaling and HGF receptor signaling. The invention also provides compositions and methods for treating cell proliferative diseases and conditions

  本发明涉及抑制VEGF受体信号和HGF受体信号的技术。本发明提供了用于抑制VEGF受体信号和HGF受体信号的化合物和方法。本发明还提供了用于治疗细胞增殖性疾病和病状的组合物和方法。