4-chloro-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidine | 173458-88-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 4-chloro-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidine
• CAS: 173458-88-3
• 化学式: C₁₈H₁₂ClN₃
• 分子量: 305.766
• InChiKey: MLGRUANZCCRGIQ-UHFFFAOYSA-N

物化性质

• 沸点：
  462.4±55.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chloro-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidine 、 异丙醇胺 反应 1.0h， 生成 1-(5,6-Diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-propan-2-ol
  参考文献：
  名称：

  Structure-Based Design of Novel Chk1 Inhibitors:  Insights into Hydrogen Bonding and Protein−Ligand Affinity

  摘要：

  We report the discovery, synthesis, and crystallographic binding mode of novel furanopyrimidine and pyrrolopyrimidine inhibitors of the Chk1 kinase, an oncology target. These inhibitors are synthetically tractable and inhibit Chk1 by competing for its ATP site. A chronological account allows an objective comparison of modeled compound docking modes to the subsequently obtained crystal structures. The comparison provides insights regarding the interpretation of modeling results, in relationship to the multiple reasonable docking modes which may be obtained in a kinase-ATP site. The crystal structures were used to guide medicinal chemistry efforts. This led to a thorough characterization of a pair of ligand-protein complexes which differ by a single hydrogen bond. An analysis indicates that this hydrogen bond is expected to contribute a fraction of the 10-fold change in binding affinity, adding a valuable observation to the debate about the energetic role of hydrogen bonding in molecular recognition.

  DOI：

  10.1021/jm049022c
• 作为产物：
  描述：

  7-苄基-4-氯-5,6-二苯基-7H-吡咯并-[2,3-d]嘧啶 在 aluminum (III) chloride 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以39%的产率得到4-chloro-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  新型呋喃嘧啶极光激酶A抑制剂的鉴定，SAR研究和X射线共晶体分析

  摘要：

  本文中，我们揭示了一种通过内部化合物库的亚结构搜索来鉴定新的Aurora激酶A抑制剂的简单方法，以选择要测试的化合物。赋予Aurora激酶活性的片段和激酶抑制剂中最常报告的杂环用作子结构查询，以在测试前过滤内部化合物库的馆藏。五个新的系列的极光激酶抑制剂是通过这种策略识别与IC 50个值范围为约300Ñ中号至〜15μ中号，通过从~125 000化合物数据库仅测试133的化合物。最有效的化合物呋喃并嘧啶衍生物与IC的结构活性关系研究和X射线共晶体分析50的309的n值中号朝向极光激酶A，进行了。通过这些研究获得的知识可能有助于将来设计有效的Aurora激酶抑制剂。

  DOI：

  10.1002/cmdc.200900339

文献信息

• Pyrrolopyrimidinderivate mit antiproliferativer Wirkung
  申请人：Novartis AG

  公开号：EP0682027B1

  公开（公告）日：1997-10-15
• US6096749A
  申请人：——

  公开号：US6096749A

  公开（公告）日：2000-08-01
• Identification, SAR Studies, and X-ray Co-crystallographic Analysis of a Novel Furanopyrimidine Aurora Kinase A Inhibitor
  作者：Mohane Selvaraj Coumar、Ming-Tsung Tsai、Chang-Ying Chu、Biing-Jiun Uang、Wen-Hsing Lin、Chun-Yu Chang、Teng-Yuan Chang、Jiun-Shyang Leou、Chi-Huang Teng、Jian-Sung Wu、Ming-Yu Fang、Chun-Hwa Chen、John T.-A. Hsu、Su-Ying Wu、Yu-Sheng Chao、Hsing-Pang Hsieh

  DOI：10.1002/cmdc.200900339

  日期：2010.2.1

  simple method for the identification of novel Aurora kinase A inhibitors through substructure searching of an in‐house compound library to select compounds for testing. A hydrazone fragment conferring Aurora kinase activity and heterocyclic rings most frequently reported in kinase inhibitors were used as substructure queries to filter the in‐house compound library collection prior to testing. Five

  本文中，我们揭示了一种通过内部化合物库的亚结构搜索来鉴定新的Aurora激酶A抑制剂的简单方法，以选择要测试的化合物。赋予Aurora激酶活性的片段和激酶抑制剂中最常报告的杂环用作子结构查询，以在测试前过滤内部化合物库的馆藏。五个新的系列的极光激酶抑制剂是通过这种策略识别与IC 50个值范围为约300Ñ中号至〜15μ中号，通过从~125 000化合物数据库仅测试133的化合物。最有效的化合物呋喃并嘧啶衍生物与IC的结构活性关系研究和X射线共晶体分析50的309的n值中号朝向极光激酶A，进行了。通过这些研究获得的知识可能有助于将来设计有效的Aurora激酶抑制剂。
• Structure-Based Design of Novel Chk1 Inhibitors:  Insights into Hydrogen Bonding and Protein−Ligand Affinity
  作者：Nicolas Foloppe、Lisa M. Fisher、Rob Howes、Peter Kierstan、Andrew Potter、Alan G. S. Robertson、Allan E. Surgenor

  DOI：10.1021/jm049022c

  日期：2005.6.1

  We report the discovery, synthesis, and crystallographic binding mode of novel furanopyrimidine and pyrrolopyrimidine inhibitors of the Chk1 kinase, an oncology target. These inhibitors are synthetically tractable and inhibit Chk1 by competing for its ATP site. A chronological account allows an objective comparison of modeled compound docking modes to the subsequently obtained crystal structures. The comparison provides insights regarding the interpretation of modeling results, in relationship to the multiple reasonable docking modes which may be obtained in a kinase-ATP site. The crystal structures were used to guide medicinal chemistry efforts. This led to a thorough characterization of a pair of ligand-protein complexes which differ by a single hydrogen bond. An analysis indicates that this hydrogen bond is expected to contribute a fraction of the 10-fold change in binding affinity, adding a valuable observation to the debate about the energetic role of hydrogen bonding in molecular recognition.