2-[(5,6-Diphenylfuro[2,3-d]pyrimidin-4-yl)azaniumyl]acetate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃
• 英文名称: 2-[(5,6-Diphenylfuro[2,3-d]pyrimidin-4-yl)azaniumyl]acetate
• 化学式: C₂₀H₁₅N₃O₃
• 分子量: 345.357
• InChiKey: VXTCEUDVOCLEJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  88.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5,6-二苯基-3H-呋喃并[2,3-d]嘧啶-4-酮 在 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 10.0h， 生成 2-[(5,6-Diphenylfuro[2,3-d]pyrimidin-4-yl)azaniumyl]acetate
  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

文献信息

• Novel, Acyclically Substituted Furopyrimidine Derivatives and Use Thereof
  申请人：Lampe Thomas

  公开号：US20090318475A1

  公开（公告）日：2009-12-24

  The present application relates to novel, acyclically substituted furopyrimidine derivatives, methods for their production, their use for the treatment and/or prophylaxis of diseases and their use for the production of medicinal products for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular diseases.

  本申请涉及新颖的、非环式取代的呋噻嘧啶衍生物，其生产方法，它们用于治疗和/或预防疾病以及用于生产治疗和/或预防疾病的药物制剂，特别是用于治疗和/或预防心血管疾病。
• TARGETING AN HIV-1 NEF-HOST CELL KINASE COMPLEX
  申请人：Emert-Sedlak Lori

  公开号：US20110190241A1

  公开（公告）日：2011-08-04

  Drug candidates for inhibition of HIV-I replication can target Src family kinases (SFK), such as Hck, that interact with Nef protein of the virus. Compounds characterized by such inhibitory activity were identified via an assay for kinase activity of an SFK in a Nef:SFK complex. Illustrative of inhibitors identified using the kinase assay are various 2,3-diaminoquinaxolines and furo[2,3-d]pyrimidines. The inventive inhibitors were found to arrest HIV-I viral replication in vitro.

  用于抑制HIV-I复制的药物候选物可以针对Src家族激酶（SFK），如与病毒的Nef蛋白相互作用的Hck进行靶向。通过对Nef:SFK复合物中SFK的激酶活性进行测定，鉴定了具有这种抑制活性的化合物。使用激酶测定鉴定的抑制剂的例子包括各种2,3-二氨基喹啉和呋喃[2,3-d]嘧啶。这些创新的抑制剂被发现可以在体外阻止HIV-I病毒的复制。
• US8183246B2
  申请人：——

  公开号：US8183246B2

  公开（公告）日：2012-05-22
• US8541415B2
  申请人：——

  公开号：US8541415B2

  公开（公告）日：2013-09-24
• [EN] TARGETING AN HIV-1 NEF-HOST CELL KINASE COMPLEX<br/>[FR] CIBLAGE D'UN COMPLEXE NEF DE VIH 1/KINASE DE CELLULE HÔTE
  申请人：UNIV PITTSBURGH

  公开号：WO2009139886A2

  公开（公告）日：2009-11-19

  Drug candidates for inhibition of HIV-I replication can target Src family kinases (SFK), such as Hck, that interact with Nef protein of the virus. Compounds characterized by such inhibitory activity were identified via an assay for kinase activity of an SFK in a Nef:SFK complex. Illustrative of inhibitors identified using the kinase assay are various 2,3- diaminoquinaxolines and furo[2,3-d]pyrimidines. The inventive inhibitors were found to arrest HIV-I viral replication in vitro.