N-(3-cyano-4,5-diphenylfuran-2-yl)formamide | 107833-28-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃
• 英文名称: N-(3-cyano-4,5-diphenylfuran-2-yl)formamide
• CAS: 107833-28-3
• 化学式: C₁₈H₁₂N₂O₂
• 分子量: 288.305
• InChiKey: ATJZOCNBALYASI-UHFFFAOYSA-N

物化性质

• 熔点：
  136-138 °C(Solv: methanol (67-56-1); water (7732-18-5))
• 沸点：
  529.5±50.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3-cyano-4,5-diphenylfuran-2-yl)formamide 在 溶剂黄146 作用下， 反应 1.0h， 以75%的产率得到5,6-二苯基-3H-呋喃并[2,3-d]嘧啶-4-酮
  参考文献：
  名称：

  METHODS FOR THE TREATMENT OF DISORDERS RELATED TO PHOSPHORYLATION OF HISTONES

  摘要：

  用于疾病诊断、预后和治疗选择的方法。还公开了用于这些方法的组合物和选择的治疗方法。

  公开号：

  US20160091498A1
• 作为产物：
  描述：

  2-氨基-4,5-二苯基-3-呋喃甲腈 反应 6.0h， 生成 N-(3-cyano-4,5-diphenylfuran-2-yl)formamide
  参考文献：
  名称：

  CH-01 is a Hypoxia-Activated Prodrug That Sensitizes Cells to Hypoxia/Reoxygenation Through Inhibition of Chk1 and Aurora A

  摘要：

  The increased resistance of hypoxic cells to all forms of cancer therapy presents a major barrier to the successful treatment of most solid tumors. Inhibition of the essential kinase Checkpoint kinase 1 (Chk1) has been described as a promising cancer therapy for tumors with high levels of hypoxia-induced replication stress. However, as inhibition of Chk1 affects normal replication and induces DNA damage, these agents also have the potential to induce genomic instability and contribute to tumorigenesis. To overcome this problem, we have developed a bioreductive prodrug, which functions as a Chk1/Aurora A inhibitor specifically in hypoxic conditions. To achieve this activity, a key functionality on the Chk1 inhibitor (CH-01) is masked by a bioreductive group, rendering the compound inactive as a Chk1/Aurora A inhibitor. Reduction of the bioreductive group nitro moiety, under hypoxic conditions, reveals an electron-donating substituent that leads to fragmentation of the molecule, affording the active inhibitor. Most importantly, we show a significant loss of viability in cancer cell lines exposed to hypoxia in the presence of CH-01. This novel approach targets the most aggressive and therapy-resistant tumor fraction while protecting normal tissue from therapy-induced genomic instability.

  DOI：

  10.1021/cb4001537

文献信息

• METHODS FOR THE TREATMENT OF DISORDERS RELATED TO PHOSPHORYLATION OF HISTONES
  申请人：Mahajan Nupam P.

  公开号：US20160091498A1

  公开（公告）日：2016-03-31

  Methods for disease diagnosis, prognosis and therapy selection. Compositions for use in these methods and selected therapies for treatment are also disclosed.

  用于疾病诊断、预后和治疗选择的方法。还公开了用于这些方法的组合物和选择的治疗方法。
• PHOSPHORYLATION OF HISTONES AND USES THEREOF
  申请人：H. Lee Moffitt Cancer Center And Research Institute

  公开号：US20150011567A1

  公开（公告）日：2015-01-08

  Phosphorylation of histones was observed at certain tyrosine residues which have not been associated with epigenetic modification. These sites include H2B Tyr37, H4 Tyr88 and Tyr 51 and H3 Tyr99. Kinases responsible for the phosphorylation as well as downstream genes regulated by such phosphorylation were also identified. Antibodies that are specific to such phosphorylated histones have been generated, which are useful for detecting the phosphorylation and related events. With such findings, the present disclosure provides compositions and methods for disease diagnosis, prognosis and therapy selection, in particular for cancer, obesity and diabetes.

  观察到组蛋白在某些酪氨酸残基上的磷酸化，这些残基尚未与表观遗传修饰相关联。这些位点包括H2B Tyr37，H4 Tyr88和Tyr 51以及H3 Tyr99。负责磷酸化的激酶以及由此磷酸化调节的下游基因也已被确定。已生成特异性针对此类磷酸化组蛋白的抗体，可用于检测磷酸化及相关事件。凭借这些发现，本公开提供了用于疾病诊断、预后和治疗选择的组合物和方法，特别是用于癌症、肥胖症和糖尿病。
• JONANNSEN F.; JZHUSTORGENSEN A.; REDERSEN E. V., CHEM. SCR., 26,(1986) N 2, 347-351
  作者：JONANNSEN F.、 JZHUSTORGENSEN A.、 REDERSEN E. V.

  DOI：——

  日期：——
• US9594084B2
  申请人：——

  公开号：US9594084B2

  公开（公告）日：2017-03-14
• 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.