4-氯-5,6-二苯基呋喃并[2,3-D]嘧啶 | 65148-07-4

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃
• 中文名称: 4-氯-5,6-二苯基呋喃并[2,3-D]嘧啶
• 英文名称: 4-chloro-5,6-diphenylfuro[2,3-d]pyrimidine
• CAS: 65148-07-4
• 化学式: C₁₈H₁₁ClN₂O
• 分子量: 306.751
• InChiKey: DZCDERJEEHCRHG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 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：
  38.9
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  4-氯-5,6-二苯基呋喃并[2,3-D]嘧啶 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 24.0h， 生成 1-(4-{2-[(5,6-diphenylfuro[2,3-d]pyrimidin-4-yl)amino]-ethyl}phenyl)-3-methylurea
  参考文献：
  名称：

  Optimization of Ligand and Lipophilic Efficiency To Identify an in Vivo Active Furano-Pyrimidine Aurora Kinase Inhibitor

  摘要：

  Ligand efficiency (LE) and lipophilic efficiency (LipE) are two important indicators of "drug-likeness", which are dependent on the molecules activity and physicochemical properties. We recently reported a furano-pyrimidine Aurora kinase inhibitor 4 (LE = 0.25; LipE = 1.75), with potent activity in vitro; however, 4 was inactive in vivo. On the basis of insights obtained from the X-ray co-crystal structure of the lead 4, various solubilizing functional groups were introduced to optimize both the activity and physicochemical properties. Emphasis was placed on identifying potential leads with improved activity as well as better LE and LipE by exercising tight control over the molecular weight and lipophilicity of the molecules. Rational optimization has led to the identification of Aurora kinase inhibitor 27 (IBPR001; LE = 0.26; LipE = 4.78), with improved in vitro potency and physicochemical properties, resulting in an in vivo active (HCT-116 colon cancer xenograft mouse model) anticancer agent.

  DOI：

  10.1021/jm4006059
• 作为产物：
  描述：

  2-氨基-4,5-二苯基-3-呋喃甲腈 在 乙酸酐 、 溶剂黄146 、 三氯氧磷 作用下， 反应 21.0h， 生成 4-氯-5,6-二苯基呋喃并[2,3-D]嘧啶
  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

文献信息

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

  公开号：US20110124665A1

  公开（公告）日：2011-05-26

  The present application relates to novel, cyclically 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.

  本申请涉及新型的、环状取代的呋喃嘧啶衍生物，其生产方法，以及它们用于治疗和/或预防疾病的应用，特别用于治疗和/或预防心血管疾病的治疗和/或预防药物的生产。
• FUSED BICYCLIC PYRIMIDINE COMPOUNDS AS AURORA KINASE INHIBITORS
  申请人：Hsieh Hsing-Pang

  公开号：US20090275533A1

  公开（公告）日：2009-11-05

  Fused bicyclic pyrimidine compounds of formula (I): wherein R 1 , R 3 , R 4 , X 1 , X 2 , Y, Z, A, B, C, D, n, and the two bonds are defined herein. Also disclosed are a method for inhibiting Aurora kinase activity and a method for treating cancer with these compounds.

  式（I）的融合双环嘧啶化合物： 其中R1、R3、R4、X1、X2、Y、Z、A、B、C、D、n和两个键在此处定义。还公开了一种抑制极化激酶活性的方法以及使用这些化合物治疗癌症的方法。
• Fused Bicyclic and Tricyclic Pyrimidine Compounds as Tyrosine Kinase Inhibitors
  申请人：Hsieh Hsing-Pang

  公开号：US20100120805A1

  公开（公告）日：2010-05-13

  Fused bicyclic or tricyclic compounds of formula (I): wherein A, B, C, X, Y, m, and n are defined herein. Also disclosed are a method for inhibiting EGFR kinase activity and a method for treating cancer with these compounds.

  式(I)的融合双环或三环化合物： 其中A、B、C、X、Y、m和n在此处定义。还公开了一种抑制EGFR激酶活性的方法以及使用这些化合物治疗癌症的方法。
• Amide Synthesis by Nickel/Photoredox‐Catalyzed Direct Carbamoylation of (Hetero)Aryl Bromides
  作者：Nurtalya Alandini、Luca Buzzetti、Gianfranco Favi、Tim Schulte、Lisa Candish、Karl D. Collins、Paolo Melchiorre

  DOI：10.1002/anie.202000224

  日期：2020.3.23

  Herein, we report a one‐electron strategy for catalytic amide synthesis that enables the direct carbamoylation of (hetero)aryl bromides. This radical cross‐coupling approach, which is based on the combination of nickel and photoredox catalysis, proceeds at ambient temperature and uses readily available dihydropyridines as precursors of carbamoyl radicals. The method's mild reaction conditions make

  在本文中，我们报告了一种催化酰胺合成的单电子策略，该策略可实现（杂）芳基溴化物的直接氨基甲酰基化。这种自由基交叉偶联方法基于镍和光氧化还原催化的结合，在环境温度下进行，并使用现成的二氢吡啶作为氨基甲酰基自由基的前体。该方法温和的反应条件使其能够耐受敏感的官能团底物，并允许在生物学相关的杂环中安装酰胺支架。此外，我们安装了带有电子贫乏和空间受阻胺部分的酰胺官能团，而这是用传统的脱水缩合方法难以制备的。
• 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。