4-(3-(but-3-en-1-yloxy)phenyl)-2-chloropyrimidine | 937271-45-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-(3-(but-3-en-1-yloxy)phenyl)-2-chloropyrimidine
• 英文别名: IM-16-2；4-(3-but-3-enyloxy-phenyl)-2-chloropyrimidine；4-(3-but-3-enoxyphenyl)-2-chloropyrimidine
• CAS: 937271-45-9
• 化学式: C₁₄H₁₃ClN₂O
• 分子量: 260.723
• InChiKey: YDBVOEASSGRCAS-UHFFFAOYSA-N

物化性质

• 沸点：
  431.4±33.0 °C(Predicted)
• 密度：
  1.175±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(3-(but-3-en-1-yloxy)phenyl)-2-chloropyrimidine 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 盐酸 、 水 、 potassium carbonate 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 水 、 正丁醇 为溶剂， 反应 6.0h， 生成 (16E)-20-oxa-5,7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene
  参考文献：
  名称：

  Discovery of Kinase Spectrum Selective Macrocycle (16E)-14-Methyl-20-oxa-5,7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene (SB1317/TG02), a Potent Inhibitor of Cyclin Dependent Kinases (CDKs), Janus Kinase 2 (JAK2), and Fms-like Tyrosine Kinase-3 (FLT3) for the Treatment of Cancer

  摘要：

  Herein, we describe the design, synthesis, and SAR of a series of unique small molecule macrocycles that show spectrum selective kinase inhibition of CDKs, JAK2, and FLT3. The most promising leads were assessed in vitro for their inhibition of cancer cell proliferation, solubility, CYP450 inhibition, and microsomal stability. This screening cascade revealed 26h as a preferred compound with target IC50 of 13, 73, and 56 nM for CDK2, JAK2 and FLT3, respectively. Pharmacokinetic (PK) studies of 26h in preclinical species showed good oral exposures. Oral efficacy was observed in colon (HCT-116) and lymphoma (Ramos) xenograft studies, in line with the observed PK/PD correlation. 26h (SB1317/TG02) was progressed into development in 2010 and is currently undergoing phase 1 clinical trials in advanced leukemias and multiple myeloma.

  DOI：

  10.1021/jm201112g
• 作为产物：
  描述：

  3-羟基苯硼酸 在 四(三苯基膦)钯 、 caesium carbonate 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-(3-(but-3-en-1-yloxy)phenyl)-2-chloropyrimidine
  参考文献：
  名称：

  Acid Mediated Ring Closing Metathesis: A Powerful Synthetic Tool Enabling the Synthesis of Clinical Stage Kinase Inhibitors

  摘要：

  强大的烯烃转化反应被用于合成晚期临床药剂SB1317和SB1518。在这两种情况下，环戊烯烃开环反应似乎只在酸的存在下进行，并主要生成反异构体。对于SB1518，它在HCl酸的存在下进行，而对于SB1317，主要在三氟乙酸（TFA）的存在下进行。

  DOI：

  10.2533/chimia.2015.142
• 作为试剂：
  描述：

  3-[(allylmethylamino)methyl]phenylamine 、 4-(3-(but-3-en-1-yloxy)phenyl)-2-chloropyrimidine 在 4-(3-(but-3-en-1-yloxy)phenyl)-2-chloropyrimidine 作用下， 以92的产率得到4-(3-but-3-enoxyphenyl)-N-[3-[[methyl(prop-2-enyl)amino]methyl]phenyl]pyrimidin-2-amine
  参考文献：
  名称：

  J. Med. Chem. 2012, 55, 169-196

  摘要：

  DOI：

文献信息

• [EN] COVALENT INHIBITORS OF CDK-7<br/>[FR] INHIBITEURS COVALENTS DE CDK-7
  申请人：NEWAVE PHARMACEUTICAL LLC

  公开号：WO2016149031A1

  公开（公告）日：2016-09-22

  This disclosure includes compounds of Formula (I), wherein A, B, C, R1, R2, R3, R5, R6, m, n, W1, W2, Z1, Z2, Z3, Z4, L1, L2, and warhead are defined herein. Also disclosed is a method for treating a neoplastic disease with these compounds.

  这份披露包括式（I）的化合物，其中A、B、C、R1、R2、R3、R5、R6、m、n、W1、W2、Z1、Z2、Z3、Z4、L1、L2和战斗头部在此定义。还披露了一种使用这些化合物治疗恶性肿瘤疾病的方法。
• Solid state forms of macrocyclic kinase inhibitors
  申请人：Mansfield Robert K.

  公开号：US09120815B2

  公开（公告）日：2015-09-01

  Provided herein are salt forms of macrocyclic protein kinase inhibitors, pharmaceutical compositions containing the same, methods of making and using these compounds and compositions to treat proliferative disease mediated by kinase activity.

  本文提供了大环蛋白激酶抑制剂的盐形式，包含这些盐形式的药物组合物，制备和使用这些化合物和组合物的方法，用于治疗由激酶活性介导的增殖性疾病。
• Homogeneous and Functional Group Tolerant Ring-Closing Metathesis for DNA-Encoded Chemical Libraries
  作者：Olivier B. C. Monty、Pranavanand Nyshadham、Kurt M. Bohren、Murugesan Palaniappan、Martin M. Matzuk、Damian W. Young、Nicholas Simmons

  DOI：10.1021/acscombsci.9b00199

  日期：2020.2.10

  control, and catalyst decomposition in the ring-closing metathesis (RCM) of DNA–chemical conjugates lead to poor yields of the cyclized products. Herein we address these issues with a RCM reaction system that includes a novel aqueous solvent combination to enable reaction homogeneity, an acidic buffer system which masks traditionally problematic functional groups, and a decomposition-resistant catalyst which

  反应异质性，不良的pH控制以及DNA-化学偶联物的闭环复分解（RCM）中的催化剂分解导致环化产物收率不佳。本文中，我们通过RCM反应系统解决了这些问题，该系统包括使反应均一的新型水性溶剂组合，可掩盖传统上有问题的官能团的酸性缓冲系统以及可最大限度地转化为环化产物的抗分解催化剂。此外，我们提供了对DNA RCM反应底物范围的系统研究，证明了其对单底物DNA编码的化学文库的适用性，包括测序分析，以及首次成功装订未受保护的on-DNA [i，i + 4]肽。
• OXYGEN LINKED PYRIMIDINE DERIVATIVES
  申请人：Blanchard Stephanie

  公开号：US20120196855A1

  公开（公告）日：2012-08-02

  The present invention relates to pyrimidine compounds that are useful as anti-proliferative agents. More particularly, the present invention relates to oxygen linked and substituted pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders. These compounds may be useful as medicaments for the treatment of a number of proliferative disorders including tumours and cancers as well as other disorders or conditions related to or associated with kinases.

  本发明涉及嘧啶化合物，其作为抗增殖剂具有用处。更具体地说，本发明涉及氧连接和取代的嘧啶化合物，其制备方法，含有这些化合物的制药组合物以及这些化合物在治疗增殖性疾病方面的用途。这些化合物可用作治疗许多增殖性疾病，包括肿瘤和癌症以及与激酶相关或相关的其他疾病或病况的药物。
• HETEROALKYL LINKED PYRIMIDINE DERIVATIVES
  申请人：Blanchard Stephanie

  公开号：US20090258886A1

  公开（公告）日：2009-10-15

  The present invention relates to pyrimidine compounds that are useful as anti-proliferative agents. More particularly, the present invention relates to heteroalkyl linked and substituted pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders. These compounds may be useful as medicaments for the treatment of a number of proliferative disorders including tumours and cancers as well as other conditions or disorders associated with kinases.

  本发明涉及用作抗增殖剂的嘧啶化合物。更具体地说，本发明涉及杂原子烷基连接和取代的嘧啶化合物，其制备方法，含有这些化合物的制药组合物以及在治疗增殖性疾病中使用这些化合物的用途。这些化合物可能作为药物对许多增殖性疾病，包括肿瘤和癌症以及与激酶相关的其他疾病或疾病的治疗有用。