3-乙酰氧基-4-甲氧基苯硼酸频哪醇酯 | 917757-44-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 中文名称: 3-乙酰氧基-4-甲氧基苯硼酸频哪醇酯
• 中文别名: 1,3-戊二酮，2,4-二甲基-1-[[(3aS，6R，7aR)-四氢-8,8-二甲基-2,2-二氧化物-3H-3a，6-甲基-2,1-苯并噻唑-1(4H)-基]-，(2R)-
• 英文名称: 3-acetoxy-4-methoxyphenylboronic acid pinacol ester
• 英文别名: 2-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl acetate；[2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl] acetate
• CAS: 917757-44-9
• 化学式: C₁₅H₂₁BO₅
• 分子量: 292.14
• InChiKey: XNQOYRPBJQKOGV-UHFFFAOYSA-N

物化性质

• 沸点：
  373.1±32.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.92
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-乙酰氧基-4-甲氧基苯硼酸频哪醇酯 在 四(三苯基膦)钯 、 水 、 caesium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 4-(3-but-3-enyloxy-4-methoxyphenyl)-2-chloropyrimidine
  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

文献信息

• [EN] NOVEL GAK MODULATORS<br/>[FR] NOUVEAUX MODULATEURS DE LA GAK
  申请人：UNIV LEUVEN KATH

  公开号：WO2015001076A1

  公开（公告）日：2015-01-08

  The present invention relates to a class of novel isothiazolo[4,3-b]pyridine derivatives and a method for their preparation, as well as to pharmaceutical compositions comprising one or more of said isothiazolo[4,3-b]pyridine derivatives and one or more pharmaceutically acceptable excipients. The present invention further relates to the use of said novel isothiazolo[4,3-b]pyridine derivatives as biologically active ingredients, more specifically as medicaments for the treatment of disorders and pathologic conditions such as, but not limited to, cell-proliferative and neurodegenerative diseases.

  本发明涉及一类新型的异噻唑并[4,3-b]吡啶衍生物及其制备方法，以及包含一种或多种所述异噻唑并[4,3-b]吡啶衍生物和一种或多种药学上可接受的赋形剂的药物组合物。本发明还涉及所述新型异噻唑并[4,3-b]吡啶衍生物作为生物活性成分的用途，更具体地，作为用于治疗诸如但不限于细胞增殖性和神经退行性疾病等障碍和病理状况的药物。
• Synthesis and Cytotoxic Activity of Combretastatin A-4 and 2,3-Diphenyl-2H-indazole Hybrids
  作者：Jaime Pérez-Villanueva、Félix Matadamas-Martínez、Lilián Yépez-Mulia、Vadim Pérez-Koldenkova、Martha Leyte-Lugo、Karen Rodríguez-Villar、Francisco Cortés-Benítez、Ana Perla Macías-Jiménez、Ignacio González-Sánchez、Ariana Romero-Velásquez、Juan Francisco Palacios-Espinosa、Olivia Soria-Arteche

  DOI：10.3390/ph14080815

  日期：——

  and seven derivatives based on the structure of combretastatin A-4 and 2,3-diphenyl-2H-indazole. Practical modifications of reported synthetic protocols for 2-pheny-2H-indazole and 2,3-dipheny-2H-indazole derivatives under microwave irradiation were implemented. The cytotoxicity assays showed that our designed hybrid compounds possess strong activity, especially compound 5, which resulted even better

  癌症是仅次于心血管疾病的第二大死因。已经开发出不同的策略来治疗癌症；然而，使用细胞毒药物的化疗仍然是最广泛使用的治疗方法。尽管如此，对现有化学治疗剂的耐药性仍然是一个严重的问题，开发新的活性化合物仍然是一个持续的需求。利用分子杂交方法，在目前的工作中，我们基于考布他汀 A-4 和 2,3-二苯基-2 H-吲唑的结构设计、合成并测试了两种杂化化合物和七种衍生物的细胞毒活性。2-pheny-2 H - indazole 和 2,3-dipheny-2 H合成方案的实际修改实施微波辐射下的-吲唑衍生物。细胞毒性试验表明，我们设计的杂化化合物具有很强的活性，尤其是化合物5，其对 HeLa 和 SK-LU-1 细胞的作用甚至优于参考药物顺铂（IC 50 分别为 0.16 和 6.63 µM），并且具有与参考药物伊马替尼对抗 K562 细胞的效力相似。此外，计算机和体外研究强烈建议微管蛋白作为杂交化合物5的分子靶标。
• NOVEL GAK MODULATORS
  申请人：KATHOLIEKE UNIVERSITEIT LEUVEN

  公开号：US20160122364A1

  公开（公告）日：2016-05-05

  The present invention relates to a class of novel isothiazolo[4,3-b]pyridine derivatives and a method for their preparation, as well as to pharmaceutical compositions comprising one or more of said isothiazolo[4,3-b]pyridine derivatives and one or more pharmaceutically acceptable excipients. The present invention further relates to the use of said novel isothiazolo[4,3-b]pyridine derivatives as biologically active ingredients, more specifically as medicaments for the treatment of disorders and pathologic conditions such as, but not limited to, cell-proliferative and neurodegenerative diseases.

  本发明涉及一类新型异噻唑并[4,3-b]吡啶衍生物及其制备方法，以及包含一种或多种所述异噻唑并[4,3-b]吡啶衍生物和一种或多种药学上可接受的辅料的制药组合物。本发明还涉及使用所述新型异噻唑并[4,3-b]吡啶衍生物作为生物活性成分，更具体地作为治疗细胞增殖和神经退行性疾病等疾病和病理情况的药物。
• WO2006/135993
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2008/138834
  申请人：——

  公开号：——

  公开（公告）日：——