3-bromo-2-hydroxynaphthalene-1-carbaldehyde | 486996-45-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-bromo-2-hydroxynaphthalene-1-carbaldehyde
• 英文别名: 3-Bromo-2-hydroxy-1-naphthaldehyde
• CAS: 486996-45-6
• 化学式: C₁₁H₇BrO₂
• 分子量: 251.079
• InChiKey: JNMWFAZXITZICI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-bromo-2-hydroxynaphthalene-1-carbaldehyde 在 哌啶 、 吡啶 、 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Development of Pyrazolone and Isoxazol-5-one Cambinol Analogues as Sirtuin Inhibitors

  摘要：

  Sirtuins are a family of NAD+-dependent protein deacetylases that play critical roles in epigenetic regulation, stress responses, and cellular aging in eukaryotic cells. In an effort to identify small molecule inhibitors of sirtuins for potential use as chemotherapeutics as well as tools to modulate sirtuin activity, we previously identified a nonselective sirtuin inhibitor called cambinol (IC50 approximate to 50 mu M for SIRT1 and SIRT2) with in vitro and in vivo antilymphoma activity. In the current study, we used saturation transfer difference (STD) NMR experiments with recombinant SIRT1 and 20 to map parts of the inhibitor that interacted with the protein. Our ongoing efforts to optimize cambinol analogues for potency and selectivity have resulted in the identification of isoform selective analogues: 17 with >7.8-fold selectivity for SIRT1, 24 with >15.4-fold selectivity for SIRT2, and 8 with 6.8- and 5.3-fold selectivity for SIRT3 versus SIRT1 and SIRT2, respectively. In vitro cytotoxicity studies with these compounds as well as EX527, a potent and selective SIRT1 inhibitor, suggest that antilymphoma activity of this compound class. may be predominantly due to SIRT2 inhibition.

  DOI：

  10.1021/jm4018064
• 作为产物：
  描述：

  1,1-二氯甲醚 、 3-溴-2-萘酚 在 四氯化钛 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 生成 3-bromo-2-hydroxynaphthalene-1-carbaldehyde
  参考文献：
  名称：

  钌催化还原胺化和动态动力学拆分轴向联芳基的对苯二酚选择性合成

  摘要：

  描述了通过级联转移氢化和动态动力学拆分策略，空前的钌催化的烷基胺对醛的对苯二酸选择性还原胺化反应。该方案具有广泛的底物范围和良好的官能团耐受性，并允许以高至高收率和高至优异的对映选择性快速组装轴向手性联芳基。另外，这样的结构基序可以作为手性配体或催化剂在对映选择性催化中具有潜在的应用。

  DOI：

  10.1021/acs.orglett.8b02785

文献信息

• Ruthenium-Catalyzed Atropoenantioselective Synthesis of Axial Biaryls via Reductive Amination and Dynamic Kinetic Resolution
  作者：Donghui Guo、Jianwei Zhang、Bei Zhang、Jian Wang

  DOI：10.1021/acs.orglett.8b02785

  日期：2018.10.5

  via a cascade transfer hydrogenation and dynamic kinetic resolution strategy is described. This protocol features broad substrate scope and good functional group tolerance and allows the rapid assembly of axially chiral biaryls in good to high yields with high to excellent enantioselectivities. In addition, such structural motifs may have potential applications in enantioselective catalysis as chiral

  描述了通过级联转移氢化和动态动力学拆分策略，空前的钌催化的烷基胺对醛的对苯二酸选择性还原胺化反应。该方案具有广泛的底物范围和良好的官能团耐受性，并允许以高至高收率和高至优异的对映选择性快速组装轴向手性联芳基。另外，这样的结构基序可以作为手性配体或催化剂在对映选择性催化中具有潜在的应用。
• Discovery of Selective SIRT2 Inhibitors as Therapeutic Agents in B-Cell Lymphoma and Other Malignancies
  作者：Sarwat Chowdhury、Smitha Sripathy、Alyssa A. Webster、Angela Park、Uyen Lao、Joanne H. Hsu、Taylor Loe、Antonio Bedalov、Julian A. Simon

  DOI：10.3390/molecules25030455

  日期：——

  Genetic ablation as well as pharmacological inhibition of sirtuin 2 (SIRT2), an NAD+-dependent protein deacylase, have therapeutic effects in various cancers and neurodegenerative diseases. Previously, we described the discovery of a dual SIRT1/SIRT2 inhibitor called cambinol (IC50 56 and 59 µM, respectively), which showed cytotoxic activity against cancer cells in vitro and a marked anti-proliferative effect in a Burkitt lymphoma mouse xenograft model. A number of recent studies have shown a protective effect of SIRT1 and SIRT3 in neurodegenerative and metabolic diseases as well as in certain cancers prompting us to initiate a medicinal chemistry effort to develop cambinol-based SIRT2-specific inhibitors devoid of SIRT1 or SIRT3 modulating activity. Here we describe potent cambinol-based SIRT2 inhibitors, several of which show potency of ~600 nM with >300 to >800-fold selectivity over SIRT1 and 3, respectively. In vitro, these inhibitors are found to be toxic to lymphoma and epithelial cancer cell lines. In particular, compounds 55 (IC50 SIRT2 0.25 µM and <25% inhibition at 50 µM against SIRT1 and SIRT3) and 56 (IC50 SIRT2 0.78 µM and <25% inhibition at 50 µM against SIRT1 and SIRT3) showed apoptotic as well as strong anti-proliferative properties against B-cell lymphoma cells.

  基因消融以及对SIRT2（一种NAD+依赖性蛋白去乙酰化酶）的药物抑制在各种癌症和神经退行性疾病中具有治疗效果。我们先前描述了一种双重SIRT1/SIRT2抑制剂称为cambinol（IC50分别为56和59微米），在体外对癌细胞显示细胞毒活性，并在Burkitt淋巴瘤小鼠异种移植模型中表现出明显的抗增殖效果。最近的一些研究表明，SIRT1和SIRT3在神经退行性和代谢性疾病以及某些癌症中具有保护作用，促使我们启动了一项药物化学工作，以开发基于cambinol的SIRT2特异性抑制剂，不具有SIRT1或SIRT3调节活性。在这里，我们描述了有效的基于cambinol的SIRT2抑制剂，其中几种显示出约600纳米的效力，对SIRT1和SIRT3的选择性分别为>300至>800倍。在体外，这些抑制剂对淋巴瘤和上皮癌细胞系具有毒性。特别是，化合物55（IC50 SIRT2 0.25微米，在50微米下对SIRT1和SIRT3的抑制<25%）和56（IC50 SIRT2 0.78微米，在50微米下对SIRT1和SIRT3的抑制<25%）显示出对B细胞淋巴瘤细胞具有凋亡以及强烈的抗增殖特性。
• Atropoenantioselective Redox-Neutral Amination of Biaryl Compounds through Borrowing Hydrogen and Dynamic Kinetic Resolution
  作者：Jianwei Zhang、Jian Wang

  DOI：10.1002/anie.201711126

  日期：2018.1.8

  triggered by a cascade of borrowing hydrogen and dynamic kinetic resolution under the cooperative catalysis of a chiral iridium complex and an achiral Brønsted acid. This protocol features broad substrate scope and good functional‐group tolerance, and allows the rapid assembly of axially chiral biaryl compounds in good to high yields and with high to excellent enantioselectivity.

  我们在此报告了一种新颖的对芳基化合物的新型对苯二酚选择性氧化还原中性胺化反应，该反应是由手性铱配合物和非手性布朗斯台德酸的协同催化下的借入氢和动态动力学拆分级联触发的。该方案具有广泛的底物范围和良好的官能团耐受性，并允许以高至高收率和高至优异的对映选择性快速组装轴向手性联芳基化合物。
• Thermosettable compounds prepared from monohydroxy aromatic aldehydes and methylated pyridines or pyrazines
  申请人：THE DOW CHEMICAL COMPANY

  公开号：EP0212095A1

  公开（公告）日：1987-03-04

  Thermostable compounds are prepared by reac­ting methylated pyridines and/or pyrazines with one or more monohydroxy aromatic aldehydes having the ortho and para positions to the hydroxy group block with groups inert to condensation reactions. These com­pounds are useful to make unsaturated derivatives which can cure into high temperature resistant polymers and/or laminates without giving off condensation products.

  将甲基化的吡啶和/或吡嗪与一种或多种单羟基芳香醛反应，制备耐热化合物。这些化合物用于制造不饱和衍生物，可以固化成耐高温聚合物和/或层压板，而不会产生缩合产物。
• US4256900A
  申请人：——

  公开号：US4256900A

  公开（公告）日：1981-03-17