1,3-bis(9H-carbazol-9-yl)propan-2-ol | 57386-39-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1,3-bis(9H-carbazol-9-yl)propan-2-ol
• 英文别名: 1,3-di(9H-carbazol-9-yl)propan-2-ol；1,3-bis(carbazol-9-yl)propan-2-ol；1,3-di(carbazol-9-yl)-2-propanole；1,3-Di(9-carbazolyl)-2-propanol；1,3-di(carbazol-9-yl)propan-2-ol
• CAS: 57386-39-7
• 化学式: C₂₇H₂₂N₂O
• 分子量: 390.484
• InChiKey: UXQNXMYBZRBGRN-UHFFFAOYSA-N

物化性质

• 熔点：
  189-190 °C(Solv: ethanol (64-17-5))
• 沸点：
  369.2±9.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  30.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1,3-bis(9H-carbazol-9-yl)propan-2-ol 在 羟胺 、 sodium methylate 、 sodium sulfate 、 potassium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 (S)-1-(3-((1,3-di(9H-carbazol-9-yl)propan-2-yl)oxy)-2-hydroxypropyl)-N-hydroxypiperidine-4-carboxamide
  参考文献：
  名称：

  多功能DNMT和HDAC抑制剂CO2S的开发可调节多种癌症标志物，用于乳腺癌治疗。

  摘要：

  DNMT和HDAC彼此密切相关，并涉及各种人类疾病，尤其是癌症。这两种酶已被广泛认为是药物发现的抗肿瘤靶标。此外，研究表明由DNMT和HDAC抑制剂组成的联合疗法具有治疗优势。我们已经报告了DNMT和HDAC双重抑制剂15a，其中DNMT的酶促抑制效能需要提高。本文中，我们报道了新型DNMT和HDAC双重抑制剂CO2S的开发，该抑制剂显示出对DNMT1，DNMT3A，DNMT3B和HDAC1的有效酶抑制活性，IC 50值分别为2.05、0.93、1.32和4.16 µM。进一步评估表明，CO2S可以在细胞水平上抑制DNMT和HDAC，从而逆转突变的甲基化和乙酰化并增加肿瘤抑制蛋白的表达。此外，CO 2 S调节多种生物学过程，包括诱导凋亡和G0 / G1细胞周期停滞，抑制血管生成，阻断迁移和侵袭，并最终抑制体外肿瘤细胞增殖和体内肿瘤生长。

  DOI：

  10.1016/j.bioorg.2019.03.027
• 作为产物：
  描述：

  9-(环氧-2-甲基)-9H-咔唑 、 咔唑 在 potassium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以75%的产率得到1,3-bis(9H-carbazol-9-yl)propan-2-ol
  参考文献：
  名称：

  多靶点神经保护剂的分子构建 4.* 咔唑和四氢咔唑偶联物的合成和生物活性

  摘要：

  咔唑和四氢咔唑的未知共轭物是通过咔唑和四氢咔唑与 3,6-取代的 9-环氧乙烷基甲基咔唑的烷基化获得的。合成1-(9Н-咔唑-9-基)-3-(1,2,3,4-四氢-5Н-吡啶并[4,3-b]-吲哚-5-基)丙-2-的影响对脑线粒体功能特性的研究。已使用谷氨酸毒性模型证明了几种代表性缀合物的潜在神经保护活性。

  DOI：

  10.1007/s11172-016-1582-x

文献信息

• Amino, amido and heterocyclic compounds as modulators of rage activity and uses thereof
  申请人：Schmidt Ann Marie

  公开号：US10265320B2

  公开（公告）日：2019-04-23

  Amino, amido, and heterocyclic compounds are disclosed. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, diabetes complications, inflammation, and neurodegeneration, obesity, cancer, ischemia/reperfusion injury, cardiovascular disease and other diseases related to RAGE activity.

  本发明公开了氨基化合物、氨基化合物和杂环化合物。这些化合物可制备成药物组合物，并可用于预防和治疗包括人类在内的哺乳动物的多种疾病，包括非限制性的糖尿病并发症、炎症、神经变性、肥胖症、癌症、缺血/再灌注损伤、心血管疾病和其他与 RAGE 活性有关的疾病。
• Amino, amido and heterocyclic compounds as modulators of RAGE activity and uses thereof
  申请人：Schmidt Ann Marie

  公开号：US10729695B2

  公开（公告）日：2020-08-04

  Amino, amido, and heterocyclic compounds are disclosed. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, diabetes complications, inflammation, and neurodegeneration, obesity, cancer, ischemia/reperfusion injury, cardiovascular disease and other diseases related to RAGE activity.

  本发明公开了氨基化合物、氨基化合物和杂环化合物。这些化合物可制备成药物组合物，并可用于预防和治疗包括人类在内的哺乳动物的多种疾病，包括非限制性的糖尿病并发症、炎症、神经变性、肥胖症、癌症、缺血/再灌注损伤、心血管疾病和其他与 RAGE 活性有关的疾病。
• Synthesis and structure–activity relationship studies of 1,3-disubstituted 2-propanols as BACE-1 inhibitors
  作者：Arun Babu Kumar、Jordan Micheal Anderson、Anthony Lester Melendez、Roman Manetsch

  DOI：10.1016/j.bmcl.2012.05.072

  日期：2012.7

  A library of 1,3-disubstituted 2-propanols was synthesized and evaluated as low molecular weight probes for beta-secretase inhibition. By screening a library of 121 1,3-disubstituted 2-propanol derivatives, we identified few compounds inhibiting the enzyme at low micromolar concentrations. The initial hits were optimized to yield a potent BACE-1 inhibitor exhibiting an IC50 constant in the nanomolar range. Exploration of the pharmacological properties revealed that these small molecular inhibitors possessed a high selectivity over cathepsin D and desirable physicochemical properties beneficial to cross the blood-brain barrier. (C) 2012 Elsevier Ltd. All rights reserved.
• Identifying Novel Selective Non-Nucleoside DNA Methyltransferase 1 Inhibitors through Docking-Based Virtual Screening
  作者：Shijie Chen、Yulan Wang、Wen Zhou、Shanshan Li、Jianlong Peng、Zhe Shi、Junchi Hu、Yu-Chih Liu、Hong Ding、Yijyun Lin、Linjuan Li、Sufang Cheng、Jingqiu Liu、Tao Lu、Hualiang Jiang、Bo Liu、Mingyue Zheng、Cheng Luo

  DOI：10.1021/jm501134e

  日期：2014.11.13

  The DNA methyltransferases (DNMTs) found in mammals include DNMT1, DNMT3A, and DNMT3B and are attractive targets in cancer chemotherapy. DNMT1 was the first among the DNMTs to be characterized, and it is responsible for maintaining DNA methylation patterns. A number of DNMT inhibitors have been reported, but most of them are nucleoside analogs that can lead to toxic side effects and lack specificity. By combining docking-based virtual screening with biochemical analyses, we identified a novel compound, DC_05. DC_05 is a non-nucleoside DNMT1 inhibitor with low micromolar IC50 values and significant selectivity toward other AdoMet-dependent protein methyltransferases. Through a process of similarity-based analog searching, compounds DC_501 and DC_517 were found to be more potent than DC_05. These three potent compounds significantly inhibited cancer cell proliferation. The structure-activity relationship (SAR) and binding modes of these inhibitors were also analyzed to assist in the future development of more potent and more specific DNMT1 inhibitors.
• Glass-forming 1,3-bis(carbazol-9-yl)propan-2-ol based monomers and polymers
  作者：Egle Andrikaityte、Monika Cekaviciute、Jurate Simokaitiene、Gintaras Buika、Juozas Vidas Grazulevicius、Vitalija Rubeziene

  DOI：10.1016/j.reactfunctpolym.2011.08.010

  日期：2012.1

  Three glass-forming 1,3-bis(carbazol-9-yl)propan-2-ol based monomers, i.e. oxirane, thiirane and oxetane were synthesized. Photopolymerization of their solid amorphous layers initiated with diphenyliodonium tetrafluoroborate and the dark polymerization in solutions initiated with boron trifluoride etherate were performed. The number-average molecular weights of the obtained polymers are in the range of 1000-19,400. The highest initial polymerization rate, the highest limit conversion and the highest molecular weight were observed for the polymerization of thiirane. Optical, photophysical, electrochemical and thermal properties of the synthesized compounds were studied. UV and fluorescence spectra of the compounds have the similar profiles, due to the presence of the same chromophore. No excimer emission was observed neither for dilute solutions of monomers nor polymers. The electrochemical coupling was observed for all the synthesized 1,3-bis(carbazol-9-yl)propan-2-ol based monomers and polymers by cyclic voltammetry. The thermal degradation of the derivatives of 1,3-bis(carbazol-9-yl)propan-2-ol derivatives starts in the range of the temperatures from 317 to 402. The glass transition temperatures of the monomers range from 43 to 58 while glass transition temperatures of the polymers are in the range of 103-125. (C) 2011 Elsevier Ltd. All rights reserved.