1-(4-chlorobenzyl)-5-chloroindole-3-carbaldehyde | 226883-78-9

• 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-(4-chlorobenzyl)-5-chloroindole-3-carbaldehyde
• 英文别名: 1-[(4-chlorophenyl)methyl]-5-chloro-1H-indole-3-carboxaldehyde；5-Chloro-1-[(4-chlorophenyl)methyl]indole-3-carbaldehyde
• CAS: 226883-78-9
• 化学式: C₁₆H₁₁Cl₂NO
• 分子量: 304.175
• InChiKey: UVDMAHQTDZYHDD-UHFFFAOYSA-N

物化性质

• 熔点：
  146-147 °C (decomp)
• 沸点：
  492.9±40.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  22
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(4-chlorobenzyl)-5-chloroindole-3-carbaldehyde 在 镍 sodium hydroxide 、 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 2.0h， 生成 3-[5-Chloro-1-(4-chloro-benzyl)-1H-indol-3-yl]-propionic acid
  参考文献：
  名称：

  Synthetic N-pyridinyl(methyl)-indol-3-ylpropanamides as new potential immunosuppressive agents

  摘要：

  Several N-pyridinyl(methyl)-indol-3-ylpropanamides were synthesized and pharmacological evaluations of their immumosuppressive potential were performed. Among thirteen compounds tested in vitro on murine T proliferation, three showed interesting inhibiting activity. For the most active compound (propanamide 18), immunosuppressive activity was documented both in vitro on human T lymphocytes proliferation and in vivo on mice delayed-type hypersensitivity. These experimental data demonstrated that these compounds hold potential as immunosuppressive agents. (c) 2007 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2006.12.013
• 作为产物：
  描述：

  5-氯吲哚 在 sodium hydride 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 7.5h， 生成 1-(4-chlorobenzyl)-5-chloroindole-3-carbaldehyde
  参考文献：
  名称：

  新型吲哚衍生物含3-亚甲基二氢呋喃-2（3H）-不可逆LSD1抑制剂的发现与合成

  摘要：

  赖氨酸特异性脱甲基酶1（LSD1），针对单和二甲基化组蛋白3赖氨酸4的脱甲基酶，已成为肿瘤学中有希望的靶标。更具体地说，已证明它是急性髓细胞性白血病（AML）的关键启动子，并且几种LSD1抑制剂已进入治疗AML的临床试验。在本文中，基于通过我们内部化合物库的高通量筛选获得的先导化合物，设计和合成了一系列新的吲哚衍生物。在合成化合物中，9e被表征为具有IC 50的有效LSD1抑制剂浓度为1.230μM，可有效抑制THP-1细胞的增殖。最重要的是，这是第一种不可逆的LSD1抑制剂，它不是单胺氧化酶抑制剂衍生的。因此，发现9e可以作为AML治疗的概念证明工作。

  DOI：

  10.1016/j.ejmech.2019.04.065

文献信息

• Analogues and Derivatives of Oncrasin-1, a Novel Inhibitor of the C-Terminal Domain of RNA Polymerase II and Their Antitumor Activities
  作者：Shuhong Wu、Li Wang、Wei Guo、Xiaoying Liu、Jinsong Liu、Xiaoli Wei、Bingliang Fang

  DOI：10.1021/jm101417n

  日期：2011.4.28

  To optimize the antitumor activity of oncrasin-1, a small molecule RNA polymerase II inhibitor, We evaluated 69 oncrasin-1 analogues for their cytotoxic activity against normal human epithelial cells and K-Ras mutant tumor cells. About 40 of those compounds were as potent as or more potent than oncrasin-1 in tumor cells and had a minimal cytotoxic effect on normal cells. Structure activity relationship analysis revealed that most of the active compounds contained either a hydroxymethyl group or an aldehyde group as a substitute at the 3-position of the indole. Both electron-donating and electron-withdrawing groups in the benzene ring were well tolerated. The hydroxymethyl compounds ranged from equipotent with to 100 times as potent as the corresponding aldehyde compounds. We tested three active analogues' effect on RNA, polymerase phosphorylation and found that they all inhibited phosphorylation of the C-terminal domain of RNA polymerase suggesting that the active compounds might act through the same mechanisms as oncrasin-1.
• Indole amide derivatives: synthesis, structure–activity relationships and molecular modelling studies of a new series of histamine H1-receptor antagonists
  作者：Sandra Battaglia、Enrico Boldrini、Federico Da Settimo、Giulio Dondio、Concettina La Motta、Anna Maria Marini、Giampaolo Primofiore

  DOI：10.1016/s0223-5234(99)80044-0

  日期：1999.2

  A number of indole amide derivatives bearing a basic side chain, in which the indole ring replaces the isoster benzimidazole nucleus typical of some well-known antihistamines, were prepared and tested for their H-1-antihistaminic activity. The 1-benzyl-3-indolecarboxamides 32-42 showed antihistaminic (H-1) activity (pA(2) 6-8); the 3-indolylglyoxylylamides 7-16 and the 2-indolecarboxamides 48-56 showed little or no activity. Insertion of the basic side chain of the active 3-indolecarboxamide derivatives into a piperazine ring (compounds 57-59) led to a dramatic loss of activity. All the active compounds proved to be competitive antagonists, since the values of the regression slope were not statistically different from 1. The most active compounds, 32, 33, 38-41, were also tested both in vitro for their anticholinergic activity and in vivo for their ability to antagonize histamine-induced cutaneous vascular permeability in rats. The biological results and the structure-activity relationships of the novel compounds are discussed in the light of molecular modelling studies, taking the molecule of astemizole as a model, and referring to proposed H-1-receptor pharmacophore models. (C) Elsevier, Paris.
• New N-pyridinyl(methyl)-indolalkanamides acting as topical inflammation inhibitors
  作者：Alexandra Dassonville、Anne Bretéché、Johan Evano、Muriel Duflos、Guillaume le Baut、Nicole Grimaud、Jean-Yves Petit

  DOI：10.1016/j.bmcl.2004.07.057

  日期：2004.11

  The authors have described the synthetic way to new N-pyridinyl(methyl)indolylpropanamides acting as non acidic NSAIDs. Pharmacomodulation was carried out at N-1 and C-5 of the indole ring and at the level of the propanamide chain. N-(pyridin-3-ylmethyl)-3-[5-chloro-1-(4-chlorobenzyl)-indol-3-yl]propanamide 32 represents one of the most potent compounds evaluated in the TPA-induced mouse ear swelling assay, with a level of activity higher than that of ibuprofen and comparable to that of dexamethasone. (C) 2004 Published by Elsevier Ltd.
• Synthesis and Activity of Novel 1-Halogenobenzylindole Linked Triazole Derivatives as Antifungal Agents
  作者：Young-Min Na

  DOI：10.5012/bkcs.2011.32.1.307

  日期：2011.1.20
• Discovery and synthesis of novel indole derivatives-containing 3-methylenedihydrofuran-2(3H)-one as irreversible LSD1 inhibitors
  作者：Hong-Min Liu、Feng-Zhi Suo、Xiao-Bo Li、Ying-Hua You、Chun-Tao Lv、Chen-Xing Zheng、Guo-Chen Zhang、Yue-Jiao Liu、Wen-Ting Kang、Yi-Chao Zheng、Hai-Wei Xu

  DOI：10.1016/j.ejmech.2019.04.065

  日期：2019.8

  in-house compound library. Among the synthetic compounds, 9e was characterized as a potent LSD1 inhibitor with an IC50 of 1.230 μM and can inhibit the proliferation of THP-1 cells effectively. And most importantly, this is the first irreversible LSD1 inhibitor that is not derived from monoamine oxidase inhibitors. Hence, the discovery of 9e may serve as a proof of concept work for AML treatment.

  赖氨酸特异性脱甲基酶1（LSD1），针对单和二甲基化组蛋白3赖氨酸4的脱甲基酶，已成为肿瘤学中有希望的靶标。更具体地说，已证明它是急性髓细胞性白血病（AML）的关键启动子，并且几种LSD1抑制剂已进入治疗AML的临床试验。在本文中，基于通过我们内部化合物库的高通量筛选获得的先导化合物，设计和合成了一系列新的吲哚衍生物。在合成化合物中，9e被表征为具有IC 50的有效LSD1抑制剂浓度为1.230μM，可有效抑制THP-1细胞的增殖。最重要的是，这是第一种不可逆的LSD1抑制剂，它不是单胺氧化酶抑制剂衍生的。因此，发现9e可以作为AML治疗的概念证明工作。