1-(3-(trifluoromethyl)phenyl)-1H-indole-3-carbaldehyde | 1086582-55-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-(3-(trifluoromethyl)phenyl)-1H-indole-3-carbaldehyde
• 英文别名: 1-[3-(Trifluoromethyl)phenyl]indole-3-carbaldehyde；1-[3-(trifluoromethyl)phenyl]indole-3-carbaldehyde
• CAS: 1086582-55-9
• 化学式: C₁₆H₁₀F₃NO
• 分子量: 289.257
• InChiKey: RCYZWWSVMFTGJG-UHFFFAOYSA-N

物化性质

• 沸点：
  323.3±42.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  21
• 可旋转键数：
  2
• 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：
  4

反应信息

• 作为反应物：
  描述：

  1-(3-(trifluoromethyl)phenyl)-1H-indole-3-carbaldehyde 在 盐酸羟胺 作用下， 以 吡啶 、 乙醇 为溶剂， 反应 16.0h， 以87%的产率得到1-(3-(trifluoromethyl)phenyl)-1H-indole-3-carbaldehyde oxime
  参考文献：
  名称：

  Synthesis and biological activity of novel MIF antagonists

  摘要：

  Two series of novel furan and indole compounds were synthesized and probed for inhibition of macrophage migration inhibitory factor (MIF) activity. Several compounds from both series inhibited the enzymatic activity of MIF at levels equal to or significantly better than ISO-1 (an early MIF inhibitor). The majority of the compounds that robustly inhibited the spontaneous secretion/release/recognition of MIF from freshly isolated human peripheral blood mononuclear cells were from the furan series (compounds 5, 9, 13, 15, and 16). In contrast, compounds that markedly inhibited the MIF-induced production of pro-inflammatory cytokines were predominantly from the indole series (compounds 26, 29, and 32). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.127
• 作为产物：
  描述：

  methyl 2-(2-bromophenyl)-3-[3-(trifluoromethyl)anilino]prop-2-enoate 在 manganese(IV) oxide 、 potassium tert-butylate 、 二异丁基氢化铝 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 1-(3-(trifluoromethyl)phenyl)-1H-indole-3-carbaldehyde
  参考文献：
  名称：

  通过电子催化的分子内CN键形成吲哚

  摘要：

  已经开发了用于制备N-取代的吲哚-3-羧酸酯的新方案。在没有过渡金属的条件下，采用t -BuOK / DMF系统且无特殊引发剂或添加剂的情况下，关键的C–N键形成。在许多底物上，吲哚的产率与过渡金属催化条件下的产率相比更高或相当。在表现出高官能团耐受性的同时，新条件对于制造使用其他基于金属的催化方法无法制成纯净形式的卤代吲哚特别有吸引力。

  DOI：

  10.1021/acs.orglett.8b02784

文献信息

• [EN] TARGETED BIFUNCTIONAL DEGRADERS<br/>[FR] AGENTS DE DÉGRADATION BIFONCTIONNELS CIBLÉS
  申请人：UNIV YALE

  公开号：WO2021072269A1

  公开（公告）日：2021-04-15

  The present invention provides, in one aspect, bifunctional compounds that can be used to promote or enhance degradation of certain circulating proteins. In another aspect, the present invention provides bifunctional compounds that can be used to promote or enhance degradation of certain autoantibodies. In certain embodiments, treatment or management of a disease and/or disorder requires degradation, removal, or reduction in concentration of the circulating protein or the autoantibody in the subject. Thus, in certain embodiments, administration of a compound of the invention to the subject removes or reduces the circulation concentration of the circulating protein or the autoantibody, thus treating, ameliorating, or preventing the disease and/or disorder. In certain embodiments, the circulating protein is TNF.

  本发明在一个方面提供了可以用来促进或增强降解某些循环蛋白的双功能化合物。在另一个方面，本发明提供了可以用来促进或增强降解某些自身抗体的双功能化合物。在某些实施方式中，治疗或管理疾病和/或疾病需要降解、去除或减少受试者体内循环蛋白或自身抗体的浓度。因此，在某些实施方式中，将本发明的化合物给予受试者可去除或减少循环蛋白或自身抗体的循环浓度，从而治疗、改善或预防疾病和/或疾病。在某些实施方式中，循环蛋白是TNF。
• Synthesis of Chiral <i>cis</i>-Cyclopropane Bearing Indole and Chromone as Potential TNFα Inhibitors
  作者：Ryutaro Kanada、Makoto Tanabe、Ryuta Muromoto、Yukina Sato、Tomoki Kuwahara、Hayato Fukuda、Mitsuhiro Arisawa、Tadashi Matsuda、Mizuki Watanabe、Satoshi Shuto

  DOI：10.1021/acs.joc.8b00466

  日期：2018.8.3

  Conformationally restricted analogues of SPD-304, the first small-molecule TNFα inhibitor, in which two heteroaryl groups, indole and chromone, are connected by chiral methyl- or ethyl-cis-cyclopropane, were designed. Synthesis of these molecules was achieved via Suzuki–Miyaura or Stille coupling reactions with chiral bromomethylenecyclopropane or iodovinyl-cis-cyclopropane as the substrate, both of

  设计了第一个小分子TNFα抑制剂SPD-304的构象受限类似物，其中两个杂芳基（吲哚和色酮）通过手性甲基或乙基-顺式-环丙烷连接。这些分子的合成是通过以手性溴亚甲基环丙烷或碘乙烯基-顺-环丙烷为底物的Suzuki-Miyaura或Stille偶联反应实现的，两者均由手性亚甲基环丙烷作为常见中间体制备，构建了杂芳基-甲基或-乙基-顺式-环丙烷结构是关键步骤。这项研究提出了具有两个杂芳基的一系列手性顺式-环丙烷共轭物的有效合成。
• Rationally Designed Less Toxic SPD-304 Analogs and Preliminary Evaluation of Their TNF Inhibitory Effects
  作者：Polyxeni Alexiou、Athanasios Papakyriakou、Evangelos Ntougkos、Christos P. Papaneophytou、Fotini Liepouri、Anthi Mettou、Ioannis Katsoulis、Anna Maranti、Katerina Tsiliouka、Alexandros Strongilos、Sotiria Chaitidou、Eleni Douni、George Kontopidis、George Kollias、Elias Couladouros、Elias Eliopoulos

  DOI：10.1002/ardp.201400198

  日期：2014.11

  alpha (TNF) antagonist that promotes dissociation of TNF trimers and therefore blocks the interaction of TNF and its receptor. However, SPD‐304 contains a potentially toxic 3‐alkylindole moiety, which can be bioactivated to a reactive electrophilic intermediate. A series of SPD‐304 analogs was synthesized with the aim to diminish its toxicophore groups while maintaining the binding affinity for TNF. Incorporation

  SPD-304 被发现是一种很有前途的肿瘤坏死因子 α (TNF) 拮抗剂，可促进 TNF 三聚体的解离，从而阻断 TNF 与其受体的相互作用。然而，SPD-304 含有潜在有毒的 3-烷基吲哚部分，它可以被生物活化为反应性亲电中间体。合成了一系列 SPD-304 类似物，目的是减少其毒物基团，同时保持对 TNF 的结合亲和力。在吲哚部分引入吸电子取代基，结合消除 4-色酮部分的 6'-甲基，导致毒性显着降低且同样有效的 TNF 抑制剂。
• Synthesis and biological evaluation of potential small moleculeinhibitors of tumor necrosis factor
  作者：Christos Papaneophytou、Polyxeni Alexiou、Athanasios Papakyriakou、Evangelos Ntougkos、Katerina Tsiliouka、Anna Maranti、Fotini Liepouri、Alexandros Strongilos、Anthi Mettou、Elias Couladouros、Elias Eliopoulos、Eleni Douni、George Kollias、George Kontopidis

  DOI：10.1039/c5md00023h

  日期：——

  A series of 39 novel SPD-304 analogs were designed synthesized and evaluated as inhibitors of TNF.

  一系列39种新型SPD-304类似物被设计、合成和评估，作为TNF的抑制剂。
• [EN] BIFUNCTIONAL SMALL MOLECULES TO TARGET THE SELECTIVE DEGRADATION OF CIRCULATING PROTEINS<br/>[FR] PETITES MOLÉCULES BIFONCTIONNELLES POUR CIBLER LA DÉGRADATION SÉLECTIVE DE PROTÉINES CIRCULANTES
  申请人：UNIV YALE

  公开号：WO2019199634A4

  公开（公告）日：2019-12-05