1-(cyanobutyl)indole | 143217-51-0

• 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-(cyanobutyl)indole
• 英文别名: 5-(1h-Indol-1-yl)pentanenitrile；5-indol-1-ylpentanenitrile
• CAS: 143217-51-0
• 化学式: C₁₃H₁₄N₂
• 分子量: 198.268
• InChiKey: FVODMAANBKBLBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  28.7
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(cyanobutyl)indole 在 sodium hydrazide 作用下， 生成 Diethyl 3-(4-indol-1-ylbutyl)-1,2,4-triazine-5,6-dicarboxylate
  参考文献：
  名称：

  Indole as a dienophile in inverse electron demand Diels-Alder reactions. 3. Intramolecular reactions with 1,2,4-triazines to access the canthine skeleton

  摘要：

  The intramolecular inverse electron demand cycloaddition of indole with 1,2,4-triazines connected by a tri- or tetramethylene tether linking the indole N-1 position with the triazinyl 3-position successfully produces the canthine skeleton and the homologous system with a seven-membered D-ring.

  DOI：

  10.1021/jo00046a005
• 作为产物：
  描述：

  5-吲哚-1-基戊酸 在 磷酸单乙基酯 、 ethyl polyphosphate (ppe) 、 氨 作用下， 生成 1-(cyanobutyl)indole
  参考文献：
  名称：

  Indole as a dienophile in inverse electron demand Diels-Alder reactions. 3. Intramolecular reactions with 1,2,4-triazines to access the canthine skeleton

  摘要：

  The intramolecular inverse electron demand cycloaddition of indole with 1,2,4-triazines connected by a tri- or tetramethylene tether linking the indole N-1 position with the triazinyl 3-position successfully produces the canthine skeleton and the homologous system with a seven-membered D-ring.

  DOI：

  10.1021/jo00046a005

文献信息

• Novel synthetic bisindolylmaleimide alkaloids inhibit STAT3 activation by binding to the SH2 domain and suppress breast xenograft tumor growth
  作者：Xia Li、Hongguang Ma、Lin Li、Yifan Chen、Xiao Sun、Zizheng Dong、Jing-Yuan Liu、Weiming Zhu、Jian-Ting Zhang

  DOI：10.1038/s41388-017-0076-0

  日期：2018.5

  Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in malignant tumors and plays important roles in multiple aspects of cancer aggressiveness. Thus, targeting STAT3 promises to be an attractive strategy for the treatment of advanced metastatic tumors. Bisindolylmaleimide alkaloid (BMA) has been shown to have anti-cancer activities and was thought to suppress tumor cell growth by inhibiting protein kinase C. In this study, we show that a newly synthesized BMA analog, BMA097, is effective in suppressing tumor cell and xenograft growth and in inducing spontaneous apoptosis. We also provide evidence that BMA097 binds directly to the SH2 domain of STAT3 and inhibits STAT3 phosphorylation and activation, leading to reduced expression of STAT3 downstream target genes. Structure activity relationship analysis revealed that the hydroxymethyl group in the 2,5-dihydropyrrole-2,5-dione prohibits STAT3 inhibitory activity of BMA analogs. Altogether, we conclude that the synthetic BMA analogs may be developed as anti-cancer drugs by targeting and binding to the SH2 domain of STAT3 and inhibiting the STAT3 signaling pathway.

  信号转导和转录激活因子3（STAT3）在恶性肿瘤中始终处于活化状态，并在癌症侵袭性的多个方面发挥重要作用。因此，靶向STAT3被认为是治疗晚期转移性肿瘤的一个有吸引力的策略。双吲哚马来酰亚胺生物碱（BMA）已被证明具有抗癌活性，并被认为通过抑制蛋白激酶C来抑制肿瘤细胞生长。在本研究中，我们展示了一种新合成的BMA类似物BMA097在抑制肿瘤细胞和异种移植生长以及诱导自发凋亡方面的有效性。我们还提供了证据表明BMA097直接结合STAT3的SH2域，抑制STAT3的磷酸化和激活，从而减少STAT3下游靶基因的表达。结构活性关系分析显示，2,5-二氢吡咯-2,5-二酮中的羟甲基基团阻碍了BMA类似物的STAT3抑制活性。总之，我们得出结论，合成的BMA类似物可以通过靶向并结合STAT3的SH2域抑制STAT3信号通路，从而作为抗癌药物进行开发。
• Broadly Neutralizing Synthetic Cannabinoid Vaccines
  作者：Mingliang Lin、Jinny Claire Lee、Steven Blake、Beverly Ellis、Lisa M. Eubanks、Kim D. Janda

  DOI：10.1021/jacsau.0c00057

  日期：2021.1.25

  forming a major public health risk. Due to the wide variety of SCs, broadly neutralizing antibodies generated by active immunization present an intriguing pathway to combat cannabinoid use disorder. Here, we probed hapten design for antibody affinity and cross reactivity against two classes of SCs. Of the 10 haptens screened, 3 vaccine groups revealed submicromolar IC50, each targeting 5–6 compounds in

  合成大麻素 (SC) 是构成主要公共卫生风险的精神活性物质的重要组成部分。由于 SCs 种类繁多，主动免疫产生的广泛中和抗体提供了一种有趣的途径来对抗大麻素使用障碍。在这里，我们探讨了针对两类 SCs 的抗体亲和力和交叉反应性的半抗原设计。在筛选的 10 个半抗原中，3 个疫苗组显示亚微摩尔 IC 50，每个针对我们的 22 种药物中的 5-6 种化合物。此外，当通过电子烟或腹腔注射给药时，SCs 被成功隔离，这在动物模型中通过观察运动、体温和药代动力学得到证实。我们还发现了通过混合疫苗方法同时减弱两种药物类别的协同效应。总的来说，我们的研究为开发针对 SCs 的疫苗提供了全面的基础。
• Indole as a dienophile in inverse electron demand Diels-Alder reactions. 3. Intramolecular reactions with 1,2,4-triazines to access the canthine skeleton
  作者：Scott C. Benson、Jia He Li、John K. Snyder

  DOI：10.1021/jo00046a005

  日期：1992.9

  The intramolecular inverse electron demand cycloaddition of indole with 1,2,4-triazines connected by a tri- or tetramethylene tether linking the indole N-1 position with the triazinyl 3-position successfully produces the canthine skeleton and the homologous system with a seven-membered D-ring.