N¹-(9-ethyl-9H-carbazol-3-yl)-N²-(2-methoxyethyl)phthalamide

• 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: N¹-(9-ethyl-9H-carbazol-3-yl)-N²-(2-methoxyethyl)phthalamide
• 英文别名: 2-N-(9-ethylcarbazol-3-yl)-1-N-(2-methoxyethyl)benzene-1,2-dicarboxamide
• 化学式: C₂₅H₂₅N₃O₃
• 分子量: 415.492
• InChiKey: FERDMZGJQSVSMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  72.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-氨基-9-乙基咔唑 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 N¹-(9-ethyl-9H-carbazol-3-yl)-N²-(2-methoxyethyl)phthalamide
  参考文献：
  名称：

  新型咔唑衍生物作为抗癌和抗迁移剂的设计、合成和生物学评价

  摘要：

  基于EHop-016作为迁移和Rac1激活抑制剂的功效，合成了一系列新的咔唑衍生物。在 MCF-7 和 MDA-MB-231 乳腺癌细胞系中评估了这些化合物的细胞毒性和抗迁移作用。对其抗癌活性的初步研究表明，几种化合物对 GI 50值在 13–50 µM 范围内的癌细胞系具有中等抗增殖作用。此外，化合物3b和11b分别抑制转移细胞系MDA-MB-231的迁移活性32%和34%。在 MDA-MB-231 和 MDA-MB-435 细胞系中，化合物11b在 250 nM 时可抑制 Rho GTPase Rac1 的激活 55%。与先导化合物 EHop-016 的 1.1 µM Rac1 抑制作用的IC 50相比，化合物11b 的体外功效提高了 4 倍。

  DOI：

  10.1016/j.bmc.2018.01.003

文献信息

• NOVEL CARBAZOLE EHOP-016 DERIVATIVES AS ANTI-CANCER AND ANTI-MIGRATORY AGENTS
  申请人：UNIVERSITY OF PUERTO RICO

  公开号：US20190125746A1

  公开（公告）日：2019-05-02

  A series of novel of EHop-016 derivatives is presented herein via designing and synthesizing compounds that mimics its more favorable “U-shaped” conformation that appears to be critical for inhibitory activity against Rac. Based on modeling studies on EHop-016, compounds with a more rigid structural conformation can mimic this “U-shaped” conformation would improve the anti-migration activity against metastatic cells. Compounds are disclosed that inhibit RhoGTPases that are useful for inhibiting hyperprofilerative and neoplastic diseases. Specifically, the compounds inhibit the GTPases Rac and Cdc42 that are overactive or overexpressed in signaling pathways in cancer and metastasis. Methods for treatment of cancer and hyperproliferative diseases are disclosed.

  本文介绍了一系列EHop-016衍生物，通过设计和合成模拟其更有利的“U”形构象的化合物，这对于抑制Rac的活性至关重要。基于对EHop-016的建模研究，具有更严格结构构象的化合物可以模拟这种“U”形构象，从而提高对转移性细胞的抗迁移活性。披露了抑制对抗过度增殖和肿瘤性疾病有用的RhoGTP酶的化合物。具体来说，这些化合物抑制了在癌症和转移中信号通路中过度活跃或过度表达的Rac和Cdc42 GTP酶。还披露了治疗癌症和过度增殖性疾病的方法。
• Carbazole EHop-016 derivatives as anti-cancer and anti-migratory agents
  申请人：UNIVERSITY OF PUERTO RICO

  公开号：US10729689B2

  公开（公告）日：2020-08-04

  A series of novel EHop-016 derivatives is presented herein via designing and synthesizing compounds that mimics its more favorable “U-shaped” conformation that appears to be critical for inhibitory activity against Rac. Based on modeling studies on EHop-016, compounds with a more rigid structural conformation can mimic this “U-shaped” conformation would improve the anti-migration activity against metastatic cells. Compounds are disclosed that inhibit RhoGTPases that are useful for inhibiting hyperprofilerative and neoplastic diseases, for instance compounds of formula (I) Specifically, the compounds inhibit the GTPases Rac and Cdc42 that are overactive or overexpressed in signaling pathways in cancer and metastasis. Methods for treatment of cancer and hyperproliferative diseases are disclosed.

  本文介绍了一系列新型 EHop-016 衍生物，通过设计和合成化合物来模拟其更有利的 "U 形 "构象，这种构象似乎是抑制 Rac 活性的关键。根据对 EHop-016 的建模研究，具有更坚硬结构构象的化合物可以模拟这种 "U 形 "构象，从而提高对转移细胞的抗迁移活性。已公开的抑制 RhoGTP 酶的化合物可用于抑制畸形和肿瘤性疾病，例如式 (I) 的化合物 具体而言，这些化合物可抑制在癌症和转移的信号通路中过度活跃或过度表达的 GTP 酶 Rac 和 Cdc42。本研究还公开了治疗癌症和过度增殖性疾病的方法。
• Carbazole EHop-016 derivatives as anticancer and anti-migratory agents
  申请人：UNIVERSITY OF PUERTO RICO

  公开号：US11446299B2

  公开（公告）日：2022-09-20

  A series of novel EHop-016 derivatives is presented herein via designing and synthesizing compounds that mimics its more favorable “U-shaped” conformation that appears to be critical for inhibitory activity against Rac. Based on modeling studies on EHop-016, compounds with a more rigid structural conformation can mimic this “U-shaped” conformation and would improve the anti-migration activity against metastatic cells. Compounds are disclosed that inhibit RhoGTPases that are useful for inhibiting hyperprofilerative and neoplastic diseases, for instance compounds of formula Specifically, the compounds inhibit the GTPases Rac and Cdc42 that are overactive or overexpressed in signaling pathways in cancer and metastasis. Methods for treatment of cancer and hyperproliferative diseases are disclosed.

  本文介绍了一系列新型 EHop-016 衍生物，通过设计和合成化合物来模拟其更有利的 "U 形 "构象，这种构象似乎对 Rac 的抑制活性至关重要。根据对 EHop-016 的建模研究，具有更刚性结构构象的化合物可以模拟这种 "U 形 "构象，从而提高对转移细胞的抗迁移活性。已公开的抑制 RhoGTP 酶的化合物可用于抑制畸形和肿瘤性疾病，例如式 具体而言，这些化合物可抑制在癌症和转移的信号通路中过度活跃或过度表达的 GTP 酶 Rac 和 Cdc42。本研究还公开了治疗癌症和过度增殖性疾病的方法。
• Design, synthesis and biological evaluation of new carbazole derivatives as anti-cancer and anti-migratory agents
  作者：Cornelis P. Vlaar、Linette Castillo-Pichardo、Julia I. Medina、Cathyria M. Marrero-Serra、Ericka Vélez、Zulma Ramos、Eliud Hernández

  DOI：10.1016/j.bmc.2018.01.003

  日期：2018.2

  Based on the efficacy of EHop-016 as an inhibitor of migration and Rac1 activation, a new series of carbazole derivatives has been synthesized. Cytotoxic and anti-migratory effects of these compounds were evaluated in MCF-7 and MDA-MB-231 breast cancer cell lines. Preliminary investigations of their anticancer activity demonstrated that several compounds have moderate antiproliferative effects on cancer

  基于EHop-016作为迁移和Rac1激活抑制剂的功效，合成了一系列新的咔唑衍生物。在 MCF-7 和 MDA-MB-231 乳腺癌细胞系中评估了这些化合物的细胞毒性和抗迁移作用。对其抗癌活性的初步研究表明，几种化合物对 GI 50值在 13–50 µM 范围内的癌细胞系具有中等抗增殖作用。此外，化合物3b和11b分别抑制转移细胞系MDA-MB-231的迁移活性32%和34%。在 MDA-MB-231 和 MDA-MB-435 细胞系中，化合物11b在 250 nM 时可抑制 Rho GTPase Rac1 的激活 55%。与先导化合物 EHop-016 的 1.1 µM Rac1 抑制作用的IC 50相比，化合物11b 的体外功效提高了 4 倍。