(2-chloro-pyrimidin-4-yl)-(9-ethyl-9H-carbazol-3-yl)-amine | 1380432-31-4

• 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: (2-chloro-pyrimidin-4-yl)-(9-ethyl-9H-carbazol-3-yl)-amine
• 英文别名: N-(2-chloropyrimidin-4-yl)-9-ethyl-9H-carbazol-3-amine；(2-Chloro-pyrimidin-4-yl)-(9-ethyl-9H-carbazol-3-yl)-amine；N-(2-chloropyrimidin-4-yl)-9-ethylcarbazol-3-amine
• CAS: 1380432-31-4
• 化学式: C₁₈H₁₅ClN₄
• 分子量: 322.797
• InChiKey: RRBYULAJUYYHOB-UHFFFAOYSA-N

物化性质

• 沸点：
  522.2±38.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  42.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3-氨丙基)吗啉 、 (2-chloro-pyrimidin-4-yl)-(9-ethyl-9H-carbazol-3-yl)-amine 在 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 以52.1%的产率得到RACGTPASE抑制剂(EHOP-016)
  参考文献：
  名称：

  NOVEL CARBAZOLE EHOP-016 DERIVATIVES AS ANTI-CANCER AND ANTI-MIGRATORY AGENTS

  摘要：

  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。

  公开号：

  US20190125746A1
• 作为产物：
  描述：

  2,4-二氯嘧啶 、 3-氨基-9-乙基咔唑 在 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 反应 10.0h， 以53%的产率得到(2-chloro-pyrimidin-4-yl)-(9-ethyl-9H-carbazol-3-yl)-amine
  参考文献：
  名称：

  NOVEL CARBAZOLE EHOP-016 DERIVATIVES AS ANTI-CANCER AND ANTI-MIGRATORY AGENTS

  摘要：

  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。

  公开号：

  US20190125746A1

文献信息

• Novel Small-Molecule Inhibitors of Rac1 in Metastatic Breast Cancer
  申请人：University of Puerto Rico

  公开号：US20130172552A1

  公开（公告）日：2013-07-04

  A novel inhibitor of Rac activity based on the structure of the established Rac/Rac-GEF inhibitor NSC23766 is discloses. The compound EHop-016, with an IC50 of 1.1 μM, is a 100-fold more efficient inhibitor of Rac activity than NSC23766. EHop-016 is specific for Rac1 and Rac3 at concentrations ≦5 mM. At higher concentrations, EHop-016 inhibits the close homolog Cdc42. In MDA-MB-435 cells, EHop-016 (≦5 mM) inhibits the association of the Rac-GEF Vav2 with a nucleotide-free Rac1(G15A), which has a high affinity for activated GEFs. EHop-016 does not affect the association of the Rac-GEF Tiam-1 with Rac1(G15A) at similar concentrations. EHop-016 also inhibits the Rac activity of MDA-MB-231 metastatic breast cancer cells and reduces Rac-directed lamellipodia formation in both cell lines. EHop-016 decreases Rac-downstream effects of p21-activated kinase (PAK)1 activity and directed migration of metastatic cancer cells. At low concentrations (<5 μM), EHop-016 does not affect cell viability.

  基于已建立的Rac/Rac-GEF抑制剂NSC23766的结构，揭示了一种新的Rac活性抑制剂。该化合物EHop-016的IC50为1.1μM，比NSC23766更有效地抑制Rac活性100倍。EHop-016在浓度≦5 mM时对Rac1和Rac3具有特异性。在较高浓度下，EHop-016会抑制密切同源物Cdc42。在MDA-MB-435细胞中，EHop-016（≦5 mM）抑制了Rac-GEF Vav2与核苷酸游离的Rac1(G15A)的结合，后者对激活的GEFs具有高亲和力。在相似浓度下，EHop-016不会影响Rac-GEF Tiam-1与Rac1(G15A)的结合。EHop-016还抑制了MDA-MB-231转移性乳腺癌细胞的Rac活性，并减少了两种细胞系中Rac定向的膜足形成。EHop-016降低了Rac下游效应p21激活的激酶（PAK）1活性和转移性癌细胞的定向迁移。在低浓度（<5μM）下，EHop-016不影响细胞存活。
• Small-molecule inhibitors of Rac1 in metastatic breast cancer
  申请人：University of Puerto Rico

  公开号：US08884006B2

  公开（公告）日：2014-11-11

  A novel inhibitor of Rac activity based on the structure of the established Rac/Rac-GEF inhibitor NSC23766 is discloses. The compound EHop-016, with an IC50 of 1.1 μM, is a 100-fold more efficient inhibitor of Rac activity than NSC23766. EHop-016 is specific for Rac1 and Rac3 at concentrations ≦5 mM. At higher concentrations, EHop-016 inhibits the close homolog Cdc42. In MDA-MB-435 cells, EHop-016 (≦5 mM) inhibits the association of the Rac-GEF Vav2 with a nucleotide-free Rac1(G15A), which has a high affinity for activated GEFs. EHop-016 does not affect the association of the Rac-GEF Tiam-1 with Rac1(G15A) at similar concentrations. EHop-016 also inhibits the Rac activity of MDA-MB-231 metastatic breast cancer cells and reduces Rac-directed lamellipodia formation in both cell lines. EHop-016 decreases Rac-downstream effects of p21-activated kinase (PAK)1 activity and directed migration of metastatic cancer cells. At low concentrations (<5 μM), EHop-016 does not affect cell viability.

  披露了一种基于已建立的Rac / Rac-GEF抑制剂NSC23766的结构的新型Rac活性抑制剂。该化合物EHop-016的IC50为1.1μM，是NSC23766的100倍有效的Rac活性抑制剂。EHop-016对Rac1和Rac3在≦5 mM浓度下具有特异性。在更高的浓度下，EHop-016会抑制近似同源物Cdc42。在MDA-MB-435细胞中，EHop-016（≦5 mM）抑制了核苷酸自由的Rac1（G15A）与Rac-GEF Vav2的结合，该结合具有高亲和力的激活GEFs。EHop-016不会影响Rac-GEF Tiam-1与Rac1（G15A）的结合。EHop-016还抑制MDA-MB-231转移性乳腺癌细胞的Rac活性，并减少了两种细胞系的Rac定向的薄膜伸展形成。EHop-016降低了Rac下游效应的p21激活激酶（PAK）1活性和转移性癌细胞的定向迁移。在低浓度（<5μM）下，EHop-016不会影响细胞存活。
• Small-molecule inhibitors of Rac1 in metastatic cancer cells
  申请人：Hernandez Eliud

  公开号：US09278956B1

  公开（公告）日：2016-03-08

  A novel inhibitor of Rac activity based on the structure of the established Rac/Rac-GEF inhibitor NSC23766 is discloses. The compound EHop-016, with an IC50 of 1.1 μM, is a 100-fold more efficient inhibitor of Rac activity than NSC23766. EHop-016 is specific for Rac1 and Rac3 at concentrations ≦5 mM. At higher concentrations, EHop-016 inhibits the close homolog Cdc42. In MDA-MB-435 cells, EHop-016 (≦5 mM) inhibits the association of the Rac-GEF Vav2 with a nucleotide-free Rac1(G15A), which has a high affinity for activated GEFs. EHop-016 does not affect the association of the Rac-GEF Tiam-1 with Rac1(G15A) at similar concentrations. EHop-016 also inhibits the Rac activity of MDA-MB-231 metastatic breast cancer cells and reduces Rac-directed lamellipodia formation in both cell lines. EHop-016 decreases Rac-downstream effects of p21-activated kinase (PAK)1 activity and directed migration of metastatic cancer cells. At low concentrations (<5 μM), EHop-016 does not affect cell viability.

  披露了一种基于已知Rac / Rac-GEF抑制剂NSC23766结构的新型Rac活性抑制剂。该化合物EHop-016的IC50为1.1微米，是NSC23766的100倍有效的Rac活性抑制剂。EHop-016在浓度≦5毫摩尔时对Rac1和Rac3具有特异性。在较高浓度下，EHop-016会抑制密切同源物Cdc42。在MDA-MB-435细胞中，EHop-016（≦5毫摩尔）抑制了核苷酸自由Rac1（G15A）与Rac-GEF Vav2的结合，后者对激活的GEFs具有高亲和力。在类似浓度下，EHop-016不会影响Rac-GEF Tiam-1与Rac1（G15A）的结合。EHop-016还抑制了MDA-MB-231转移性乳腺癌细胞的Rac活性，并减少了两种细胞系中Rac定向的鞭毛形成。EHop-016降低了Rac下游效应的p21激活激酶（PAK）1活性和转移性癌细胞的定向迁移。在低浓度（<5微米）下，EHop-016不会影响细胞存活率。
• 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。