N-(4-aminophenyl)heptanamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-aminophenyl)heptanamide
• 化学式: C₁₃H₂₀N₂O
• 分子量: 220.315
• InChiKey: JZVPWSAMABVYSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.461
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(4-aminophenyl)heptanamide 、 1-溴-三氟对二甲苯 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以72%的产率得到N-(4-((4-(trifluoromethyl)benzyl)amino)phenyl)heptanamide
  参考文献：
  名称：

  超越瑞替加滨：具有抗惊厥活性的有效且化学稳定的神经元 Kv7 通道激活剂的设计、合成和药理学表征

  摘要：

  神经元 Kv7 通道代表了包括癫痫在内的过度兴奋性障碍的重要药理学靶点。Retigabine 是临床批准用于癫痫治疗的原型 Kv7 激活剂；然而，与长期使用相关的严重副作用导致其市场停产。基于最近描述的与瑞替加滨复合的 Kv7.2 的 cryoEM 结构以及先前的结构-活性关系研究，已经设计、合成了一个小型瑞替加滨类似物库，并使用基于荧光和电生理学的方法对其 Kv7 开放能力进行了表征化验。在所有测试的化合物中，有60 种作为有效且光化学稳定的神经元 Kv7 通道激活剂出现。与瑞替加滨相比，化合物60在小鼠急性癫痫发作模型中显示出更高的脑/血浆分布比、更长的消除半衰期和更有效的抗惊厥作用。总的来说，这些数据强调了化合物60作为一种有前途的先导化合物，可用于开发用于治疗过度兴奋性疾病的新型 Kv7 激活剂。

  DOI：

  10.1021/acs.jmedchem.2c00911
• 作为产物：
  描述：

  庚酸 、 对苯二胺 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 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以40%的产率得到N-(4-aminophenyl)heptanamide
  参考文献：
  名称：

  Discovery of N1-(4-((7-Cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)phenyl)-N8-hydroxyoctanediamide as a Novel Inhibitor Targeting Cyclin-dependent Kinase 4/9 (CDK4/9) and Histone Deacetlyase1 (HDAC1) against Malignant Cancer

  摘要：

  A series of novel, highly potent, selective inhibitors targeting both CDK4/9 and HDAC1 have been designed and synthesized. N1-(4-((7-Cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo [2,3-d]pyrimidin-2-yl)amino)phenyl)-N8-hydroxyo ctan ediamide (6e) was discovered. The lead compound 6e with excellent CDK4/9 and HDAC1 inhibitory activity of IC50 = 8.8, 12, and 2.2 nM, respectively, can effectively induce apoptosis of cancer cell lines. The kinase profiling of compound 6e showed excellent selectivity and specificity. Compound 6e induces G2/M arrest in high concentration and G0/G1 arrest in low concentration to prevent the proliferation and differentiation of cancer cells. Mice bared-breast cancer treated with 6e showed significant antitumor efficacy. The insight into mechanisms of 6e indicated that it could induce cancer cell death via cell apoptosis based on CDK4/9 and HDAC1 repression and phosphorylation of p53. Our data demonstrated the novel compound 6e could be a promising drug candidate for cancer therapy.

  DOI：

  10.1021/acs.jmedchem.8b00209

文献信息

• [EN] MODULATORS OF POTASSIUM ION CHANNELS AND USES THEREOF<br/>[FR] MODULATEURS DE CANAUX IONIQUES POTASSIQUES ET LEURS UTILISATIONS
  申请人：UNIVERSITÀ DEGLI STUDI DI SALERNO

  公开号：WO2020157126A1

  公开（公告）日：2020-08-06

  The present invention relates to a class of novel compounds of general formula (I), their use as medicaments and pharmaceutical compositions comprising them. Specifically, the compounds of the invention are useful as voltage-gated potassium ion channels modulators.

  本发明涉及一类新颖化合物，其一般式为（I），它们作为药物的用途以及包含它们的药物组合物。具体而言，本发明的化合物可用作电压门控钾离子通道调节剂。
• Discovery of <i>N</i>1-(4-((7-Cyclopentyl-6-(dimethylcarbamoyl)-7<i>H</i>-pyrrolo[2,3-<i>d</i>]pyrimidin-2-yl)amino)phenyl)-<i>N</i>8-hydroxyoctanediamide as a Novel Inhibitor Targeting Cyclin-dependent Kinase 4/9 (CDK4/9) and Histone Deacetlyase1 (HDAC1) against Malignant Cancer
  作者：Yongtao Li、Xiaohe Luo、Qingxiang Guo、Yongwei Nie、Tianqi Wang、Chao Zhang、Zhi Huang、Xin Wang、Yanhua Liu、Yanan Chen、Jianyu Zheng、Shengyong Yang、Yan Fan、Rong Xiang

  DOI：10.1021/acs.jmedchem.8b00209

  日期：2018.4.12

  A series of novel, highly potent, selective inhibitors targeting both CDK4/9 and HDAC1 have been designed and synthesized. N1-(4-((7-Cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo [2,3-d]pyrimidin-2-yl)amino)phenyl)-N8-hydroxyo ctan ediamide (6e) was discovered. The lead compound 6e with excellent CDK4/9 and HDAC1 inhibitory activity of IC50 = 8.8, 12, and 2.2 nM, respectively, can effectively induce apoptosis of cancer cell lines. The kinase profiling of compound 6e showed excellent selectivity and specificity. Compound 6e induces G2/M arrest in high concentration and G0/G1 arrest in low concentration to prevent the proliferation and differentiation of cancer cells. Mice bared-breast cancer treated with 6e showed significant antitumor efficacy. The insight into mechanisms of 6e indicated that it could induce cancer cell death via cell apoptosis based on CDK4/9 and HDAC1 repression and phosphorylation of p53. Our data demonstrated the novel compound 6e could be a promising drug candidate for cancer therapy.
• Beyond Retigabine: Design, Synthesis, and Pharmacological Characterization of a Potent and Chemically Stable Neuronal Kv7 Channel Activator with Anticonvulsant Activity
  作者：Simona Musella、Lidia Carotenuto、Nunzio Iraci、Giulia Baroli、Tania Ciaglia、Piera Nappi、Manuela Giovanna Basilicata、Emanuela Salviati、Vincenzo Barrese、Vincenzo Vestuto、Giuseppe Pignataro、Giacomo Pepe、Eduardo Sommella、Veronica Di Sarno、Michele Manfra、Pietro Campiglia、Isabel Gomez-Monterrey、Alessia Bertamino、Maurizio Taglialatela、Carmine Ostacolo、Francesco Miceli

  DOI：10.1021/acs.jmedchem.2c00911

  日期：2022.8.25

  both fluorescence- and electrophysiology-based assays. Among all tested compounds, 60 emerged as a potent and photochemically stable neuronal Kv7 channel activator. Compared to retigabine, compound 60 displayed a higher brain/plasma distribution ratio, a longer elimination half-life, and more potent and effective anticonvulsant effects in an acute seizure model in mice. Collectively, these data highlight

  神经元 Kv7 通道代表了包括癫痫在内的过度兴奋性障碍的重要药理学靶点。Retigabine 是临床批准用于癫痫治疗的原型 Kv7 激活剂；然而，与长期使用相关的严重副作用导致其市场停产。基于最近描述的与瑞替加滨复合的 Kv7.2 的 cryoEM 结构以及先前的结构-活性关系研究，已经设计、合成了一个小型瑞替加滨类似物库，并使用基于荧光和电生理学的方法对其 Kv7 开放能力进行了表征化验。在所有测试的化合物中，有60 种作为有效且光化学稳定的神经元 Kv7 通道激活剂出现。与瑞替加滨相比，化合物60在小鼠急性癫痫发作模型中显示出更高的脑/血浆分布比、更长的消除半衰期和更有效的抗惊厥作用。总的来说，这些数据强调了化合物60作为一种有前途的先导化合物，可用于开发用于治疗过度兴奋性疾病的新型 Kv7 激活剂。