N-(4-aminophenyl)octanamide

• 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)octanamide
• 英文别名: octanoic acid-(4-amino-anilide)；Octansaeure-(4-amino-anilid)；N-Octanoyl-p-phenylendiamin
• 化学式: C₁₄H₂₂N₂O
• mdl: MFCD09997474
• 分子量: 234.341
• InChiKey: HNAZVQNBRXUPOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  2-氯-7-环戊基-N,N-二甲基-7H-吡咯并[2,3-d]嘧啶-6-甲酰胺 、 N-(4-aminophenyl)octanamide 在 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 1,4-二氧六环 为溶剂， 反应 12.0h， 以81%的产率得到7-cyclopentyl-N,N-dimethyl-2-((4-octanamidophenyl)-amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide
  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
• 作为产物：
  描述：

  N-(4-nitrophenyl)octanamide 在 盐酸 、 锌 作用下， 生成 N-(4-aminophenyl)octanamide
  参考文献：
  名称：

  偶氮蛋白的血清学研究：包含具有脂肪族侧链的偶氮组分的抗原。

  摘要：

  对含有脂肪链的人工复合抗原的特异性进行了研究。短链含羧基化合物的反应表现出惊人的特异性；例如，琥珀酸可以区别于丙二酸或戊二酸，它们分别含有少一个和一个多的碳原子。对于含有较长链的物质，观察到的反应虽然在一定程度上具有特异性，但似乎主要取决于长脂肪链的一般物理化学性质。使用数量有限的物质研究了取代基-卤素、OH、NH(2)-对血清学特异性的影响。通过抑制反应，可以证明顺反异构体如马来酸和富马酸的血清学特异性。

  DOI：

  10.1084/jem.59.6.751

文献信息

• 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.
• SEROLOGICAL STUDIES ON AZOPROTEINS
  作者：E. Landsteiner、J. van der Scheer

  DOI：10.1084/jem.59.6.751

  日期：1934.6.1

  containing aliphatic chains. Striking specificity was exhibited in the reactions of compounds with short chains containing a carboxyl group; for instance succinic acid could be differentiated from malonic or glutaric acid which contain one fewer and one more carbon atom respectively. With the substances containing longer chains, reactions were observed which, although specific to a certain extent, appear

  对含有脂肪链的人工复合抗原的特异性进行了研究。短链含羧基化合物的反应表现出惊人的特异性；例如，琥珀酸可以区别于丙二酸或戊二酸，它们分别含有少一个和一个多的碳原子。对于含有较长链的物质，观察到的反应虽然在一定程度上具有特异性，但似乎主要取决于长脂肪链的一般物理化学性质。使用数量有限的物质研究了取代基-卤素、OH、NH(2)-对血清学特异性的影响。通过抑制反应，可以证明顺反异构体如马来酸和富马酸的血清学特异性。