(4-ethylpiperazin-1-yl)(3-methyl-4-nitrophenyl)methanone | 432503-80-5

• 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: (4-ethylpiperazin-1-yl)(3-methyl-4-nitrophenyl)methanone
• 英文别名: Cambridge id 6806125；(4-ethylpiperazin-1-yl)-(3-methyl-4-nitrophenyl)methanone
• CAS: 432503-80-5
• 化学式: C₁₄H₁₉N₃O₃
• mdl: MFCD03143736
• 分子量: 277.323
• InChiKey: ZSHXOBLXFDDREA-UHFFFAOYSA-N

物化性质

• 沸点：
  453.2±45.0 °C(Predicted)
• 密度：
  1.199±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  69.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4-ethylpiperazin-1-yl)(3-methyl-4-nitrophenyl)methanone 在 吡啶 、 N-乙酰-L-半胱氨酸 、 palladium 10% on activated carbon 、 氢气 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 14.5h， 生成 4-(2-aminopyrimidin-5-yl)-N-(4-(4-ethylpiperazine-1-carbonyl)-2-methylphenyl)-2-morpholino-5,6-dihydro-7Hpyrrolo[2,3-d]pyrimidine-7-carboxamide
  参考文献：
  名称：

  Optimization of the phenylurea moiety in a phosphoinositide 3-kinase (PI3K) inhibitor to improve water solubility and the PK profile by introducing a solubilizing group and ortho substituents

  摘要：

  Phosphoinositide 3-kinase (PI3K) is a promising anti-cancer target, because various mutations and amplifications are observed in human tumors isolated from cancer patients. Our dihydropyrrolopyrimidine derivative with a phenylurea moiety showed strong PI3K enzyme inhibitory activity, but its pharmacokinetic property was poor because of lack of solubility. Herein, we report how we improved the solubility of our PI3K inhibitors by introducing a solubilizing group and ortho substituents to break molecular planarity. (C) 2016 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2016.04.060
• 作为产物：
  描述：

  N-乙基哌嗪 、 3-甲基-4-硝基苯甲酸 在 氯化亚砜 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (4-ethylpiperazin-1-yl)(3-methyl-4-nitrophenyl)methanone
  参考文献：
  名称：

  Novel and Potent 5-Piperazinyl Methyl-N₁-aryl Sulfonyl Indole Derivatives as 5-HT₆ Receptor Ligands

  摘要：

  The exclusive distribution of 5-HT6 receptors in the brain regions associated with learing and memory makes it an ideal target for cognitive disorders. A novel series of 5-piperazinyl methyl-N-1-aryl sulfonyl indoles were designed and synthesized as 5-HT6R ligands. Most of the synthesized compounds are potent when tested by in vitro radiogland binding assay. The lead compound from the series does not have the CYP liabilities and is active in an animal model of cognition.

  DOI：

  10.1021/ml100101u

文献信息

• Novel and Potent 5-Piperazinyl Methyl-<i>N</i>₁-aryl Sulfonyl Indole Derivatives as 5-HT₆ Receptor Ligands
  作者：Ramakrishna V. S. Nirogi、Prabhakar Kothmirkar、Ramasastri Kambhampati、Jagadish Babu Konda、Sobhanadri Arepalli、Narasimhareddy G. Pamuleti、Amol D. Deshpande、Trinathreddy Bandyala、Anil K. Shinde、P. K. Dubey

  DOI：10.1021/ml100101u

  日期：2010.10.14

  The exclusive distribution of 5-HT6 receptors in the brain regions associated with learing and memory makes it an ideal target for cognitive disorders. A novel series of 5-piperazinyl methyl-N-1-aryl sulfonyl indoles were designed and synthesized as 5-HT6R ligands. Most of the synthesized compounds are potent when tested by in vitro radiogland binding assay. The lead compound from the series does not have the CYP liabilities and is active in an animal model of cognition.
• Optimization of the phenylurea moiety in a phosphoinositide 3-kinase (PI3K) inhibitor to improve water solubility and the PK profile by introducing a solubilizing group and ortho substituents
  作者：Hatsuo Kawada、Hirosato Ebiike、Masao Tsukazaki、Shun Yamamoto、Kohei Koyama、Mitsuaki Nakamura、Kenji Morikami、Kiyoshi Yoshinari、Miyuki Yoshida、Kotaro Ogawa、Nobuo Shimma、Takuo Tsukuda、Jun Ohwada

  DOI：10.1016/j.bmc.2016.04.060

  日期：2016.7

  Phosphoinositide 3-kinase (PI3K) is a promising anti-cancer target, because various mutations and amplifications are observed in human tumors isolated from cancer patients. Our dihydropyrrolopyrimidine derivative with a phenylurea moiety showed strong PI3K enzyme inhibitory activity, but its pharmacokinetic property was poor because of lack of solubility. Herein, we report how we improved the solubility of our PI3K inhibitors by introducing a solubilizing group and ortho substituents to break molecular planarity. (C) 2016 Published by Elsevier Ltd.