[2-[bis(4-methoxybenzyl)amino]-4-methylpyrimidin-5-yl]boronic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: [2-[bis(4-methoxybenzyl)amino]-4-methylpyrimidin-5-yl]boronic acid
• 英文别名: [2-[Bis[(4-methoxyphenyl)methyl]amino]-4-methylpyrimidin-5-yl]boronic acid
• 化学式: C₂₁H₂₄BN₃O₄
• 分子量: 393.25
• InChiKey: MBYGCYNKEZSRCT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.69
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  87.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [2-[bis(4-methoxybenzyl)amino]-4-methylpyrimidin-5-yl]boronic acid 在 2-双环己基膦-2',6'-二甲氧基联苯 、 potassium phosphate 、 palladium diacetate 、 magnesium sulfate 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 bis-(4-methoxybenzyl)-[4-methyl-5-(2-morpholin-4-yl-7-pyridin-3-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]amine
  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：

  2-氨基-4-甲基-5-溴嘧啶 在 正丁基锂 、 sodium hydride 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 、 mineral oil 为溶剂， 反应 6.0h， 生成 [2-[bis(4-methoxybenzyl)amino]-4-methylpyrimidin-5-yl]boronic acid
  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

文献信息

• 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.