| 1629023-85-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• CAS: 1629023-85-3
• 化学式: C₃₆H₂₄BrF₃N₄
• 分子量: 649.513
• InChiKey: BVHWKQWYHFXVCG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.27
• 重原子数：
  44.0
• 可旋转键数：
  6.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  54.5
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  在 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 sodium hypochlorite 、 二(三叔丁基膦)钯 、 2-[[三(羟甲基)甲基]氨基]乙磺酸 、 N,N-二异丙基乙胺 、 三氟乙酸 、 sodium bromide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 丙酮 为溶剂， 130.0 ℃ 、101.33 kPa 条件下， 反应 8.83h， 生成 2-[3-(1-cyanocyclopropyl)-5-[3-(trifluoromethyl)-2H-pyrazolo[3,4-b]pyridin-4-yl]phenyl]acetic acid
  参考文献：
  名称：

  Strategies for the modulation of phase II metabolism in a series of PKCε inhibitors

  摘要：

  Extensive phase II metabolism of an advanced PKC epsilon inhibitor resulted in sub-optimal pharmacokinetics in rat marked by elevated clearance. Synthesis of the O-glucuronide metabolite as a standard was followed by three distinct strategies to specifically temper phase II metabolic degradation of the parent molecule. In this study, it was determined that the introduction of proximal polarity to the primary alcohol generally curbed O-glucuronidation and improved PR and physical chemical properties while maintaining potency against the target. Utilization of a Jacobsen hydrolytic kinetic resolution to obtain optically enriched final compounds is also discussed. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.082
• 作为产物：
  描述：

  cyano-(3,5-dibromophenyl)acetic acid ethyl ester 在 lithium chloro-isopropyl-magnesium chloride 、 丁腈 、 四丁基溴化铵 、 palladium diacetate 、 叔丁胺 、 1,4-双(二苯基膦)丁烷 、 lithium chloride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 、 甲苯 为溶剂， 反应 52.5h， 生成
  参考文献：
  名称：

  Strategies for the modulation of phase II metabolism in a series of PKCε inhibitors

  摘要：

  Extensive phase II metabolism of an advanced PKC epsilon inhibitor resulted in sub-optimal pharmacokinetics in rat marked by elevated clearance. Synthesis of the O-glucuronide metabolite as a standard was followed by three distinct strategies to specifically temper phase II metabolic degradation of the parent molecule. In this study, it was determined that the introduction of proximal polarity to the primary alcohol generally curbed O-glucuronidation and improved PR and physical chemical properties while maintaining potency against the target. Utilization of a Jacobsen hydrolytic kinetic resolution to obtain optically enriched final compounds is also discussed. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.082