2-氨基-4-(三氟甲基)嘧啶-5-基硼酸 | 1045861-30-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 2-氨基-4-(三氟甲基)嘧啶-5-基硼酸
• 英文名称: (2-Amino-4-(trifluoromethyl)pyrimidin-5-yl)boronic acid
• 英文别名: [2-amino-4-(trifluoromethyl)pyrimidin-5-yl]boronic acid
• CAS: 1045861-30-0
• 化学式: C₅H₅BF₃N₃O₂
• 分子量: 206.92
• InChiKey: JBMGOFGRYOYOSW-UHFFFAOYSA-N

物化性质

• 沸点：
  451.5±55.0 °C(Predicted)
• 密度：
  1.61±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.24
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  92.3
• 氢给体数：
  3
• 氢受体数：
  8

安全信息

• 海关编码：
  2933599090

反应信息

• 作为产物：
  描述：

  4-三氟甲基-2-氨基嘧啶 在 N-溴代丁二酰亚胺(NBS) 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 联硼酸频那醇酯 作用下， 以 1,4-二氧六环 、 氯仿 为溶剂， 反应 26.0h， 生成 2-氨基-4-(三氟甲基)嘧啶-5-基硼酸
  参考文献：
  名称：

  Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer

  摘要：

  Phosphoinositide-3-kinases (PI3Ks) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocydic pyrirnidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrirnidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clinical trials for the treatment of cancer.

  DOI：

  10.1021/ml200156t

文献信息

• Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer
  作者：Matthew T. Burger、Sabina Pecchi、Allan Wagman、Zhi-Jie Ni、Mark Knapp、Thomas Hendrickson、Gordana Atallah、Keith Pfister、Yanchen Zhang、Sarah Bartulis、Kelly Frazier、Simon Ng、Aaron Smith、Joelle Verhagen、Joshua Haznedar、Kay Huh、Ed Iwanowicz、Xiaohua Xin、Daniel Menezes、Hanne Merritt、Isabelle Lee、Marion Wiesmann、Susan Kaufman、Kenneth Crawford、Michael Chin、Dirksen Bussiere、Kevin Shoemaker、Isabel Zaror、Sauveur-Michel Maira、Charles F. Voliva

  DOI：10.1021/ml200156t

  日期：2011.10.13

  Phosphoinositide-3-kinases (PI3Ks) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocydic pyrirnidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrirnidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clinical trials for the treatment of cancer.