N-[4-(3-氨基苯并[d]异恶唑-4-基)苯基]-3-(3-三氟甲基苯基)丙烯酰胺 | 1012367-57-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 中文名称: N-[4-(3-氨基苯并[d]异恶唑-4-基)苯基]-3-(3-三氟甲基苯基)丙烯酰胺
• 英文名称: N-[4-(3-aminobenzo[d]isoxazol-4-yl)phenyl]-3-(3-trifluoromethylphenyl)acrylamide
• 英文别名: (2E)-N-[4-(3-amino-1,2-benzoxazol-4-yl)phenyl]-3-[3-(trifluoromethyl)phenyl]prop-2-enamide；(E)-N-[4-(3-amino-1,2-benzoxazol-4-yl)phenyl]-3-[3-(trifluoromethyl)phenyl]prop-2-enamide
• CAS: 1012367-57-5
• 化学式: C₂₃H₁₆F₃N₃O₂
• 分子量: 423.394
• InChiKey: PYKWUFWGJLDSGF-KPKJPENVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  81.2
• 氢给体数：
  2
• 氢受体数：
  7

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	4-(4-aminophenyl)-1,2-benzoisooxazol-3-amine	819057-53-9	C13H11N3O	225.25

反应信息

• 作为产物：
  描述：

  4-(4-aminophenyl)-1,2-benzoisooxazol-3-amine 、 (2E)-3-[3-(三氟甲基)苯基]丙烯酰氯 在 吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N-[4-(3-氨基苯并[d]异恶唑-4-基)苯基]-3-(3-三氟甲基苯基)丙烯酰胺
  参考文献：
  名称：

  3-Amino-benzo[d]isoxazoles as Novel Multitargeted Inhibitors of Receptor Tyrosine Kinases

  摘要：

  A series of benzoisoxazoles and benzoisothiazoles have been synthesized and evaluated as inhibitors of receptor tyrosine kinases (RTKs). Structure-activity relationship studies led to the identification of 3-amino benzo[d]isoxazoles, incorporating a N,N'-diphenyl urea moiety of the 4-position that potently inhibited both the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor families of RTKs. Within this series, orally bioavailable compounds possessing promising pharmacokinetic profiles were identified, and a number of compounds demonstrated in vivo efficacy in models of VEGF-stimulated vascular permeability and tumor growth. In particular, compound 50 exhibited an ED50 of 2.0 mg/kg in the VEGF-stimulated uterine edema model and 81% inhibition in the human fibrosarcoma (HT1080) tumor growth model when given orally at a dose of 10 mg/kg/day.

  DOI：

  10.1021/jm701096v

文献信息

• 3-Amino-benzo[<i>d</i>]isoxazoles as Novel Multitargeted Inhibitors of Receptor Tyrosine Kinases
  作者：Zhiqin Ji、Asma A. Ahmed、Daniel H. Albert、Jennifer J. Bouska、Peter F. Bousquet、George, A. Cunha、Gilbert Diaz、Keith B. Glaser、Jun Guo、Christopher M. Harris、Junling Li、Patrick A. Marcotte、Maria D. Moskey、Tetsuro Oie、Lori Pease、Nirupama B. Soni、Kent D. Stewart、Steven K. Davidsen、Michael R. Michaelides

  DOI：10.1021/jm701096v

  日期：2008.3.13

  A series of benzoisoxazoles and benzoisothiazoles have been synthesized and evaluated as inhibitors of receptor tyrosine kinases (RTKs). Structure-activity relationship studies led to the identification of 3-amino benzo[d]isoxazoles, incorporating a N,N'-diphenyl urea moiety of the 4-position that potently inhibited both the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor families of RTKs. Within this series, orally bioavailable compounds possessing promising pharmacokinetic profiles were identified, and a number of compounds demonstrated in vivo efficacy in models of VEGF-stimulated vascular permeability and tumor growth. In particular, compound 50 exhibited an ED50 of 2.0 mg/kg in the VEGF-stimulated uterine edema model and 81% inhibition in the human fibrosarcoma (HT1080) tumor growth model when given orally at a dose of 10 mg/kg/day.