7-(4-amino-2-methoxyphenoxy)-1H-imidazo[4,5-b]pyridin-2(3H)-one | 1160825-66-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 7-(4-amino-2-methoxyphenoxy)-1H-imidazo[4,5-b]pyridin-2(3H)-one
• 英文别名: 7-(4-Amino-2-methoxyphenoxy)-1,3-dihydroimidazo[4,5-b]pyridin-2-one
• CAS: 1160825-66-0
• 化学式: C₁₃H₁₂N₄O₃
• 分子量: 272.263
• InChiKey: SDTQRIUCNOAWSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  98.5
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-(4-amino-2-methoxyphenoxy)-1H-imidazo[4,5-b]pyridin-2(3H)-one 、 3-(三氟甲基)异氰酸苯酯 以 四氢呋喃 为溶剂， 反应 14.0h， 以78%的产率得到1-(4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yloxy)-3-methoxyphenyl)-3-(3-(trifluoromethyl)phenyl)urea
  参考文献：
  名称：

  Novel Potent BRAF Inhibitors: Toward 1 nM Compounds through Optimization of the Central Phenyl Ring

  摘要：

  BRAF, a serine/threonine specific protein kinase that is part of the MAPK pathway and acts as a downstream effector of RAS, is a potential therapeutic target in melanoma. We have developed a series of small-molecule BRAF inhibitors based on a 1H-imidazo[4,5-b]pyridine-2(3H)-one scaffold (ring A) as the hinge binding moiety and a number Of Substituted phenyl rings C that interact with the allosteric binding site. The introduction of various groups on the central phenyl ring B combined with appropriate A- and C-ring modifications afford very potent compounds that inhibit (V600E)BRAF kinase activity in vitro and oncogqnic BRAF signaling in melanoma cells. Substitution on the central phenyl ring of a 3-fluoro, a naphthyl, or a 3-thiomethyl group improves activity to yield compounds with an IC50 of 1 nM for purified (V600E)BRAF and nanomolar activity in cells.

  DOI：

  10.1021/jm900242c
• 作为产物：
  描述：

  tert-butyl-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yloxy)-3-methoxyphenylcarbamate 在 三氟乙酸 、 sodium carbonate 作用下， 以 水 为溶剂， 反应 1.5h， 以18%的产率得到7-(4-amino-2-methoxyphenoxy)-1H-imidazo[4,5-b]pyridin-2(3H)-one
  参考文献：
  名称：

  Novel Potent BRAF Inhibitors: Toward 1 nM Compounds through Optimization of the Central Phenyl Ring

  摘要：

  BRAF, a serine/threonine specific protein kinase that is part of the MAPK pathway and acts as a downstream effector of RAS, is a potential therapeutic target in melanoma. We have developed a series of small-molecule BRAF inhibitors based on a 1H-imidazo[4,5-b]pyridine-2(3H)-one scaffold (ring A) as the hinge binding moiety and a number Of Substituted phenyl rings C that interact with the allosteric binding site. The introduction of various groups on the central phenyl ring B combined with appropriate A- and C-ring modifications afford very potent compounds that inhibit (V600E)BRAF kinase activity in vitro and oncogqnic BRAF signaling in melanoma cells. Substitution on the central phenyl ring of a 3-fluoro, a naphthyl, or a 3-thiomethyl group improves activity to yield compounds with an IC50 of 1 nM for purified (V600E)BRAF and nanomolar activity in cells.

  DOI：

  10.1021/jm900242c

文献信息

• Novel Potent BRAF Inhibitors: Toward 1 nM Compounds through Optimization of the Central Phenyl Ring
  作者：Delphine Ménard、Ion Niculescu-Duvaz、Harmen P. Dijkstra、Dan Niculescu-Duvaz、Bart M. J. M. Suijkerbuijk、Alfonso Zambon、Arnaud Nourry、Esteban Roman、Lawrence Davies、Helen A. Manne、Frank Friedlos、Ruth Kirk、Steven Whittaker、Adrian Gill、Richard D. Taylor、Richard Marais、Caroline J. Springer

  DOI：10.1021/jm900242c

  日期：2009.7.9

  BRAF, a serine/threonine specific protein kinase that is part of the MAPK pathway and acts as a downstream effector of RAS, is a potential therapeutic target in melanoma. We have developed a series of small-molecule BRAF inhibitors based on a 1H-imidazo[4,5-b]pyridine-2(3H)-one scaffold (ring A) as the hinge binding moiety and a number Of Substituted phenyl rings C that interact with the allosteric binding site. The introduction of various groups on the central phenyl ring B combined with appropriate A- and C-ring modifications afford very potent compounds that inhibit (V600E)BRAF kinase activity in vitro and oncogqnic BRAF signaling in melanoma cells. Substitution on the central phenyl ring of a 3-fluoro, a naphthyl, or a 3-thiomethyl group improves activity to yield compounds with an IC50 of 1 nM for purified (V600E)BRAF and nanomolar activity in cells.