2-[[3-[(1S)-5-bromo-2,3-dihydro-1H-inden-1-yl]-2-ethyl-4-oxoimidazo[4,5-c]pyridin-5-yl]methyl]benzonitrile | 1421597-38-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 2-[[3-[(1S)-5-bromo-2,3-dihydro-1H-inden-1-yl]-2-ethyl-4-oxoimidazo[4,5-c]pyridin-5-yl]methyl]benzonitrile
• CAS: 1421597-38-7
• 化学式: C₂₅H₂₁BrN₄O
• 分子量: 473.372
• InChiKey: PUPDUOGMEAPKEZ-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  61.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[[3-[(1S)-5-bromo-2,3-dihydro-1H-inden-1-yl]-2-ethyl-4-oxoimidazo[4,5-c]pyridin-5-yl]methyl]benzonitrile 在 盐酸 、 palladium diacetate 、 potassium carbonate 、 三苯基膦 作用下， 以 乙二醇二甲醚 、 水 、 丙酮 为溶剂， 生成 2-[[2-ethyl-4-oxo-3-[(1S)-5-[2-(2H-tetrazol-5-yl)phenyl]-2,3-dihydro-1H-inden-1-yl]imidazo[4,5-c]pyridin-5-yl]methyl]benzonitrile
  参考文献：
  名称：

  Design, synthesis, and evaluation of imidazo[4,5-c]pyridin-4-one derivatives with dual activity at angiotensin II type 1 receptor and peroxisome proliferator-activated receptor-γ

  摘要：

  Identification of a series of imidazo[4,5-c]pyridin-4-one derivatives that act as dual angiotensin II type 1 (AT1) receptor antagonists and peroxisome proliferator-activated receptor-gamma (PPAR gamma) partial agonists is described. Starting from a known AT1 antagonist template, conformational restriction was introduced by incorporation of an indane ring that when combined with appropriate substitution at the imidazo[4,5-c]pyridin-4-one provided novel series 5 possessing the desired dual activity. The mode of interaction of this series with PPAR gamma was corroborated through the X-ray crystal structure of 12b bound to the human PPAR gamma ligand binding domain. Modulation of activity at both receptors through substitution at the pyridone nitrogen led to the identification of potent dual AT1 antagonists/PPAR gamma partial agonists. Among them, 21b was identified possessing potent dual pharmacology (AT1 IC50 = 7 nM; PPAR gamma EC50 = 295 nM, 27% max) and good ADME properties. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.088
• 作为产物：
  描述：

  2-Ethyl-3,5-dihydro-imidazo[4,5-c]pyridin-4-one 在 potassium tert-butylate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 生成 2-[[3-[(1S)-5-bromo-2,3-dihydro-1H-inden-1-yl]-2-ethyl-4-oxoimidazo[4,5-c]pyridin-5-yl]methyl]benzonitrile
  参考文献：
  名称：

  Design, synthesis, and evaluation of imidazo[4,5-c]pyridin-4-one derivatives with dual activity at angiotensin II type 1 receptor and peroxisome proliferator-activated receptor-γ

  摘要：

  Identification of a series of imidazo[4,5-c]pyridin-4-one derivatives that act as dual angiotensin II type 1 (AT1) receptor antagonists and peroxisome proliferator-activated receptor-gamma (PPAR gamma) partial agonists is described. Starting from a known AT1 antagonist template, conformational restriction was introduced by incorporation of an indane ring that when combined with appropriate substitution at the imidazo[4,5-c]pyridin-4-one provided novel series 5 possessing the desired dual activity. The mode of interaction of this series with PPAR gamma was corroborated through the X-ray crystal structure of 12b bound to the human PPAR gamma ligand binding domain. Modulation of activity at both receptors through substitution at the pyridone nitrogen led to the identification of potent dual AT1 antagonists/PPAR gamma partial agonists. Among them, 21b was identified possessing potent dual pharmacology (AT1 IC50 = 7 nM; PPAR gamma EC50 = 295 nM, 27% max) and good ADME properties. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.088

文献信息

• Design, synthesis, and evaluation of imidazo[4,5-c]pyridin-4-one derivatives with dual activity at angiotensin II type 1 receptor and peroxisome proliferator-activated receptor-γ
  作者：Agustin Casimiro-Garcia、Ronald J. Heemstra、Christopher F. Bigge、Jing Chen、Fred A. Ciske、Jo Ann Davis、Teresa Ellis、Nadia Esmaeil、Declan Flynn、Seungil Han、Mehran Jalaie、Jeffrey F. Ohren、Noel A. Powell

  DOI：10.1016/j.bmcl.2012.11.088

  日期：2013.2

  Identification of a series of imidazo[4,5-c]pyridin-4-one derivatives that act as dual angiotensin II type 1 (AT1) receptor antagonists and peroxisome proliferator-activated receptor-gamma (PPAR gamma) partial agonists is described. Starting from a known AT1 antagonist template, conformational restriction was introduced by incorporation of an indane ring that when combined with appropriate substitution at the imidazo[4,5-c]pyridin-4-one provided novel series 5 possessing the desired dual activity. The mode of interaction of this series with PPAR gamma was corroborated through the X-ray crystal structure of 12b bound to the human PPAR gamma ligand binding domain. Modulation of activity at both receptors through substitution at the pyridone nitrogen led to the identification of potent dual AT1 antagonists/PPAR gamma partial agonists. Among them, 21b was identified possessing potent dual pharmacology (AT1 IC50 = 7 nM; PPAR gamma EC50 = 295 nM, 27% max) and good ADME properties. (c) 2012 Elsevier Ltd. All rights reserved.