tert-butyl 2-ethyl-4-oxo-5H-imidazo[4,5-c]pyridine-1-carboxylate | 1421596-92-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: tert-butyl 2-ethyl-4-oxo-5H-imidazo[4,5-c]pyridine-1-carboxylate
• CAS: 1421596-92-0
• 化学式: C₁₃H₁₇N₃O₃
• 分子量: 263.296
• InChiKey: DTHYYELOLGJIQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  73.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-ethyl-4-oxo-5H-imidazo[4,5-c]pyridine-1-carboxylate 在 偶氮二甲酸二叔丁酯 、 potassium tert-butylate 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 3-[(1S)-5-bromo-2,3-dihydro-1H-inden-1-yl]-5-[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]-2-ethylimidazo[4,5-c]pyridin-4-one
  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：

  二碳酸二叔丁酯 、 2-Ethyl-3,5-dihydro-imidazo[4,5-c]pyridin-4-one 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以49%的产率得到tert-butyl 2-ethyl-4-oxo-5H-imidazo[4,5-c]pyridine-1-carboxylate
  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.