N-(1-(isoquinolin-3-yl)-2-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)ethyl)-4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamide | 855777-30-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-(1-(isoquinolin-3-yl)-2-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)ethyl)-4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamide
• 英文别名: N-[1-isoquinolin-3-yl-2-[7-methyl-2-(2-trimethylsilylethoxymethyl)indazol-5-yl]ethyl]-4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carboxamide
• CAS: 855777-30-9
• 化学式: C₃₉H₄₇N₇O₃Si
• 分子量: 689.933
• InChiKey: UMSBCTHPOONMLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.71
• 重原子数：
  50
• 可旋转键数：
  10
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(1-(isoquinolin-3-yl)-2-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)ethyl)-4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamide 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 生成 N-(1-(isoquinolin-3-yl)-2-(7-methyl-1H-indazol-5-yl)ethyl)-4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamide
  参考文献：
  名称：

  Calcitonin gene-related peptide (CGRP) receptor antagonists: Pyridine as a replacement for a core amide group

  摘要：

  In our continuing efforts to identify CGRP receptor antagonists that can be dosed orally for the treatment of migraine headache, we have investigated a pyridine bioisosteric replacement of a polar amide portion of a previous lead compound, BMS-694153. Pyridine derivatives were discovered and their SAR was studied. Some of them showed excellent binding potency. However, oral bioavailability was low, even for compounds with good Caco-2 cell permeability. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.065
• 作为产物：
  描述：

  异喹啉-3-甲醛 在 盐酸 、 sodium tetrahydroborate 、 偶氮二甲酸二异丙酯 、 caesium carbonate 、 N,N-二异丙基乙胺 、 三苯基膦 、 肼 作用下， 以 四氢呋喃 、 甲醇 、 丙醇 、 二氯甲烷 、 水 、 异丙醇 为溶剂， 生成 N-(1-(isoquinolin-3-yl)-2-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)ethyl)-4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamide
  参考文献：
  名称：

  Calcitonin gene-related peptide (CGRP) receptor antagonists: Pyridine as a replacement for a core amide group

  摘要：

  In our continuing efforts to identify CGRP receptor antagonists that can be dosed orally for the treatment of migraine headache, we have investigated a pyridine bioisosteric replacement of a polar amide portion of a previous lead compound, BMS-694153. Pyridine derivatives were discovered and their SAR was studied. Some of them showed excellent binding potency. However, oral bioavailability was low, even for compounds with good Caco-2 cell permeability. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.065