diphenyl isoquinolin-3-yl(phenylamino)methylphosphonate | 855776-92-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: diphenyl isoquinolin-3-yl(phenylamino)methylphosphonate
• 英文别名: N-[diphenoxyphosphoryl(isoquinolin-3-yl)methyl]aniline
• CAS: 855776-92-0
• 化学式: C₂₈H₂₃N₂O₃P
• 分子量: 466.476
• InChiKey: WKXSGDFBKPPUFU-UHFFFAOYSA-N

物化性质

• 沸点：
  649.7±55.0 °C(Predicted)
• 密度：
  1.300±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  60.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diphenyl isoquinolin-3-yl(phenylamino)methylphosphonate 在 盐酸 、 sodium tetrahydroborate 、 sodium hydride 、 caesium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 丙醇 、 水 为溶剂， 生成 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-carboxylate
  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 、 亚磷酸二苯酯 、 苯胺 以 异丙醇 为溶剂， 生成 diphenyl isoquinolin-3-yl(phenylamino)methylphosphonate
  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

文献信息

• US7569578B2
  申请人：——

  公开号：US7569578B2

  公开（公告）日：2009-08-04
• Calcitonin gene-related peptide (CGRP) receptor antagonists: Pyridine as a replacement for a core amide group
  作者：Guanglin Luo、Ling Chen、Rita Civiello、Sokhom S. Pin、Cen Xu、Walter Kostich、Michelle Kelley、Charles M. Conway、John E. Macor、Gene M. Dubowchik

  DOI：10.1016/j.bmcl.2012.02.065

  日期：2012.4

  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.