N-((6S,9R)-6-(2,3-difluorophenyl)-3-(2-(methylamino)ethyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-yl)-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide | 1300100-44-0

• 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: N-((6S,9R)-6-(2,3-difluorophenyl)-3-(2-(methylamino)ethyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-yl)-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide
• 英文别名: N-[(6S,9R)-6-(2,3-difluorophenyl)-3-[2-(methylamino)ethyl]-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-yl]-4-(2-oxo-3H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide
• CAS: 1300100-44-0
• 化学式: C₂₉H₃₄F₂N₈O₂
• 分子量: 564.638
• InChiKey: PQPXBDNOQMKDCE-WZONZLPQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  41
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  tert-butyl (3R,6S)-6-(2,3-difluorophenyl)-2-thioxoazepan-3-ylcarbamate 在 重铬酸吡啶 、 三乙胺 、 三氟乙酸 、 mercury dichloride 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 生成 N-((6S,9R)-6-(2,3-difluorophenyl)-3-(2-(methylamino)ethyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-yl)-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide
  参考文献：
  名称：

  Orally bioavailable imidazoazepanes as calcitonin gene-related peptide (CGRP) receptor antagonists: Discovery of MK-2918

  摘要：

  In our ongoing efforts to develop CGRP receptor antagonists for the treatment of migraine, we aimed to improve upon telecagepant by targeting a compound with a lower projected clinical dose. Imidazoazepanes were identified as potent caprolactam replacements and SAR of the imidazole yielded the tertiary methyl ether as an optimal substituent for potency and hERG selectivity. Combination with the azabenzoxazinone spiropiperidine ultimately led to preclinical candidate 30 (MK-2918). (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.054

文献信息

• Orally bioavailable imidazoazepanes as calcitonin gene-related peptide (CGRP) receptor antagonists: Discovery of MK-2918
  作者：Daniel V. Paone、Diem N. Nguyen、Anthony W. Shaw、Christopher S. Burgey、Craig M. Potteiger、James Z. Deng、Scott D. Mosser、Christopher A. Salvatore、Sean Yu、Shane Roller、Stefanie A. Kane、Harold G. Selnick、Joseph P. Vacca、Theresa M. Williams

  DOI：10.1016/j.bmcl.2010.12.054

  日期：2011.5

  In our ongoing efforts to develop CGRP receptor antagonists for the treatment of migraine, we aimed to improve upon telecagepant by targeting a compound with a lower projected clinical dose. Imidazoazepanes were identified as potent caprolactam replacements and SAR of the imidazole yielded the tertiary methyl ether as an optimal substituent for potency and hERG selectivity. Combination with the azabenzoxazinone spiropiperidine ultimately led to preclinical candidate 30 (MK-2918). (C) 2010 Elsevier Ltd. All rights reserved.