tert-butyl (3R,6S)-6-(2,3-difluorophenyl)-2-thioxoazepan-3-ylcarbamate | 880144-46-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环庚烷
• 英文名称: tert-butyl (3R,6S)-6-(2,3-difluorophenyl)-2-thioxoazepan-3-ylcarbamate
• 英文别名: tert-butyl N-[(3R,6S)-6-(2,3-difluorophenyl)-2-sulfanylideneazepan-3-yl]carbamate
• CAS: 880144-46-7
• 化学式: C₁₇H₂₂F₂N₂O₂S
• 分子量: 356.437
• InChiKey: PJNPAINTUGJDDS-ZWNOBZJWSA-N

物化性质

• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  82.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (3R,6S)-6-(2,3-difluorophenyl)-2-thioxoazepan-3-ylcarbamate 在 重铬酸吡啶 、 三氟乙酸 、 mercury dichloride 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 生成 tert-butyl (6S,9R)-6-(2,3-difluorophenyl)-3-(1-methoxy-1-methylethyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-ylcarbamate
  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
• 作为产物：
  描述：

  benzyl (5S)-N,N-bis(tert-butoxycarbonyl)-5-(2,3-difluorophenyl)-6-nitro-D-norleucinate 在 palladium 10% on activated carbon 劳森试剂 、 N-羟基-7-氮杂苯并三氮唑 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 90.0 ℃ 、379.22 kPa 条件下， 反应 38.0h， 生成 tert-butyl (3R,6S)-6-(2,3-difluorophenyl)-2-thioxoazepan-3-ylcarbamate
  参考文献：
  名称：

  WO2008/153849

  摘要：

  公开号：

文献信息

• Cgrp Receptor Antagonists
  申请人：Paone V. Daniel

  公开号：US20070287697A1

  公开（公告）日：2007-12-13

  Compounds of Formula (I) and Formula (II) (where variables R 1 , R 2 , R 4 , A, B, W, X, Y and Z are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  化合物I和化合物II的公式（其中变量R1，R2，R4，A，B，W，X，Y和Z如本文所定义）可用作CGRP受体的拮抗剂，并在治疗或预防CGRP参与的疾病（如头痛，偏头痛和群头痛）方面有用。本发明还涉及包含这些化合物的制药组合物以及在预防或治疗CGRP参与的这些疾病中使用这些化合物和组合物的用途。
• Carboxamide Spirolactam Cgrp Receptor Antagonists
  申请人：Williams M. Theresa

  公开号：US20070293470A1

  公开（公告）日：2007-12-20

  The present invention is directed to compounds of Formula I: I (where variables A 1 , A 2 , B, J, K, m, n, R 4 , R 5a , R 5b and R 5c are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及式I的化合物：I（其中变量A1、A2、B、J、K、m、n、R4、R5a、R5b和R5c如本文所定义），用作CGRP受体的拮抗剂，并用于治疗或预防涉及CGRP的疾病，例如头痛、偏头痛和群头痛。本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及CGRP的疾病中的使用。
• Carboxamide spirolactam CGRP receptor antagonists
  申请人：Merck & Co., Inc.

  公开号：US07390798B2

  公开（公告）日：2008-06-24

  The present invention is directed to compounds of Formula I: I (where variables A1, A2, B, J, K, m, n, R4, R5a, R5b and R5c are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved

  本发明涉及式I的化合物：I（其中变量A1，A2，B，J，K，m，n，R4，R5a，R5b和R5c的定义如本文所述），其作为CGRP受体拮抗剂在治疗或预防CGRP参与的疾病，例如头痛，偏头痛和群头痛方面有用。本发明还涉及包含这些化合物的制药组合物以及在预防或治疗CGRP参与的这些疾病方面使用这些化合物和组合物。
• CGRP receptor antagonists
  申请人：Merck Sharp & Dohme Corp.

  公开号：US07732438B2

  公开（公告）日：2010-06-08

  Compounds of Formula (I) and Formula (II) (where variables R1, R2, R4, A, B, W, X, Y and Z are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  化合物公式(I)和公式(II)的复合物（其中变量R1、R2、R4、A、B、W、X、Y和Z的定义如本文所述），可用作CGRP受体的拮抗剂，并且可用于治疗或预防CGRP参与的疾病，例如头痛、偏头痛和群头痛。本发明还涉及包含这些化合物的制药组合物以及在预防或治疗CGRP参与的这些疾病中使用这些化合物和组合物。
• CARBOXAMIDE HETEROCYCLIC CGRP RECEPTOR ANTAGONISTS
  申请人：Bell Ian

  公开号：US20100179166A1

  公开（公告）日：2010-07-15

  Compounds of formula I: wherein variables A 1 , A 2 , B, m, n, J, R 4 , G 1 , G 2 , G 3 and Y are as described herein, which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  化学式为I的化合物：其中变量A1、A2、B、m、n、J、R4、G1、G2、G3和Y如本文所述，它们是CGRP受体拮抗剂，可用于治疗或预防CGRP参与的疾病，如偏头痛。本发明还涉及含有这些化合物的制药组合物以及将这些化合物和组合物用于预防或治疗CGRP参与的疾病。