benzyl [(3R)-6-bromo-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-yl]carbamate | 781650-19-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzyl [(3R)-6-bromo-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-yl]carbamate
• 英文别名: Benzyl (3R)-6-bromo-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-ylcarbamate；benzyl N-[(6R)-3-bromo-7-oxo-1,2,5,6-tetrahydroazepin-6-yl]carbamate
• CAS: 781650-19-9
• 化学式: C₁₄H₁₅BrN₂O₃
• 分子量: 339.189
• InChiKey: GOODUWWKRUWJKR-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  benzyl [(3R)-6-bromo-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-yl]carbamate 、 异丙基硼酸 在 PdCl₂[1,1'-bis(diphenylphosphino)ferrocene]*CH₂Cl₂ sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Potent, Orally Bioavailable Calcitonin Gene-Related Peptide Receptor Antagonists for the Treatment of Migraine:  Discovery of N-[(3R,6S)-6-(2,3-Difluorophenyl)-2-oxo-1- (2,2,2-trifluoroethyl)azepan-3-yl]-4- (2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin- 1-yl)piperidine-1-carboxamide (MK-0974)

  摘要：

  Calcitonin gene-related peptide (CGRP) has been implicated in the pathogenesis of migraine. Herein we describe optimization of CGRP receptor antagonists based on an earlier lead structure containing a (3R)-amino-(6S)-phenylcaprolactam core. Replacement of the phenylimidazolinone with an azabenzimidazolone gave stable derivatives with lowered serum shifts. Extensive SAR studies of the C-6 aryl moiety revealed the potency-enhancing effect of the 2,3-difluorophenyl group, and trifluoroethylation of the N-1 amide position resulted in improved oral bioavailabilities, ultimately leading to clinical candidate 38 (MK-0974).

  DOI：

  10.1021/jm070668p
• 作为产物：
  描述：

  benzyl (3R)-6-bromo-1-(2,4-dimethoxybenzyl)-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-ylcarbamate 在 L-蛋氨酸 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以27%的产率得到benzyl [(3R)-6-bromo-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-yl]carbamate
  参考文献：
  名称：

  Potent, Orally Bioavailable Calcitonin Gene-Related Peptide Receptor Antagonists for the Treatment of Migraine:  Discovery of N-[(3R,6S)-6-(2,3-Difluorophenyl)-2-oxo-1- (2,2,2-trifluoroethyl)azepan-3-yl]-4- (2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin- 1-yl)piperidine-1-carboxamide (MK-0974)

  摘要：

  Calcitonin gene-related peptide (CGRP) has been implicated in the pathogenesis of migraine. Herein we describe optimization of CGRP receptor antagonists based on an earlier lead structure containing a (3R)-amino-(6S)-phenylcaprolactam core. Replacement of the phenylimidazolinone with an azabenzimidazolone gave stable derivatives with lowered serum shifts. Extensive SAR studies of the C-6 aryl moiety revealed the potency-enhancing effect of the 2,3-difluorophenyl group, and trifluoroethylation of the N-1 amide position resulted in improved oral bioavailabilities, ultimately leading to clinical candidate 38 (MK-0974).

  DOI：

  10.1021/jm070668p

文献信息

• Cgrp Receptor Antagonists
  申请人：Burgey S. Christopher

  公开号：US20070287696A1

  公开（公告）日：2007-12-13

  Compounds of Formula I: and Formula II: (where variables R 1 , R 2 , R 3 , R 4 , A, B, D, G, J, Q, T, W, X and Y 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, pharmaceutical compositions comprising these compounds, use of these compounds and compositions to prevent or treat diseases involving CGRP.

  化合物的化学式I：和化学式II：（其中变量R1、R2、R3、R4、A、B、D、G、J、Q、T、W、X和Y的定义如下）可作为CGRP受体拮抗剂，在涉及CGRP的疾病的治疗或预防中有用，包括这些化合物的药物组合物、使用这些化合物和组合物来预防或治疗涉及CGRP的疾病。
• CGRP receptor antagonists
  申请人：Burgey S. Christopher

  公开号：US20050256098A1

  公开（公告）日：2005-11-17

  The present invention is directed to compounds of Formula I: and Formula II: (where variables R 1 , R 2 , R 3 , R 4 , A, B, G, J, Q, T, U, V, W, X and Y 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和式II的化合物：（其中变量R1、R2、R3、R4、A、B、G、J、Q、T、U、V、W、X和Y如此定义），这些化合物可用作CGRP受体的拮抗剂，并可用于治疗或预防CGRP参与的疾病，如头痛、偏头痛和集群头痛。本发明还涉及包含这些化合物的制药组合物以及使用这些化合物和组合物预防或治疗参与CGRP的这些疾病。
• CGRP RECEPTOR ANTAGONISTS
  申请人：Burgey Christopher S.

  公开号：US20100113419A1

  公开（公告）日：2010-05-06

  The present invention is directed to compounds of Formula I: Formula I: Formula II: (where variables R 1 , R 2 , R 3 , R 4 , A, B, J, Q, T, V, W, X and Y 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I式化合物：I式：II式：（其中变量R1、R2、R3、R4、A、B、J、Q、T、V、W、X和Y的定义如本文所述），用作CGRP受体拮抗剂，有助于治疗或预防CGRP参与的疾病，如头痛、偏头痛和集群头痛。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CGRP参与的疾病方面的使用。
• [EN] CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DES RECEPTEURS CGRP
  申请人：MERCK & CO INC

  公开号：WO2004092166A3

  公开（公告）日：2005-01-20
• US7235545B2
  申请人：——

  公开号：US7235545B2

  公开（公告）日：2007-06-26