4-nitrophenyl 4-(2-oxo-4,5-dihydro-1H-benzo[d][1,3]diazepin-3(2H)-yl)piperidine-1-carboxylate | 1190363-92-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-nitrophenyl 4-(2-oxo-4,5-dihydro-1H-benzo[d][1,3]diazepin-3(2H)-yl)piperidine-1-carboxylate
• 英文别名: (4-nitrophenyl) 4-(2-oxo-4,5-dihydro-1H-1,3-benzodiazepin-3-yl)piperidine-1-carboxylate
• CAS: 1190363-92-8
• 化学式: C₂₁H₂₂N₄O₅
• 分子量: 410.429
• InChiKey: HPNQBRVAWYWXEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (6R,9R)-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol 、 4-nitrophenyl 4-(2-oxo-4,5-dihydro-1H-benzo[d][1,3]diazepin-3(2H)-yl)piperidine-1-carboxylate 在 sodium hydride 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 18.0h， 以73%的产率得到(6R,9R)-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl 4-(2-oxo-4,5-dihydro-1H-benzo[d][1,3]diazepin-3(2H)-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  CGRP Receptor Antagonists

  摘要：

  本公开通常涉及公式I的新化合物，包括它们的盐，这些盐是CGRP受体拮抗剂。本公开还涉及用于治疗CGRP相关疾病，包括偏头痛和其他头痛、神经源性血管扩张、神经源性炎症、热损伤、循环性休克、与更年期相关的潮红、气道炎症性疾病如哮喘和慢性阻塞性肺病（COPD）的药物组合物和方法。

  公开号：

  US20090258866A1
• 作为产物：
  描述：

  3-(4-piperidinyl)-1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one 、 对硝基苯基氯甲酸酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 4-nitrophenyl 4-(2-oxo-4,5-dihydro-1H-benzo[d][1,3]diazepin-3(2H)-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

文献信息

• PIPERIDINE DERIVATIVES AS CGRP RECEPTOR ANTAGONISTS
  申请人：Bristol-Myers Squibb Company

  公开号：EP2271640A2

  公开（公告）日：2011-01-12
• Piperidine derivatives as CGRP receptor antagonists
  申请人：Bristol-Myers Squibb Company

  公开号：EP2271640B1

  公开（公告）日：2012-09-05
• US8044043B2
  申请人：——

  公开号：US8044043B2

  公开（公告）日：2011-10-25
• US8143403B2
  申请人：——

  公开号：US8143403B2

  公开（公告）日：2012-03-27
• [EN] CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DU RÉCEPTEUR CGRP
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2009126530A2

  公开（公告）日：2009-10-15

  The disclosure generally relates to the novel compounds of formula I, including their salts, which are CGRP receptor antagonists. The disclosure also relates to pharmaceutical compositions and methods for using the compounds in the treatment of CGRP related disorders including migraine and other headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases such as asthma, and chronic obstructive pulmonary disease (COPD). (I)