methyl {(2R)-1-[(3,4-dichlorophenyl)sulfonyl]-3-oxo-1,2,3,4-tetrahydroquinoxalin-2-yl}acetate | 565460-56-2

• 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: methyl {(2R)-1-[(3,4-dichlorophenyl)sulfonyl]-3-oxo-1,2,3,4-tetrahydroquinoxalin-2-yl}acetate
• 英文别名: methyl 2-[(2R)-1-(3,4-dichlorophenyl)sulfonyl-3-oxo-2,4-dihydroquinoxalin-2-yl]acetate
• CAS: 565460-56-2
• 化学式: C₁₇H₁₄Cl₂N₂O₅S
• 分子量: 429.281
• InChiKey: HCAVYLQUYHZLGU-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl {(2R)-1-[(3,4-dichlorophenyl)sulfonyl]-3-oxo-1,2,3,4-tetrahydroquinoxalin-2-yl}acetate 在 盐酸 、 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 生成 N-[2-(4-cyanophenyl)ethyl]-2-{(2R)-1-[(3,4-dichlorophenyl)sulfonyl]-3-oxo-1,2,3,4-tetrahydroquinoxalin-2-yl}acetamide
  参考文献：
  名称：

  Discovery of a Potent, Non-peptide Bradykinin B₁ Receptor Antagonist

  摘要：

  Bradykinin (BK) plays an important role in the pathophysiological processes accompanying pain and inflammation. Selective bradykinin B1 receptor antagonists have been shown to be anti-nociceptive in animal models and could be novel therapeutic agents for the treatment of pain and inflammation. We have explored chemical modifications in a series of dihydroquinoxalinone sulfonamides to evaluate the effects of various structural changes on biological activity. The optimization of a screening lead compound, facilitated by a homology model of the BK B1 receptor, culminated in the discovery of a potent human BK B1 receptor antagonist. Results from site-directed mutagenesis studies and experiments in an animal pain model are presented.

  DOI：

  10.1021/ja0353457
• 作为产物：
  描述：

  dimethyl D-aspartate 在 palladium 10% on activated carbon 氢气 、 碳酸氢钠 作用下， 以 吡啶 、 甲醇 、 乙醇 为溶剂， 反应 96.0h， 生成 methyl {(2R)-1-[(3,4-dichlorophenyl)sulfonyl]-3-oxo-1,2,3,4-tetrahydroquinoxalin-2-yl}acetate
  参考文献：
  名称：

  2-Quinoxalinone derivatives as bradykinin antagonists and novel compounds

  摘要：

  2-喹喔啉酮衍生物是布雷金肽B1拮抗剂或逆向激动剂，可用于治疗或预防与布雷金肽B1途径相关的症状，如疼痛和炎症。

  公开号：

  US20050020591A1

文献信息

• [EN] NOVEL QUINOXALINONE DERIVATIVES AS BRADYKININ B1 ANTAGONISTS<br/>[FR] NOUVEAUX DERIVES DE QUINOXALINONE CONSTITUANT DES ANTAGONISTES B1 DE LA BRADYKININE
  申请人：MERCK & CO INC

  公开号：WO2004054584A1

  公开（公告）日：2004-07-01

  2-Quinoxalinone derivatives are bradykinin B1 antagonists or inverse agonists useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.

  2-喹啉酮衍生物是布雷金肽B1拮抗剂或逆向激动剂，在治疗或预防与布雷金肽B1途径相关的疼痛和炎症症状方面具有用处。
• Novel quinoxalinone derivatives as bradykinin B1 antagonists
  申请人：——

  公开号：US20040132733A1

  公开（公告）日：2004-07-08

  2-Quinoxalinone derivatives are bradykinin B1 antagonists or inverse agonists useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.

  2-喹喔啉酮衍生物是布雷金肽B1拮抗剂或逆向激动剂，可用于治疗或预防与布雷金肽B1途径相关的疼痛和炎症等症状。
• Quinoxalinone derivatives as bradykinin B1 antagonists
  申请人：Su Dai-Shi

  公开号：US06908921B2

  公开（公告）日：2005-06-21

  2-Quinoxalinone derivatives are bradykinin B1 antagonists or inverse agonists useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.

  2-喹喔啉酮衍生物是Bradykinin B1拮抗剂或反向激动剂，在治疗或预防与Bradykinin B1通路相关的疼痛和炎症等症状方面有用。
• Discovery of dihydroquinoxalinone acetamides containing bicyclic amines as potent Bradykinin B1 receptor antagonists
  作者：Jian Jeffrey Chen、Wenyuan Qian、Kaustav Biswas、Vellarkad N. Viswanadhan、Benny C. Askew、Stephen Hitchcock、Randall W. Hungate、Leyla Arik、Eileen Johnson

  DOI：10.1016/j.bmcl.2008.07.055

  日期：2008.8

  Replacement of the core P-amino acid in our previously reported piperidine acetic acid and beta-phenylalanine-based Bradykinin B1 antagonists by dihydroquinoxalinone acetic acid increases the in vitro potency and metabolic stability. The most potent compounds from this series have IC(50)s < 0.2 nM in a human B1 receptor functional assay. A molecular modeling study of the binding modes of key compounds, based on a B1 homology model, explains the structure-activity relationship (SAR) for these analogs. (c) 2008 Elsevier Ltd. All rights reserved.