4-[(1E)-3-({2-[3-({[4-(1-azepanyl)-2-methyl-8-quinolinyl]oxy}methyl)-2,4-dichloromethylanilino]-2-oxoethyl}amino)-3-oxo-1-propenyl]-N-methylbenzamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-[(1E)-3-({2-[3-({[4-(1-azepanyl)-2-methyl-8-quinolinyl]oxy}methyl)-2,4-dichloromethylanilino]-2-oxoethyl}amino)-3-oxo-1-propenyl]-N-methylbenzamide
• 英文别名: 4-Hexamethyleneimino-8-[2,6-dichloro-3-[N-methyl-N-[4-(methylcarbamoyl)cinnamoylglycyl]amino]benzyloxy]-2-methylquinoline；4-{(E)-2-[({[3-(4-Azepan-1-yl-2-methyl-quinolin-8-yloxymethyl)-2,4-dichloro-phenyl]-methyl-carbamoyl}-methyl)-carbamoyl]-vinyl}-N-methyl-benzamide; Dihydrochloride；4-[(E)-3-[[2-[3-[[4-(azepan-1-yl)-2-methylquinolin-8-yl]oxymethyl]-2,4-dichloro-N-methylanilino]-2-oxoethyl]amino]-3-oxoprop-1-enyl]-N-methylbenzamide
• 化学式: C₃₇H₃₉Cl₂N₅O₄
• 分子量: 688.654
• InChiKey: ALWWZZYTQLZEAK-QGOAFFKASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  48
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-氯-8-羟基-2-甲基喹啉 在 四丁基碘化铵 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 4-[(1E)-3-({2-[3-({[4-(1-azepanyl)-2-methyl-8-quinolinyl]oxy}methyl)-2,4-dichloromethylanilino]-2-oxoethyl}amino)-3-oxo-1-propenyl]-N-methylbenzamide
  参考文献：
  名称：

  A New Class of Nonpeptide Bradykinin B₂ Receptor Ligand, Incorporating a 4-Aminoquinoline Framework. Identification of a Key Pharmacophore To Determine Species Difference and Agonist/Antagonist Profile

  摘要：

  Introduction of various aliphatic amino groups at the 4-position of the quinoline moiety of our nonpeptide bradykinin (BK) B-2 receptor antagonists afforded highly potent ligands for human B-2 receptor with various affinities for guinea pig B-2 receptor, indicating remarkable species difference. A representative 4-dimethyamino derivative 40a exhibited subnanomolar and nanomolar binding affinities for human and guinea pig B-2 receptors, respectively, and significantly inhibited BK-induced bronchoconstriction in guinea pigs at 10 mug/kg by intravenous administration. Further chemical modification led us to discover unique partial agonists for the human B-2 receptor that increase inositol phosphates (IPs) production by themselves in Chinese hamster ovary (CHO) cells expressing the cloned human B-2 receptor. Although their potency and efficacy were much lower than those of BK, we identified them as screening leads for nonpeptide B-2 agonists. In these studies it was revealed the 4-substituent of the quinoline moiety is the key pharmacophore to determine species difference and agonist/antagonist profiles.

  DOI：

  10.1021/jm030326t

文献信息

• US5994368A
  申请人：——

  公开号：US5994368A

  公开（公告）日：1999-11-30
• A New Class of Nonpeptide Bradykinin B₂ Receptor Ligand, Incorporating a 4-Aminoquinoline Framework. Identification of a Key Pharmacophore To Determine Species Difference and Agonist/Antagonist Profile
  作者：Yuki Sawada、Hiroshi Kayakiri、Yoshito Abe、Tsuyoshi Mizutani、Noriaki Inamura、Masayuki Asano、Ichiro Aramori、Chie Hatori、Teruo Oku、Hirokazu Tanaka

  DOI：10.1021/jm030326t

  日期：2004.5.1

  Introduction of various aliphatic amino groups at the 4-position of the quinoline moiety of our nonpeptide bradykinin (BK) B-2 receptor antagonists afforded highly potent ligands for human B-2 receptor with various affinities for guinea pig B-2 receptor, indicating remarkable species difference. A representative 4-dimethyamino derivative 40a exhibited subnanomolar and nanomolar binding affinities for human and guinea pig B-2 receptors, respectively, and significantly inhibited BK-induced bronchoconstriction in guinea pigs at 10 mug/kg by intravenous administration. Further chemical modification led us to discover unique partial agonists for the human B-2 receptor that increase inositol phosphates (IPs) production by themselves in Chinese hamster ovary (CHO) cells expressing the cloned human B-2 receptor. Although their potency and efficacy were much lower than those of BK, we identified them as screening leads for nonpeptide B-2 agonists. In these studies it was revealed the 4-substituent of the quinoline moiety is the key pharmacophore to determine species difference and agonist/antagonist profiles.