6-chloro-3-quinuclidinyl-1H-quinazoline-2,4-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-chloro-3-quinuclidinyl-1H-quinazoline-2,4-dione
• 英文别名: 3-(1-Aza-bicyclo[2.2.2]oct-3-yl)-6-chloro-1H-quinazoline-2,4-dione；3-(1-azabicyclo[2.2.2]octan-3-yl)-6-chloro-1H-quinazoline-2,4-dione
• 化学式: C₁₅H₁₆ClN₃O₂
• 分子量: 305.764
• InChiKey: PODVLAAAWFKIRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  52.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3'-(5-chloro-2-ethoxycarbonylaminobenzoylamino)quinuclidine 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以41%的产率得到6-chloro-3-quinuclidinyl-1H-quinazoline-2,4-dione
  参考文献：
  名称：

  Synthesis of quinazoline-2,4-dione and naphthalimide derivatives as new 5-HT3 receptor antagonists

  摘要：

  New potent 5-HT3 receptor antagonists have been designed from the naphthalimide moiety and a quinuclidine heterocycle and the structure-activity relationships are discussed here on the basis of the nature of the substituent on the aromatic system. The biological activity of the compounds was evaluated in binding assays with [H-3]BRL-43694 and by inhibition of the Bezold-Jarisch reflex. Compound 22 with a 4-amino substituent was equipotent to the reference compounds. In contrast to the benzamide derivatives, the activity resides essentially in the (R) enantiomer (K-i = 0.15 +/- 0.05 nM, ID50 = 1.6 mu g/kg/iv) and it is demonstrated that the additional carbonyl group is involved in the inversion of the enantioselectivity of the receptor. Conformational studies of (R)-22 demonstrated the presence of a locked structure with 4 minimal energy conformers which were compared to those of (S)-zacopride. The superimposition of the putative active conformers emphasized the presence of a second polar group in the binding site. The fluorescent properties of the compounds were studied and indicate that (R)-22 and its derivatives may be promising tools for the direct visualization of 5-HT3 receptors.

  DOI：

  10.1016/0223-5234(94)90192-9

文献信息

• Synthesis of quinazoline-2,4-dione and naphthalimide derivatives as new 5-HT3 receptor antagonists
  作者：M Langlois、JL Soulier、V Rampillon、C Gallais、B Brémont、S Shen、D Yang、A Giudice、F Sureau

  DOI：10.1016/0223-5234(94)90192-9

  日期：1994.1

  New potent 5-HT3 receptor antagonists have been designed from the naphthalimide moiety and a quinuclidine heterocycle and the structure-activity relationships are discussed here on the basis of the nature of the substituent on the aromatic system. The biological activity of the compounds was evaluated in binding assays with [H-3]BRL-43694 and by inhibition of the Bezold-Jarisch reflex. Compound 22 with a 4-amino substituent was equipotent to the reference compounds. In contrast to the benzamide derivatives, the activity resides essentially in the (R) enantiomer (K-i = 0.15 +/- 0.05 nM, ID50 = 1.6 mu g/kg/iv) and it is demonstrated that the additional carbonyl group is involved in the inversion of the enantioselectivity of the receptor. Conformational studies of (R)-22 demonstrated the presence of a locked structure with 4 minimal energy conformers which were compared to those of (S)-zacopride. The superimposition of the putative active conformers emphasized the presence of a second polar group in the binding site. The fluorescent properties of the compounds were studied and indicate that (R)-22 and its derivatives may be promising tools for the direct visualization of 5-HT3 receptors.