9-chloro-7-(2-chlorophenyl)-6,7-dihydro-5H-pyrimido<5,4-d><2>benzazepine 3-oxide | 76988-79-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 9-chloro-7-(2-chlorophenyl)-6,7-dihydro-5H-pyrimido<5,4-d><2>benzazepine 3-oxide
• 英文别名: 9-chloro-7-(2-chlorophenyl)-3-oxido-6,7-dihydro-5H-pyrimido[5,4-d][2]benzazepin-3-ium
• CAS: 76988-79-9
• 化学式: C₁₈H₁₃Cl₂N₃O
• 分子量: 358.227
• InChiKey: HNUYGAFVROYBQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  50.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  9-chloro-7-(2-chlorophenyl)-6,7-dihydro-5H-pyrimido<5,4-d><2>benzazepine 3-oxide 在 溴 、 sodium methylate 、 potassium acetate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 27.25h， 生成 9-chloro-7-(2-chlorophenyl)-5H-pyrimido<5,4-d><2>benzazepine 3-oxide
  参考文献：
  名称：

  2-Benzazepines. 6. Synthesis and pharmacological properties of the metabolites of 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d][2]benzazepine

  摘要：

  The 2-benzazepine 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d] [2]benzazepine (1) has been selected for development as an anxiolytic agent. In support of this program, we have confirmed by chemical synthesis the structures of three in vitro (rat liver homogenate) metabolites of 1 and confirmed the structure of the major in vivo (dog and man) metabolite of 1, compound 2. Two of the metabolites, arising from hydroxylation of the pyrimidobenzazepine ring at the 5-position (2) and N-oxide formation at the 3-position of the pyrimidobenzazepine ring (3), were found to be as active as 1 in a series of pharmacological tests. The third metabolite, formed by hydroxylation of the 7-phenyl group in the 4-position (4), was found to be inactive in the same pharmacological screens.

  DOI：

  10.1021/jm00365a009
• 作为产物：
  描述：

  9-氯-7-(2-氯苯基)-5H-嘧啶并[5,4-d][2]苯并氮杂卓 在 吡啶 、 sodium hydroxide 、 溶剂黄146 、 间氯过氧苯甲酸 、 锌 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 50.0h， 生成 9-chloro-7-(2-chlorophenyl)-6,7-dihydro-5H-pyrimido<5,4-d><2>benzazepine 3-oxide
  参考文献：
  名称：

  2-Benzazepines. 6. Synthesis and pharmacological properties of the metabolites of 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d][2]benzazepine

  摘要：

  The 2-benzazepine 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d] [2]benzazepine (1) has been selected for development as an anxiolytic agent. In support of this program, we have confirmed by chemical synthesis the structures of three in vitro (rat liver homogenate) metabolites of 1 and confirmed the structure of the major in vivo (dog and man) metabolite of 1, compound 2. Two of the metabolites, arising from hydroxylation of the pyrimidobenzazepine ring at the 5-position (2) and N-oxide formation at the 3-position of the pyrimidobenzazepine ring (3), were found to be as active as 1 in a series of pharmacological tests. The third metabolite, formed by hydroxylation of the 7-phenyl group in the 4-position (4), was found to be inactive in the same pharmacological screens.

  DOI：

  10.1021/jm00365a009

文献信息

• TRYBULSKI, E. J.;FRYER, R. I.;REEDER, E.;WALSER, A.;BLOUNT, J., J. MED. CHEM., 1983, 26, N 11, 1596-1601
  作者：TRYBULSKI, E. J.、FRYER, R. I.、REEDER, E.、WALSER, A.、BLOUNT, J.

  DOI：——

  日期：——
• FRYER, R. I.;GILMAN, N. W.;TRYBULSKI, E. J.;WALSER, A.
  作者：FRYER, R. I.、GILMAN, N. W.、TRYBULSKI, E. J.、WALSER, A.

  DOI：——

  日期：——
• US4481142A
  申请人：——

  公开号：US4481142A

  公开（公告）日：1984-11-06
• US4546183A
  申请人：——

  公开号：US4546183A

  公开（公告）日：1985-10-08
• US4547581A
  申请人：——

  公开号：US4547581A

  公开（公告）日：1985-10-15