hydrazinecarboxamide, N-(3-cyanophenyl)-2-[3,4-dihydro-3-[3-(dimethylamino)phenyl]-4-oxo-2-quinazolinyl]-

• 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: hydrazinecarboxamide, N-(3-cyanophenyl)-2-[3,4-dihydro-3-[3-(dimethylamino)phenyl]-4-oxo-2-quinazolinyl]-
• 英文别名: 1-(3-Cyanophenyl)-3-[[3-[3-(dimethylamino)phenyl]-4-oxoquinazolin-2-yl]amino]urea
• 化学式: C₂₄H₂₁N₇O₂
• 分子量: 439.476
• InChiKey: AJMRNBSGTOOMHD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  异氰酸间氰基苯酯 、 3-(3-dimethylamino-phenyl)-2-hydrazino-3H-quinazolin-4-one 以 乙腈 为溶剂， 反应 16.0h， 生成 hydrazinecarboxamide, N-(3-cyanophenyl)-2-[3,4-dihydro-3-[3-(dimethylamino)phenyl]-4-oxo-2-quinazolinyl]-
  参考文献：
  名称：

  Novel Nonpeptide CCK-B Antagonists:  Design and Development of Quinazolinone Derivatives as Potent, Selective, and Orally Active CCK-B Antagonists

  摘要：

  We have designed a novel series of CCK-B receptor antagonists by combining key pharmacophores, an arylurea moiety of 1 and a quinazolinone ring of 3, from two known series. Our earlier studies showed that compounds with methylene linkers in our "target" produced moderate binding affinity and selectivity for CCK-B receptors, whereas its higher and lower homologues resulted in loss of affinity. Introduction of -NH- as a linker dramatically enhanced binding affinity and selectivity for CCK-B receptors, thus providing several compounds with single-digit nanomolar binding affinity and excellent selectivity. Analogous to the earlier studies of the series of quinazolinone derivatives 3, we also found 3-isopropoxyphenyl as a preferred substitution on the N-3 quinazolinone. Electron-withdrawing substitutions on the urea terminal phenyl ring enhanced the CCK-B potency. Representative compounds of this series were tested in the functional assay and showed pure antagonist profiles. Compounds 51 and 61 were orally active in the elevated rat X-maze test. These compounds were also evaluated for their pharmacokinetic profile. The absolute oral bioavailability of compound 61 was 22% in rats.

  DOI：

  10.1021/jm970373j