3-(3-Ethoxyphenyl)-2-hydrazinylquinazolin-4-one | 68357-88-0

• 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: 3-(3-Ethoxyphenyl)-2-hydrazinylquinazolin-4-one
• CAS: 68357-88-0
• 化学式: C₁₆H₁₆N₄O₂
• 分子量: 296.329
• InChiKey: CUTAXXVJTYBWJM-UHFFFAOYSA-N

物化性质

• 熔点：
  174-176 °C(Solv: ethanol (64-17-5))
• 沸点：
  505.0±52.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  80
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  异氰酸间氰基苯酯 、 3-(3-Ethoxyphenyl)-2-hydrazinylquinazolin-4-one 以 乙腈 为溶剂， 反应 16.0h， 生成 1-(3-Cyanophenyl)-3-[[3-(3-ethoxyphenyl)-4-oxoquinazolin-2-yl]amino]urea
  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
• 作为产物：
  描述：

  3-(3-Ethoxy-phenyl)-2-mercapto-3H-quinazolin-4-one 在 一水合肼 作用下， 以 乙醇 为溶剂， 以48%的产率得到3-(3-Ethoxyphenyl)-2-hydrazinylquinazolin-4-one
  参考文献：
  名称：

  Kottke; Kuhmstedt, Pharmazie, 1982, vol. 37, # 9, p. 635 - 637

  摘要：

  DOI：

文献信息

• Kottke; Kuhmstedt; Knoke, Pharmazie, 1983, vol. 38, # 1, p. 25 - 28
  作者：Kottke、Kuhmstedt、Knoke

  DOI：——

  日期：——
• KOTTKE K.;KUEHMSTEDT H.;KNOKE D,, PHAMAZIE, 1983, 38, NO 1, 25-28
  作者：KOTTKE K.、KUEHMSTEDT H.、KNOKE D,

  DOI：——

  日期：——
• KOTTKE, K.;KUEHMSTEDT, H.;LANDMANN, H.;KNOKE, D.;WEHLAN, H.
  作者：KOTTKE, K.、KUEHMSTEDT, H.、LANDMANN, H.、KNOKE, D.、WEHLAN, H.

  DOI：——

  日期：——
• Novel Nonpeptide CCK-B Antagonists:  Design and Development of Quinazolinone Derivatives as Potent, Selective, and Orally Active CCK-B Antagonists
  作者：Janak K. Padia、Mark Field、Joanna Hinton、Ken Meecham、Julius Pablo、Rob Pinnock、Bruce D. Roth、Lakhbir Singh、Nirmala Suman-Chauhan、Bharat K. Trivedi、Louise Webdale

  DOI：10.1021/jm970373j

  日期：1998.3.1

  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.
• Kottke; Kuhmstedt, Pharmazie, 1982, vol. 37, # 9, p. 635 - 637
  作者：Kottke、Kuhmstedt

  DOI：——

  日期：——