3-(3,4-dimethoxy-phenyl)-2-hydrazino-3H-quinazolin-4-one | 180423-58-9

• 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-(3,4-dimethoxy-phenyl)-2-hydrazino-3H-quinazolin-4-one
• 英文别名: 3-(3,4-Dimethoxyphenyl)-2-hydrazinylquinazolin-4-one
• CAS: 180423-58-9
• 化学式: C₁₆H₁₆N₄O₃
• 分子量: 312.328
• InChiKey: UKCSXEKECGDGGF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  23
• 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：
  89.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(乙氧基羰基)苯异氰酸酯 、 3-(3,4-dimethoxy-phenyl)-2-hydrazino-3H-quinazolin-4-one 以 乙腈 为溶剂， 反应 16.0h， 生成 benzoic acid, 3-[[[2-[3,4-dihydro-3-(3,4-dimethoxyphenyl)-4-oxo-2-quinazolinyl]hydrazino]carbonyl]amino]-, ethyl ester
  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

文献信息

• US6897213B1
  申请人：——

  公开号：US6897213B1

  公开（公告）日：2005-05-24
• [EN] NOVEL HETEROCYCLES AS CHOLECYSTOKININ (CCK) LIGANDS<br/>[FR] NOUVEAUX HETEROCYCLES UTILISES COMME LIGANDS DE LA CHOLECYSTOKININE (CCK)
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1996020178A1

  公开（公告）日：1996-07-04

  (EN) Novel quinazolinone derivatives with good binding affinity for the CCK-A and CCK-B receptors, pharmaceutical compositions containing them and methods of using them are taught. The compounds are useful agents to suppress appetite, reduce gastric acid secretion, and the like.(FR) La présente invention concerne de nouveaux dérivés de quinazolinone qui présentent une bonne affinité de liaison avec les récepteurs CCK-A et CCK-B; elle concerne également des compositions pharmaceutiques qui contiennent ces dérivés ainsi que des procédés d'utilisation. Ces composés s'avèrent efficaces pour modérer l'appétit, réduire l'acidité gastrique et dans des situations similaires.
• 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.