2-amino-3-(3-isopropoxy-phenyl)-3H-quinazolin-4-one | 189937-65-3

• 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: 2-amino-3-(3-isopropoxy-phenyl)-3H-quinazolin-4-one
• 英文别名: 4(3H)-Quinazolinone, 2-amino-3-[3-(1-methylethoxy)phenyl]-；2-amino-3-(3-propan-2-yloxyphenyl)quinazolin-4-one
• CAS: 189937-65-3
• 化学式: C₁₇H₁₇N₃O₂
• 分子量: 295.341
• InChiKey: CWQXWGZOKWRTTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-溴异氰酸苯酯 、 2-amino-3-(3-isopropoxy-phenyl)-3H-quinazolin-4-one 在 sodium hydride 作用下， 生成 1-(4-Bromo-phenyl)-3-[3-(3-isopropoxy-phenyl)-4-oxo-3,4-dihydro-quinazolin-2-yl]-urea
  参考文献：
  名称：

  Design and synthesis of novel nonpeptide CCK-B receptor antagonists

  摘要：

  A novel hybrid series of nonpeptide CCK-B receptor antagonists has been designed from two known series derived from asperlicin. An efficient synthesis of 2-aminoquinazolinone, an intermediate for the synthesis of a targeted analog, has been developed. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00108-x
• 作为产物：
  描述：

  3-氨基苯异丙醚 在 镍 氢气 、 溶剂黄146 、 三乙胺 、 肼 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 25.0~50.0 ℃ 、101.33 kPa 条件下， 反应 106.0h， 生成 2-amino-3-(3-isopropoxy-phenyl)-3H-quinazolin-4-one
  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

• Quinazolinone derivatives as cholyecystokinin (CCK) ligands
  申请人：Warner-Lambert Company

  公开号：US05756502A1

  公开（公告）日：1998-05-26

  Novel quinazolinone derivatives with good binding affinity for the CCK-A and CCK-B receptors, pharmaceutical compositions containing them, methods of using them and a novel process for their preparation are taught. The compounds are useful agents to suppress appetite, reduce gastric acid secretion, and the like.

  本发明涉及一种新型喹唑啉衍生物，具有良好的CCK-A和CCK-B受体结合亲和力，包含它们的制药组合物，使用它们的方法以及一种新型的制备方法。这些化合物是有用的制剂，可以抑制食欲，减少胃酸分泌等。
• Quinazolinone derivatives as cholecystokinin (CCK) ligands
  申请人：Warner-Lambert Company

  公开号：US05869665A1

  公开（公告）日：1999-02-09

  Novel quinazolinone derivatives with good binding affinity for the CCK-A and CCK-B receptors, pharmaceutical compositions containing them, methods of using them and a novel process for their preparation are taught. The compounds are useful agents to suppress appetite, reduce gastric acid secretion, and the like.

  本发明涉及新型喹唑啉衍生物，其对CCK-A和CCK-B受体具有良好的结合亲和力，以及含有它们的制药组合物、使用它们的方法和一种新型制备它们的方法。这些化合物是有用的药剂，用于抑制食欲、减少胃酸分泌等。
• Design and synthesis of novel nonpeptide CCK-B receptor antagonists
  作者：J.K. Padia、H. Chilvers、P. Daum、R. Pinnock、N. Suman-Chauhan、L. webdale、B.K. Trivedi

  DOI：10.1016/s0960-894x(97)00108-x

  日期：1997.1

  A novel hybrid series of nonpeptide CCK-B receptor antagonists has been designed from two known series derived from asperlicin. An efficient synthesis of 2-aminoquinazolinone, an intermediate for the synthesis of a targeted analog, has been developed. (C) 1997 Elsevier Science Ltd.
• US5756502A
  申请人：——

  公开号：US5756502A

  公开（公告）日：1998-05-26
• US5869665A
  申请人：——

  公开号：US5869665A

  公开（公告）日：1999-02-09