benzyl N-[[4-oxo-3-(3-propan-2-yloxyphenyl)quinazolin-2-yl]methyl]carbamate | 205063-49-6

• 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: benzyl N-[[4-oxo-3-(3-propan-2-yloxyphenyl)quinazolin-2-yl]methyl]carbamate
• CAS: 205063-49-6
• 化学式: C₂₆H₂₅N₃O₄
• 分子量: 443.502
• InChiKey: JACSJAAPABEZHO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  80.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl N-[[4-oxo-3-(3-propan-2-yloxyphenyl)quinazolin-2-yl]methyl]carbamate 在 palladium on activated charcoal 氢气 作用下， 生成 3-{3-[3-(3-Isopropoxy-phenyl)-4-oxo-3,4-dihydro-quinazolin-2-ylmethyl]-ureido}-benzoic acid ethyl ester
  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：

  2-(2-benzyloxycarbonylamino-acetylamino)-benzoic acid methyl ester 在 lithium hydroxide 、 N,N'-羰基二咪唑 作用下， 以 1,4-二氧六环 为溶剂， 反应 49.0h， 生成 benzyl N-[[4-oxo-3-(3-propan-2-yloxyphenyl)quinazolin-2-yl]methyl]carbamate
  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

• 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.
• 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.