(S)-N-(3-(3,4-dichlorobenzyl)-4-oxo-3,4-dihydroquinazolin-6-yl)-2-hydroxypropanamide | 1172583-77-5

• 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: (S)-N-(3-(3,4-dichlorobenzyl)-4-oxo-3,4-dihydroquinazolin-6-yl)-2-hydroxypropanamide
• 英文别名: (2S)-N-[3-[(3,4-dichlorophenyl)methyl]-4-oxoquinazolin-6-yl]-2-hydroxypropanamide
• CAS: 1172583-77-5
• 化学式: C₁₈H₁₅Cl₂N₃O₃
• 分子量: 392.241
• InChiKey: DGZBCKSHKIBZKD-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  82
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  L-乳酸 、 3-(3,4-二氯苄基)-6-氨基喹唑啉-4-(3H)-酮 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 氯仿 为溶剂， 生成 (S)-N-(3-(3,4-dichlorobenzyl)-4-oxo-3,4-dihydroquinazolin-6-yl)-2-hydroxypropanamide
  参考文献：
  名称：

  Orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD) inhibitors

  摘要：

  We discovered a structurally novel SCD (Delta 9 desaturase) inhibitor 4a (CVT-11,563) that has 119 nM potency in a human cell-based (HEPG2) SCD assay and selectivity against Delta 5 and Delta 6 desaturases. This compound has 90% oral bioavailability (rat) and excellent plasma exposure (dAUC 935 ng h/mL). Additionally, 4a shows moderately selective liver distribution (three times vs plasma and adipose tissue) and relatively low brain penetration. In a five-day study (high sucrose diet, rat) compound 4a significantly reduced SCD activity as determined by GC analysis of fatty acid composition in plasma and liver. We describe the discovery of 4a from HTS hit 1 followed by scaffold replacement and SAR studies focused on DMPK properties. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.04.004

文献信息

• Orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD) inhibitors
  作者：Dmitry O. Koltun、Natalya I. Vasilevich、Eric Q. Parkhill、Andrei I. Glushkov、Timur M. Zilbershtein、Elena I. Mayboroda、Melanie A. Boze、Andrew G. Cole、Ian Henderson、Nathan A. Zautke、Sandra A. Brunn、Nancy Chu、Jia Hao、Nevena Mollova、Kwan Leung、Jeffrey W. Chisholm、Jeff Zablocki

  DOI：10.1016/j.bmcl.2009.04.004

  日期：2009.6

  We discovered a structurally novel SCD (Delta 9 desaturase) inhibitor 4a (CVT-11,563) that has 119 nM potency in a human cell-based (HEPG2) SCD assay and selectivity against Delta 5 and Delta 6 desaturases. This compound has 90% oral bioavailability (rat) and excellent plasma exposure (dAUC 935 ng h/mL). Additionally, 4a shows moderately selective liver distribution (three times vs plasma and adipose tissue) and relatively low brain penetration. In a five-day study (high sucrose diet, rat) compound 4a significantly reduced SCD activity as determined by GC analysis of fatty acid composition in plasma and liver. We describe the discovery of 4a from HTS hit 1 followed by scaffold replacement and SAR studies focused on DMPK properties. (C) 2009 Elsevier Ltd. All rights reserved.