4-(2-Aminoethyl)-2-methyl-6-nitro-1,4-benzoxazin-3-one | 1267782-04-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 4-(2-Aminoethyl)-2-methyl-6-nitro-1,4-benzoxazin-3-one
• 英文别名: 4-(2-aminoethyl)-2-methyl-6-nitro-1,4-benzoxazin-3-one
• CAS: 1267782-04-6
• 化学式: C₁₁H₁₃N₃O₄
• 分子量: 251.242
• InChiKey: ZWPFUDFSVNHLLN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(2-Aminoethyl)-2-methyl-6-nitro-1,4-benzoxazin-3-one 、 乙酰氧基乙酰氯 在 TATU 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

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

  摘要：

  Two structurally distinct series of SCD (Delta 9 desaturase) inhibitors (1 and 2) have been previously reported by our group. In the present work, we merged the structural features of the two series. This led to the discovery of compound 5b (CVT-12,012) which is highly potent in a human cell-based (HEPG2) SCD assay (IC(50) = 6 nM). This compound has 78% oral bioavailability in rats and is preferentially distributed into liver (76 times vs plasma) with relatively low brain penetration. In a five-day study (sucrose fed rats) compound 5b significantly reduced SCD activity in a dose-dependent manner as determined by GC analysis of fatty acid composition in plasma and liver, and significantly reduced liver triglycerides versus the control group (similar to 50%). (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.06.017
• 作为产物：
  描述：

  2-(2-(2-methyl-6-nitro-3-oxo-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)ethyl)isoindoline-1,3-dione 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 4-(2-Aminoethyl)-2-methyl-6-nitro-1,4-benzoxazin-3-one
  参考文献：
  名称：

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

  摘要：

  Two structurally distinct series of SCD (Delta 9 desaturase) inhibitors (1 and 2) have been previously reported by our group. In the present work, we merged the structural features of the two series. This led to the discovery of compound 5b (CVT-12,012) which is highly potent in a human cell-based (HEPG2) SCD assay (IC(50) = 6 nM). This compound has 78% oral bioavailability in rats and is preferentially distributed into liver (76 times vs plasma) with relatively low brain penetration. In a five-day study (sucrose fed rats) compound 5b significantly reduced SCD activity in a dose-dependent manner as determined by GC analysis of fatty acid composition in plasma and liver, and significantly reduced liver triglycerides versus the control group (similar to 50%). (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.06.017

文献信息

• Potent, orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD) inhibitors
  作者：Dmitry O. Koltun、Timur M. Zilbershtein、Vasily A. Migulin、Natalya I. Vasilevich、Eric Q. Parkhill、Andrei I. Glushkov、Malcolm J. McGregor、Sandra A. Brunn、Nancy Chu、Jia Hao、Nevena Mollova、Kwan Leung、Jeffrey W. Chisholm、Jeff Zablocki

  DOI：10.1016/j.bmcl.2009.06.017

  日期：2009.8

  Two structurally distinct series of SCD (Delta 9 desaturase) inhibitors (1 and 2) have been previously reported by our group. In the present work, we merged the structural features of the two series. This led to the discovery of compound 5b (CVT-12,012) which is highly potent in a human cell-based (HEPG2) SCD assay (IC(50) = 6 nM). This compound has 78% oral bioavailability in rats and is preferentially distributed into liver (76 times vs plasma) with relatively low brain penetration. In a five-day study (sucrose fed rats) compound 5b significantly reduced SCD activity in a dose-dependent manner as determined by GC analysis of fatty acid composition in plasma and liver, and significantly reduced liver triglycerides versus the control group (similar to 50%). (C) 2009 Elsevier Ltd. All rights reserved.