2-[2-(6-Nitro-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-ethyl]-isoindole-1,3-dione | 1186393-68-9

• 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: 2-[2-(6-Nitro-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-ethyl]-isoindole-1,3-dione
• 英文别名: 2-[2-(6-Nitro-3-oxo-1,4-benzoxazin-4-yl)ethyl]isoindole-1,3-dione
• CAS: 1186393-68-9
• 化学式: C₁₈H₁₃N₃O₆
• 分子量: 367.318
• InChiKey: SYCBOCCDUKSNPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  113
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[2-(6-Nitro-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-ethyl]-isoindole-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)-6-nitro-4H-benzo[1,4]oxazin-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
• 作为产物：
  描述：

  N-羟乙基酞酰亚胺 在 咪唑 、 碘 、 sodium hydride 、 三苯基膦 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 生成 2-[2-(6-Nitro-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-ethyl]-isoindole-1,3-dione
  参考文献：
  名称：

  2H-BENZO[b][1,4]OXAZIN-3(4H)-ONE DERIVATIVES FOR USE AS STEAROYL CoA DESATURASE INHIBITORS

  摘要：

  本发明揭示了用作硬脂酰辅酶A去饱和酶抑制剂的2H-苯并[b][1,4]噁嗪-3(4H)-酮衍生物，其具有Formula I的结构：这些化合物在治疗和/或预防由硬脂酰辅酶A去饱和酶（SCD）酶介导的各种人类疾病方面具有用途，特别是与异常脂质水平、心血管疾病、糖尿病、肥胖症、代谢综合征等相关的疾病。

  公开号：

  US20090253693A1

文献信息

• [EN] 2H-BENZO[B][1,4]OXAZIN-3(4H)-ONE DERIVATIVES FOR USE AS STEAROYL COA DESATURASE INHIBITORS<br/>[FR] DÉRIVÉS DE 2H-BENZO[B][1,4]OXAZIN-3(4H)-ONE À UTILISER COMME INHIBITEURS DE LA STÉAROYL-COA DÉSATURASE
  申请人：CV THERAPEUTICS INC

  公开号：WO2009126527A1

  公开（公告）日：2009-10-15

  The present invention discloses 2H-benzo[b][1,4]oxazin-3(4H)-one derivatives for use as inhibitors of stearoyl-CoA desaturase having the structure of Formula I. The compounds are useful in treating and/or preventing various human diseases, mediated by stearoyl-CoA desaturase (SCD) enzymes, especially diseases related to abnormal lipid levels, cardiovascular disease, diabetes, obesity, metabolic syndrome and the like.
• 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.
• 2H-BENZO[b][1,4]OXAZIN-3(4H)-ONE DERIVATIVES FOR USE AS STEAROYL CoA DESATURASE INHIBITORS
  申请人：Koltun Dmitry

  公开号：US20090253693A1

  公开（公告）日：2009-10-08

  The present invention discloses 2H-benzo[b][1,4]oxazin-3(4H)-one derivatives for use as inhibitors of stearoyl-CoA desaturase having the structure of Formula I: The compounds are useful in treating and/or preventing various human diseases, mediated by stearoyl-CoA desaturase (SCD) enzymes, especially diseases related to abnormal lipid levels, cardiovascular disease, diabetes, obesity, metabolic syndrome and the like.

  本发明揭示了用作硬脂酰辅酶A去饱和酶抑制剂的2H-苯并[b][1,4]噁嗪-3(4H)-酮衍生物，其具有Formula I的结构：这些化合物在治疗和/或预防由硬脂酰辅酶A去饱和酶（SCD）酶介导的各种人类疾病方面具有用途，特别是与异常脂质水平、心血管疾病、糖尿病、肥胖症、代谢综合征等相关的疾病。