{2-[3-methyl-2-oxo-7-(3-trifluoromethyl-benzylamino)-2H-quinoxalin-1-yl]-ethylcarbamoyl}-methyl acetate | 1018675-34-7

• 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-[3-methyl-2-oxo-7-(3-trifluoromethyl-benzylamino)-2H-quinoxalin-1-yl]-ethylcarbamoyl}-methyl acetate
• 英文别名: [2-[2-[3-Methyl-2-oxo-7-[[3-(trifluoromethyl)phenyl]methylamino]quinoxalin-1-yl]ethylamino]-2-oxoethyl] acetate
• CAS: 1018675-34-7
• 化学式: C₂₃H₂₃F₃N₄O₄
• 分子量: 476.455
• InChiKey: JBJQLIQHPXGRPO-UHFFFAOYSA-N

物化性质

• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  {2-[3-methyl-2-oxo-7-(3-trifluoromethyl-benzylamino)-2H-quinoxalin-1-yl]-ethylcarbamoyl}-methyl acetate 在 甲醇 、 lithium hydrochloride monohydrate 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 CVT-12,012
  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：

  1-(2-aminoethyl)-3-methyl-7-(3-(trifluoromethyl)benzylamino)quinoxalin-2(1H)-one 、 乙酰氧基乙酰氯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 {2-[3-methyl-2-oxo-7-(3-trifluoromethyl-benzylamino)-2H-quinoxalin-1-yl]-ethylcarbamoyl}-methyl acetate
  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

• Bicyclic Nitrogen-containing Heterocyclic compounds for use as Stearoyl CoA Desaturase inhibitors
  申请人：Koltun Dmitry

  公开号：US20080255130A1

  公开（公告）日：2008-10-16

  The present invention discloses bicyclic nitrogen-containing heterocyclic compounds for use as inhibitors of stearoyl-CoA desaturase. 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, oily skin conditions, metabolic syndrome, and the like.

  本发明揭示了用作硬脂酰辅酶A去饱和酶抑制剂的双环氮杂环化合物。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非常有用，特别是与异常脂质水平、心血管疾病、糖尿病、肥胖、油性皮肤状况、代谢综合征等相关的疾病。
• BICYCLIC NITROGEN-CONTAINING HETEROCYCLIC COMPOUNDS FOR USE AS STEAROYL CoA DESATURASE INHIBITORS
  申请人：Chisholm Jeffrey

  公开号：US20080139570A1

  公开（公告）日：2008-06-12

  The present invention discloses bicyclic nitrogen-containing heterocyclic compounds for use as inhibitors of stearoyl-CoA desaturase. 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, oily skin conditions, metabolic syndrome, and the like.

  本发明揭示了双环氮杂环化合物，用作硬脂酰辅酶A去饱和酶的抑制剂。这些化合物在治疗和/或预防各种由硬脂酰辅酶A去饱和酶（SCD）酶介导的人类疾病中很有用，尤其是与异常脂质水平、心血管疾病、糖尿病、肥胖、油性皮肤状况、代谢综合征等相关的疾病。
• BICYCLIC NITROGEN-CONTAINING HETEROCYCLIC COMPOUNDS FOR USE AS STEAROYL COA DESATURASE INHIBITORS
  申请人：CV THERAPEUTICS, INC.

  公开号：EP2066665A2

  公开（公告）日：2009-06-10
• US7893066B2
  申请人：——

  公开号：US7893066B2

  公开（公告）日：2011-02-22
• US8148376B2
  申请人：——

  公开号：US8148376B2

  公开（公告）日：2012-04-03