(2R)-methyl 2-ethyl-7-hydroxychromane-2-carboxylate | 406488-89-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (2R)-methyl 2-ethyl-7-hydroxychromane-2-carboxylate
• 英文别名: methyl (2R)-2-ethyl-7-hydroxy-3,4-dihydrochromene-2-carboxylate
• CAS: 406488-89-9
• 化学式: C₁₃H₁₆O₄
• 分子量: 236.268
• InChiKey: SISYISHTVGLUDM-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R)-methyl 2-ethyl-7-hydroxychromane-2-carboxylate 在 sodium hydroxide 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 5.0h， 生成 (2R)-7-(3-(2-Chloro-4-phenoxyphenoxy)propoxy)-2-ethylchromane-2-carboxylic acid
  参考文献：
  名称：

  (2R)-2-Ethylchromane-2-carboxylic Acids:  Discovery of Novel PPARα/γ Dual Agonists as Antihyperglycemic and Hypolipidemic Agents

  摘要：

  A series of chromane-2-carboxylic acid derivatives was synthesized and evaluated for PPAR agonist activities. A structure-activity relationship was developed toward PPARalpha/gamma dual agonism. As a result, (2R)-7-{3-[2-chloro-4-(4-fluorophenoxy)phenoxy]propoxy}-2-ethylchromane-2-carboxylic acid (48) was identified as a potent, structurally novel, selective PPARalpha/gamma dual agonist. Compound 48 exhibited substantial antihyperglycemic and hypolipidemic activities when orally administered in three different animal models: the db/db mouse type 2 diabetes model, a Syrian hamster lipid model, and a dog lipid model.

  DOI：

  10.1021/jm030621d
• 作为产物：
  描述：

  ethyl 7-hydroxychromane-2-carboxylate 在 六甲基磷酰三胺 、 4-二甲氨基吡啶 、 sodium hydroxide 、 氢气 、 sodium hexamethyldisilazane 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 二氯甲烷 、 水 、 异丙醇 、 丙酮 为溶剂， -78.0~70.0 ℃ 、344.74 kPa 条件下， 反应 61.0h， 生成 (2R)-methyl 2-ethyl-7-hydroxychromane-2-carboxylate
  参考文献：
  名称：

  (2R)-2-Ethylchromane-2-carboxylic Acids:  Discovery of Novel PPARα/γ Dual Agonists as Antihyperglycemic and Hypolipidemic Agents

  摘要：

  A series of chromane-2-carboxylic acid derivatives was synthesized and evaluated for PPAR agonist activities. A structure-activity relationship was developed toward PPARalpha/gamma dual agonism. As a result, (2R)-7-{3-[2-chloro-4-(4-fluorophenoxy)phenoxy]propoxy}-2-ethylchromane-2-carboxylic acid (48) was identified as a potent, structurally novel, selective PPARalpha/gamma dual agonist. Compound 48 exhibited substantial antihyperglycemic and hypolipidemic activities when orally administered in three different animal models: the db/db mouse type 2 diabetes model, a Syrian hamster lipid model, and a dog lipid model.

  DOI：

  10.1021/jm030621d

文献信息

• Benzopyrancarboxylic acid derivatives for the treatment of diabetes and lipid disorders
  申请人：——

  公开号：US20020082292A1

  公开（公告）日：2002-06-27

  A class of benzopyrancarboxylic acid derivatives comprises compounds that are potent agonists of PPAR alpha and/or gamma, and are therefore useful in the treatment, control or prevention of non-insulin dependent diabetes mellitus (NIDDM), hyperglycemia, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, obesity, vascular restenosis, inflammation, and other PPAR alpha and/or gamma mediated diseases, disorders and conditions.

  苯并吡喃羧酸衍生物类别包括强效PPARα和/或γ激动剂化合物，因此在治疗、控制或预防非胰岛素依赖型糖尿病（NIDDM）、高血糖、血脂异常、高血脂症、高胆固醇血症、高甘油三酯血症、动脉粥样硬化、肥胖、血管再狭窄、炎症和其他PPARα和/或γ介导的疾病、紊乱和状况中具有用处。
• (2R)-2-Methylchromane-2-carboxylic acids: Discovery of selective PPARα agonists as hypolipidemic agents
  作者：Hiroo Koyama、Julia K. Boueres、Daniel J. Miller、Joel P. Berger、Karen L. MacNaul、Pei-ran Wang、Marc C. Ippolito、Samuel D. Wright、Arun K. Agrawal、David E. Moller、Soumya P. Sahoo

  DOI：10.1016/j.bmcl.2005.05.028

  日期：2005.7

  A SAR study was conducted on chromane-2-carboxylic acid toward selective PPAR alpha agonisim. As a result, highly potent, and selective PPAR alpha agonists were discovered. The optimized compound 43 exhibited robust lowering of total cholesterol levels in hamster and dog animal models. (c) 2005 Elsevier Ltd. All rights reserved.
• BENZOPYRANCARBOXYLIC ACID DERIVATIVES FOR THE TREATMENT OF DIABETES AND LIPID DISORDERS
  申请人：Merck & Co., Inc.

  公开号：EP1324995A2

  公开（公告）日：2003-07-09
• US6645997B2
  申请人：——

  公开号：US6645997B2

  公开（公告）日：2003-11-11
• US6713508B2
  申请人：——

  公开号：US6713508B2

  公开（公告）日：2004-03-30