ethyl 5-methoxy-2,3-dihydro-1H-indene-2-carboxylate | 136191-07-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: ethyl 5-methoxy-2,3-dihydro-1H-indene-2-carboxylate
• 英文别名: Ethyl 5-methoxy-indan-2-carboxylate
• CAS: 136191-07-6
• 化学式: C₁₃H₁₆O₃
• 分子量: 220.268
• InChiKey: ROVQFWZCBZQIJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 5-methoxy-2,3-dihydro-1H-indene-2-carboxylate 在 盐酸 、 sodium hydroxide 、 三溴化硼 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 5-hydroxyindane-2-carboxylic acid
  参考文献：
  名称：

  Antithrombotic iso- and heterocyclic phenylsulphonamides

  摘要：

  可以通过将相应的异构和杂环胺与苯磺酸衍生物反应来制备异构和杂环苯磺酰胺。这些异构和杂环苯磺酰胺具有抑制血小板聚集和血栓素A.sub.2拮抗作用，可用于药物。

  公开号：

  US05191092A1
• 作为产物：
  描述：

  6-甲氧基-1-茚酮 在 三乙基硅烷 、 sodium hydride 、 三氟乙酸 作用下， 以 甲苯 、 mineral oil 为溶剂， 反应 7.5h， 生成 ethyl 5-methoxy-2,3-dihydro-1H-indene-2-carboxylate
  参考文献：
  名称：

  Identification of Fused-Ring Alkanoic Acids with Improved Pharmacokinetic Profiles that Act as G Protein-Coupled Receptor 40/Free Fatty Acid Receptor 1 Agonists

  摘要：

  The G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1) has emerged as an attractive target for a novel insulin secretagogue with glucose dependency. We previously identified phenylpropanoic acid derivative 1 (3-{4-[(2',6'-dimethylbiphenyl-3-yl)methoxy]-2-fluorophenyl}propanoic acid) as a potent and orally available GPR40/FFA1 agonist; however, 1 exhibited high clearance and low oral bioavailability, which was likely due to its susceptibility to beta-oxidation at the phenylpropanoic acid moiety. To identify long-acting compounds, we attempted to block the metabolically labile sites at the phenylpropanoic acid moiety by introducing a fused-ring structure. Various fused-ring alkanoic acids with potent GPR40/FFA1 activities and good PK profiles were produced. Further optimizations of the lipophilic portion and the acidic moiety led to the discovery of dihydrobenzofuran derivative 53 ((6-{[4'-(2-ethoxyethoxy)-2',6'-dimethylbiphenyl-3-yl]methoxy}-2,3-dihydro-1-benzofuran-3-yl)acetic acid), which acted as a GPR40/FFA1 agonist with in vivo efficacy during an oral glucose tolerance test (OGTT) in rats with impaired glucose tolerance.

  DOI：

  10.1021/jm2012968

文献信息

• Iso- and heterocyclic phenylsulphonamides
  申请人：BAYER AG

  公开号：EP0425946A2

  公开（公告）日：1991-05-08

  Iso- and heterocyclic phenylsulphonamides can be prepared by reaction of corresponding iso- and hetero­cyclic amines with phenylsulphonic acid derivatives. The iso- and heterocyclic phenylsulphonamides have thrombo­cyte aggregation-inhibiting and thromboxane A₂ antagonist action and can be used in medicaments.

  异环和杂环苯磺酰胺可通过相应的异环和杂环胺与苯磺酸衍生物反应制备。异环和杂环苯基磺酰胺具有抑制血小板聚集和血栓素 A₂拮抗剂的作用，可用于药物。
• US5191092A
  申请人：——

  公开号：US5191092A

  公开（公告）日：1993-03-02
• US5264458A
  申请人：——

  公开号：US5264458A

  公开（公告）日：1993-11-23
• Identification of Fused-Ring Alkanoic Acids with Improved Pharmacokinetic Profiles that Act as G Protein-Coupled Receptor 40/Free Fatty Acid Receptor 1 Agonists
  作者：Nobuyuki Negoro、Shinobu Sasaki、Masahiro Ito、Shuji Kitamura、Yoshiyuki Tsujihata、Ryo Ito、Masami Suzuki、Koji Takeuchi、Nobuhiro Suzuki、Junichi Miyazaki、Takashi Santou、Tomoyuki Odani、Naoyuki Kanzaki、Miyuki Funami、Toshimasa Tanaka、Tsuneo Yasuma、Yu Momose

  DOI：10.1021/jm2012968

  日期：2012.2.23

  The G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1) has emerged as an attractive target for a novel insulin secretagogue with glucose dependency. We previously identified phenylpropanoic acid derivative 1 (3-4-[(2',6'-dimethylbiphenyl-3-yl)methoxy]-2-fluorophenyl}propanoic acid) as a potent and orally available GPR40/FFA1 agonist; however, 1 exhibited high clearance and low oral bioavailability, which was likely due to its susceptibility to beta-oxidation at the phenylpropanoic acid moiety. To identify long-acting compounds, we attempted to block the metabolically labile sites at the phenylpropanoic acid moiety by introducing a fused-ring structure. Various fused-ring alkanoic acids with potent GPR40/FFA1 activities and good PK profiles were produced. Further optimizations of the lipophilic portion and the acidic moiety led to the discovery of dihydrobenzofuran derivative 53 ((6-[4'-(2-ethoxyethoxy)-2',6'-dimethylbiphenyl-3-yl]methoxy}-2,3-dihydro-1-benzofuran-3-yl)acetic acid), which acted as a GPR40/FFA1 agonist with in vivo efficacy during an oral glucose tolerance test (OGTT) in rats with impaired glucose tolerance.
• Antithrombotic iso- and heterocyclic phenylsulphonamides
  申请人：Bayer Aktiengesellschaft

  公开号：US05191092A1

  公开（公告）日：1993-03-02

  Iso- and heterocyclic phenylsulphonamides can be prepared by reaction of corresponding iso- and heterocyclic amines with phenylsulphonic acid derivatives. The iso- and heterocyclic phenylsulphonamides have thrombocyte aggregation-inhibiting and thromboxane A.sub.2 antagonist action and can be used in medicaments.

  可以通过将相应的异构和杂环胺与苯磺酸衍生物反应来制备异构和杂环苯磺酰胺。这些异构和杂环苯磺酰胺具有抑制血小板聚集和血栓素A.sub.2拮抗作用，可用于药物。