(6-{[(2-nitrophenyl)sulfonyl]amino}-1-benzofuran-3-yl)acetic acid | 865138-03-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (6-{[(2-nitrophenyl)sulfonyl]amino}-1-benzofuran-3-yl)acetic acid
• 英文别名: 2-[6-[(2-nitrophenyl)sulfonylamino]-1-benzofuran-3-yl]acetic acid
• CAS: 865138-03-0
• 化学式: C₁₆H₁₂N₂O₇S
• 分子量: 376.346
• InChiKey: WRFGOTCIINOQNK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  151
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (6-{[(2-nitrophenyl)sulfonyl]amino}-1-benzofuran-3-yl)acetic acid 在 氯化亚砜 、 lithium hydroxide monohydrate 、 palladium 10% on activated carbon 、 氢气 、 巯基乙酸 、 三苯基膦 、 sodium hydroxide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 130.5h， 生成 2-[6-[[3-[4-(2-Ethoxyethoxy)-2,6-dimethylphenyl]phenyl]methylamino]-2,3-dihydro-1-benzofuran-3-yl]acetic acid
  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
• 作为产物：
  描述：

  N-(3-hydroxyphenyl)-2-nitrobenzenesulfonamide 在 硫酸 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 24.0h， 生成 (6-{[(2-nitrophenyl)sulfonyl]amino}-1-benzofuran-3-yl)acetic acid
  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

• Aminophenylpropanoic Acid Derivative
  申请人：Yasuma Tsuneo

  公开号：US20080269220A1

  公开（公告）日：2008-10-30

  A compound represented by the formula (1): wherein each symbol is as defined in the specification, and a salt thereof and a prodrug thereof unexpectedly have superior GPR40 receptor agonist activity, superior in the properties as a pharmaceutical product such as stability and the like, and can be a safe and useful pharmaceutical agent as a drug for the prophylaxis or treatment of GPR40 receptor related pathology or diseases such as diabetes and the like.

  化合物的化学式为（1）：其中每个符号如规范所定义，其盐和前药意外地具有更优越的GPR40受体激动剂活性，在药品产品的稳定性等方面具有优越性，并且可以作为安全有效的药物用于预防或治疗GPR40受体相关的病理或疾病，例如糖尿病等。
• Aminophenylpropanoic acid derivative
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US07786165B2

  公开（公告）日：2010-08-31

  A compound represented by the formula (1): wherein each symbol is as defined in the specification, and a salt thereof and a prodrug thereof unexpectedly have superior GPR40 receptor agonist activity, superior in the properties as a pharmaceutical product such as stability and the like, and can be a safe and useful pharmaceutical agent as a drug for the prophylaxis or treatment of GPR40 receptor related pathology or diseases such as diabetes and the like.

  化合物的化学式为(1)：其中每个符号如规范中所定义，其盐和前药意外地具有优越的GPR40受体激动剂活性，具有制药产品的优越性能，例如稳定性等，并且可以作为治疗或预防GPR40受体相关病理或疾病，如糖尿病等的药物而成为安全有效的药物。
• AMINOPHENYLPROPANOIC ACID DERIVATIVE
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1726580A1

  公开（公告）日：2006-11-29

  A compound represented by the formula (1): wherein each symbol is as defined in the specification, and a salt thereof and a prodrug thereof unexpectedly have superior GPR40 receptor agonist activity, superior in the properties as a pharmaceutical product such as stability and the like, and can be a safe and useful pharmaceutical agent as a drug for the prophylaxis or treatment of GPR40 receptor related pathology or diseases such as diabetes and the like.

  式 (1) 所代表的化合物： 其中各符号如说明书中所定义，其盐及其原药意外地具有优异的 GPR40 受体激动剂活性、优异的稳定性等药剂特性，可作为预防或治疗 GPR40 受体相关病理或疾病（如糖尿病等）的安全有用的药剂。
• EP1726580
  申请人：——

  公开号：——

  公开（公告）日：——
• US7786165B2
  申请人：——

  公开号：US7786165B2

  公开（公告）日：2010-08-31