3-(2,4-二甲基苯基)苯甲酸乙酯 | 805250-18-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-(2,4-二甲基苯基)苯甲酸乙酯
• 英文名称: ethyl 2',4'-dimethylbiphenyl-3-carboxylate
• 英文别名: Ethyl 2',4'-dimethyl[1,1'-biphenyl]-3-carboxylate；ethyl 3-(2,4-dimethylphenyl)benzoate
• CAS: 805250-18-4
• 化学式: C₁₇H₁₈O₂
• 分子量: 254.329
• InChiKey: FBHSQYNWRRJGDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(2,4-二甲基苯基)苯甲酸乙酯 在 lithium aluminium tetrahydride 、 三丁基膦 、 sodium hydroxide 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 甲醇 、 水 、 甲苯 为溶剂， 生成 2-[6-[(2',4'-dimethylbiphenyl-3-yl)methoxy]-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：

  3-溴苯甲酸乙酯 、 2,4-二甲基苯硼酸 在 四(三苯基膦)钯 caesium carbonate 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 18.0h， 以100%的产率得到3-(2,4-二甲基苯基)苯甲酸乙酯
  参考文献：
  名称：

  [EN] 3-(4-BENZYLOXYPHENYL)PROPANOIC ACID DERIVATIVES
  [FR] DERIVES D'ACIDE 3-(4-BENZYLOXYPHENYL) PROPANOIQUE

  摘要：

  本发明提供了一种由公式(I)表示的新的化合物，其中每个符号如说明书中所定义，以及其盐和前药，具有优越的GPR40受体功能调节作用，可用作胰岛素分泌剂，用于预防或治疗糖尿病等的药剂。它们出人意料地显示出优越的GPR40受体激动剂活性，并且还显示出作为药物产品的优越性质，如稳定性等。因此，它们可以成为预防或治疗哺乳动物中与GPR40受体相关疾病的既安全又有用的药物。

  公开号：

  WO2005063729A1

文献信息

• [EN] 3-(4-BENZYLOXYPHENYL)PROPANOIC ACID DERIVATIVES<br/>[FR] DERIVES D'ACIDE 3-(4-BENZYLOXYPHENYL) PROPANOIQUE
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2005063729A1

  公开（公告）日：2005-07-14

  The present invention provides a novel compound represented by the formula (I) wherein each symbol is as defined in the specification, a salt thereof and a prodrug thereof having a superior GPR40 receptor function modulating action, which can be used as an insulin secretagogue, an agent for the prophylaxis or treatment of diabetes and the like. They unexpectedly show superior GPR40 receptor agonist activity, and also show superior properties as a pharmaceutical product, such as stability and the like. Thus, they can be safe and useful pharmaceutical agents for the prophylaxis or treatment of GPR40 receptor related diseases in mammals.

  本发明提供了一种由公式(I)表示的新的化合物，其中每个符号如说明书中所定义，以及其盐和前药，具有优越的GPR40受体功能调节作用，可用作胰岛素分泌剂，用于预防或治疗糖尿病等的药剂。它们出人意料地显示出优越的GPR40受体激动剂活性，并且还显示出作为药物产品的优越性质，如稳定性等。因此，它们可以成为预防或治疗哺乳动物中与GPR40受体相关疾病的既安全又有用的药物。
• Condensed ring compound
  申请人：Yasuma Tsuneo

  公开号：US20060258722A1

  公开（公告）日：2006-11-16

  The present invention aims at providing a novel fused ring compound having a GPR40 receptor function modulating action and being useful as an insulin secretagogue or a pharmaceutical agent for the prophylaxis or treatment of diabetes, more particularly, a compound represented by the formula: wherein Ar is an optionally substituted cyclic group, ring A is a ring optionally further substituted (provided that the ring is not thiazole, oxazole, imidazole and pyrazole), Xa and Xb are each independently a bond or a spacer having a main chain of 1 to 5 atom(s), Xc is O, S, SO or SO 2 , ring B is a 5- to 7-membered ring, Xd is a bond, CH or CH 2 , is a single bond when Xd is a bond or CH 2 , or a double bond when Xd is CH, and R 1 is an optionally substituted hydroxy group, and a salt thereof.

  本发明旨在提供一种新的融合环化合物，具有GPR40受体功能调节作用，并可用作胰岛素分泌剂或用于预防或治疗糖尿病的药物，更具体地说，是一种由以下公式表示的化合物：其中Ar是一个可选取代的环状基团，环A是一个环状基团，可选地进一步取代（前提是该环不是噻唑、噁唑、咪唑和吡唑），Xa和Xb分别是1到5个原子的主链具有键或间隔物，Xc是O、S、SO或SO2，环B是一个5-至7-成员环，Xd是键、CH或CH2，当Xd是键或CH2时为单键，当Xd为CH时为双键，R1为可选取代的羟基，以及其盐。
• 3-(4-Benzyloxyphenyl) propanoic acid derivatives
  申请人：Yasuma Tsuneo

  公开号：US20070149608A1

  公开（公告）日：2007-06-28

  The present invention provides a novel compound represented by the formula (I) wherein each symbol is as defined in the specification, a salt thereof and a prodrug thereof having a superior GPR40 receptor function modulating action, which can be used as an insulin secretagogue, an agent for the prophylaxis or treatment of diabetes and the like. They unexpectedly show superior GPR40 receptor agonist activity, and also show superior properties as a pharmaceutical product, such as stability and the like. Thus, they can be safe and useful pharmaceutical agents for the prophylaxis or treatment of GPR40 receptor related diseases in mammals.

  本发明提供一种新型化合物，其表示为式（I），其中每个符号如规范中所定义，其盐和前药具有优越的GPR40受体功能调节作用，可用作胰岛素分泌促进剂、糖尿病预防或治疗剂等。它们意外地表现出优越的GPR40受体激动剂活性，并且还表现出优越的药物产品特性，如稳定性等。因此，它们可以作为安全和有用的药物剂量，用于哺乳动物的GPR40受体相关疾病的预防或治疗。
• 3-(4-benzyloxyphenyl) propanoic acid derivatives
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US07456218B2

  公开（公告）日：2008-11-25

  The present invention provides a novel compound represented by the formula (I) wherein each symbol is as defined in the specification, a salt thereof and a prodrug thereof having a superior GPR40 receptor function modulating action, which can be used as an insulin secretagogue, an agent for the prophylaxis or treatment of diabetes and the like. They unexpectedly show superior GPR40 receptor agonist activity, and also show superior properties as a pharmaceutical product, such as stability and the like. Thus, they can be safe and useful pharmaceutical agents for the prophylaxis or treatment of GPR40 receptor related diseases in mammals.

  本发明提供了一种新型化合物，其由公式（I）所表示，其中每个符号如规范中所定义，其盐和前药具有优越的GPR40受体功能调节作用，可用作胰岛素分泌剂、糖尿病预防或治疗剂等。它们意外地表现出优越的GPR40受体激动剂活性，并且还表现出优越的药物产品性质，如稳定性等。因此，它们可以是哺乳动物GPR40受体相关疾病预防或治疗的安全和有用的药物剂。
• CONDENSED RING COMPOUND
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1630152A1

  公开（公告）日：2006-03-01

  The present invention aims at providing a novel fused ring compound having a GPR40 receptor function modulating action and being useful as an insulin secretagogue or a pharmaceutical agent for the prophylaxis or treatment of diabetes, more particularly, a compound represented by the formula: wherein Ar is an optionally substituted cyclic group, ring A is a ring optionally further substituted (provided that the ring is not thiazole, oxazole, imidazole and pyrazole), Xa and Xb are each independently a bond or a spacer having a main chain of 1 to 5 atom(s), Xc is O, S, SO or SO2, is ring B is a 5- to 7-membered ring, Xd is a bond, CH or CH2, •••••• is a single bond when Xd is a bond or CH2, or a double bond when Xd is CH, and R1 is an optionally substituted hydroxy group, and a salt thereof.

  本发明旨在提供一种新型融合环化合物，该化合物具有调节 GPR40 受体功能的作用，可用作预防或治疗糖尿病的胰岛素分泌剂或药物制剂，特别是由式表示的化合物： 其中 Ar 是任选取代的环状基团，环 A 是任选进一步取代的环（条件是该环不是噻唑、噁唑、咪唑和吡唑），Xa 和 Xb 各自独立地是键或主链为 1 至 5 个原子的间隔物，Xc 是 O、S、SO 或 SO2、 是 环 B 是 5 至 7 元环、 Xd 是键、CH 或 CH2、 ------ 是单键（当 Xd 是键或 CH2 时）或双键（当 Xd 是 CH 时），以及 R1 是任选取代的羟基及其盐。