(3-(2,6-dimethyl-4-(2-ethoxyethoxy)phenyl)phenyl)methanol | 805250-51-5

• 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: (3-(2,6-dimethyl-4-(2-ethoxyethoxy)phenyl)phenyl)methanol
• 英文别名: [4'-(2-ethoxyethoxy)-2',6'-dimethylbiphenyl-3-yl]methanol；[3-[4-(2-ethoxyethoxy)-2,6-dimethylphenyl]phenyl]methanol
• CAS: 805250-51-5
• 化学式: C₁₉H₂₄O₃
• 分子量: 300.398
• InChiKey: ONACCTXHDICLCZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3-(2,6-dimethyl-4-(2-ethoxyethoxy)phenyl)phenyl)methanol 在 lithium hydroxide monohydrate 、 palladium 10% on activated carbon 、 氢气 、 巯基乙酸 、 三苯基膦 、 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 58.0h， 生成 methyl [6-({[4'-(2-ethoxyethoxy)-2',6'-dimethylbiphenyl-3-yl]methyl}amino)-2,3-dihydro-1-benzofuran-3-yl]acetate
  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：

  4'-羟基-2',6'-二甲基联苯-3-甲醛 在 sodium tetrahydroborate 、 potassium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 (3-(2,6-dimethyl-4-(2-ethoxyethoxy)phenyl)phenyl)methanol
  参考文献：
  名称：

  Discovery of Phenylpropanoic Acid Derivatives Containing Polar Functionalities as Potent and Orally Bioavailable G Protein-Coupled Receptor 40 Agonists for the Treatment of Type 2 Diabetes

  摘要：

  As part of a program to identify potent GPR40 agonists with drug-like properties suitable for clinical development, the incorporation of polar substituents was explored with the intention of decreasing the lipophilicity of our recently disclosed phenylpropanoic acid derivative 1. This incorporation would allow us to mitigate the cytotoxicity issues observed with compound 1 and enable us to move away from the multifunctional free fatty acid-like structure. Substitutions on the 2',6'-dimethylbiphenyl ring were initially undertaken, which revealed the feasibility of introducing polar functionalities at the biphenyl 4'-position. Further optimization of this position and the linker led to the discovery of several 4'-alkoxybiphenyl derivatives, which showed potent GPR40 agonist activities with the best balance in terms of improved cytotoxicity profiles and favorable pharmacokinetic properties. Among them, 3-{2-fluoro-4[({4'-[(4-hydroxy-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)methoxy]-2',6'-dimethylbiphenyl-3-yl}methyl)amino]phenyl}propanoic acid (35) exhibited a robust plasma glucose-lowering effect and insulinotropic action during an oral glucose tolerance test in rats with impaired glucose tolerance.

  DOI：

  10.1021/jm2016123

文献信息

• NOVEL 3-HYDROXY-5-ARYLISOTHIAZOLE DERIVATIVE
  申请人：Okano Akihiro

  公开号：US20120157459A1

  公开（公告）日：2012-06-21

  [Problem] To provide a GPR40 activating agent having, as an active ingredient, a novel compound having a GPR40 agonist action, a salt of the compound, a solvate of the salt or the compound, or the like, particularly, an insulin secretagogue and a prophylactic and/or therapeutic agent against diabetes, obesity, or other diseases. [Means of solving the problem] A compound of Formula (I): (where n is 0 to 2; p is 0 to 4; j is 0 to 3; k is 0 to 2; a ring A is an aryl group which is optionally substituted with L or a heterocyclic group which is optionally substituted with L; a ring B is a benzene ring, a pyridine ring, or a pyrimidine ring; X is O, S, —NR 7 —; and R 1 to R 7 are specific groups), a salt of the compound, or a solvate of the salt or the compound.

  提供一个以新型化合物作为活性成分的GPR40激活剂，该化合物具有GPR40激动剂作用，该化合物的盐，该盐或化合物的溶剂合物，或者类似物，尤其是胰岛素分泌促进剂以及对糖尿病、肥胖症或其他疾病的预防及/或治疗剂。[解决该问题的方法] 公式(I)的化合物：（其中n为0至2；p为0至4；j为0至3；k为0至2；环A是一个芳基团，可选择性被L取代或是一个杂环团，可选择性被L取代；环B是一个苯环、一个吡啶环或一个嘧啶环；X是O，S，—NR7—；R1至R7是特定基团），该化合物的盐，或该盐或化合物的溶剂合物。
• CYCLIC AMIDE DERIVATIVE
  申请人：Okano Akihiro

  公开号：US20130203739A1

  公开（公告）日：2013-08-08

  [Problem] To provide a GPR40 activating agent having, as an active ingredient, a novel compound having a GPR40 agonist action, a salt of the compound, a solvate of the salt or the compound, or the like, particularly, an insulin secretagogues and a prophylactic and/or therapeutic agent against diabetes, obesity, or other diseases. [Means of solving the problem] A compound of Formula (1): (where n is 0 to 2; p is 0 to 4; h is 0 to 3; j is 0 to 3; k is 0 to 2; a ring B is an aryl group or a heteroaryl group; X is O, S, or —NR 7 —; J 1 is —CR 11a R 11b — or —NR 11c —; J 2 is —CR 12a R 12b — or —NR 12c —; and R 1 to R 12c are specific groups), a salt of the compound, or a solvate of the salt or the compound.

  为提供一种具有GPR40激活剂作用的新化合物、该化合物的盐、盐或化合物的溶剂合物，尤其是胰岛素分泌剂和预防和/或治疗糖尿病、肥胖或其他疾病的药剂，解决问题的方法是使用Formula (1)的化合物：(其中n为0至2；p为0至4；h为0至3；j为0至3；k为0至2；环B为芳香族或杂环芳基；X为O、S或-NR7-；J1为-CR11aR11b-或-NR11c-；J2为-CR12aR12b-或-NR12c-；R1到R12为特定基团)，该化合物的盐，或盐或化合物的溶剂合物。
• 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。
• 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。