3’-(hydroxymethyl)-2,6-dimethyl-[1,1‘-biphenyl]-4-ol

• 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’-(hydroxymethyl)-2,6-dimethyl-[1,1‘-biphenyl]-4-ol
• 英文别名: 3'-(hydroxymethyl)-2,6-dimethyl-[1,1'-biphenyl]-4-ol；3'-(hydroxymethyl)-2,6-dimethylbiphenyl-4-ol；4-[3-(hydroxymethyl)phenyl]-3,5-dimethylphenol
• 化学式: C₁₅H₁₆O₂
• 分子量: 228.291
• InChiKey: NJJRYJPBXXEAFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3’-(hydroxymethyl)-2,6-dimethyl-[1,1‘-biphenyl]-4-ol 在 三丁基膦 、 potassium carbonate 、 potassium iodide 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 90.0h， 生成 methyl [(3S)-6-({4'-[2-(ethylsulfanyl)ethoxy]-2',6'-dimethylbiphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetate
  参考文献：
  名称：

  Optimization of (2,3-Dihydro-1-benzofuran-3-yl)acetic Acids: Discovery of a Non-Free Fatty Acid-Like, Highly Bioavailable G Protein-Coupled Receptor 40/Free Fatty Acid Receptor 1 Agonist as a Glucose-Dependent Insulinotropic Agent

  摘要：

  G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1) is a free fatty acid (FFA) receptor that mediates FFA-amplified glucose-stimulated insulin secretion in pancreatic beta-cells. We previously identified (2,3-dihydro-1-benzofuran-3-yl)acetic acid derivative 2 as a candidate, but it had relatively high lipophilicity. Adding a polar functional group on 2 yielded several compounds with lower lipophilicity and little effect on caspase-3/7 activity at 30 mu M (a marker of toxicity in human HepG2 hepatocytes). Three optimized compounds showed promising pharmacokinetic profiles with good in vivo effects. Of these, compound 16 had the lowest lipophilicity. Metabolic analysis of 16 showed a long-acting PK profile due to high resistance to beta-oxidation. Oral administration of 16 significantly reduced plasma glucose excursion and increased insulin secretion during an OGTT in type 2 diabetic rats. Compound 16 (TAK-875) is being evaluated in human clinical trials for the treatment of type 2 diabetes.

  DOI：

  10.1021/jm300170m
• 作为产物：
  描述：

  4'-羟基-2',6'-二甲基联苯-3-甲醛 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以69%的产率得到3’-(hydroxymethyl)-2,6-dimethyl-[1,1‘-biphenyl]-4-ol
  参考文献：
  名称：

  [EN] BIPHENYL COMPOUNDS AND USES THEREOF
  [FR] COMPOSÉS BIPHÉNYLIQUES ET LEURS UTILISATIONS

  摘要：

  本发明涉及联苯化合物及其在医药中的用途。具体地，本发明涉及一种具有化学式（I）的化合物，或其立体异构体、几何异构体、互变异构体、共振异构体、消旋体、对映体、非对映异构体、N-氧化物、水合物、溶剂合物、代谢物、水解物、药学上可接受的盐或其前药。本文披露的化合物被用作治疗剂，特别是GPR40激动剂，用于治疗糖尿病和代谢性疾病的患者。

  公开号：

  WO2015062486A1

文献信息

• POLYCYCLIC DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF
  申请人：Jiangsu Hengrui Medicine Co., Ltd.

  公开号：US20150005282A1

  公开（公告）日：2015-01-01

  Disclosed in the present invention are polycyclic derivatives as represented by general formula (I), the preparation method thereof, pharmaceutical compositions containing the derivatives and uses thereof as therapeutic agents, especially the GPR40 agonist and in preparation of drugs for treating diseases such as diabetes and metabolic disorders, etc., wherein each substituent in the general formula (I) has the same definition as in the description.

  本发明揭示了由一般式（I）表示的多环衍生物，其制备方法，含有这些衍生物的药物组合物以及其作为治疗剂的用途，特别是GPR40激动剂，以及用于治疗糖尿病和代谢性疾病等疾病的药物的制备，其中一般式（I）中的每个取代基具有与描述中相同的定义。
• [EN] SUBSTITUTED HETEROCYCLIC DERIVATIVES AS GPR AGONISTS AND USES THEREOF<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES SUBSTITUÉS EN TANT QU'AGONISTES DE GPR ET LEURS UTILISATIONS
  申请人：PIRAMAL ENTPR LTD

  公开号：WO2015028960A1

  公开（公告）日：2015-03-05

  The present invention generally relates to substituted heterocyclic derivatives (the compounds of Formula (I)), processes for their preparation, pharmaceutical compositions containing said compounds, their use as G-protein coupled receptor (GPR) agonists, particularly as GPR40 agonists and methods of using these compounds in the treatment of GPR40 mediated diseases or conditions such as Type 2 diabetes, obesity, dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.

  本发明通常涉及取代杂环衍生物（式（I）化合物），其制备方法，含有所述化合物的药物组合物，它们作为G-蛋白偶联受体（GPR）激动剂的用途，特别是作为GPR40激动剂，并且使用这些化合物治疗GPR40介导的疾病或症状，如2型糖尿病、肥胖症、血脂异常、高脂血症、高胆固醇血症和高甘油三酯血症的方法。
• [EN] BIPHENYL COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS BIPHÉNYLIQUES ET LEURS UTILISATIONS
  申请人：SUNSHINE LAKE PHARMA CO LTD

  公开号：WO2015062486A1

  公开（公告）日：2015-05-07

  The present invention relates to biphenyl compounds and uses thereof in medicine. Specifically, the present invention relates to a compound of Formula (I), or a stereoisomer, a geometric isomer, a tautomer, a mesomer, a racemate, an enantiomer, a diastereoisomer, an N-oxide, a hydrate, a solvate, a metabolite, a hydrolysate, a pharmaceutically acceptable salt or a prodrug thereof. The compound disclosed herein is used as a therapeutic agent particularly a GPR40 agonist for treating diabetes and metabolic disease in a patient.

  本发明涉及联苯化合物及其在医药中的用途。具体地，本发明涉及一种具有化学式（I）的化合物，或其立体异构体、几何异构体、互变异构体、共振异构体、消旋体、对映体、非对映异构体、N-氧化物、水合物、溶剂合物、代谢物、水解物、药学上可接受的盐或其前药。本文披露的化合物被用作治疗剂，特别是GPR40激动剂，用于治疗糖尿病和代谢性疾病的患者。
• [EN] CARBOXYLIC ACID COMPOUNDS IN TREATMENT OF DIABETES MELLITUS<br/>[FR] COMPOSÉS D'ACIDE CARBOXYLIQUE DANS LE TRAITEMENT DU DIABÈTE SUCRÉ
  申请人：FUJIAN HAIXI PHARMACEUTICALS CO LTD

  公开号：WO2015024526A1

  公开（公告）日：2015-02-26

  The invention relates to compounds for increasing GPR40 recetpor activity and application thereof. These compounds include of a compound of Formula (I), pharmaceutically acceptable salts thereof, solvates thereof, isomers thereof, or produgs of the compounds mentioned above, or the mixture of any form above mentioned. The invention also relates to the use of the compounds in manufacturing a medicament for the treatment and/or prevention of diabetes, obesity or for Insulin secretagogue.

  该发明涉及增加GPR40受体活性的化合物及其应用。这些化合物包括公式（I）的化合物，其药学上可接受的盐、溶剂化合物、异构体、上述化合物的前药，或上述任何形式的混合物。该发明还涉及将这些化合物用于制造用于治疗和/或预防糖尿病、肥胖或胰岛素分泌素的药物。
• FUSED CYCLIC COMPOUNDS
  申请人：Yasuma Tsuneo

  公开号：US20100004312A1

  公开（公告）日：2010-01-07

  The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the description, or a salt thereof. The compound or a salt thereof or a prodrug thereof has a GPR40 receptor function modulating action and is useful as an insulin secretagogue or an agent for the prophylaxis or treatment of diabetes and the like.

  本发明提供一种化合物，其表示为公式（I）：其中每个符号如描述中所定义，或其盐。该化合物或其盐或其前药具有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等药物。