2-(4-bromo-3,5-dimethylphenoxy)tetrahydro-2H-pyran | 858096-41-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-(4-bromo-3,5-dimethylphenoxy)tetrahydro-2H-pyran
• 英文别名: 2-(4-bromo-3,5-dimethylphenoxy)tetrahydropyran；2-(4-bromo-3,5-dimethylphenoxy)oxane
• CAS: 858096-41-0
• 化学式: C₁₃H₁₇BrO₂
• 分子量: 285.181
• InChiKey: DEOAWQYEDJBSIU-UHFFFAOYSA-N

物化性质

• 沸点：
  369.8±42.0 °C(Predicted)
• 密度：
  1.321±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(4-bromo-3,5-dimethylphenoxy)tetrahydro-2H-pyran 在 sodium tetrahydroborate 、 四(三苯基膦)钯 、 对甲苯磺酸一水合物 、 sodium carbonate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 甲苯 为溶剂， 反应 50.0h， 生成 methyl 3-{4-[(4'-hydroxy-2',6'-dimethylbiphenyl-3-yl)methoxy]phenyl}propanoate
  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
• 作为产物：
  描述：

  3,4-二氢-2H-吡喃 、 4-溴-3,5-二甲酚 在 混旋樟脑磺酸 sodium hydroxide 、 乙酸乙酯 、 水 、 Sodium sulfate-III 、 silica gel 作用下， 以 二氯甲烷 为溶剂， 反应 21.0h， 以to give 2-(4-bromo-3,5-dimethylphenoxy)tetrahydro-2H-pyran (23.68 g, 92%)的产率得到2-(4-bromo-3,5-dimethylphenoxy)tetrahydro-2H-pyran
  参考文献：
  名称：

  BORON-CONTAINING SMALL MOLECULES

  摘要：

  本发明揭示了化合物、药物制剂以及治疗抗炎症状况和/或寄生虫相关疾病的方法。

  公开号：

  US20150376210A1

文献信息

• [EN] BORON-CONTAINING SMALL MOLECULES<br/>[FR] PETITES MOLECULES CONTENANT DU BORE
  申请人：ANACOR PHARMACEUTICALS INC

  公开号：WO2011094450A1

  公开（公告）日：2011-08-04

  Compounds, pharmaceutical formulations, and methods of treating anti-inflammatory conditions and/or helminth-associated diseases are disclosed.

  公开了化合物、药物配方以及治疗抗炎条件和/或蠕虫相关疾病的方法。
• [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。
• CARBOXYLIC ACID COMPOUND
  申请人：Negoro Kenji

  公开号：US20120035196A1

  公开（公告）日：2012-02-09

  [Problem] The present invention has an object to provide a compound having a GPR40 agonistic activity, which is useful as a pharmaceutical composition, an insulin secretion promoter, or an agent for preventing/treating diabetes. [Means for Solution] The present inventors have extensively studied a compound having a GPR40 agonistic activity, and as a result, they have found that the compound (I) of the present invention or a pharmaceutically acceptable salt thereof, in which a carboxylic acid is bonded to a bicyclic or tricyclic moiety through methylene, and further, a benzene ring substituted with a monocyclic 6-membered aromatic ring is bonded to a bicyclic or tricyclic moiety through —O-methylene or —NH-methylene, has an excellent GPR40 agonistic activity. They have also found that the compound has an excellent insulin secretion promoting action and strongly inhibits increase in the blood glucose after glucose loading, thereby completing the present invention.

  本发明的目的是提供一种具有GPR40激动活性的化合物，可用作药物组合物、胰岛素分泌促进剂或预防/治疗糖尿病的药物。本发明的发明人广泛研究了具有GPR40激动活性的化合物，结果发现，本发明的化合物(I)或其药学上可接受的盐具有卓越的GPR40激动活性，其中羧酸通过亚甲基与双环或三环部分结合，并且苯环通过—O-亚甲基或—NH-亚甲基与单环6-成员芳香环结合到双环或三环部分。他们还发现该化合物具有卓越的胰岛素分泌促进作用，并强烈抑制葡萄糖负荷后血糖的增加，从而完成了本发明。
• CONJUGATED AROMATIC COMPOUND, OPTICAL MATERIAL, AND OPTICAL ELEMENT
  申请人：Saitoh Terunobu

  公开号：US20120330052A1

  公开（公告）日：2012-12-27

  The present invention relates to a conjugated aromatic compound represented by the Formula (1) in claim 1 (in the formula, Ar 1 represents a hydrogen atom or an aryl group optionally having a substituent; Ar 2 and Ar 3 each represent a hydrogen atom or an aryl group optionally having a substituent but at least one of Ar 2 and Ar 3 represents an aryl group optionally having a substituent; and A represents an aromatic hydrocarbon group) and relates to an optical material containing the conjugated aromatic compound. The conjugated aromatic compound and the optical material have characteristics of a high chromatic aberration correction function, high refractive-index dispersion characteristics (Abbe number (vd)) and high secondary dispersion characteristics (θg,F) (anomalous dispersion characteristics).

  本发明涉及一种由权利要求书中的式（1）表示的共轭芳香化合物（在该式中，Ar1代表氢原子或可选择具有取代基的芳基；Ar2和Ar3各自代表氢原子或可选择具有取代基的芳基，但至少Ar2和Ar3中的一个代表可选择具有取代基的芳基；A代表芳香烃基），并涉及包含该共轭芳香化合物的光学材料。该共轭芳香化合物和光学材料具有高色差校正功能、高折射率色散特性（阿贝数（vd））和高二次色散特性（θg，F）（异常色散特性）的特点。
• [EN] HETEROAROMATIC-CONTAINING COMPOUND, OPTICAL MATERIAL AND OPTICAL ELEMENT<br/>[FR] COMPOSÉ CONTENANT DES DÉRIVÉS HÉTÉRO-AROMATIQUES, MATÉRIAU OPTIQUE ET ÉLÉMENT OPTIQUE
  申请人：CANON KK

  公开号：WO2011081078A1

  公开（公告）日：2011-07-07

  There are provided a heteroaromatic-containing compound represented by the following general formula (1), and an optical material including the heteroaromatic-containing compound. Formula 1 General Formula (1) wherein R1 and R2 are each independently a hydrogen atom or a methyl group, Ar1 is an aryl group which may have a substituent, and A is an aromatic hydrocarbon group. The R1 and R2 can be a hydrogen atom, and Ar1 can be a phenyl group.

  提供了一种含杂环芳香基团的化合物，其通式如下（1），以及包含该含杂环芳香基团的光学材料。通式1如下：其中，R1和R2分别独立地是氢原子或甲基基团，Ar1是一个芳基基团，可以具有取代基，A是一个芳香烃基团。R1和R2可以是氢原子，Ar1可以是苯基团。