2-(4-甲基磺酰基苯基)-3-四氢吡喃-4-基-丙酸 | 745053-22-9

• 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: 2-(4-甲基磺酰基苯基)-3-四氢吡喃-4-基-丙酸
• 英文名称: 2-(4-methanesulfonylphenyl)-3-(tetrahydropyran-4-yl)propionic acid
• 英文别名: 2-[4-(methylsulfonyl)phenyl]-3-(tetrahydro-2H-pyran-4-yl)propanoic acid；2-(4-(Methylsulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)propanoic acid；2-(4-methylsulfonylphenyl)-3-(oxan-4-yl)propanoic acid
• CAS: 745053-22-9
• 化学式: C₁₅H₂₀O₅S
• 分子量: 312.387
• InChiKey: FRPKQSPLXRXUJF-UHFFFAOYSA-N

物化性质

• 熔点：
  217 °C(Solv: ethyl ether (60-29-7); hexane (110-54-3))
• 沸点：
  526.3±46.0 °C(Predicted)
• 密度：
  1.252±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  89
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-甲基磺酰基苯基)-3-四氢吡喃-4-基-丙酸 、 2-氨基-4-苯基噻唑 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 以26.7%的产率得到2-(4-(methylsulfonyl)phenyl)-N-(4-phenylthiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)-propanamide
  参考文献：
  名称：

  Design, synthesis, and pharmacological evaluation of N-(4-mono and 4,5-disubstituted thiazol-2-yl)-2-aryl-3-(tetrahydro-2H-pyran-4-yl)propanamides as glucokinase activators

  摘要：

  A series of N-thiazole substituted arylacetamides were designed on the basis of metabolic mechanism of the aminothiazole fragment as glucokinase (GK) activators for the treatment of type 2 diabetes. Instead of introducing a substituent to block the metabolic sensitive C-5 position on the thiazole core directly, a wide variety of C-4 or both C-4 and C-5 substitutions were explored. Compound R-9k bearing an iso-propyl group as the C-4 substituent was found possessing the highest GK activation potency with an EC50 of 0.026 mu M. This compound significantly increased both glucose uptake and glycogen synthesis in rat primary cultured hepatocytes. Moreover, single oral administration of compound R-9k exerted significant reduction of blood glucose levels in both ICR and ob/ob mice. These promising results indicated that compound R-9k is a potent orally active GK activator, and is warranted for further investigation as a new antidiabetic treatment. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.04.038
• 作为产物：
  描述：

  (E)-2-(4-methanesulfonylphenyl)-3-(tetrahydropyran-4-yl)acrylic acid 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 16.0h， 以100%的产率得到2-(4-甲基磺酰基苯基)-3-四氢吡喃-4-基-丙酸
  参考文献：
  名称：

  SAR, Pharmacokinetics, Safety, and Efficacy of Glucokinase Activating 2-(4-Sulfonylphenyl)-N-thiazol-2-ylacetamides: Discovery of PSN-GK1

  摘要：

  Allosteric activators of the glucose-sensing enzyme glucokinase (GK) are currently attracting much interest as potential antidiabetic therapies because they can achieve powerful blood glucose lowering through actions in multiple organs. Here, the optimization of a weakly active high-throughput screening hit to (2R)-2-(4-cyclopropanesulfonylphenyl)-N-(5-fluorothiazol-2-yl)-3-(tetrahydropyran-4-yl)propionamide (PSN-GK1), a potent GK activator with an improved pharmacokinetic and safety profile, is described. Following oral administration, this compound elicited robust glucose lowering in rats.

  DOI：

  10.1021/jm8003202

文献信息

• NITROGEN-CONTAINING FIVE-MEMBERED HETEROCYCLIC COMPOUND
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2149550A1

  公开（公告）日：2010-02-03

  The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof. The compound of the present invention has a glucokinase activity, and is useful as a medicament such as an agent for the prophylaxis or treatment of diabetes, obesity and the like, and the like.

  本发明提供了一种由以下式（I）表示的化合物： 其中每个符号如规范中定义，或其盐。本发明的化合物具有葡萄糖激酶活性，并且可用作药物，如预防或治疗糖尿病、肥胖等的药剂，诸如此类。
• Tri(cyclo) substituted amide compounds
  申请人：——

  公开号：US20040181067A1

  公开（公告）日：2004-09-16

  Compounds of Formula (I): 1 or pharmaceutically acceptable salts thereof, are useful in the prophylactic and therapeutic treatment of hyperglycemia and diabetes.

  公式（I）化合物或其药学上可接受的盐，可用于预防和治疗高血糖和糖尿病。
• TRI(CYCLO) SUBSTITUTED AMIDE COMPOUNDS
  申请人：Fyfe Colin Thor Matthew

  公开号：US20070281946A1

  公开（公告）日：2007-12-06

  Compounds of Formula (I): or pharmaceutically acceptable salts thereof, are useful in the prophylactic and therapeutic treatment of hyperglycemia and diabetes.

  式（I）的化合物或其药学上可接受的盐，在预防和治疗高血糖和糖尿病方面是有用的。
• [EN] PHENYLACETAMIDES AND THEIR USE AS GLUCOKINASE MODULATORS<br/>[FR] COMPOSES D'AMIDES SUBSTITUES TRI(CYCLO)
  申请人：OSI PHARM INC

  公开号：WO2004072031A3

  公开（公告）日：2004-12-02
• PHENYLACETAMIDES AND THEIR USE AS GLUCOKINASE MODULATORS
  申请人：Prosidion Limited

  公开号：EP1594867A2

  公开（公告）日：2005-11-16