(2R)-2-(3-chloro-4-methanesulfonylphenyl)-3-[(1R)-3-oxocyclopentyl]propanoic acid | 625114-43-4

• 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: (2R)-2-(3-chloro-4-methanesulfonylphenyl)-3-[(1R)-3-oxocyclopentyl]propanoic acid
• 英文别名: (R)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-((R)-3-oxo-cyclopentyl)-propionic acid；2(R)-(3-chloro-4-methanesulfonylphenyl)-3-((R)-3-oxocyclopentyl)propionic acid；(2R)-2-(3-chloro-4-methylsulfonylphenyl)-3-[(1R)-3-oxocyclopentyl]propanoic acid
• CAS: 625114-43-4
• 化学式: C₁₅H₁₇ClO₅S
• 分子量: 344.816
• InChiKey: SBLBBEKWCCZEQM-JOYOIKCWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  96.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R)-2-(3-chloro-4-methanesulfonylphenyl)-3-[(1R)-3-oxocyclopentyl]propanoic acid 在 N,N-二甲基甲酰胺 2,6-二甲基吡啶 、 草酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 17.0h， 生成 (R)-N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-2-(3-chloro-4-methanesulfonyl-phenyl)-3-((R)-3-oxo-cyclopentyl)-propionamide
  参考文献：
  名称：

  Pyrazole glucokinase activators

  摘要：

  本文披露了一种式(I)的吡唑葡萄糖激酶激活剂，用于治疗代谢性疾病和紊乱，最好是糖尿病。

  公开号：

  US20080021032A1
• 作为产物：
  描述：

  3-氯-4-甲硫基苯乙酸 在 正丁基锂 、 硫酸 、 二甲基二环氧乙烷 、 三甲基乙酰氯 、 potassium carbonate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 、 水 、 丙酮 为溶剂， 反应 22.83h， 生成 (2R)-2-(3-chloro-4-methanesulfonylphenyl)-3-[(1R)-3-oxocyclopentyl]propanoic acid
  参考文献：
  名称：

  Discovery of Piragliatin—First Glucokinase Activator Studied in Type 2 Diabetic Patients

  摘要：

  Glucokinase (GK) activation as a potential strategy to treat type 2 diabetes (T2D) is well recognized. Compound 1, a glucokinase activator (GKA) lead that we have previously disclosed, caused reversible hepatic lipidosis in repeat-dose toxicology studies. We hypothesized that the hepatic lipidosis was due to the structure-based toxicity and later established that it was due to the formation of a thiourea metabolite, 2. Subsequent SAR studies of 1 led to the identification of a pyrazine-based lead analogue 3, lacking the thiazole moiety. In vivo metabolite identification studies, followed by the independent synthesis and profiling of the cyclopentyl keto- and hydroxyl- metabolites of 3, led to the selection of piragliatin, 4, as the clinical lead. Piragliatin was found to lower pre- and postprandial glucose levels, improve the insulin secretory profile, increase beta-cell sensitivity to glucose, and decrease hepatic glucose output in patients with T2D.

  DOI：

  10.1021/jm3008689

文献信息

• Substituted-cycloalkyl and oxygenated-cycloalkyl glucokinase activators
  申请人：——

  公开号：US20030225283A1

  公开（公告）日：2003-12-04

  2,3-Di-substituted N-heteroaromatic propionamides with said substitution at the 2-position being a substituted phenyl group and at the 3-position being a polar ring, said propionamides being glucokinase activators which increase insulin secretion in the treatment of type II diabetes.

  2,3-二取代N-杂环丙酰胺，其中2-位置的取代物是取代苯基，3-位置的取代物是极性环，这些丙酰胺是葡萄糖激酶激活剂，可增加胰岛素分泌，用于治疗2型糖尿病。
• Aromatic sulfonated ketals
  申请人：Schwindt Mark A.

  公开号：US20080161564A1

  公开（公告）日：2008-07-03

  The present invention advantageously provides ketal functional compounds that can be strong electrophiles under conditions compatible with ketal groups, are stable, crystalline solids at room temperature, and are much safer to handle than ketal iodides. The present invention accomplishes by incorporating aromatic sulfonyl moieties into ketal functional materials. The compounds are useful starting materials or intermediates in the synthesis of more complex organic molecules.

  本发明有利地提供了在与缩酮基团兼容的条件下可成为强亲电试剂的缩酮官能化合物，这些化合物在室温下是稳定的结晶固体，比缩酮碘化物更安全。本发明通过将芳香基磺酰基结构引入缩酮官能材料中来实现。这些化合物在合成更复杂的有机分子过程中可作为有用的起始物质或中间体。
• Reduction methodologies for converting ketal acids, salts, and esters to ketal alcohols
  申请人：Topping Robert J.

  公开号：US20080161563A1

  公开（公告）日：2008-07-03

  The present invention relates to methods of reducing ketal acids, salts and esters to form corresponding ketal alcohols. More particularly, the reducing methods convert the ketal acids, salts, or esters to ketal alcohols by using a reducing agent that comprises a hydride that comprises one or more alkoxy moieties. The ketal alcohol is prepared in a hydrophobic reagent. This is purified by washing the hydrophobic reagent with one or more water washes. Because the ketal alcohol has some water solubility, the water washes are back-extracted with a hydrophobic solvent to recover additional ketal alcohol from such one or more water washes. The alcohol products are useful in many applications such as intermediates in the synthesis of pharmacologically important molecules.

  本发明涉及将酮酸、盐和酯还原为相应的酮醇的方法。更具体地说，还原方法通过使用包含一个或多个烷氧基的氢化物的还原剂将酮酸、盐或酯转化为酮醇。酮醇是在疏水试剂中制备的。通过用一个或多个水洗涤疏水试剂来纯化。由于酮醇具有一定的水溶性，所以水洗涤用疏水溶剂进行反萃取，以从一个或多个水洗涤中回收额外的酮醇。这些醇类产品在许多应用中很有用，例如在合成药理学重要分子的中间体中。
• Process for the preparation of an isopropanol solvate of a glucokinase activator
  申请人：Daniewski Andrzej Robert

  公开号：US20070244129A1

  公开（公告）日：2007-10-18

  Provided is a process for the preparation of 2(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-((R)-3-oxo-cyclopentyl)-N-pyrazin-2-yl-propionamide and its isopropanol solvate as a glucokinase activator which increases insulin secretion in the treatment of, for example, type II diabetes.

  提供了一种制备2(R)-(3-氯-4-甲磺酰基苯基)-3-((R)-3-氧代环戊基)-N-吡啶-2-基-丙酰胺及其异丙醇溶剂化合物的过程，作为一种葡萄糖激酶激活剂，可增加胰岛素分泌，用于治疗例如II型糖尿病。
• [EN] TRI(CYCLO) SUBSTITUTED AMIDE COMPOUNDS<br/>[FR] COMPOSES AMIDE TRI(CYCLO)-SUBSTITUES
  申请人：PROSIDION LTD

  公开号：WO2005103021A1

  公开（公告）日：2005-11-03

  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具有用处。