Piragliatin | 625114-41-2

• 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: Piragliatin
• 英文别名: RO4389620；2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-[1(R)-3-oxo-cyclopentyl]-N-(pyrazin-2-yl)-propionamide；2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-[(R)-3-oxo-cyclopentyl]-N-(pyrazin-2-yl)-propionamide；2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-((R)-3-oxo-cyclopentyl)-N-pyrazin-2-yl-propionamide；2(R)-(3-chloro-4-methanesulfonylphenyl)-3-((S)-3-oxocyclopentyl)-N-pyrazin-2-ylpropionamide；(2R)-2-(3-chloro-4-methylsulfonylphenyl)-3-[(1R)-3-oxocyclopentyl]-N-pyrazin-2-ylpropanamide
• CAS: 625114-41-2
• 化学式: C₁₉H₂₀ClN₃O₄S
• 分子量: 421.904
• InChiKey: XEANIURBPHCHMG-SWLSCSKDSA-N

物化性质

• 沸点：
  699.2±55.0 °C(Predicted)
• 密度：
  1.397±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  115
• 氢给体数：
  1
• 氢受体数：
  6

制备方法与用途

Piragliatin（罗格列酮）是一种药物。

反应信息

• 作为反应物：
  描述：

  Piragliatin 在 butyl hydroxyanisole 、 butyl hydroxytolulene 作用下， 以 Gelucire 44/14 为溶剂， 反应 4383.0h， 生成 2(S)-(3-chloro-4-methanesulfonyl-phenyl)-3-[(R)-3-oxo-cyclopentyl]-N-(pyrazin-2-yl)-propionamide
  参考文献：
  名称：

  WO2008/74694

  摘要：

  公开号：
• 作为产物：
  描述：

  (3-chloro-4-methylsulfanyl-phenyl)-oxo-acetic acid 在 正丁基锂 、 草酰氯 、 硫酸 、 二甲基二环氧乙烷 、 三甲基乙酰氯 、 potassium carbonate 、 一水合肼 、 N,N-二甲基甲酰胺 、 potassium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 、 二氯甲烷 、 水 、 丙酮 、 甲苯 为溶剂， 反应 57.83h， 生成 Piragliatin
  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。
• CHEMOSELECTIVE METHYLENE HYDROXYLATION IN AROMATIC MOLECULES
  申请人：The Board of Trustees of the University of Illinois

  公开号：US20200087331A1

  公开（公告）日：2020-03-19

  A chemoselective and reactive Mn(CF 3 -PDP) catalyst system that enables for the first time the strategic advantages of late-stage aliphatic C—H hydroxylation to be leveraged in aromatic compounds. This discovery will benefit small molecule therapeutics by enabling the rapid diversification of aromatic drugs and natural products and identification of their metabolites.

  一种化学选择性和反应性的Mn(CF3-PDP)催化体系首次实现了后期脂肪族C—H羟基化在芳香化合物中的战略优势。这一发现将有助于小分子药物的快速多样化和芳香类药物以及天然产物的代谢产物的鉴定。
• 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。
• Epimerization methodologies for recovering stereoisomers in high yield and purity
  申请人：Nicholas Gillian M.

  公开号：US20080161583A1

  公开（公告）日：2008-07-03

  The present invention relates to methods of subjecting a mixture of stereoisomers to epimerization and optionally recrystallization procedures to obtain a desired stereoisomer in high yield and purity. Relying upon solubility differences, the epimerization desirably is carried out in a solvent mixture that extends the epimerization equilibrium in favor of the desired stereoisomer. Recrystallization from a solvent mixture upgrades the purity even more. Purified stereoisomers are useful in many applications such as intermediates in the synthesis of pharmacologically important molecules.

  本发明涉及将立体异构体混合物经受对映异构化和可选再结晶程序，以获得高产率和纯度的所需立体异构体的方法。依靠溶解度差异，对映异构化通常在使所需立体异构体处于有利位置的溶剂混合物中进行。从溶剂混合物中再结晶可以进一步提高纯度。纯化的立体异构体在许多应用中非常有用，例如在合成药理学重要分子的中间体中。