(3-chloro-4-methylsulfanylphenyl)acetic acid ethyl ester | 300355-14-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: (3-chloro-4-methylsulfanylphenyl)acetic acid ethyl ester
• 英文别名: ethyl 2-(3-chloro-4-(methylthio)phenyl)acetate；ethyl [3-chloro-4-(methylthio)phenyl]acetate；(3-Chloro-4-methylsulfanyl-phenyl)-acetic acid ethyl ester；ethyl 2-(3-chloro-4-methylsulfanylphenyl)acetate
• CAS: 300355-14-0
• 化学式: C₁₁H₁₃ClO₂S
• 分子量: 244.742
• InChiKey: MWVQNJRUTWNGJI-UHFFFAOYSA-N

物化性质

• 沸点：
  318.7±37.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  51.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3-chloro-4-methylsulfanylphenyl)acetic acid ethyl ester 在 正丁基锂 、 水 、 二异丙胺 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 46.5h， 生成 2-(3-chloro-4-methylsulfanylphenyl)-3-cyclopentyl-N-thiazol-2-yl-propionamide
  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
• 作为产物：
  描述：

  2-氯茴香硫醚 在 吡啶 、 六甲基磷酰三胺 、 4-二甲氨基吡啶 、 aluminum (III) chloride 、 sodium tetrahydroborate 、 samarium diiodide 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 为溶剂， 反应 20.85h， 生成 (3-chloro-4-methylsulfanylphenyl)acetic acid ethyl ester
  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

• Heteroaromatic glucokinase activators
  申请人：——

  公开号：US20010039344A1

  公开（公告）日：2001-11-08

  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 cycloalkyl 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-位取代为取代苯基，3-位取代为环烷基环，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。
• Chlorotrimethylsilane and Sodium Iodide: A Useful Combination for the Regioselective Deoxygenation of Arylalkyl-α-Diketones
  作者：Ling-Zhi Yuan、Guangkuan Zhao、Abdallah Hamze、Mouad Alami、Olivier Provot

  DOI：10.1002/adsc.201700276

  日期：2017.8.7

  series of variously functionalized alkylbenzylketones. A large range of functional groups were well tolerated on the ortho‐, meta‐ and para‐positions by this mild process regardless of their electronic effects, demonstrating the general character of the present methodology. The trimethylsilylchloride/sodium iodide reducing process was also successfully applied to reduce α‐ketoacid and α‐ketoester substrates

  据报道，三甲基甲硅烷基氯化物/碘化钠可有效地对芳基烷基1,2-二酮进行区域选择性脱氧。在所有情况下，脱氧都在室温下在二氯甲烷中芳族环附近的羰基基团（Cα= O）上以高收率进行，从而提供了一系列各种官能化的烷基苄基酮。不管它们的电子作用如何，通过这种温和的过程，对邻位，间位和对位的各种官能团都具有良好的耐受性，这证明了本方法学的一般特征。三甲基甲硅烷基氯/碘化钠还原工艺也成功地用于还原α-酮酸和α-酮酸酯底物。
• 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。
• 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。