methyl (R)-3-cyclohexyl-2-(trifluoromethylsulfonyloxy)propanoate | 191731-21-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 英文名称: methyl (R)-3-cyclohexyl-2-(trifluoromethylsulfonyloxy)propanoate
• 英文别名: (R)-methyl 3-cyclohexyl-2-(trifluoromethylsulfonyloxy) propanoate；(R)-2-(Trifluoromethylsulfonyloxy)-3-cyclohexylpropanoic acid methyl ester；methyl (2R)-3-cyclohexyl-2-(trifluoromethylsulfonyloxy)propanoate
• CAS: 191731-21-2
• 化学式: C₁₁H₁₇F₃O₅S
• 分子量: 318.314
• InChiKey: XNQQYHFNYIZTFD-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  78
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl (R)-3-cyclohexyl-2-(trifluoromethylsulfonyloxy)propanoate 在 盐酸 、 水 、 potassium carbonate 作用下， 以 乙酸乙酯 为溶剂， 生成
  参考文献：
  名称：

  Discovery of an intravenous hepatoselective glucokinase activator for the treatment of inpatient hyperglycemia

  摘要：

  Glucokinase (hexokinase IV) continues to be a compelling target for the treatment of type 2 diabetes given the wealth of supporting human genetics data and numerous reports of robust clinical glucose lowering in patients treated with small molecule allosteric activators. Recent work has demonstrated the ability of hepatoselective activators to deliver glucose lowering efficacy with minimal risk of hypoglycemia. While orally administered agents require a considerable degree of passive permeability to promote suitable exposures, there is no such restriction on intravenously delivered drugs. Therefore, minimization of membrane diffusion in the context of an intravenously agent should ensure optimal hepatic targeting and therapeutic index. This work details the identification a hepatoselective GKA exhibiting the aforementioned properties. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2013.10.057
• 作为产物：
  描述：

  环己基溴化镁 在 2,6-二甲基吡啶 作用下， 以 四氢呋喃 、 乙醚 、 正庚烷 、 二氯甲烷 为溶剂， 生成 methyl (R)-3-cyclohexyl-2-(trifluoromethylsulfonyloxy)propanoate
  参考文献：
  名称：

  Discovery of an intravenous hepatoselective glucokinase activator for the treatment of inpatient hyperglycemia

  摘要：

  Glucokinase (hexokinase IV) continues to be a compelling target for the treatment of type 2 diabetes given the wealth of supporting human genetics data and numerous reports of robust clinical glucose lowering in patients treated with small molecule allosteric activators. Recent work has demonstrated the ability of hepatoselective activators to deliver glucose lowering efficacy with minimal risk of hypoglycemia. While orally administered agents require a considerable degree of passive permeability to promote suitable exposures, there is no such restriction on intravenously delivered drugs. Therefore, minimization of membrane diffusion in the context of an intravenously agent should ensure optimal hepatic targeting and therapeutic index. This work details the identification a hepatoselective GKA exhibiting the aforementioned properties. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2013.10.057

文献信息

• Substituted Pyrazinone Amides
  申请人：Benbow John William

  公开号：US20100184777A1

  公开（公告）日：2010-07-22

  The present invention provides compounds of Formula (I) that act as glucokinase activators; pharmaceutical compositions thereof; and methods of treating diseases, disorders, or conditions mediated by glucokinase. The variables R 1 , R 2 , R 3 and R 4 are as described herein.

  本发明提供了式(I)的化合物，这些化合物作为葡萄糖激酶激活剂；其药物组合物；以及治疗由葡萄糖激酶介导的疾病、障碍或状况的方法。变量R1、R2、R3和R4如本文所述。
• [EN] HETEROARYLS AMIDE DERIVATIVES AND THEIR USE AS GLUCOKINASE ACTIVATORS<br/>[FR] DÉRIVÉS D'AMIDES D'HÉTÉROARYLES ET LEUR UTILISATION COMME ACTIVATEURS DE LA GLUCOKINASE
  申请人：PFIZER

  公开号：WO2010029461A1

  公开（公告）日：2010-03-18

  The present invention provides Formula (1A) compounds that act as glucokinase activators; pharmaceutical compositions thereof; and methods of treating diseases, disorders, or conditions mediated by glucokinase. X, Y, Z, R1, R2, R3, and R4 are as described herein.

  本发明提供了作为葡糖激酶激活剂的式(1A)化合物；其药物组合物；以及治疗由葡糖激酶介导的疾病、紊乱或状况的方法。其中，X、Y、Z、R1、R2、R3和R4如本文所述。
• A Stereocontrolled Synthesis of Monofluoro Ketomethylene Dipeptide Isosteres
  作者：Robert V. Hoffman、Junhua Tao

  DOI：10.1021/jo981334y

  日期：1999.1.1

  A simple, stereocontrolled synthesis of monofluoro ketomethylene dipeptide isosteres has been developed. N-Tritylated ketomethylene dipeptide isosteres, prepared from N-tritylated amino acids, are converted to their Z-TMS enol ethers and fluorinated with Selectfluor. There is cooperative stereocontrol between the N-tritylamine group and the alkyl group at C-2. The method is short (six steps), diastereoselective

  已经开发了简单的立体控制的单氟酮亚甲基二肽等排体的合成。由N-三苯甲基化的氨基酸制备的N-三苯甲基化的酮亚甲基二肽等位基因被转化为其Z-TMS烯醇醚并用Selectfluor进行氟化。N-三苯甲基胺基和C-2处的烷基之间存在协同立体控制。该方法很短（六个步骤），非对映选择性（85-> 95％）和对映选择性（> 95％）。
• A simple, stereoselective synthesis of ketomethylene dipeptide isosteres
  作者：Robert V. Hoffman、Junhua Tao

  DOI：10.1016/s0040-4020(97)00410-9

  日期：1997.5

  An exceedingly simple, general, and stereoselective method for the preparation of ketomethylene dipeptide isosteres (5-(carbobenzyloxyamino)-2-alkyl-γ-ketoesters) from Cbz-protected amino acids and scalemic 2-triflyloxy esters has been developed. The method is short (three steps), efficient, and highly diastereoselective and enantioselective.

  已经开发了一种非常简单，通用和立体选择性的方法，该方法可从Cbz保护的氨基酸和规模的2-triflyloxy酯制备酮亚甲基二肽等位异构体（5-（羰基苄氧基氨基）-2-烷基-γ-酮酸酯）。该方法是短的（三个步骤），有效的，高度非对映选择性和对映选择性的。
• Selective Monovalent Galectin‐8 Ligands Based on 3‐Lactoylgalactoside
  作者：Benedetta Girardi、Martina Manna、Sjors Van Klaveren、Tihomir Tomašič、Žiga Jakopin、Hakon Leffler、Ulf J. Nilsson、Daniel Ricklin、Janez Mravljak、Oliver Schwardt、Marko Anderluh

  DOI：10.1002/cmdc.202100514

  日期：2022.2.4

  A potent galectin-8 ligand! Galectin-8 is a promising therapeutic target for cancer and diseases associated with inflammations. In this work we aimed to improve the affinity and selectivity of a recently published galectin-8 ligand. By introducing modifications at positions 1 and 3 of the galactose core, we obtained one of the most potent galectin-8 ligands known to date, improving the affinity by

  一种有效的半乳糖凝集素 8 配体！Galectin-8 是癌症和与炎症相关的疾病的有希望的治疗靶点。在这项工作中，我们旨在提高最近发表的 galectin-8 配体的亲和力和选择性。通过在半乳糖核心的 1 和 3 位引入修饰，我们获得了迄今为止已知的最有效的 galectin-8 配体之一，将亲和力提高了近 200 倍，并具有良好的选择性。