(R)-methyl 3-cyclopentyl-2-hydroxypropanoate | 1174013-24-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (R)-methyl 3-cyclopentyl-2-hydroxypropanoate
• 英文别名: (R)-methyl 3-cyclopentyl-2-hydroxypropanoic acid；methyl (2R)-3-cyclopentyl-2-hydroxypropanoate
• CAS: 1174013-24-1
• 化学式: C₉H₁₆O₃
• 分子量: 172.224
• InChiKey: GWTJBKFLOXKLBT-MRVPVSSYSA-N

物化性质

• 沸点：
  251.8±13.0 °C(Predicted)
• 密度：
  1.071±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-methyl 3-cyclopentyl-2-hydroxypropanoate 在 吡啶 、 2,6-二甲基吡啶 、 盐酸 、 草酰氯 、 N,N-二甲基甲酰胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 37.08h， 生成 (S)-2-(6-(3-cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanamido)pyridin-3-yl)acetic acid
  参考文献：
  名称：

  Discovery of (S)-6-(3-Cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic Acid as a Hepatoselective Glucokinase Activator Clinical Candidate for Treating Type 2 Diabetes Mellitus

  摘要：

  Glucokinase is a key regulator of glucose homeostasis, and small molecule allosteric activators of this enzyme represent a promising opportunity for the treatment of type 2 diabetes. Systemically acting glucokinase activators (liver and pancreas) have been reported to be efficacious but in many cases present hypoglycaemia risk due to activation of the enzyme at low glucose levels in the pancreas, leading to inappropriately excessive insulin secretion. It was therefore postulated that a liver selective activator may offer effective glycemic control with reduced hypoglycemia risk. Herein, we report structure-activity studies on a carboxylic acid containing series of glucokinase activators with preferential activity in hepatocytes versus pancreatic beta-cells. These activators were designed to have low passive permeability thereby minimizing distribution into extrahepatic tissues; concurrently, they were also optimized as substrates for active liver uptake via members of the organic anion transporting polypeptide (OATP) family. These studies lead to the identification of 19 as a potent glucokinase activator with a greater than 50-fold liver-to-pancreas ratio of tissue distribution in rodent and non-rodent species. In preclinical diabetic animals, 19 was found to robustly lower fasting and postprandial glucose with no hypoglycemia, leading to its selection as a clinical development candidate for treating type 2 diabetes.

  DOI：

  10.1021/jm2014887
• 作为产物：
  描述：

  3-cyclopentylpropane-1,2-diol 在 sodium hypochlorite 、 2,2,6,6-四甲基哌啶氧化物 、 potassium bromide 作用下， 以 乙醚 、 丙酮 为溶剂， 反应 1.5h， 生成 (R)-methyl 3-cyclopentyl-2-hydroxypropanoate 、 Methyl (S)-3-cyclopentyl-2-hydroxypropanoate
  参考文献：
  名称：

  单取代乙二醇的化学选择性氧化：光学活性α-羟基酸的便捷合成†

  摘要：

  描述了一种使用TEMPO-NaOCl试剂系统通过单取代乙二醇的化学选择性氧化合成旋光性α-羟基酸的温和有效方法。从我们的研究中可以明显看出，溶剂，pH和反应温度对于这种氧化的成功至关重要。已经用带有各种官能团的各种脂族，芳族和碳水化合物底物证明了该方法的多功能性。

  DOI：

  10.1039/c4ob00601a

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。
• [EN] FLUORINATED HETEROARYLS<br/>[FR] HÉTÉROARYLES FLUORÉS
  申请人：PFIZER

  公开号：WO2010013161A1

  公开（公告）日：2010-02-04

  The present invention provides Formula (1A) XN O R 3 HN R 5 O R 4 R 2 R 1 (1A) 5 compounds that act as glucokinase activators; pharmaceutical compositions thereof; and methods of treating diseases, disorders, or conditions mediated by the glucokinase enzyme, where X, R 1, R 2, R 3, R 4, and R 5 are as described herein.

  本发明提供了一种作为葡萄糖激酶激活剂的化合物Formula (1A) XN O R 3 HN R 5 O R 4 R 2 R 1 (1A) 5；以及其药物组合物；以及治疗由葡萄糖激酶酶介导的疾病、障碍或状况的方法，其中X、R 1、R 2、R 3、R 4和R 5如本文所述。
• Substituted Heteroaryls
  申请人：Benbow John William

  公开号：US20100063063A1

  公开（公告）日：2010-03-11

  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, R 1 , R 2 , R 3 , and R 4 are as described herein.

  本发明提供了作为葡萄糖激酶激活剂的1A式化合物；其药物组合物；以及治疗由葡萄糖激酶介导的疾病，疾病或病状的方法。 X，Y，Z，R1，R2，R3和R4如本文所述。
• Substituted imidazole propanamide glucokinase activators
  申请人：Pfizer Inc

  公开号：US07977367B2

  公开（公告）日：2011-07-12

  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萄糖激酶激活剂的化合物Formula（1A）；其制药组合物；以及治疗由葡萄糖激酶介导的疾病、障碍或病况的方法。其中，X、Y、Z、R1、R2、R3和R4如本文所述。