(3-chloro-4-methylsulfanyl-phenyl)hydroxyacetic acid ethyl ester | 300355-12-8

• 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-methylsulfanyl-phenyl)hydroxyacetic acid ethyl ester
• 英文别名: (3-Chloro-4-methylsulfanyl-phenyl)-hydroxy-acetic acid ethyl ester；ethyl 2-(3-chloro-4-methylsulfanylphenyl)-2-hydroxyacetate
• CAS: 300355-12-8
• 化学式: C₁₁H₁₃ClO₃S
• 分子量: 260.741
• InChiKey: NLMGHLSZGGRFSO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 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：
  71.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3-chloro-4-methylsulfanyl-phenyl)hydroxyacetic acid ethyl ester 在 吡啶 、 六甲基磷酰三胺 、 4-二甲氨基吡啶 、 正丁基锂 、 samarium diiodide 、 水 、 二异丙胺 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 62.6h， 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 aluminum (III) chloride 、 sodium tetrahydroborate 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 4.75h， 生成 (3-chloro-4-methylsulfanyl-phenyl)hydroxyacetic 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。
• GLUCOKINASE ACTIVATORS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1169312A2

  公开（公告）日：2002-01-09
• US6320050B1
  申请人：——

  公开号：US6320050B1

  公开（公告）日：2001-11-20
• US6610846B1
  申请人：——

  公开号：US6610846B1

  公开（公告）日：2003-08-26
• US6951945B2
  申请人：——

  公开号：US6951945B2

  公开（公告）日：2005-10-04