2-(4-环丙基硫烷基苯基)乙酸 | 868614-27-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 中文名称: 2-(4-环丙基硫烷基苯基)乙酸
• 英文名称: 2-(4-cyclopropylsulfanylphenyl)acetic acid
• 英文别名: (4-cyclopropylsulfanyl-phenyl)-acetic acid；[4-(Cyclopropylthio)phenyl] acetic acid；[4-(Cyclopropylsulfanyl)phenyl]acetic acid
• CAS: 868614-27-1
• 化学式: C₁₁H₁₂O₂S
• 分子量: 208.281
• InChiKey: NQHUDEQPAAWIFS-UHFFFAOYSA-N

物化性质

• 沸点：
  380.2±25.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  62.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-环丙基硫烷基苯基)乙酸 在 N-溴代丁二酰亚胺(NBS) 、 氯化亚砜 、 间氯过氧苯甲酸 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 methyl 2-bromo-2-(4-cyclopropylsulfonylphenyl)acetate
  参考文献：
  名称：

  Discovery of liver-directed glucokinase activator having anti-hyperglycemic effect without hypoglycemia

  摘要：

  Glucokinase activators (GKAs) are among the emerging drug candidates for the treatment of type 2 diabetes (T2D). Despite effective blood glucose lowering in clinical trials, many pan-GKAs "acting both in pancreas and liver" have been discontinued from clinical development mainly because of their potential to cause hypoglycemia. Pan-GKAs over sensitize pancreatic GK, resulting in insulin secretion even at sub-normoglycemic level which might be a possible explanation for hypoglycemia. An alternative approach to minimize the risk of hypoglycemia is to use liver-directed GKAs, which are reported to be advancing well in clinical development. Here, we report the discovery and structure-activity relationship (SAR) studies on a novel 2-phenoxy-acetamide series with the aim of identifying a liver-directed GKA. Incorporation of a carboxylic acid moiety as an active hepatocyte uptake recognizing element at appropriate position of 2-phenoxy-acetamide core led to the identification of 26, a potent GKA with predominant liver-directed pharmacokinetics in mice. Compound 26 on oral administration significantly reduced blood glucose levels during an oral glucose tolerance test (oGTT) performed in diet-induced obese (DIO) mice, while showing no sign of hypoglycemia in normal C57 mice over a 10-fold dose range, even when dosed at fasted condition. Together, these data demonstrate a liver-directed GKA has beneficial effect on glucose homeostasis with reduced risk of hypoglycemia. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.03.042
• 作为产物：
  描述：

  环丙基苯基硫 在 aluminum (III) chloride 、 hydrazine hydrate 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 22.83h， 生成 2-(4-环丙基硫烷基苯基)乙酸
  参考文献：
  名称：

  Discovery of liver-directed glucokinase activator having anti-hyperglycemic effect without hypoglycemia

  摘要：

  Glucokinase activators (GKAs) are among the emerging drug candidates for the treatment of type 2 diabetes (T2D). Despite effective blood glucose lowering in clinical trials, many pan-GKAs "acting both in pancreas and liver" have been discontinued from clinical development mainly because of their potential to cause hypoglycemia. Pan-GKAs over sensitize pancreatic GK, resulting in insulin secretion even at sub-normoglycemic level which might be a possible explanation for hypoglycemia. An alternative approach to minimize the risk of hypoglycemia is to use liver-directed GKAs, which are reported to be advancing well in clinical development. Here, we report the discovery and structure-activity relationship (SAR) studies on a novel 2-phenoxy-acetamide series with the aim of identifying a liver-directed GKA. Incorporation of a carboxylic acid moiety as an active hepatocyte uptake recognizing element at appropriate position of 2-phenoxy-acetamide core led to the identification of 26, a potent GKA with predominant liver-directed pharmacokinetics in mice. Compound 26 on oral administration significantly reduced blood glucose levels during an oral glucose tolerance test (oGTT) performed in diet-induced obese (DIO) mice, while showing no sign of hypoglycemia in normal C57 mice over a 10-fold dose range, even when dosed at fasted condition. Together, these data demonstrate a liver-directed GKA has beneficial effect on glucose homeostasis with reduced risk of hypoglycemia. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.03.042

文献信息

• NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME
  申请人：Ryono Denis E.

  公开号：US20080009465A1

  公开（公告）日：2008-01-10

  Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure wherein is a heteroaryl ring; R 4 is —(CH 2 ) n -Z-(CH 2 ) m —PO(OR 7 )(OR 8 ), —(CH 2 ) n Z-(CH 2 ) m —PO(OR 7 )R g , —(CH 2 ) n -Z-(CH 2 ) m —OPO(OR 7 )R g , —(CH 2 ) n Z—(CH 2 ) m —OPO(R 9 )(R 10 ), or —(CH 2 ) n Z—(CH 2 ) m —PO(R 9 )(R 10 ); R 5 and R 6 are independently selected from H, alkyl and halogen; Y is R 7 (CH 2 ) s or is absent; and X, n, Z, m, R 4 , R 5 , R 6 , R 7 , and s are as defined herein; or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.

  提供了磷酸酯和磷酸酯激活剂，因此在治疗糖尿病和相关疾病方面非常有用，并具有以下结构： 其中 是杂环芳基环； R 4 为—(CH 2 ) n -Z-(CH 2 ) m —PO(OR 7 )(OR 8 )、—(CH 2 ) n Z-(CH 2 ) m —PO(OR 7 )R g 、—(CH 2 ) n -Z-(CH 2 ) m —OPO(OR 7 )R g 、—(CH 2 ) n Z—(CH 2 ) m —OPO(R 9 )(R 10) 或—(CH 2 ) n Z—(CH 2 ) m —PO(R 9 )(R 10) ； R 5 和R 6 分别选择自H、烷基和卤素； Y为R 7 (CH 2 ) s 或不存在；以及 X、n、Z、m、R 4 、R 5 、R 6 、R 7 和s如本文所定义；或其药用盐。 还提供了一种利用上述化合物治疗糖尿病和相关疾病的方法。
• Pyrazole glucokinase activators
  申请人：Berthel Steven Joseph

  公开号：US20080021032A1

  公开（公告）日：2008-01-24

  Disclosed herein are pyrazole glucokinase activators of the formula (I) useful for the treatment of metabolic diseases and disorders, preferably diabetes mellitus.

  本文披露了一种式(I)的吡唑葡萄糖激酶激活剂，用于治疗代谢性疾病和紊乱，最好是糖尿病。
• [EN] FLUORINATION PROCESS OF PROTECTED AMINOTHIAZOLE<br/>[FR] PROCÉDÉ DE FLUORATION D'AMINOTHIAZOLE PROTÉGÉE
  申请人：PROSIDION LTD

  公开号：WO2006016174A1

  公开（公告）日：2006-02-16

  A process for the production of fluorinated compound formula (I) comprising fluorination of a protected aminothiazole. Compounds formula (I) are useful in the preparation of activators of glucokinase.

  一种生产氟化合物化学式（I）的过程，包括对受保护的氨基噻唑进行氟化。化合物化学式（I）在制备葡萄糖激酶活化剂方面很有用。
• [EN] SUBSTITUTED PHENYLACETAMIDES AND THEIR USE AS GLUCOKINASE ACTIVATORS<br/>[FR] PHÉNYLACÉTAMIDES SUBSTITUÉS ET LEUR UTILISATION EN TANT QU'ACTIVATEURS DE LA GLUCOKINASE
  申请人：PROSIDION LTD

  公开号：WO2006016194A1

  公开（公告）日：2006-02-16

  Compounds of Formula (I) wherein R1 is a cycloalkylsulphonyl group, or pharmaceutically acceptable salts thereof, are useful in the prophylactic and therapeutic treatment of hyperglycemia and diabetes.

  式(I)中R1为环烷磺酰基，或其药用可接受的盐，可用于预防和治疗高血糖和糖尿病。
• [EN] TRI(CYCLO) SUBSTITUTED AMIDE COMPOUNDS<br/>[FR] COMPOSES AMIDE TRI(CYCLO)-SUBSTITUES
  申请人：PROSIDION LTD

  公开号：WO2005103021A1

  公开（公告）日：2005-11-03

  Compounds of Formula (I) or pharmaceutically acceptable salts thereof, are useful in the prophylactic and therapeutic treatment of hyperglycemia and diabetes.

  式(I)的化合物或其药学上可接受的盐，在预防和治疗高血糖和糖尿病方面具有用处。