3-cyclopentyl-2-(4-cyclopropylsulfamoyl-phenyl)-N-(5-methoxy-thiazolo[5,4-b]pyridin-2-yl)propionamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-cyclopentyl-2-(4-cyclopropylsulfamoyl-phenyl)-N-(5-methoxy-thiazolo[5,4-b]pyridin-2-yl)propionamide
• 英文别名: 3-cyclopentyl-2-[4-(cyclopropylsulfamoyl)phenyl]-N-(5-methoxy-[1,3]thiazolo[5,4-b]pyridin-2-yl)propanamide
• 化学式: C₂₄H₂₈N₄O₄S₂
• 分子量: 500.643
• InChiKey: BFVMMROZEZLKNK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  147
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-甲氧基三阿咪唑 、 3-Cyclopentyl-2-[4-(cyclopropylsulfamoyl)phenyl]propanoic acid 在 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 80.5h， 生成 3-cyclopentyl-2-(4-cyclopropylsulfamoyl-phenyl)-N-(5-methoxy-thiazolo[5,4-b]pyridin-2-yl)propionamide
  参考文献：
  名称：

  Investigation of Functionally Liver Selective Glucokinase Activators for the Treatment of Type 2 Diabetes

  摘要：

  Type 2 diabetes is a polygenic disease which afflicts nearly 200 million people worldwide and is expected to increase to near epidemic levels over the next 10-15 years. Glucokinase (GK) activators are currently under investigation by a number of pharmaceutical companies with only a few reaching early clinical evaluation. A GK activator has the promise of potentially affecting both the beta-cells of the pancreas, by improving glucose sensitive insulin secretion, as well as the liver, by reducing uncontrolled glucose output and restoring post-prandial glucose uptake and storage as glycogen. Herein, we report our efforts on a sulfonamide chemotype with the aim to generate liver selective GK activators which culminated in the discovery of 3-cyclopentyl-N-(5-methoxy-thiazolo[5,4-b]pyridin-2-yl)-2-[4-(4-methylpiperazine-1-sulfonyl)-phenyl]-propionamide (17c). This compound activated the GK enzyme (alpha K(a) = 39 nM) in vitro at low nanomolar concentrations and significantly reduced glucose levels during an oral glucose tolerance test in normal mice.

  DOI：

  10.1021/jm900839k

文献信息

• [EN] SULFONAMIDE-THIAZOLPYRIDINE DERIVATIVES AS GLUCOKINASE ACTIVATORS USEFUL THE TREATMENT OF TYPE 2 DIABETES<br/>[FR] DERIVES DE SULFONAMIDE-THIAZOLPYRIDINE EN TANT QU'ACTIVATEURS DE GLUCOKINASE UTILES DANS LE TRAITEMENT DU DIABETE DE TYPE 2
  申请人：NOVARTIS AG

  公开号：WO2005095418A1

  公开（公告）日：2005-10-13

  The present invention provides compounds of the formula (I), which are activators of glucokinase activity and, thus, may be employed as therapeutic agents for the treatment of glucokinase mediated conditions. Accordingly, the compounds of formula (I) may be employed for the prevention and the treatment of impaired glucose tolerance, Type 2 diabetes and obesity.

  本发明提供了化合物(I)的公式，这些化合物是葡萄糖激酶活性的激活剂，因此可以作为治疗葡萄糖激酶介导疾病的治疗剂。因此，公式(I)的化合物可用于预防和治疗糖耐量受损、2型糖尿病和肥胖症。
• Sulfonamide-Thiazolpyridine Derivatives As Glucokinase Activators Useful The Treatment Of Type 2 Diabetes
  申请人：Bebernitz Gregory Raymond

  公开号：US20080103167A1

  公开（公告）日：2008-05-01

  The present invention provides compounds of the formula (I), which are activators of glucokinase activity and, thus, may be employed as therapeutic agents for the treatment of glucokinase mediated conditions. Accordingly, the compounds of formula (I) may be employed for the prevention and the treatment of impaired glucose tolerance, Type 2 diabetes and obesity.

  本发明提供了公式(I)的化合物，它们是葡萄糖激酶活性的激活剂，因此可以用作治疗葡萄糖激酶介导的疾病的治疗剂。因此，公式(I)的化合物可用于预防和治疗糖耐量受损、2型糖尿病和肥胖症。
• SULFONAMIDE-THIAZOLPYRIDINE DERIVATIVES AS GLUCOKINASE ACTIVATORS USEFUL THE TREATMENT OF TYPE 2 DIABETES
  申请人：Novartis AG

  公开号：EP1735322A1

  公开（公告）日：2006-12-27
• SULFONAMIDE-THIAZOLPYRIDINE DERIVATIVES AS GLUCOKINASE ACTIVATORS USEFUL FOR THE TREATMENT OF TYPE 2 DIABETES
  申请人：Novartis AG

  公开号：EP1735322B1

  公开（公告）日：2011-09-14
• ２型糖尿病の処置に有用なグルコキナーゼアクティベーターとしてのスルホンアミド−チアゾロピリジン誘導体
  申请人：ノバルティス アクチエンゲゼルシャフト

  公开号：JP4700684B2

  公开（公告）日：2007-11-01