N-(5-bromo-4-isopropylthiazol-2-yl)-2-(4-(cyclopropylsulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)propanamide | 1236285-95-2

• 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: N-(5-bromo-4-isopropylthiazol-2-yl)-2-(4-(cyclopropylsulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)propanamide
• 英文别名: N-(5-bromo-4-propan-2-yl-1,3-thiazol-2-yl)-2-(4-cyclopropylsulfonylphenyl)-3-(oxan-4-yl)propanamide
• CAS: 1236285-95-2
• 化学式: C₂₃H₂₉BrN₂O₄S₂
• 分子量: 541.53
• InChiKey: PQTMWNFGWWQCSK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  122
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-[4-(cyclopropylsulfonyl)phenyl]-3-(tetrahydro-2H-pyran-4-yl)propionic acid 、 5-bromo-4-isopropylthiazol-2-amine hydrobromide 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 以46.9%的产率得到N-(5-bromo-4-isopropylthiazol-2-yl)-2-(4-(cyclopropylsulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)propanamide
  参考文献：
  名称：

  Design, synthesis, and pharmacological evaluation of N-(4-mono and 4,5-disubstituted thiazol-2-yl)-2-aryl-3-(tetrahydro-2H-pyran-4-yl)propanamides as glucokinase activators

  摘要：

  A series of N-thiazole substituted arylacetamides were designed on the basis of metabolic mechanism of the aminothiazole fragment as glucokinase (GK) activators for the treatment of type 2 diabetes. Instead of introducing a substituent to block the metabolic sensitive C-5 position on the thiazole core directly, a wide variety of C-4 or both C-4 and C-5 substitutions were explored. Compound R-9k bearing an iso-propyl group as the C-4 substituent was found possessing the highest GK activation potency with an EC50 of 0.026 mu M. This compound significantly increased both glucose uptake and glycogen synthesis in rat primary cultured hepatocytes. Moreover, single oral administration of compound R-9k exerted significant reduction of blood glucose levels in both ICR and ob/ob mice. These promising results indicated that compound R-9k is a potent orally active GK activator, and is warranted for further investigation as a new antidiabetic treatment. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.04.038

文献信息

• Design, synthesis, and pharmacological evaluation of N-(4-mono and 4,5-disubstituted thiazol-2-yl)-2-aryl-3-(tetrahydro-2H-pyran-4-yl)propanamides as glucokinase activators
  作者：Fuying Li、Qingzhang Zhu、Yi Zhang、Ying Feng、Ying Leng、Ao Zhang

  DOI：10.1016/j.bmc.2010.04.038

  日期：2010.6.1

  A series of N-thiazole substituted arylacetamides were designed on the basis of metabolic mechanism of the aminothiazole fragment as glucokinase (GK) activators for the treatment of type 2 diabetes. Instead of introducing a substituent to block the metabolic sensitive C-5 position on the thiazole core directly, a wide variety of C-4 or both C-4 and C-5 substitutions were explored. Compound R-9k bearing an iso-propyl group as the C-4 substituent was found possessing the highest GK activation potency with an EC50 of 0.026 mu M. This compound significantly increased both glucose uptake and glycogen synthesis in rat primary cultured hepatocytes. Moreover, single oral administration of compound R-9k exerted significant reduction of blood glucose levels in both ICR and ob/ob mice. These promising results indicated that compound R-9k is a potent orally active GK activator, and is warranted for further investigation as a new antidiabetic treatment. (C) 2010 Elsevier Ltd. All rights reserved.