6-benzo[b]thiophen-2-yl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 6-benzo[b]thiophen-2-yl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole
• 英文别名: 6-(Benzo[B]thiophen-2-YL)-2,3,5,6-tetrahydroimidazo[2,1-B]thiazole；6-(1-benzothiophen-2-yl)-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole
• 化学式: C₁₃H₁₂N₂S₂
• 分子量: 260.384
• InChiKey: KTWDBZSFGOVAJT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  69.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-benzo[b]thiophen-2-yl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole 在 盐酸 作用下， 以 乙醚 、 水 、 丙酮 为溶剂， 生成 6-benzo[b]thiophen-2-yl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole hydrochloride
  参考文献：
  名称：

  Inhibitors of tissue-nonspecific alkaline phosphatase: Design, synthesis, kinetics, biomineralization and cellular tests

  摘要：

  Chronic kidney disease (CKD) is associated with numerous metabolic and endocrine disturbances, including abnormalities of calcium and phosphate metabolism and an inflammatory syndrome. The latter occurs early in the course of CKD and contributes to the development and progression of vascular calcification. A few therapeutic strategies are today contemplated to target vascular calcification in patients with CKD: vitamin K2, calcimimetics and phosphate binders. However, none has provided complete prevention of vascular calcification and there is an urgent need for alternate efficient treatments. Recent findings indicate that tissue-nonspecific alkaline phosphatase (TNAP) may represent a very promising drug target due to its participation in mineralization by vascular smooth muscle cells. We report the synthesis of four levamisole derivatives having better inhibition property on TNAP than levamisole. Their IC50, Ki and water solubility have been determined. We found that the four inhibitors bind to TNAP in an uncompetitive manner and are selective to TNAP. Indeed, they do not inhibit intestinal and placental alkaline phosphatases. Survival MTT tests on human MG-63 and Saos-2 osteoblast-like cells have been performed in the presence of inhibitors. All the inhibitors are not toxic at concentrations that block TNAP activity. Moreover, they are able to significantly reduce mineralization in MG63 and Saos-2 osteoblast-like cells, indicating that they are promising molecules to prevent vascular calcification. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.053
• 作为产物：
  描述：

  2-乙酰基苯并噻吩 在 吡啶 、 sodium tetrahydroborate 、 氯化亚砜 、 苯基三甲基溴化铵 、 溶剂黄146 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 、 异丙醇 为溶剂， 反应 34.0h， 生成 6-benzo[b]thiophen-2-yl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole
  参考文献：
  名称：

  Inhibitors of tissue-nonspecific alkaline phosphatase: Design, synthesis, kinetics, biomineralization and cellular tests

  摘要：

  Chronic kidney disease (CKD) is associated with numerous metabolic and endocrine disturbances, including abnormalities of calcium and phosphate metabolism and an inflammatory syndrome. The latter occurs early in the course of CKD and contributes to the development and progression of vascular calcification. A few therapeutic strategies are today contemplated to target vascular calcification in patients with CKD: vitamin K2, calcimimetics and phosphate binders. However, none has provided complete prevention of vascular calcification and there is an urgent need for alternate efficient treatments. Recent findings indicate that tissue-nonspecific alkaline phosphatase (TNAP) may represent a very promising drug target due to its participation in mineralization by vascular smooth muscle cells. We report the synthesis of four levamisole derivatives having better inhibition property on TNAP than levamisole. Their IC50, Ki and water solubility have been determined. We found that the four inhibitors bind to TNAP in an uncompetitive manner and are selective to TNAP. Indeed, they do not inhibit intestinal and placental alkaline phosphatases. Survival MTT tests on human MG-63 and Saos-2 osteoblast-like cells have been performed in the presence of inhibitors. All the inhibitors are not toxic at concentrations that block TNAP activity. Moreover, they are able to significantly reduce mineralization in MG63 and Saos-2 osteoblast-like cells, indicating that they are promising molecules to prevent vascular calcification. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.053

文献信息

• [EN] NOVEL BENZOTHIOPHENE DERIVATIVES WITH TNAP-INHIBITING ACTIVITY<br/>[FR] NOUVEAUX DERIVES DE BENZOTHIOPHENE, PRESENTANT UNE ACTIVITE INHIBITRICE DE LA TNAP
  申请人：UNIV CLAUDE BERNARD LYON

  公开号：WO2012052668A1

  公开（公告）日：2012-04-26

  La présente invention concerne des composés de formule (I) : dans laquelle R1, R2, R3, R4, R5, R6, X et Y sont tels que définis à la revendications 1, leur utilisation en tant que médicament, et notamment pour le traitement de l'arthrose ou de calcifications vasculaires, ainsi que les compositions pharmaceutiques les contenant en association avec au moins un excipient pharmaceutiquement acceptable.
• Inhibitors of tissue-nonspecific alkaline phosphatase: Design, synthesis, kinetics, biomineralization and cellular tests
  作者：Julien Debray、Lei Chang、Stéphanie Marquès、Stéphane Pellet-Rostaing、Do Le Duy、Saida Mebarek、René Buchet、David Magne、Florence Popowycz、Marc Lemaire

  DOI：10.1016/j.bmc.2013.09.053

  日期：2013.12

  Chronic kidney disease (CKD) is associated with numerous metabolic and endocrine disturbances, including abnormalities of calcium and phosphate metabolism and an inflammatory syndrome. The latter occurs early in the course of CKD and contributes to the development and progression of vascular calcification. A few therapeutic strategies are today contemplated to target vascular calcification in patients with CKD: vitamin K2, calcimimetics and phosphate binders. However, none has provided complete prevention of vascular calcification and there is an urgent need for alternate efficient treatments. Recent findings indicate that tissue-nonspecific alkaline phosphatase (TNAP) may represent a very promising drug target due to its participation in mineralization by vascular smooth muscle cells. We report the synthesis of four levamisole derivatives having better inhibition property on TNAP than levamisole. Their IC50, Ki and water solubility have been determined. We found that the four inhibitors bind to TNAP in an uncompetitive manner and are selective to TNAP. Indeed, they do not inhibit intestinal and placental alkaline phosphatases. Survival MTT tests on human MG-63 and Saos-2 osteoblast-like cells have been performed in the presence of inhibitors. All the inhibitors are not toxic at concentrations that block TNAP activity. Moreover, they are able to significantly reduce mineralization in MG63 and Saos-2 osteoblast-like cells, indicating that they are promising molecules to prevent vascular calcification. (C) 2013 Elsevier Ltd. All rights reserved.