2-(2-ethylbutylthio)benzo[d]thiazol-6-ol | 1421917-11-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 2-(2-ethylbutylthio)benzo[d]thiazol-6-ol
• 英文别名: 2-(2-ethylbutylthio)benzothiazol-6-ol；2-(2-Ethylbutylsulfanyl)-1,3-benzothiazol-6-ol；2-(2-ethylbutylsulfanyl)-1,3-benzothiazol-6-ol
• CAS: 1421917-11-4
• 化学式: C₁₃H₁₇NOS₂
• 分子量: 267.416
• InChiKey: QHRHMCINGRZCFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  86.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-乙氧基-2-巯基苯并噻唑 在 aluminum (III) chloride 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 2-(2-ethylbutylthio)benzo[d]thiazol-6-ol
  参考文献：
  名称：

  Synthesis and Mechanism of Hypoglycemic Activity of Benzothiazole Derivatives

  摘要：

  Adenosine 5'-monophosphate activated protein kinase (AMPK) has emerged as a major potential target for novel antidiabetic drugs. We studied the structure of 2-chloro-5-((Z)-((E)-5-((5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl)methylene)-4-oxothiazolidin-2-ylidene)amino)benzoic acid (PT-1), which attenuates the autoinhibition of the enzyme AMPK, for the design and synthesis of different benzothiazoles with potential antidiabetic activity. We synthesized several structurally related benzothiazole derivatives that increased the rate of glucose uptake in L6 myotubes in an AMPK-dependent manner. One compound, 2-(benzo[d]thiazol-2-ylmethylthio)-6-ethoxybenzo[d]thiazole (34), augmented the rate of glucose uptake up to 2.5-fold compared with vehicle-treated cells and up to 1.1-fold compared to PT-1. Concomitantly, it elevated the abundance of GLUT4 in the plasma membrane of the myotubes and activated AMPK. Subcutaneous administration of 34 to hyperglycemic Kuo Kondo rats carrying the Ay-yellow obese gene (KKAy) mice lowered blood glucose levels toward the normoglycemic range. In accord with its activity, compound 34 showed a high fit value to a pharmacophore model derived from the PT-1.

  DOI：

  10.1021/jm4001488

文献信息

• COMPOUNDS AND COMPOSITIONS FOR USE IN AUGMENTATION OF GLUCOSE
  申请人：Sasson Shlomo

  公开号：US20150025094A1

  公开（公告）日：2015-01-22

  The present invention is directed to compounds such as: formula wherein linker is independently selected from the group consisting of —S—, —S—S—, —S—(CH2)n—, —NH—, —NH—(CH2)n—, —O—, —S02-, arylene, heteroarylene; R1 is selected from the group consisting of straight or branched C4-C20 alkyl, straight or branched C4-C20 alkenyl, straight or branched C4-C20 alkynyl, each optionally interrupted with at least one NH, C5-C7 saturated cycloalkyl or heteroalkyl ring, C5-C12 aromatic or heteroaromatic ring, each optionally substituted with at least one group selected from —COOH, —NH2, C1-C8 alkoxy, C1-C5 amidyle, C1-C5 carboxyl, halogen; and R2 is independently selected from the group consisting of H, OH, SH, NH2, NO2, halogen, CN, C1-C8 alkoxy, C1-C5 carboxylic acid, straight or branched C1-C8 alkyl, straight or branched C2-C10 alkenyl, straight or branched C2-C12 alkynyl each optionally substituted by at least one substituent selected from the group consisting of C1-C5 alkoxy, C1-C5 carboxylic acid, OH, SH, NH2, halogen; and compositions for use in the treatment of diabetes and related dis orders.

  本发明涉及化合物，例如：式中，连接体独立地选自由以下组成的群组：—S—、—S—S—、—S—(CH2)n—、—NH—、—NH—(CH2)n—、—O—、—S02-、芳基和杂环芳基；R1选自由以下组成的群组：直链或支链的C4-C20烷基、直链或支链的C4-C20烯基、直链或支链的C4-C20炔基，每个选项均可中断至少一个NH、C5-C7饱和环烷基或杂基环、C5-C12芳香或杂环芳香环，每个选项均可用至少一种从—COOH、—NH2、C1-C8烷氧基、C1-C5酰胺基、C1-C5羧基和卤素中选取的基团进行取代；R2独立地选自由以下组成的群组：H、OH、SH、NH2、NO2、卤素、CN、C1-C8烷氧基、C1-C5羧酸、直链或支链的C1-C8烷基、直链或支链的C2-C10烯基、直链或支链的C2-C12炔基，每个选项均可用至少一种从C1-C5烷氧基、C1-C5羧酸、OH、SH、NH2和卤素中选取的取代基团进行取代；以及用于治疗糖尿病及相关疾病的组合物。
• COMPOUNDS AND COMPOSITIONS FOR USE IN AUGMENTATION OF GLUCOSE UPTAKE AND INSULIN SECRETION
  申请人：Yissum Research Development Company of The Hebrew University of Jerusalem Ltd.

  公开号：EP2739612A1

  公开（公告）日：2014-06-11
• US9409904B2
  申请人：——

  公开号：US9409904B2

  公开（公告）日：2016-08-09
• [EN] COMPOUNDS AND COMPOSITIONS FOR USE IN AUGMENTATION OF GLUCOSE UPTAKE AND INSULIN SECRETION<br/>[FR] COMPOSÉS ET COMPOSITIONS POUR UNE UTILISATION DANS L'AUGMENTATION DE L'ABSORPTION DU GLUCOSE ET DE LA SÉCRÉTION D'INSULINE
  申请人：YISSUM RES AND DEV OF THE HEBREW UNIVERSITY OF JERUSALEM LTD

  公开号：WO2013018095A1

  公开（公告）日：2013-02-07

  The present invention is directed to compounds such as: formula wherein linker is independently selected from the group consisting of -S-, -S-S-, -S-(CH2)n-, -NH-, -NH-(CH2)n-, -0-, -S02-, arylene, heteroarylene; Rl is selected from the group consisting of straight or branched C4- C20 alkyl, straight or branched C4-C20 alkenyl, straight or branched C4-C20 alkynyl, each optionally interrupted with at least one NH, C5- C7 saturated cycloalkyl or heteroalkyl ring, C5-C12 aromatic or het- eroaromatic ring, each optionally substituted with at least one group selected from -COOH, -NH2, C1-C8 alkoxy, C1-C5 amidyle, C1-C5 car- boxyl, halogen; and R2 is independently selected from the group consisting of H, OH, SH, NH2, N02, halogen, CN, C1-C8 alkoxy, C1-C5 carboxylic acid, straight or branched C1-C8 alkyl, straight or branched C2-C10 alkenyl, straight or branched C2 - C12 alkynyl each optionally substituted by at least one substituent selected from the group consisting of C1-C5 alkoxy, C1-C5 carboxylic acid, OH, SH, NH2, halogen; and compositions for use in the treatment of diabetes and related dis¬ orders.
• Synthesis and Mechanism of Hypoglycemic Activity of Benzothiazole Derivatives
  作者：Ella Meltzer-Mats、Gali Babai-Shani、Lily Pasternak、Neta Uritsky、Tamar Getter、Olga Viskind、Jürgen Eckel、Erol Cerasi、Hanoch Senderowitz、Shlomo Sasson、Arie Gruzman

  DOI：10.1021/jm4001488

  日期：2013.7.11

  Adenosine 5'-monophosphate activated protein kinase (AMPK) has emerged as a major potential target for novel antidiabetic drugs. We studied the structure of 2-chloro-5-((Z)-((E)-5-((5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl)methylene)-4-oxothiazolidin-2-ylidene)amino)benzoic acid (PT-1), which attenuates the autoinhibition of the enzyme AMPK, for the design and synthesis of different benzothiazoles with potential antidiabetic activity. We synthesized several structurally related benzothiazole derivatives that increased the rate of glucose uptake in L6 myotubes in an AMPK-dependent manner. One compound, 2-(benzo[d]thiazol-2-ylmethylthio)-6-ethoxybenzo[d]thiazole (34), augmented the rate of glucose uptake up to 2.5-fold compared with vehicle-treated cells and up to 1.1-fold compared to PT-1. Concomitantly, it elevated the abundance of GLUT4 in the plasma membrane of the myotubes and activated AMPK. Subcutaneous administration of 34 to hyperglycemic Kuo Kondo rats carrying the Ay-yellow obese gene (KKAy) mice lowered blood glucose levels toward the normoglycemic range. In accord with its activity, compound 34 showed a high fit value to a pharmacophore model derived from the PT-1.