5-(3-乙氧基-4-戊氧基苯基)-1,3-噻唑烷-2,4-二酮 | 79714-31-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 5-(3-乙氧基-4-戊氧基苯基)-1,3-噻唑烷-2,4-二酮
• 英文名称: risarestat
• 英文别名: 5-(3-ethoxy-4-n-pentyloxyphenyl)thiazolidine-2,4-dione；CT 112；5-[3-ethoxy-4-(pentyloxy)phenyl]-2,4-thiazolidinedione；5-(3-ethoxy-4-pentyloxyphenyl)-2,4-thiazolidinedion；CT-112；5-(3-ethoxy-4-pentyloxyphenyl)-2,4-thiazolidinedione；5-(3-ethoxy-4-pentoxyphenyl)-1,3-thiazolidine-2,4-dione
• CAS: 79714-31-1
• 化学式: C₁₆H₂₁NO₄S
• 分子量: 323.413
• InChiKey: CRPGRUONUFDYBG-UHFFFAOYSA-N

物化性质

• 沸点：
  485.9±45.0 °C(Predicted)
• 密度：
  1.189±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 储存条件：
  2-8℃

制备方法与用途

生物活性

Risarestat（CT-112）是一种醛糖还原酶抑制剂，用于研究糖尿病并发症。

体内研究

Risarestat 在剂量依赖性地抑制山梨醇的积累方面表现出良好效果，除了1.0%溶液的效果与0.25%溶液相似。在滴入后30分钟内，Risarestat 分布于角膜上皮、基质、内皮和房水中，并随着时间逐渐减弱，在24小时内基本消失。在2小时时达到峰值浓度，持续24小时内仍可在晶状体内检测到。

与Risarestat 处理组相比，对照组的浅层细胞前表面面积从平均值881微米²显著减少至728微米²。角膜敏感度显著提高，从5.36 g/mm² 增加到1.37 g/mm²。

与未治疗的 galactose 饲养大鼠相比，接受 Risarestat 滴眼液处理的大鼠在7个月研究结束时显示出明显增加的平均眨眼反应。而未治疗的 galactose 饲养大鼠和滴眼液给予 Risarestat 的大鼠在3周内均发展为双侧核性白内障。

反应信息

• 作为产物：
  描述：

  3-Ethoxy-I+/--hydroxy-4-(pentyloxy)benzeneacetonitrile 在 盐酸 、 氯化亚砜 作用下， 以 氯仿 为溶剂， 反应 16.0h， 生成 5-(3-乙氧基-4-戊氧基苯基)-1,3-噻唑烷-2,4-二酮
  参考文献：
  名称：

  Studies on antidiabetic agents. III. 5-Arylthiazolidine-2,4-diones as potent aldose reductase inhibitors.

  摘要：

  具有一个或两个取代基（如苯基、杂基和烷基）的噻唑烷-2,4-二酮衍生物在5位合成并评估为醛糖还原酶抑制剂。在鼠晶状体培养检测中，活性化合物的抑制作用也被测量。在这些化合物中，一系列5-(3,4-二烷氧基苯基)噻唑烷-2,4-二酮在两种检测中显示出显著的活性。结构-活性关系进行了讨论，并描述了一种合成5-芳基噻唑烷-2,4-二酮的新方法。

  DOI：

  10.1248/cpb.30.3601

文献信息

• [EN] 1,1'-(1,2-ETHYNEDIYL)BIS-BENZENE DERIVATIVES AS PTP 1-B INHIBITORS<br/>[FR] DERIVES DE 1,1'-(1,2-ETHYNEDIYLE)BIS-BENZENE INHIBITEURS DE PTP 1-B
  申请人：APPLIED RESEARCH SYSTEMS

  公开号：WO2005097773A1

  公开（公告）日：2005-10-20

  The present invention is related to carboxylic acids of Formula (I) and use thereof for the treatment and/or prevention of obesity and/or metabolic disorders mediated by insulin resistance or hyperglycemia, comprising diabetes type I and/or II, inadequate glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of carboxylic acids of Formula (I) to modulate, notably to inhibit the activity of PTPs.

  本发明涉及式(I)的羧酸及其用于治疗和/或预防肥胖和/或由胰岛素抵抗或高血糖介导的代谢紊乱的使用，包括I型和/或II型糖尿病、葡萄糖耐量不足、胰岛素抵抗、高脂血症、高甘油三酯血症、高胆固醇血症、多囊卵巢综合征（PCOS）。特别是，本发明涉及使用式(I)的羧酸来调节，尤其是抑制PTPs的活性。
• [EN] ARYL DICARBOXAMIDES<br/>[FR] ARYL-DICARBOXAMIDES
  申请人：APPLIED RESEARCH SYSTEMS

  公开号：WO2005011685A1

  公开（公告）日：2005-02-10

  The present invention is related to aryl dicarboxamides of formula (I) and use thereof for the treatment and/or prevention of obesity and/or metabolic disorders mediated by insulin resistance or hyperglycernia, comprising diabetes type I and/or II, inadequate glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia, hypercholes-terolemia, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of aryl dicarboxamides of formula (I) to modulate, notably to inhibit the activity of PTPs. A is an airninocarbonyl moiety; Cy is an aryl, heteroaryl, aryl-heteroaryl, heteroaryl-aryl, aryl-aryl, cycloalkyl or heterocycle group; n is either 0 or 1; R1 and R2 are independently from each other is selected from the group consisting of hydrogen or C1-C6-alkyl; R4 and R5 are each independently from each other selected from the group consisting of H, hydroxy, C1-C6 alkyl, carboxy, C1-C6 alkoxy, C1-C3 alkyl carboxy, C2-C3 alkenyl carboxy, C2-C3 alkynyl carboxy, amino or R4 and R5 may form an unsaturated or saturated heterocyclic ring, whereby at least one of R4 or R5 is not a hydrogen or C1-C6 alkyl.

  本发明涉及式(I)的芳基二羧酰胺及其用于治疗和/或预防肥胖和/或由胰岛素抵抗或高血糖介导的代谢紊乱的使用，包括I型和/或II型糖尿病、葡萄糖耐量不足、胰岛素抵抗、高脂血症、高甘油三酯血症、高胆固醇血症、多囊卵巢综合征(PCOS)。特别是，本发明涉及使用式(I)的芳基二羧酰胺调节，尤其是抑制PTPs的活性。A是氨基甲酰基团；Cy是芳基、杂芳基、芳基-杂芳基、杂芳基-芳基、芳基-芳基、环烷基或杂环组；n为0或1；R1和R2独立地选自由氢或C1-C6-烷基组成的组；R4和R5各自独立地选自由H、羟基、C1-C6烷基、羧基、C1-C6烷氧基、C1-C3烷基羧基、C2-C3烯基羧基、C2-C3炔基羧基、氨基组成的组，或者R4和R5可以形成一个不饱和或饱和的杂环，其中至少R4或R5不是氢或C1-C6烷基。
• Compositions and methods for enhancing drug delivery across and into ocular tissues
  申请人：CellGate, Inc., a Delaware corporation

  公开号：US20030022831A1

  公开（公告）日：2003-01-30

  This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including into and across ocular tissues and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transporter that has sufficient guanidino or amidino sidechain moieties to enhance delivery of a compound conjugated to the reagent across one or more layers of the tissue, compared to the non-conjugated compound. The delivery-enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 25 residues in length.

  这项发明提供了增强药物和其他药剂通过上皮组织传递的组合物和方法，包括进入和穿过眼组织等。这些组合物和方法也适用于穿过内皮组织，包括血脑屏障。这些组合物和方法利用了一种具有足够的瓜二或酰胺基侧链基团以增强与试剂结合的化合物穿过组织一层或多层的传递的传递增强转运体，与非结合化合物相比。传递增强聚合物包括，例如，多精氨酸分子，其长度在大约6到25个残基之间。
• Combination of a PTPase inhibitor and an aldose reductase inhibitor
  申请人：Wyeth

  公开号：US20020198201A1

  公开（公告）日：2002-12-26

  This invention provides methods for utilizing a PTPase inhibiting compounds and an aldose reductase inhibitor, including, but not limited to Minalrestat Tolrestat, Sorbinil, Methosorbinil, Zopolrestat, Epalrestat, Zenarestat Imirestat, and Ponalrestat, in methods for use in control and maintenance of type II diabetes in a mammal, for improving the cardiovascular and cerebrovascular risk profiles, reduction of, diabetic neuropathy, hyperlipidemia, lowering low density lipoprotein blood levels, lowering free fatty acid blood levels and triglyceride levels and inhibition, prevention or reduction of atherosclerosis in a type II diabetic, or the risk factors thereof.

  本发明提供了利用PTPase抑制剂和醛糖还原酶抑制剂的方法，包括但不限于Minalrestat Tolrestat、Sorbinil、Methosorbinil、Zopolrestat、Epalrestat、Zenarestat Imirestat和Ponalrestat，用于控制和维持哺乳动物中的2型糖尿病，改善心血管和脑血管风险，减少糖尿病神经病变、高脂血症，降低低密度脂蛋白血液水平、降低游离脂肪酸血液水平和三酰甘油水平，并抑制、预防或减少2型糖尿病或其风险因素的动脉粥样硬化的方法。
• Substituted methylene amide derivatives as modulators of protein tyrosine phosphatases(ptps)
  申请人：Swinnen Dominique

  公开号：US20050124656A1

  公开（公告）日：2005-06-09

  The present invention is related to substituted methylene amide derivatives of formula (I) and use thereof for the treatment and/or prevention of metabolic disorders mediated by insulin resistance or pyperglycemia, comprising diabetes type I and/or II, inadequate glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, obesity, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of substituted methylene amide derivatives of formula (I) to modulate, notably to inhibit the activity of PTPs. Also the present invention relates to a method of treating diabetes type II, obesity and to regulate the appetite of mammals. The present invention is furthermore related to novel substituted methylene amide derivatives and method of preparation thereof. Formula (I).

  本发明涉及公式（I）的取代亚甲基酰胺衍生物及其用于治疗和/或预防由胰岛素抵抗或高血糖引起的代谢障碍，包括1型和/或2型糖尿病、不足的葡萄糖耐受性、胰岛素抵抗、高脂血症、高三酰甘油血症、高胆固醇血症、肥胖症、多囊卵巢综合症（PCOS）。特别是，本发明涉及使用公式（I）的取代亚甲基酰胺衍生物来调节，尤其是抑制PTP的活性。本发明还涉及一种治疗2型糖尿病、肥胖症和调节哺乳动物食欲的方法。此外，本发明还涉及新的取代亚甲基酰胺衍生物及其制备方法。公式（I）。