5-{[4-[2-(5-ethylpyridin-2-ylo)ethoxy]phenyl]methyl}thiazolidine-2,4-dione | 74772-93-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-{[4-[2-(5-ethylpyridin-2-ylo)ethoxy]phenyl]methyl}thiazolidine-2,4-dione
• 英文别名: pioglitazone；Ploglitazone；5-[[4-[2-(4-ethylphenyl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione
• CAS: 74772-93-3
• 化学式: C₂₀H₂₁NO₃S
• 分子量: 355.458
• InChiKey: CZKMWGGUVIBIOI-UHFFFAOYSA-N

物化性质

• 熔点：
  87-88 °C(Solv: ethyl ether (60-29-7); hexane (110-54-3))
• 沸点：
  561.8±38.0 °C(Predicted)
• 密度：
  1.227±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-{[4-[2-(5-ethylpyridin-2-ylo)ethoxy]phenyl]methyl}thiazolidine-2,4-dione 在 盐酸 作用下， 以 甲醇 、 异丙醇 为溶剂， 以76%的产率得到pioglitazone hydrochloride
  参考文献：
  名称：

  Optimization of the Reduction of a 5-Benzylidenethiazolidine-2,4-dione Derivative Supported by the Reaction Response Surface Analysis:  Synthesis of Pioglitazone Hydrochloride

  摘要：

  A reaction response surface analysis was applied to a series of experiments carried out under various conditions (temperature, time, amount of a catalyst and reduction reagents, purification of the substrate). Significant improvements were made in the C=C bond reduction in the benzylidene-thiazolidinedione intermediate in the synthesis of pioglitazone hydrochloride.

  DOI：

  10.1021/op0300286
• 作为产物：
  描述：

  4-乙基苯乙醇 在 palladium on activated charcoal copper(I) oxide 、 盐酸 、 氢气 、 sodium hydride 、 sodium nitrite 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 5.0~120.0 ℃ 、101.33 kPa 条件下， 反应 19.0h， 生成 5-{[4-[2-(5-ethylpyridin-2-ylo)ethoxy]phenyl]methyl}thiazolidine-2,4-dione
  参考文献：
  名称：

  Studies on antidiabetic agents. II. Synthesis of 5-(4-(1-methylcyclohexylmethoxy)-benzyl)thiazolidine-2,4-dione (ADD-3878) and its derivatives.

  摘要：

  合成了100多种5-取代的噻唑烷-2,4-二酮类化合物，并通过遗传性肥胖和糖尿病小鼠（KK黄色小鼠）评估了它们的降血糖和降血脂活性。结构-活性关系研究表明，5-(4-羟基苄基)部分对于显著活性是必要的。在这些化合物中，5-(4-环己基甲氧基)苄基噻唑烷-2,4-二酮（47）、5-[4-(1-甲基环己基甲氧基)苄基]-噻唑烷-2,4-二酮（49，ADD-3878）和5-{4-[2-(3-吡啶基)乙氧基]苄基}噻唑烷-2,4-二酮（59）在活性和毒性方面表现出最佳特性。

  DOI：

  10.1248/cpb.30.3580

文献信息

• SOHDA, TAKASHI;MIZUNO, KATSUTOSHI;IMAMIYA, EIKO;SUGIYAMA, YASUO;FUJITATAK+, CHEM. AND PHARM. BULL., 1982, 30, N 10, 3580-3600
  作者：SOHDA, TAKASHI、MIZUNO, KATSUTOSHI、IMAMIYA, EIKO、SUGIYAMA, YASUO、FUJITATAK+

  DOI：——

  日期：——
• PPAR-SPARING THIAZOLIDINEDIONE SALTS FOR THE TREATMENT OF METABOLIC DISEASES
  申请人：Cirius Therapeutics, Inc.

  公开号：EP2513070B1

  公开（公告）日：2017-11-08
• PPAR-SPARING THIAZOLIDINEDIONES AND COMBINATIONS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
  申请人：Cirius Therapeutics, Inc.

  公开号：EP3202401B1

  公开（公告）日：2019-10-23
• LANTHIONINE SYNTHETASE COMPONENT C-LIKE PROTEINS AS MOLECULAR TARGETS FOR PREVENTING AND TREATING DISEASES AND DISORDERS
  申请人：BASSAGANYA-RIERA Josep

  公开号：US20110275558A1

  公开（公告）日：2011-11-10

  The present invention relates to the field of medical treatments for diseases and disorders. More specifically, the present invention relates to the use of the lanthionine synthetase component C-like (LANCL) proteins as therapeutic targets for novel classes of anti-inflammatory, immune regulatory and antidiabetic drugs. This includes but it is not limited to abscisic acid (ABA), ABA analogs, benzimidazophenyls, repurposed drugs or drug combinations, including thiazolidinediones (TZDs); naturally occurring compounds such as conjugated diene fatty acids, conjugated triene fatty acids, isoprenoids, and natural and synthetic agonists of peroxisome proliferator-activated receptors that activate this receptor through an alternative mechanism of action involving LANCL2 or other membrane proteins to treat or prevent the common inflammatory pathogenesis underlying type 2 diabetes, atherosclerosis, cancer, some inflammatory infectious diseases such as influenza and autoimmune diseases including but not limited to inflammatory bowel disease (Crohn's disease and Ulcerative colitis), rheumatoid arthritis, multiple sclerosis and type 1 diabetes and other chronic inflammatory conditions.
• Studies on antidiabetic agents. II. Synthesis of 5-(4-(1-methylcyclohexylmethoxy)-benzyl)thiazolidine-2,4-dione (ADD-3878) and its derivatives.
  作者：TAKASHI SOHDA、KATSUTOSHI MIZUNO、EIKO IMAMIYA、YASUO SUGIYAMA、TAKESHI FUJITA、YUTAKA KAWAMATSU

  DOI：10.1248/cpb.30.3580

  日期：——

  More than 100 5-substituted thiazolidine-2, 4-diones were prepared and their hypoglycemic and hypolipidemic activities were evaluated with genetically obese and diabetic mice, yellow KK. The structure-activity relationship study showed that the 5-(4-oxybenzyl) moiety is essential for substantial activity. Among these compounds, 5-(4-cyclohexylmethoxy) benzylthiazolidine-2, 4-dione (47), 5-[4-(1-methylcyclohexylmethoxy) benzyl]-thiazolidine-2, 4-dione (49, ADD-3878) and 5-4-[2-(3-pyridyl) ethoxy] benzyl} thiazolidine-2, 4-dione (59) exhibited the most favorable properties in terms of activity and toxicity.

  合成了100多种5-取代的噻唑烷-2,4-二酮类化合物，并通过遗传性肥胖和糖尿病小鼠（KK黄色小鼠）评估了它们的降血糖和降血脂活性。结构-活性关系研究表明，5-(4-羟基苄基)部分对于显著活性是必要的。在这些化合物中，5-(4-环己基甲氧基)苄基噻唑烷-2,4-二酮（47）、5-[4-(1-甲基环己基甲氧基)苄基]-噻唑烷-2,4-二酮（49，ADD-3878）和5-4-[2-(3-吡啶基)乙氧基]苄基}噻唑烷-2,4-二酮（59）在活性和毒性方面表现出最佳特性。