methyl (E)-3-(3,5-dimethoxyphenyl)-2-(4-(4-((2,4-dioxothiazolidin-5-yl)methyl)phenoxy)phenyl)acrylate | 606932-81-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: methyl (E)-3-(3,5-dimethoxyphenyl)-2-(4-(4-((2,4-dioxothiazolidin-5-yl)methyl)phenoxy)phenyl)acrylate
• 英文别名: 5-(4-(4-(1 carbomethoxy-2-(3,5-dimethoxyphenyl)-ethenyl)-phenoxy)-benzyl)-2,4-thiazolidinedione；3-(3,5-dimethoxyphenyl)-2-{4-[4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxy]-phenyl}-acrylic acid methyl ester；CLX-0921；3-(3,5-Dimethoxyphenyl)-2-(4-(4-(2,4-dioxothiazolidin-5-ylmethyl)-phenoxy)-phenyl)-acrylic acid methyl ester；methyl (E)-3-(3,5-dimethoxyphenyl)-2-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]prop-2-enoate
• CAS: 606932-81-4
• 化学式: C₂₈H₂₅NO₇S
• 分子量: 519.575
• InChiKey: IVAQJHSXBVHUQT-ZVHZXABRSA-N

物化性质

• 熔点：
  126-128 °C
• 沸点：
  706.3±60.0 °C(Predicted)
• 密度：
  1.308±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  8

制备方法与用途

THR-0921是一种过氧化物酶体增殖物激活的γ（PPARγ）激动剂，具有低脂肪生成潜力和抗高血糖活性。

反应信息

• 作为反应物：
  描述：

  methyl (E)-3-(3,5-dimethoxyphenyl)-2-(4-(4-((2,4-dioxothiazolidin-5-yl)methyl)phenoxy)phenyl)acrylate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 15.0h， 以73%的产率得到3-(3,5-dimethoxyphenyl)-2-{4-[4-(2,4-dioxothiazolidin-5-ylmethyl)-phenoxy]-phenyl}-acrylic acid
  参考文献：
  名称：

  Synthesis and structure–Activity relationship studies of cinnamic acid-based novel thiazolidinedione antihyperglycemic agents

  摘要：

  A number of 2,4-thiazolidinedione derivatives of -phenyl substituted cinnamic acid were synthesized and studied for their PPAR agonist activity. The E-isomer of cinnamic acid, 11, showed moderate PPAR transactivation. The corresponding Z-isomer, 23, and double bond reduced derivative, 15, were found to be much less potent. Although the E-isomer showed a moderate PPARgamma transactivation, it demonstrated a strong glucose-lowering effect in a genetic rodent model of diabetes. Results of pharmacokinetic, metabolism and permeability studies are consistent with 11 being an active prodrug with an active metabolite, 14, that has similar glucose lowering and PPARgamma agonist properties. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00393-6
• 作为产物：
  描述：

  3,5-二甲氧基苯甲醛 在 哌啶 、 硫酸 、 platinum on activated charcoal 、 甲酸铵 、 乙酸酐 、 potassium carbonate 、 溶剂黄146 、 三乙胺 、 苯甲酸 作用下， 以 水 、 二甲基亚砜 、 甲苯 为溶剂， 反应 62.0h， 生成 methyl (E)-3-(3,5-dimethoxyphenyl)-2-(4-(4-((2,4-dioxothiazolidin-5-yl)methyl)phenoxy)phenyl)acrylate
  参考文献：
  名称：

  噻唑烷二酮衍生物以及包含其的药物组合物

  摘要：

  本发明涉及噻唑烷二酮衍生物以及包含其的药物组合物。具体地，本发明化合物具有式(I)所示结构，其中各基团和取代基的定义如说明书中所述；本发明还公开了所述化合物作为过氧化物酶体增殖剂激活受体(PPAR)激动剂的用途，具体如用于预防和/或治疗非酒精性脂肪肝炎以及相关的疾病的用途。

  公开号：

  CN112209896B

文献信息

• Novel heterocyclic analogs of diphenylethylene compounds
  申请人：——

  公开号：US20030181494A1

  公开（公告）日：2003-09-25

  Novel diphenylethylene compounds and derivatives thereof containing thiazolidinedione or oxazolidinedione moieties are provided which are effective in lowering blood glucose level, serum insulin, triglyceride and free fatty acid levels in animal models of Type II diabetes. The compounds are disclosed as useful for a variety of treatments including the treatment of inflammation, inflammatory and immunological diseases, insulin resistance, hyperlipidemia, coronary artery disease, cancer and multiple sclerosis.

  提供含有噻唑二酮或噁唑二酮基团的新型二苯乙烯化合物及其衍生物，对II型糖尿病动物模型中的降低血糖水平、血清胰岛素、甘油三酯和游离脂肪酸水平具有有效作用。这些化合物被披露为用于多种治疗，包括治疗炎症、炎症和免疫性疾病、胰岛素抵抗、高脂血症、冠状动脉疾病、癌症和多发性硬化等。
• Novel Heterocyclic analogs of diphenylethylene compounds
  申请人：——

  公开号：US20020025975A1

  公开（公告）日：2002-02-28

  Novel diphenylethylene compounds containing thiazolidinedione or oxazolidinedione moieties are provided which are effective in lowering blood glucose level, serum insulin, triglyceride and free fatty acid levels in animal models of Type II diabetes. In contrast to previously reported thiazolidinedione compounds, known to lower leptin levels, the present compounds increase leptin levels and have no known liver toxicity. The compounds are disclosed as useful for a variety of treatments including the treatment of inflammation, inflammatory and immunological diseases, insulin resistance, hyperlipidemia, coronary artery disease, cancer and multiple sclerosis.

  提供了含有噻唑烷二酮或噁唑烷二酮基团的新型二苯乙烯化合物，这些化合物在动物模型中降低血糖水平、血清胰岛素、甘油三酯和游离脂肪酸水平方面具有有效性。与先前报道的降低瘦素水平的噻唑烷二酮化合物相比，这些化合物增加了瘦素水平，并且没有已知的肝毒性。这些化合物被披露为用于各种治疗，包括治疗炎症、炎症和免疫性疾病、胰岛素抵抗、高脂血症、冠状动脉疾病、癌症和多发性硬化等。
• Compounds for treatment of inflammation, diabetes and related disorders
  申请人：——

  公开号：US20040097593A1

  公开（公告）日：2004-05-20

  Novel acyl urea, thiourea, carbamate, thiocarbamate and related compounds are provided which are effective in inhibiting the cytokine-mediated inflammatory response in cultured cells, in ameliorating bone destruction in an animal model of arthritis and in lowering blood glucose levels in animal models of Type II diabetes mellitus. The compounds are disclosed as useful for a variety of treatments including the treatment of diabetes mellitus, insulin resistance, inflammation, inflammatory diseases, immunological diseases and cancer.

  提供了一系列新型酰基脲、硫脲、氨基甲酸酯、硫代氨基甲酸酯及相关化合物，这些化合物在培养细胞中抑制细胞因子介导的炎症反应、改善动物关节炎模型中的骨破坏以及降低动物2型糖尿病模型中的血糖水平方面具有有效性。这些化合物可用于多种治疗，包括糖尿病、胰岛素抵抗、炎症、炎症性疾病、免疫疾病和癌症的治疗。
• COMPOUNDS FOR TREATMENT OF INFLAMMATION, DIABETES AND RELATED DISORDERS
  申请人：Neogi Partha

  公开号：US20070259961A9

  公开（公告）日：2007-11-08

  Novel acyl urea, thiourea, carbamate, thiocarbamate and related compounds are provided which are effective in inhibiting the cytokine-mediated inflammatory response in cultured cells, in ameliorating bone destruction in an animal model of arthritis and in lowering blood glucose levels in animal models of Type II diabetes mellitus. The compounds are disclosed as useful for a variety of treatments including the treatment of diabetes mellitus, insulin resistance, inflammation, inflammatory diseases, immunological diseases and cancer.

  提供了一系列新型酰基脲、硫脲、氨基甲酸酯、硫代氨基甲酸酯及相关化合物，这些化合物在培养细胞中抑制细胞因子介导的炎症反应、改善关节炎动物模型中的骨破坏和降低2型糖尿病动物模型中的血糖水平方面具有有效性。这些化合物被披露为用于多种治疗，包括糖尿病、胰岛素抵抗、炎症、炎症性疾病、免疫疾病和癌症的治疗。
• [EN] THIAZOLIDINEDIONE DERIVATIVE AND PHARMACEUTICAL COMPOSITION COMPRISING SAME<br/>[FR] DÉRIVÉ DE THIAZOLIDINEDIONE ET COMPOSITION PHARMACEUTIQUE LE COMPRENANT<br/>[ZH] 噻唑烷二酮衍生物以及包含其的药物组合物
  申请人：SUZHOU ZELGEN BIOPHARMACEUTICALS CO LTD

  公开号：WO2021004487A1

  公开（公告）日：2021-01-14

  具有式(I)所示结构的噻唑烷二酮衍生物以及包含其的药物组合物，其中各基团和取代基的定义如说明书中所述。所述化合物作为过氧化物酶体增殖剂激活受体(PPAR)激动剂的用途，具体如用于预防和/或治疗非酒精性脂肪肝炎以及相关的疾病的用途。