5-(4-Phenoxy-benzylidene)-thiazolidine-2,4-dione | 438190-31-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(4-Phenoxy-benzylidene)-thiazolidine-2,4-dione
• 英文别名: (5Z)-5-[(4-phenoxyphenyl)methylidene]-1,3-thiazolidine-2,4-dione
• CAS: 438190-31-9
• 化学式: C₁₆H₁₁NO₃S
• 分子量: 297.334
• InChiKey: YDMLRGYVPHSVSL-UVTDQMKNSA-N

物化性质

• 密度：
  1.379±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 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-Phenoxy-benzylidene)-thiazolidine-2,4-dione 在 盐酸 、 potassium carbonate 、 溶剂黄146 作用下， 以 丙酮 为溶剂， 反应 26.0h， 生成 2-(2,4-Dioxo-5-(4-phenoxybenzylidene)thiazolidin-3-yl)acetic acid
  参考文献：
  名称：

  Structure–activity relationships and molecular modelling of 5-arylidene-2,4-thiazolidinediones active as aldose reductase inhibitors

  摘要：

  The structure-activity relationships (SARs) of 5-arylidene-2,4-thiazolidinediones active as aldose reductase inhibitors (ARIs) were extended by varying the substitution pattern on the 5-arylidene moiety and on N-3. In particular, the introduction of an additional aromatic ring or an H-bond donor group on the 5-benzylidene ring enhanced ALR2 inhibitory potency. Moreover, the presence of a carboxylic anionic chain on N-3 was shown to be an important, although not essential, structural requisite to produce high levels of ALR2 inhibition. The length of this carboxylic chain was critical and acetic acids 4 were the most effective inhibitors among the tested derivatives. Molecular docking simulations into the ALR2 active site accorded with the in vitro inhibition data. They allowed the rationalization of the observed SARs and provided a pharmacophoric model for this class of ARIs. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.02.026
• 作为产物：
  描述：

  2,4-噻唑烷二酮 、 4-苯氧基苯甲醛 在 C₅H₁₁N 作用下， 以 乙醇 为溶剂， 生成 5-(4-Phenoxy-benzylidene)-thiazolidine-2,4-dione
  参考文献：
  名称：

  包含2,4-噻唑烷二酮衍生物的非羧酸的合成，诱导对接研究和体外醛糖还原酶抑制活性。

  摘要：

  在继续我们的研究中，我们在这里报告了一系列含有2,4-噻唑烷二酮的非羧酸衍生物，它们是先前合成的羧酸的类似物，我们发现它们在体外是非常有效的醛糖还原酶（ALR2）抑制剂。尽管用羧酰胺或N-羟基羧酰胺取代羧基会降低体外对ALR2的抑制作用，但这导致鉴定出具有微摩尔ALR2亲和力的主要是非电离的衍生物。5-亚芳基部分深刻地影响了这些2，4-噻唑烷二酮的活性。我们的诱导拟合对接研究表明，5-（4-羟基亚苄基）取代的衍生物可能通过去质子化的酚基团结合ALR2活性位点的极性识别区，

  DOI：

  10.1016/j.bmc.2008.04.072

文献信息

• 5-Arylidene-4-Thiazolidinone Derivatives Active as Antidegenerative Agents on Human Chondrocyte Cultures
  作者：Annamaria Panico、Rosanna Maccari、Venera Cardile、Lucia Crasci、Simone Ronsisvalle、Rosaria Ottana

  DOI：10.2174/157340613804488378

  日期：2013.2.1

  5-Arylidene-2-oxo-4-thiazolidinones and 2-phenylimino analogues were evaluated for their antidegenerative activity on human chondrocyte cultures stimulated by IL-1β and for their inhibitory capability against matrix metalloproteinase- 13. Our results indicated that 5-arylidene-4-thiazolidinone derivatives 1-9 exhibit antidegenerative activity and could block multiple cartilage destruction during the osteoarthritic process. Out of the selected compounds, (5-arylidene- 2,4-dioxothiazolidin-3-yl)acetic acids 7-9 showed significant effectiveness in reducing NO release and restoring normal levels of GAGs in chondrocytes treated with IL-1β. Moreover, benzoic acids 1, 5 and 6 proved to be effective MMP-13 inhibitors and were able to restore normal levels of GAGs.

  5-芳基亚乙烯基-2-氧基-4-噻唑烷酮和2-苯基亚胺类似物被评估其在IL-1β刺激下的人类软骨细胞培养中的抗退化活性及其对基质金属蛋白酶-13的抑制能力。我们的结果表明，5-芳基亚乙烯基-4-噻唑烷酮衍生物1-9表现出抗退化活性，能够在骨关节炎过程中阻止多重软骨破坏。在选择的化合物中，(5-芳基-2,4-二氧噻唑烷-3-基)乙酸7-9在减少NO释放和恢复接受IL-1β处理的软骨细胞正常GAGs水平方面显示出显著效果。此外，苯甲酸1、5和6被证实为有效的MMP-13抑制剂，并能够恢复正常的GAGs水平。
• NOVEL THIAZOLIDINEDIONE DERIVATIVE AND USE THEREOF
  申请人：Cho Hoon

  公开号：US20110269954A1

  公开（公告）日：2011-11-03

  The present invention relates to novel thiazolidinedione derivatives expressed by the following formula (I) and the uses thereof. More specifically, the present invention relates to novel thiazolidinedione derivatives expressed by the following formula (I) and a pharmaceutical composition comprising the same. The novel thiazolidinedione derivatives of formula (I) according to the present invention can be effectively used for the prevention or treatment of cardiovascular disease, gastrointestinal disease and renal disease by inhibiting the activity of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) that decomposes prostaglandins as well as useful for the prevention of hair loss and the stimulation of hair growth, and osteogenic stimulation and wound healing.

  本发明涉及由以下式（I）表示的新型噻唑烷二酮衍生物及其用途。更具体地说，本发明涉及由以下式（I）表示的新型噻唑烷二酮衍生物以及包含其的药物组合物。根据本发明的式（I）的新型噻唑烷二酮衍生物可以通过抑制分解前列腺素的15-羟基前列腺素脱氢酶（15-PGDH）的活性，有效用于预防或治疗心血管疾病、胃肠道疾病和肾脏疾病，同时也用于预防脱发和促进头发生长，以及促进骨生成和伤口愈合。
• Identification of new non-carboxylic acid containing inhibitors of aldose reductase
  作者：Rosanna Maccari、Rosella Ciurleo、Marco Giglio、Mario Cappiello、Roberta Moschini、Antonella Del Corso、Umberto Mura、Rosaria Ottanà

  DOI：10.1016/j.bmc.2010.04.016

  日期：2010.6.1

  Non-carboxylic acid containing bioisosteres of (5-arylidene-2,4-dioxothiazolidin-3-yl)acetic acids, which are active as aldose reductase (ALR2) inhibitors, were designed by replacing the carboxylic group with the trifluoromethyl ketone moiety. The in vitro evaluation of the ALR2 inhibitory effects of these trifluoromethyl substituted derivatives led to the identification of two inhibitors effective

  通过用三氟甲基酮部分取代羧基，设计了作为醛糖还原酶（ALR2）抑制剂具有活性的（5-亚芳基-2,4-二氧噻唑并恶唑烷-3-基）乙酸的非羧酸生物甾醇。这些三氟甲基取代的衍生物对ALR2抑制作用的体外评估导致鉴定出两种在低微摩尔剂量下有效的抑制剂。进一步证实，噻唑烷二酮支架的N-3上的羧基是获得最高功效水平的决定性条件。然而，对于与靶酶的相互作用不是必需的，并且可以被不同的极性基团取代，从而获得较少的离子化或工会化的抑制剂。
• In Search for Multi-Target Ligands as Potential Agents for Diabetes Mellitus and Its Complications—A Structure-Activity Relationship Study on Inhibitors of Aldose Reductase and Protein Tyrosine Phosphatase 1B
  作者：Rosaria Ottanà、Paolo Paoli、Mario Cappiello、Trung Ngoc Nguyen、Ilenia Adornato、Antonella Del Corso、Massimo Genovese、Ilaria Nesi、Roberta Moschini、Alexandra Naß、Gerhard Wolber、Rosanna Maccari

  DOI：10.3390/molecules26020330

  日期：——

  possibility to target both aldose reductase (AR) and protein tyrosine phosphatase 1B (PTP1B), two enzymes strictly implicated in the development of DM and its complications, we synthesised 3-(5-arylidene-4-oxothiazolidin-3-yl)propanoic acids and analogous 2-butenoic acid derivatives, with the aim of balancing the effectiveness of dual AR/PTP1B inhibitors which we had identified as designed multiple ligands

  糖尿病 (DM) 是一种复杂的疾病，目前影响超过 4.6 亿人，是全球主要的死亡原因之一。它的发展意味着许多代谢功能障碍和高血糖引起的慢性并发症的发生。可以合理设计多种配体用于治疗多因素疾病，例如 DM，其精确目标是同时控制与疾病相关的多种致病机制，并提供比选择性药物组合更有效、更安全的治疗方法。我们之前的研究结果强调了靶向醛糖还原酶 (AR) 和蛋白酪氨酸磷酸酶 1B (PTP1B) 的可能性，这两种酶与 DM 及其并发症的发展密切相关，我们合成了 3-(5-arylidene-4-oxothiazolidin-3-yl) 丙酸和类似的 2-丁烯酸衍生物，目的是平衡双 AR/PTP1B 抑制剂的有效性，我们已将其鉴定为设计的多配体 (DMLs) ）。在测试的化合物中，4f 在低微摩尔浓度下表现出均衡的 AR/PTP1B 抑制作用，以及在鼠 C2C12 细胞培养物中有趣的胰岛素敏化活性。此处强调的
• Synthesis and aldose reductase inhibitory activity of 5-arylidene-2,4-thiazolidinediones
  作者：G Bruno、L Costantino、C Curinga、R Maccari、F Monforte、F Nicolò、R Ottanà、M.G Vigorita

  DOI：10.1016/s0968-0896(01)00366-2

  日期：2002.4

  synthesized and tested as aldose reductase inhibitors (ARIs). The most active of the N-unsubstituted derivatives (2) exerted the same inhibitory activity of Sorbinil. The introduction of an acetic side chain on N-3 of the thiazolidinedione moiety led to a marked increase in lending inhibitory activity, conducting to the discovery of a very potent ARI (4c), whose activity level (IC50=0.13 microM) was

  合成了几种（Z）-5-芳基-2,4-噻唑烷二酮并作为醛糖还原酶抑制剂（ARIs）进行了测试。N-未取代的衍生物中活性最高的（2）发挥了索比尼尔相同的抑制活性。在噻唑烷二酮部分的N-3上引入乙酸侧链导致放贷抑制活性显着增加，从而发现了非常有效的ARI（4c），其活性水平（IC50 = 0.13 microM）处于Tolrestat的范围相同。此外，没有任何酸性官能团的相应的甲酯（3）显示出与N-未取代的化合物相似的明显的抑制活性。还发现5-亚苄基部分上的取代模式显着影响N-未取代的2,4-噻唑烷二酮2的活性。在间位具有取代基的化合物通常比对位取代的化合物更有效；但是，在乙酸3和酸4中没有发现这种SAR。