(Z)-5-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methylene]-2,4-thiazolidinedione | 154052-44-5

• 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: (Z)-5-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methylene]-2,4-thiazolidinedione
• 英文别名: (Z)-5-<<3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl>methylene>-2,4-thiazolidinedione；(Z)-5-(3,5-di-tert-butyl-4-hydroxyphenylmethylene)-2,4-thiazolidinedione；5-(3,5-di-tert-butyl-4-hydroxy-benzylidene)-thiazolidine-2,4-dione；(Z)-5-[(3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl)methylene]-2,4-thiazolidinedione；5-((3,5-Bis(1,1-dimethylethyl)-4-hydroxyphenyl)methylene)-2,4-thiazolidinedione；(5Z)-5-[(3,5-ditert-butyl-4-hydroxyphenyl)methylidene]-1,3-thiazolidine-2,4-dione
• CAS: 154052-44-5
• 化学式: C₁₈H₂₃NO₃S
• 分子量: 333.452
• InChiKey: VMWQYEAAXYPFCW-LCYFTJDESA-N

物化性质

• 熔点：
  240-242 °C
• 密度：
  1.204±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  91.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (Z)-5-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methylene]-2,4-thiazolidinedione 在 吡啶 、 1,3-二甲基-2-咪唑啉酮 、 锂硼氢 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以89%的产率得到5-(3,5-二叔丁基-4-羟基苄基)噻唑烷-2,4-二酮
  参考文献：
  名称：

  Regiospecific Reduction of 5-Benzylidene-2,4-Thiazolidinediones and 4-Oxo-2-thiazolidinethiones using Lithium Borohydride in Pyridine and Tetrahydrofuran

  摘要：

  The novel regiospecific and general reduction of 5-benzylidene-2,4-thiazolidinediones and 5-benzylidene-4-oxo-2-thiazolidinethiones to the corresponding 5-benzyl derivatives has been accomplished using lithium borohydride in pyridine and tetrahydrofuran. Sodium borohydride and lithium chloride can also be used under these conditions, which represents a cheaper alternative to lithium borohydride. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(00)00361-6
• 作为产物：
  描述：

  2,4-噻唑烷二酮 、 3,5-二叔丁基-4-羟基苯甲醛 在 sodium acetate 、 溶剂黄146 作用下， 反应 48.0h， 以27%的产率得到(Z)-5-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methylene]-2,4-thiazolidinedione
  参考文献：
  名称：

  5-[[[3,5-双（1,1-二甲基乙基）-4-羟基苯基]亚甲基]恶唑，-噻唑和-咪唑的合成和生物学评估：新型的具有抗炎活性的双重5-脂氧合酶和环加氧酶抑制剂。

  摘要：

  制备了各种衍生自2,6-二叔丁基苯酚的亚苄基恶唑，-噻唑和-咪唑，并将其评估为大鼠嗜碱性白血病（RBL-1）细胞中5-脂氧合酶和环氧合酶的双重抑制剂。目标化合物对两种酶表现出不同程度的选择性。几种化合物在大鼠角叉菜胶足垫水肿（CFE）和分枝杆菌足垫水肿（MFE）抗炎模型中具有口服活性。讨论了构效关系。根据这项工作，将（Z）-5-[[3,5-双（1,1-二甲基乙基）-4-羟苯基]-亚甲基] -2-亚氨基-4-噻唑烷酮甲烷磺酸盐（CI-1004）鉴定为一种有效的5-脂氧合酶（IC50 = 0.77 microM）和环氧合酶（IC50 = 0.39 microM）双重抑制剂，在大鼠MFE炎症模型中具有口服活性（ID40 = 0.6 mg / kg）。

  DOI：

  10.1021/jm00028a017

文献信息

• Cytoprotective compounds, pharmaceutical and cosmetic formulations, and methods
  申请人：——

  公开号：US20030073712A1

  公开（公告）日：2003-04-17

  Cytoprotective compounds, many of which are phenolic derivatives characterized by a substituted phenol having certain conjugated bonds, are useful in the treatment of certain ischemic or inflammatory conditions, including but not limited to stroke, myocardial infarction, congestive heart failure, and skin disorders characterized by inflammation or oxidative damage. They are also useful in the manufacture of pharmaceutical and cosmetic formulations for the treatment of such conditions.

  细胞保护化合物，其中许多是酚类衍生物，其特点是具有特定共轭键的取代酚，对于治疗某些缺血或炎症性疾病非常有用，包括但不限于中风、心肌梗死、充血性心力衰竭以及以炎症或氧化损伤为特征的皮肤疾病。它们还可用于制造用于治疗这些疾病的药物和化妆品配方。
• Synthesis and biological evaluation of 5-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methylene]oxazoles, -thiazoles, and -imidazoles: novel dual 5-lipoxygenase and cyclooxygenase inhibitors with antiinflammatory activity
  作者：Paul C. Unangst、David T. Connor、Wiaczeslaw A. Cetenko、Roderick J. Sorenson、Catherine R. Kostlan、Jagadish C. Sircar、Clifford D. Wright、Denis J. Schrier、Richard D. Dyer

  DOI：10.1021/jm00028a017

  日期：1994.1

  A variety of benzylideneoxazoles, -thiazoles, and -imidazoles derived from 2,6-di-tert-butylphenol were prepared and evaluated as dual inhibitors of 5-lipoxygenase and cyclooxygenase in rat basophilic leukemia (RBL-1) cells. The target compounds exhibit varying degrees of selectivity toward the two enzymes. Several compounds are orally active in the rat carageenan footpad edema (CFE) and mycobacterium

  制备了各种衍生自2,6-二叔丁基苯酚的亚苄基恶唑，-噻唑和-咪唑，并将其评估为大鼠嗜碱性白血病（RBL-1）细胞中5-脂氧合酶和环氧合酶的双重抑制剂。目标化合物对两种酶表现出不同程度的选择性。几种化合物在大鼠角叉菜胶足垫水肿（CFE）和分枝杆菌足垫水肿（MFE）抗炎模型中具有口服活性。讨论了构效关系。根据这项工作，将（Z）-5-[[3,5-双（1,1-二甲基乙基）-4-羟苯基]-亚甲基] -2-亚氨基-4-噻唑烷酮甲烷磺酸盐（CI-1004）鉴定为一种有效的5-脂氧合酶（IC50 = 0.77 microM）和环氧合酶（IC50 = 0.39 microM）双重抑制剂，在大鼠MFE炎症模型中具有口服活性（ID40 = 0.6 mg / kg）。
• Arylmethylenyl derivatives of thiazolidnones, imidazolidinones and oxazolidinones useful as antiallergy agents and antiinflamatory agents
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0343643A2

  公开（公告）日：1989-11-29

  The present invention is for selected novel compounds, as well as, pharmaceutical compositions and methods of use for known and the selected novel compounds both of the formula having activity useful for treating allergies and inflammation.

  本发明涉及所选的新型化合物，以及已知和所选的新型化合物的药物组合物和使用方法，这两种化合物的化学式均为 具有治疗过敏症和炎症的活性。
• Pyridine derivatives, their production and use
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：EP0522606A2

  公开（公告）日：1993-01-13

  There is disclosed a pharmaceutical composition for providing antiinflammatory, antipyretic, analgesic, antiallergic, immunosuppressing or immunomodulating activity which comprises a pyridine derivative of the formula (I): wherein R is an optionally substituted pyridine ring, X is a oxygen atom or -S(O)n-, wherein n is 0, 1 or 2, A is a bivalent C₁₋₁₅ hydrocarbon residue whose branched moiety may have a substituent, Y is an oxygen or sulfur atom, R₃ is a hydrogen atom or an optionally substituted hydrocarbon residue, R₄ is an optionally substituted hydrocarbon residue or an optionally substituted monocyclic or bicyclic heterocyclic group, R₃ and R₄ may be joined together with the carbamoyl group or the thiocarbamoyl group to which they are attached to form an optionally substituted heterocyclic group, or R₃ or R₄ may be independently attached to A to form a ring, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier or diluent.

  本发明公开了一种具有抗炎、解热、镇痛、抗过敏、免疫抑制或免疫调节活性的药物组合物，它由式（I）的吡啶衍生物组成： 其中 R 是任选取代的吡啶环，X 是氧原子或-S(O)n-，其中 n 是 0、1 或 2，A 是二价 C₁₋₁₅烃残基，其支链分子可具有取代基、Y 是氧原子或硫原子，R₃ 是氢原子或任选取代的烃残基，R₄ 是任选取代的烃残基或任选取代的单环或双环杂环基团、R₃ 和 R₄ 可与所连接的氨基甲酰基或硫代氨基甲酰基连接在一起，形成任选取代的杂环基团，或 R₃ 或 R₄ 可独立连接到 A 形成环，或其药学上可接受的盐或溶液，以及药学上可接受的载体或稀释剂。
• Combined use of tace inhibitors and COX2 inhibitors as anti-inflammatory agents
  申请人：——

  公开号：US20030225054A1

  公开（公告）日：2003-12-04

  This invention relates to a method of treating inflammatory diseases in a mammal comprising administering to the mammal a therapeutically effective amount of a combination of: (i) at least one TACE inhibitor of Formula (I), (II), (III), or (IV) of the present invention or a stereoisomer or pharmaceutically acceptable salt form thereof, (ii) one or more anti-inflammatory agents selected from the group consisting of: selective COX-2 inhibitors, interleukin-1 antagonists, dihydroorotate synthase inhibitors, p38 MAP kinase inhibitors, TNF-&agr; inhibitors, TNF-&agr; sequestration agents, and methotrexate. The invention also relates to compositions and kits containing the same.

  本发明涉及一种治疗哺乳动物炎症性疾病的方法，该方法包括向哺乳动物施用治疗有效量的以下物质的组合：(i)至少一种本发明式(I)、(II)、(III)或(IV)的TACE抑制剂或其立体异构体或药学上可接受的盐形式，(ii)一种或多种选自由以下组成的组的抗炎剂：选择性 COX-2 抑制剂、白细胞介素-1 拮抗剂、二氢烟酸合成酶抑制剂、p38 MAP 激酶抑制剂、TNF-&agr; 抑制剂、TNF-&agr; 封闭剂和甲氨蝶呤。本发明还涉及含有上述成分的组合物和试剂盒。