4(5H)-噻唑酮,5-[[3,5-二(1,1-二甲基乙基)-4-羟基苯基]亚甲基]-2-(甲硫基)-,(Z)- | 139226-40-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4(5H)-噻唑酮,5-[[3,5-二(1,1-二甲基乙基)-4-羟基苯基]亚甲基]-2-(甲硫基)-,(Z)-
• 英文名称: (Z)-5-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methylene]-2-(methylthio)-4(5H)-thiazolone
• 英文别名: (5Z)-5-(3,5-ditert-butyl-4-hydroxybenzylidene)-2-(methylsulfanyl)-1,3-thiazol-4(5H)-one；(5Z)-5-[(3,5-ditert-butyl-4-hydroxyphenyl)methylidene]-2-methylsulfanyl-1,3-thiazol-4-one
• CAS: 139226-40-7
• 化学式: C₁₉H₂₅NO₂S₂
• 分子量: 363.545
• InChiKey: GUXWELWUSVXSOL-UVTDQMKNSA-N

物化性质

• 沸点：
  460.5±55.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4(5H)-噻唑酮,5-[[3,5-二(1,1-二甲基乙基)-4-羟基苯基]亚甲基]-2-(甲硫基)-,(Z)- 在 hydrozane 、 potassium tert-butylate 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以18%的产率得到(Z)-5-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-hydrazinothiazol-4-one
  参考文献：
  名称：

  Synthesis, Structure−Activity Relationships, and in Vivo Evaluations of Substituted Di-tert-butylphenols as a Novel Class of Potent, Selective, and Orally Active Cyclooxygenase-2 Inhibitors. 1. Thiazolone and Oxazolone Series

  摘要：

  Selective cyclooxygenase-2 (COX-2) inhibitors have been shown to be potent antiinflammatory agents with fewer side effects than currently marketed nonsteroidal antiinflammatory drugs (NSAIDs). Initial mass screening and subsequent structure-activity relationship (SAR) studies have identified 4b (PD138387) as the most potent and selective COX-2 inhibitor within the thiazolone and oxazolone series of di-tert-butylphenols. Compound 4b has an IC50 Of 1.7 mu M against recombinant human COX-2 and inhibited COX-2 activity in the J774A.1 cell line with an IC50 of 0.17 mu M. It was inactive against purified ovine COX-1 at 100 mu M and did not inhibit COX-1 activity in platelets at 20 mu M. Compound 4b was also orally active in vivo with an ED40 of 16 mg/kg in the carrageenan footpad edema (CFE) assay and caused no gastrointestinal (GI) damage in rats at the dose of 100 mg/kg but inhibited gastric prostaglandin E-2 (PGE(2)) production in rats' gastric mucosa by 33% following a dose of 100 mg/kg. The SAR studies of this chemical series revealed that the potency and selectivity are very sensitive to minor structural changes. A simple isosteric replacement led to the reversal of selectivity.

  DOI：

  10.1021/jm9805081
• 作为产物：
  描述：

  (Z)-5-(3,5-di-tert-butyl-4-hydroxyphenylmethylene)-4-oxo-2-thiazolidinethione 以55%的产率得到
  参考文献：
  名称：

  Unangst Paul C., Connor David T., Cetenko Wiaczeslaw A., Sorenson Roderic+, J. Med. Chem, 37 (1994) N 2, S 322-328

  摘要：

  DOI：

文献信息

• 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）。
• 3,5-di-tertiarybutyl-4-hydroxyphenylmethylene derivatives of 2-substituted thiazolidinones, oxazolidinones, and imidazolidinones as antiinflammatory agents
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0449216B1

  公开（公告）日：1996-02-07
• US5143928A
  申请人：——

  公开号：US5143928A

  公开（公告）日：1992-09-01
• US5290800A
  申请人：——

  公开号：US5290800A

  公开（公告）日：1994-03-01
• US5494927A
  申请人：——

  公开号：US5494927A

  公开（公告）日：1996-02-27