2,6-bis(1,1-dimethylethyl)-4-<5-<(4-methylphenyl)sulfonyl>-1,2,4-thiadiazol-3-yl>phenol | 143429-62-3

• 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: 2,6-bis(1,1-dimethylethyl)-4-<5-<(4-methylphenyl)sulfonyl>-1,2,4-thiadiazol-3-yl>phenol
• 英文别名: 2,6-Ditert-butyl-4-[5-(4-methylphenyl)sulfonyl-1,2,4-thiadiazol-3-yl]phenol；2,6-ditert-butyl-4-[5-(4-methylphenyl)sulfonyl-1,2,4-thiadiazol-3-yl]phenol
• CAS: 143429-62-3
• 化学式: C₂₃H₂₈N₂O₃S₂
• 分子量: 444.619
• InChiKey: HYWFULJAZGPHNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,6-bis(1,1-dimethylethyl)-4-<5-<(4-methylphenyl)sulfonyl>-1,2,4-thiadiazol-3-yl>phenol 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 N-[3-(3,5-Di-tert-butyl-4-hydroxy-phenyl)-[1,2,4]thiadiazol-5-yl]-N'-methyl-guanidine
  参考文献：
  名称：

  Novel 1,2,4-oxadiazoles and 1,2,4-thiadiazoles as dual 5-lipoxygenase and cyclooxygenase inhibitors

  摘要：

  A series of 1,2,4-oxadiazoles and 1,2,4-thiadiazoles containing a 2,6-di-tert-butylphenol substituent were prepared and evaluated as dual inhibitors of 5-lipoxygenase and cyclooxygenase in rat basophilic leukemia (RBL-1) cells. Several of these compounds show oral efficacy in the rat carageenan footpad edema (CFE) and mycobacterium footpad edema (MFE) antiinflammatory models, without concomitant gastric ulceration. Structure-activity relationships are discussed. The best compounds (ID40 values in MFE of 3-8 mg/kg po) contain guanidine-derived substituents on the heterocyclic ring.

  DOI：

  10.1021/jm00098a015
• 作为产物：
  描述：

  4-甲苯磺酰氰 、 5-(3,5-Di-tert-butyl-4-oxocyclohexa-2,5-dien-1-ylidene)-1,3,4-oxathiazolidin-2-one 以 various solvent(s) 为溶剂， 反应 1.0h， 以85%的产率得到2,6-bis(1,1-dimethylethyl)-4-<5-<(4-methylphenyl)sulfonyl>-1,2,4-thiadiazol-3-yl>phenol
  参考文献：
  名称：

  通过与4-甲基苯磺酰基氰化物（甲苯磺酰基氰化物）环化制备新型1,2,4-噻二唑†

  摘要：

  描述了在噻二唑3-位带有二叔丁基苯酚取代基的1,2,4-噻二唑的制备。在1，3-偶极环化反应中，使热产生的腈硫化物与甲苯磺酰基氰化物反应，以提供含有不稳定的5-甲苯磺酰基取代基的噻二唑中间体。

  DOI：

  10.1002/jhet.5570300211

文献信息

• Synthesis, Structure−Activity Relationships, and in Vivo Evaluations of Substituted Di-<i>tert</i>-butylphenols as a Novel Class of Potent, Selective, and Orally Active Cyclooxygenase-2 Inhibitors. 2. 1,3,4- and 1,2,4-Thiadiazole Series
  作者：Yuntao Song、David T. Connor、Anthony D. Sercel、Roderick J. Sorenson、Robert Doubleday、Paul C. Unangst、Bruce D. Roth、Vlad G. Beylin、Richard B. Gilbertsen、Kam Chan、Denis J. Schrier、Antonio Guglietta、Dirk A. Bornemeier、Richard D. Dyer

  DOI：10.1021/jm980570y

  日期：1999.4.1

  Two isoforms of the cyclooxygenase (COX) enzyme have been identified: COX-1, which is expressed constitutively, and COX-2, which is induced in inflammation. Recently, it has been shown that selective COX-2 inhibitors have antiinflammatory activity and lack the GI side effects typically associated with NSAIDs. Initial mass screening and subsequent SAR studies have identified 6b (PD164387) as a potent, selective, and orally active COX-2 inhibitor. It had IC50 values of 0.14 and 100 mu M against recombinant human COX-2 and purified ovine COX-1, respectively. It inhibited COX-2 activity in the J774A.1 cell line with an IC50 Of 0.18 mu M and inhibited COX-1 activity in platelets with an IC50 of 3.1 mu M. The choline salt of compound 6b was also orally active in vivo with an ED40 Of 7.1 mg/kg in the carrageenan footpad edema (CFE) assay. In vivo studies in rats at a dose of 100 mg/kg showed that this compound inhibited gastric prostaglandin E-2 (PGE(2)) production in gastric mucosa by 77% but caused minimal GI damage. SAR studies of this chemical series revealed that the potency and selectivity are very sensitive to minor structural changes.