5-fluoromethyl-3,4-bis(4-methoxyphenyl)-isoxazole | 1620743-17-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-fluoromethyl-3,4-bis(4-methoxyphenyl)-isoxazole
• 英文别名: 5-fluoromethyl-3,4-bis(4-methoxyphenyl)isoxazole
• CAS: 1620743-17-0
• 化学式: C₁₈H₁₆FNO₃
• 分子量: 313.3
• InChiKey: ZSNBFKKVERDHJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  44.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  [(4-甲氧苯基)次甲基]氮烷氧化 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 四丁基氟化铵 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 43.0h， 生成 5-fluoromethyl-3,4-bis(4-methoxyphenyl)-isoxazole
  参考文献：
  名称：

  Translational impact of novel widely pharmacological characterized mofezolac-derived COX-1 inhibitors combined with bortezomib on human multiple myeloma cell lines viability

  摘要：

  A set of novel diarylisoxazoles has been projected using mofezolac (1) as a lead compound to investigate structure-inhibitory activity relationships of new compounds and the cyclooxygenases (COXs) catalytic activity. Mofezolac was chosen because is the most potent and selective reversible COX-1 inhibitor [COX-1 IC50 = 0.0079 mu M and COX-2 IC50 > 50 mu M, with a selectivity index (SI) in favor of COX-1 higher than 6300]. Seventeen new compounds were synthesized in fair to good yields and evaluated for their COXs inhibitory activity and selectivity. Sls ranged between 1 and higher than 11903,4-Bis(4-methoxyphenyl)-5-vinylisoxazole (22) has the highest SI with COX-1 IC50 = 0.042 mu M and COX-2 IC50 > 50 mu M. 1 and 22 were superior to aspirin in inhibiting platelet aggregation (IC50 = 0.45, 0.63 and 1.11 mu M, respectively) in human platelet rich plasma (hPRP) assay. They did not induce blood coagulation and hemolysis, and are neither genotoxic nor mutagen. 1 and 22 slightly increase bortezomib cytotoxic effect on multiple myeloma (MM) cell lines (NCI-H929 and RPMI-8226) and affects MM cell cycle and apoptosis when co-administered with the proteasome inhibitor bortezomib, a drug clinically used to treat plasma cell neoplasms including MM. In addition, structure-based binding mode of 1 and 22, through Fingerprints for Ligands and Proteins (FLAG) calculation, allowed to explain the one order of magnitude difference between COX-1 IC50 values of the two compounds. Specifically, the higher inhibitory potency seems due to the formation of a H-bond between COX-1 S530 and the carboxyl, present in 1 and absent in 22. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.12.029

文献信息

• [EN] HETEROCYCLES AND THEIR RADIOLABELED ANALOGS USEFUL AS COX-1 SELECTIVE INHIBITORS<br/>[FR] HÉTÉROCYCLES ET LEURS ANALOGUES RADIOMARQUÉS UTILES EN TANT QU'INHIBITEURS SÉLECTIFS DE COX-1
  申请人：UNIV BARI

  公开号：WO2014115020A1

  公开（公告）日：2014-07-31

  The present invention relates to novel heterocycles which are potent and selective inhibitors of cyclooxygenase-1 (COX-1) and to their radiolabeled derivatives thereof which are both useful as theranostics of a number of pathologies.

  本发明涉及一种新型杂环化合物，这些化合物是环氧合酶-1（COX-1）的有效和选择性抑制剂，以及它们的放射标记衍生物，这些衍生物既可用作多种病理病变的诊疗药物。