3,4-bis(4-methoxyphenyl)isoxazol-5-amine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3,4-bis(4-methoxyphenyl)isoxazol-5-amine
• 英文别名: 3,4-Bis(4-methoxyphenyl)-1,2-oxazol-5-amine；3,4-bis(4-methoxyphenyl)-1,2-oxazol-5-amine
• 化学式: C₁₇H₁₆N₂O₃
• 分子量: 296.326
• InChiKey: DIHASZCPXYPHRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  70.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  对甲氧基苯乙腈 、 [(4-甲氧苯基)次甲基]氮烷氧化 在 叔丁基锂 、 盐酸羟胺 作用下， 以 四氢呋喃 、 正戊烷 、 水 为溶剂， 反应 1.0h， 以35%的产率得到3,4-bis(4-methoxyphenyl)isoxazol-5-amine
  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

• Translational impact of novel widely pharmacological characterized mofezolac-derived COX-1 inhibitors combined with bortezomib on human multiple myeloma cell lines viability
  作者：Maria Laura Pati、Paola Vitale、Savina Ferorelli、Mariaclara Iaselli、Morena Miciaccia、Angelina Boccarelli、Giuseppe Davide Di Mauro、Cosimo G. Fortuna、Thaisa Francielle Souza Domingos、Luiz Cláudio Rodrigues Pereira da Silva、Marcelo de Pádula、Lucio Mendes Cabral、Plínio Cunha Sathler、Angelo Vacca、Antonio Scilimati、Maria Grazia Perrone

  DOI：10.1016/j.ejmech.2018.12.029

  日期：2019.2

  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.