3-(4-fluorophenyl)-4-(4-methoxyphenyl)-5-methylisoxazole | 1402042-27-6

• 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-fluorophenyl)-4-(4-methoxyphenyl)-5-methylisoxazole
• 英文别名: 3-(4-Fluorophenyl)-4-(4-methoxyphenyl)-5-methyl-1,2-oxazole；3-(4-fluorophenyl)-4-(4-methoxyphenyl)-5-methyl-1,2-oxazole
• CAS: 1402042-27-6
• 化学式: C₁₇H₁₄FNO₂
• 分子量: 283.302
• InChiKey: UMTICMVTSDCINS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  35.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  二氧化碳 、 3-(4-fluorophenyl)-4-(4-methoxyphenyl)-5-methylisoxazole 在 正丁基锂 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 以50%的产率得到2-[3-(4-fluorophenyl)-4-(4-methoxyphenyl)isoxazol-5-yl]acetic acid
  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
• 作为产物：
  描述：

  对甲氧基苯基丙酮 、 p-fluorobenzonitrile oxide 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以50%的产率得到3-(4-fluorophenyl)-4-(4-methoxyphenyl)-5-methylisoxazole
  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

• Monodentate Palladium Complexes Bearing Abnormal and Normal Carbene Ligands with a Formally Identical Steric Environment
  作者：Chun-Hung Ke、Bing-Chiuan Kuo、Debkumar Nandi、Hon Man Lee

  DOI：10.1021/om4004219

  日期：2013.9.9

  environment around the metal center. The corresponding ligand precursors were prepared via the key steps based on Pd-catalyzed direct C–H arylation between imidazo[1,2-a]pyridine and aryl bromides and Cu-catalyzed C–N coupling reactions between benzoimidazole and aryl bromides. The new complexes were characterized by 1D and 2D NMR spectroscopy, X-ray crystallography, and elemental analysis. The isomeric

  我们报告了一系列具有单齿异常和正常卡宾配体的新型异构Pd（II）配合物，在金属中心周围具有形式上完全相同的空间环境。相应的配体前体是通过基于咪唑并[1,2- a]之间的Pd催化的直接CH芳基化的关键步骤制备的]吡啶和芳基溴化物以及铜催化的苯并咪唑与芳基溴化物之间的C–N偶联反应。通过1D和2D NMR光谱，X射线晶体学和元素分析对新配合物进行了表征。配体的同分异构体对在其空间性质之间显示出较小的差异，这可以通过计算其掩埋体积来检查。发现异常卡宾Pd（II）配合物在催化Mizoroki–Heck偶联，直接C–H芳基化和脱羧偶联反应方面更有效，这显然可以归因于异常卡宾配体的更强的电子捐赠作用。
• Pd(0)-Catalyzed Decarboxylative Coupling and Tandem C–H Arylation/Decarboxylation for the Synthesis of Heteroaromatic Biaryls
  作者：Debkumar Nandi、Yang-Ming Jhou、Jhen-Yi Lee、Bing-Chiuan Kuo、Chien-Yu Liu、Pei-Wen Huang、Hon Man Lee

  DOI：10.1021/jo3015837

  日期：2012.10.19

  An effective Pd(0) carbene complex was successfully employed in the decarboxylative coupling of the heteroaromatic carboxylic acids (imidazo[1,2-a]pyridine and isoxazole) with aryl halides. For carboxyindoles, either decarboxylative coupling or tandem C-H arylation and decarboxylation occurred, leading to the formation of C2-monoarylated indoles.
• 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.