3-(4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl) isoxazole

• 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-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl) isoxazole
• 英文别名: 3-(4-Methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1,2-oxazole；3-(4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1,2-oxazole
• 化学式: C₁₉H₁₉NO₅
• 分子量: 341.364
• InChiKey: BXVRVBJOOIXPMT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  63
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  对甲氧基苯甲醛肟 在 N-氯代丁二酰亚胺 、 copper(ll) sulfate pentahydrate 、 potassium hydrogencarbonate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 3-(4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl) isoxazole
  参考文献：
  名称：

  Design, synthesis and antitrypanosomatid activities of 3,5-diaryl-isoxazole analogues based on neolignans veraguensin, grandisin and machilin G

  摘要：

  AbstractUsing bioisosterism as a medicinal chemistry tool, 16 3,5‐diaryl‐isoxazole analogues of the tetrahydrofuran neolignans veraguensin, grandisin and machilin G were synthesized via 1,3‐dipolar cycloaddition reactions, with yields from 43% to 90%. Antitrypanosomatid activities were evaluated against Trypanosoma cruzi, Leishmania (L.) amazonensis and Leishmania (V.) braziliensis. All compounds were selective for the Leishmania genus and inactive against T. cruzi. Isoxazole analogues showed a standard activity on both promastigotes of L. amazonensis and L. braziliensis. The most active compounds were 15, 16 and 19 with IC50 values of 2.0, 3.3 and 9.5 μM against L. amazonensis and IC50 values of 1.2, 2.1 and 6.4 μM on L. braziliensis, respectively. All compounds were noncytotoxic, showing lower cytotoxicity (>250 μM) than pentamidine (78.9 μM). Regarding the structure–activity relationship (SAR), the methylenedioxy group was essential to antileishmanial activity against promastigotes. Replacement of the tetrahydrofuran nucleus by an isoxazole core improved the antileishmanial activity.

  DOI：

  10.1111/cbdd.13417

文献信息

• Design, synthesis and antitrypanosomatid activities of 3,5-diaryl-isoxazole analogues based on neolignans veraguensin, grandisin and machilin G
  作者：Ozildéia S. Trefzger、Amarith R. das Neves、Natália V. Barbosa、Diego B. Carvalho、Indiara C. Pereira、Renata T. Perdomo、Maria F. C. Matos、Nidia C. Yoshida、Massuo J. Kato、Sérgio de Albuquerque、Carla C. P. Arruda、Adriano C. M. Baroni

  DOI：10.1111/cbdd.13417

  日期：2019.3

  AbstractUsing bioisosterism as a medicinal chemistry tool, 16 3,5‐diaryl‐isoxazole analogues of the tetrahydrofuran neolignans veraguensin, grandisin and machilin G were synthesized via 1,3‐dipolar cycloaddition reactions, with yields from 43% to 90%. Antitrypanosomatid activities were evaluated against Trypanosoma cruzi, Leishmania (L.) amazonensis and Leishmania (V.) braziliensis. All compounds were selective for the Leishmania genus and inactive against T. cruzi. Isoxazole analogues showed a standard activity on both promastigotes of L. amazonensis and L. braziliensis. The most active compounds were 15, 16 and 19 with IC50 values of 2.0, 3.3 and 9.5 μM against L. amazonensis and IC50 values of 1.2, 2.1 and 6.4 μM on L. braziliensis, respectively. All compounds were noncytotoxic, showing lower cytotoxicity (>250 μM) than pentamidine (78.9 μM). Regarding the structure–activity relationship (SAR), the methylenedioxy group was essential to antileishmanial activity against promastigotes. Replacement of the tetrahydrofuran nucleus by an isoxazole core improved the antileishmanial activity.