4-(4-bromophenyl)-4-(2,2,2-trifluoroethoxy)-4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzothiazin-1-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: 4-(4-bromophenyl)-4-(2,2,2-trifluoroethoxy)-4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzothiazin-1-one
• 英文别名: 4-(4-Bromophenyl)-4-(2,2,2-trifluoroethoxy)-[1,2,4]oxadiazolo[3,4-c][1,4]benzothiazin-1-one；4-(4-bromophenyl)-4-(2,2,2-trifluoroethoxy)-[1,2,4]oxadiazolo[3,4-c][1,4]benzothiazin-1-one
• 化学式: C₁₇H₁₀BrF₃N₂O₃S
• 分子量: 459.243
• InChiKey: PFZOBHSCNYUKMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  76.4
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-(4-bromophenyl)-4-(2,2,2-trifluoroethoxy)-4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzothiazin-1-one 在 Chiralpak AD (amylose tris[3,5-dimethylphenylcarbamate])-coated silica gel 作用下， 以 乙醇 为溶剂， 以88%的产率得到
  参考文献：
  名称：

  Synthesis and L-type calcium channel blocking activity of new chiral oxadiazolothiazinones

  摘要：

  Oxadiazolo[3,4-c][1,4]thiazin-3-ones are cardiovascular agents that block L-type calcium channels. Previous data of cardiac and vasorelaxant activity on guinea-pig for several derivatives indicated the two positions ortho to the thiazine's sulphur as crucial for modulating the activity; but these positions are likely susceptible to metabolic biotransformations, as indicated by in silico predictions. We designed new derivatives, and obtained three negative inotropic agents with EC50 in the low nanomolar range, more potent than all the precursors published so far. In particular, benzocondensation at the thiazine ring led to 3a (EC50 = 0.013 mu M) and 3b (EC50 = 0.006 mu M). Besides negative inotropy, we also observed relaxant activity on nonvascular muscle in the micromolar range. We resolved the new derivatives by chiral chromatography, and determined their absolute configuration by comparing experimental and calculated chiroptical properties (VCD, ECD and ORD): they hold the same absolute configuration-optical rotation relationship, (S)-(+)I(R)-(-). Both cardiac and nonvascular activity are majorly or mostly retained in the R-form for all the compounds, but for the nonvascular activity we observed a strong stereoselectivity for 3a, with the R-form in the nanomolar range (IC50 = 0.020 mu M) and 259-fold more potent than the S-one. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.044
• 作为产物：
  描述：

  2-(4-bromophenyl)imidazo[2,1-b][1,3]benzothiazole 在 盐酸 、 对甲苯磺酸 、 溶剂黄146 、 sodium nitrite 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 34.0h， 生成 4-(4-bromophenyl)-4-(2,2,2-trifluoroethoxy)-4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzothiazin-1-one
  参考文献：
  名称：

  Synthesis and L-type calcium channel blocking activity of new chiral oxadiazolothiazinones

  摘要：

  Oxadiazolo[3,4-c][1,4]thiazin-3-ones are cardiovascular agents that block L-type calcium channels. Previous data of cardiac and vasorelaxant activity on guinea-pig for several derivatives indicated the two positions ortho to the thiazine's sulphur as crucial for modulating the activity; but these positions are likely susceptible to metabolic biotransformations, as indicated by in silico predictions. We designed new derivatives, and obtained three negative inotropic agents with EC50 in the low nanomolar range, more potent than all the precursors published so far. In particular, benzocondensation at the thiazine ring led to 3a (EC50 = 0.013 mu M) and 3b (EC50 = 0.006 mu M). Besides negative inotropy, we also observed relaxant activity on nonvascular muscle in the micromolar range. We resolved the new derivatives by chiral chromatography, and determined their absolute configuration by comparing experimental and calculated chiroptical properties (VCD, ECD and ORD): they hold the same absolute configuration-optical rotation relationship, (S)-(+)I(R)-(-). Both cardiac and nonvascular activity are majorly or mostly retained in the R-form for all the compounds, but for the nonvascular activity we observed a strong stereoselectivity for 3a, with the R-form in the nanomolar range (IC50 = 0.020 mu M) and 259-fold more potent than the S-one. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.044

文献信息

• Synthesis and L-type calcium channel blocking activity of new chiral oxadiazolothiazinones
  作者：Emanuele Carosati、Pierfranco Ioan、Giovanni Battista Barrano、Salvatore Caccamese、Barbara Cosimelli、Frank J. Devlin、Elda Severi、Domenico Spinelli、Stefano Superchi、Roberta Budriesi

  DOI：10.1016/j.ejmech.2014.12.044

  日期：2015.3

  Oxadiazolo[3,4-c][1,4]thiazin-3-ones are cardiovascular agents that block L-type calcium channels. Previous data of cardiac and vasorelaxant activity on guinea-pig for several derivatives indicated the two positions ortho to the thiazine's sulphur as crucial for modulating the activity; but these positions are likely susceptible to metabolic biotransformations, as indicated by in silico predictions. We designed new derivatives, and obtained three negative inotropic agents with EC50 in the low nanomolar range, more potent than all the precursors published so far. In particular, benzocondensation at the thiazine ring led to 3a (EC50 = 0.013 mu M) and 3b (EC50 = 0.006 mu M). Besides negative inotropy, we also observed relaxant activity on nonvascular muscle in the micromolar range. We resolved the new derivatives by chiral chromatography, and determined their absolute configuration by comparing experimental and calculated chiroptical properties (VCD, ECD and ORD): they hold the same absolute configuration-optical rotation relationship, (S)-(+)I(R)-(-). Both cardiac and nonvascular activity are majorly or mostly retained in the R-form for all the compounds, but for the nonvascular activity we observed a strong stereoselectivity for 3a, with the R-form in the nanomolar range (IC50 = 0.020 mu M) and 259-fold more potent than the S-one. (C) 2015 Elsevier Masson SAS. All rights reserved.