4-hydroxy-4-phenyl-4H-[1,2,4]oxadiazolo[3,4-c][1,4]-benzothiazin-1-one | 451447-59-9

• 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-hydroxy-4-phenyl-4H-[1,2,4]oxadiazolo[3,4-c][1,4]-benzothiazin-1-one
• 英文别名: 4-Hydroxy-4-phenyl-1H,4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzothiazin-1-one；4-hydroxy-4-phenyl-[1,2,4]oxadiazolo[3,4-c][1,4]benzothiazin-1-one
• CAS: 451447-59-9
• 化学式: C₁₅H₁₀N₂O₃S
• 分子量: 298.322
• InChiKey: DAEFTCQAVLRMJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  87.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-hydroxy-4-phenyl-4H-[1,2,4]oxadiazolo[3,4-c][1,4]-benzothiazin-1-one 、 环己甲醇 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 以65%的产率得到4-(cyclohexylmethoxy)-4-phenyl-4H-[1,2,4]oxadiazolo[3,4-c]-[1,4]benzothiazin-1-one
  参考文献：
  名称：

  Understanding Oxadiazolothiazinone Biological Properties: Negative Inotropic Activity versus Cytochrome P450-Mediated Metabolism

  摘要：

  We present a series of oxadiazolothiazinones, selective inotropic agents on isolated cardiac tissues, devoid of chronotropy and vasorelaxant activity. Functional and binding data for the precursor of the series (compound 1) let us hypothesize LTCC blocking activity and the existence of a recognition site specific for this scaffold. We synthesized and tested 22 new derivatives: introducing a para-methoxyphenyl at C-8 led to compound 12 (EC50 = 0.022 mu M), twice as potent as its para-bromo analogue (1). For 10 analogues, we extended the characterization of the biological properties by including the assessment of metabolic stability in human liver microsomes and cytochrome P450 inhibition potential. We observed that the methoxy group led to active compounds with low metabolic stability and high CYP inhibition, whereas the protective effect of bromine resulted in enhanced metabolic stability and reduced CYP inhibition. Thus, we identified two para-bromo benzothiazino-analogues as candidates for further studies.

  DOI：

  10.1021/acs.jmedchem.6b00030
• 作为产物：
  描述：

  2-phenylimidazo[2,1-b]benzothiazole 在 盐酸 、 溶剂黄146 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 生成 4-hydroxy-4-phenyl-4H-[1,2,4]oxadiazolo[3,4-c][1,4]-benzothiazin-1-one
  参考文献：
  名称：

  Understanding Oxadiazolothiazinone Biological Properties: Negative Inotropic Activity versus Cytochrome P450-Mediated Metabolism

  摘要：

  We present a series of oxadiazolothiazinones, selective inotropic agents on isolated cardiac tissues, devoid of chronotropy and vasorelaxant activity. Functional and binding data for the precursor of the series (compound 1) let us hypothesize LTCC blocking activity and the existence of a recognition site specific for this scaffold. We synthesized and tested 22 new derivatives: introducing a para-methoxyphenyl at C-8 led to compound 12 (EC50 = 0.022 mu M), twice as potent as its para-bromo analogue (1). For 10 analogues, we extended the characterization of the biological properties by including the assessment of metabolic stability in human liver microsomes and cytochrome P450 inhibition potential. We observed that the methoxy group led to active compounds with low metabolic stability and high CYP inhibition, whereas the protective effect of bromine resulted in enhanced metabolic stability and reduced CYP inhibition. Thus, we identified two para-bromo benzothiazino-analogues as candidates for further studies.

  DOI：

  10.1021/acs.jmedchem.6b00030

文献信息

• Understanding Oxadiazolothiazinone Biological Properties: Negative Inotropic Activity versus Cytochrome P450-Mediated Metabolism
  作者：Emanuele Carosati、Barbara Cosimelli、Pierfranco Ioan、Elda Severi、Kasiram Katneni、Francis C. K. Chiu、Simona Saponara、Fabio Fusi、Maria Frosini、Rosanna Matucci、Matteo Micucci、Alberto Chiarini、Domenico Spinelli、Roberta Budriesi

  DOI：10.1021/acs.jmedchem.6b00030

  日期：2016.4.14

  We present a series of oxadiazolothiazinones, selective inotropic agents on isolated cardiac tissues, devoid of chronotropy and vasorelaxant activity. Functional and binding data for the precursor of the series (compound 1) let us hypothesize LTCC blocking activity and the existence of a recognition site specific for this scaffold. We synthesized and tested 22 new derivatives: introducing a para-methoxyphenyl at C-8 led to compound 12 (EC50 = 0.022 mu M), twice as potent as its para-bromo analogue (1). For 10 analogues, we extended the characterization of the biological properties by including the assessment of metabolic stability in human liver microsomes and cytochrome P450 inhibition potential. We observed that the methoxy group led to active compounds with low metabolic stability and high CYP inhibition, whereas the protective effect of bromine resulted in enhanced metabolic stability and reduced CYP inhibition. Thus, we identified two para-bromo benzothiazino-analogues as candidates for further studies.