1,4-Dimethyl-10H-9-thia-10-aza-phenanthrene 9,9-dioxide

• 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: 1,4-Dimethyl-10H-9-thia-10-aza-phenanthrene 9,9-dioxide
• 英文别名: 7,10-dimethyl-6H-benzo[c][2,1]benzothiazine 5,5-dioxide
• 化学式: C₁₄H₁₃NO₂S
• 分子量: 259.329
• InChiKey: UDMBOAVOEIFANY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  54.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,4-Dimethyl-10H-9-thia-10-aza-phenanthrene 9,9-dioxide 、 硝酸 以73%的产率得到
  参考文献：
  名称：

  VAKULENKO, A. V.;DUNOVSKIJ, S. A.;BURMISTROV, S. I.;BURMISTROV, K. S., YKP. XIM. ZH., 53,(1987) N 11, 1203-1206

  摘要：

  DOI：
• 作为产物：
  描述：

  2-amino-N-(2,4-dimethylphenyl)benzenesulfonamide 以51%的产率得到
  参考文献：
  名称：

  VAKULENKO, A. V.;DUNOVSKIJ, S. A.;BURMISTROV, S. I.;BURMISTROV, K. S., YKP. XIM. ZH., 53,(1987) N 11, 1203-1206

  摘要：

  DOI：

文献信息

• FXR modulators
  申请人：Tularik Inc.

  公开号：US20020120137A1

  公开（公告）日：2002-08-29

  The present invention provides compounds, pharmaceutical compositions and methods that are useful in modulating the farnesoid X receptor (FXR). As FXR is involved in negatively controlling the expression level of cholesterol 7&agr;-hydroxylase (cyp7a), the rate-limiting enzyme involved in the oxidative metabolism of cholesterol into bile acids, the compounds described herein find utility in treating diseases associated with abnormally high or low cholesterol levels. In certain aspects, the FXR modulators (e.g., antagonists) described herein block the negative feed-back downregulation of cyp7a expression produced by certain cholic acids, the endogenous ligands for FXR. Moreover, as FXR forms heterodimers with the retinoid X receptor (RXR) in some cell types, modulation of the level of FXR activity in cells has a wide range of effects on a variety of biological processes which are mediated by RXR or other RXR-interacting proteins such as PPAR&ggr; and PPAR&agr;. Thus, compounds described herein are useful in treating other biological activities such as obesity, diabetes, lipid associated disorders, cancer, inflammatory disorders, disorders involving a disrupted or dysfunctional epidermal barrier, and various other metabolic disorders.

  本发明提供了化合物、制药组合物和方法，可用于调节法尼酰二烯醇X受体（FXR）。由于FXR参与负性调控胆固醇7α-羟化酶（cyp7a）的表达水平，该酶是将胆固醇氧化代谢成胆酸的速率限制酶，因此本文所述的化合物在治疗与胆固醇水平异常高或低相关的疾病方面具有实用价值。在某些方面，本文所述的FXR调节剂（例如拮抗剂）可阻断某些胆汁酸产生的cyp7a表达的负反馈下调。此外，由于FXR在某些细胞类型中与视黄酸X受体（RXR）形成异二聚体，因此调节细胞中FXR活性水平对由RXR或其他与RXR相互作用的蛋白质（例如PPARγ和PPARα）介导的各种生物过程具有广泛的影响。因此，本文所述的化合物在治疗其他生物活动，如肥胖症、糖尿病、与脂质有关的疾病、癌症、炎症性疾病、涉及破坏或功能障碍的表皮屏障的疾病以及各种其他代谢性疾病方面具有实用价值。
• VAKULENKO, A. V.;DUNOVSKIJ, S. A.;BURMISTROV, S. I.;BURMISTROV, K. S., YKP. XIM. ZH., 53,(1987) N 11, 1203-1206
  作者：VAKULENKO, A. V.、DUNOVSKIJ, S. A.、BURMISTROV, S. I.、BURMISTROV, K. S.

  DOI：——

  日期：——
• US6777446B2
  申请人：——

  公开号：US6777446B2

  公开（公告）日：2004-08-17
• US7511043B2
  申请人：——

  公开号：US7511043B2

  公开（公告）日：2009-03-31
• [EN] FXR MODULATORS<br/>[FR] MODULATEURS FXR
  申请人：TULARIK INC

  公开号：WO2002020463A2

  公开（公告）日：2002-03-14

  The present invention provides compounds, pharmaceutical compositions and methods that are useful in modulating the farnesoid X receptor (FXR). As FXR is involved in negatively controlling the expression level of cholesterol 7α-hydroxylase (cyp7a), the rate-limiting enzyme involved in the oxidative metabolism of cholesterol into bile acids, the compounds described herein find utility in treating diseases associated with abnormally high or low cholesterol levels. In certain aspects, the FXR modulators (e.g., antagonists) described herein block the negative feed-back downregulation of cyp7a expression produced by certain cholic acids, the endogenous ligands for FXR. Moreover, as FXR forms heterodimers with the retinoid X receptor (RXR) in some cell types, modulation of the level of FXR activity in cells has a wide range of effects on a variety of biological processes which are mediated by RXR or other RXR-interacting proteins such as PPARη and PPARα. Thus, compounds described herein are useful in treating other biological activities such as obesity, diabetes, lipid associated disorders, cancer, inflammatory disorders, disorders involving a disrupted or dysfunctional epidermal barrier, and various other metabolic disorders.