3-[2-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}amino)-1,3-benzothiazol-6-yl]benzoic acid | 1097777-50-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 3-[2-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}amino)-1,3-benzothiazol-6-yl]benzoic acid
• 英文别名: 3-[2-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methylamino]-1,3-benzothiazol-6-yl]benzoic acid
• CAS: 1097777-50-8
• 化学式: C₂₇H₂₁Cl₂N₃O₃S
• 分子量: 538.454
• InChiKey: HYJSTCZABVAHEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  methyl 3-[2-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}amino)-1,3-benzothiazol-6-yl]benzoate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以59%的产率得到3-[2-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}amino)-1,3-benzothiazol-6-yl]benzoic acid
  参考文献：
  名称：

  构象受限的GW 4064类似物的FXR激动剂活性

  摘要：

  制备了两个系列的FXR激动剂GW 4064 1的构象约束类似物。用苯并噻吩或萘环取代代谢不稳定的二苯乙烯导致了强有力的全激动剂2a和2g的鉴定。

  DOI：

  10.1016/j.bmcl.2009.06.062

文献信息

• [EN] FARNESOID X RECEPTOR AGONISTS<br/>[FR] AGONISTES DU RÉCEPTEUR DE FARNÉSOÏDE X
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009005998A1

  公开（公告）日：2009-01-08

  The present invention relates to famesoid X receptors (FXR, NR1H4) FXR is a member of the nuclear receptor class of ligand-activate transcription factors More particularly, the present invention relates to compounds useful as agonists for FXR, pharmaceutical formulations comprising such compounds, and therapeutic use of the same Novel isoxazole compounds are disclosed as part of pharmaceutical compositions for the treatment of a condition mediated by decreased FXR activity, such as obesity, diabetes, cholestatic liver disease, liver fibrosis, and metabolic syndrome

  本发明涉及法内索德X受体（FXR，NR1H4）。FXR是配体激活的转录因子核受体类的一个成员。更具体地说，本发明涉及作为FXR激动剂的化合物，包含该化合物的药物制剂，以及同一治疗用途。新颖的异恶唑化合物被披露作为药物组合物的一部分，用于治疗由FXR活性降低介导的状况，如肥胖、糖尿病、胆汁淤积性肝病、肝纤维化和代谢综合征。
• FARNESOID X RECEPTOR AGONISTS
  申请人：Akwabi-Ameyaw Adwoa

  公开号：US20110034507A1

  公开（公告）日：2011-02-10

  The present invention relates to farnesoid X receptors (FXR, NR1H4). FXR is a member of the nuclear receptor class of ligand-activate transcription factors. More particularly, the present invention relates to compounds useful as agonists for FXR, pharmaceutical formulations comprising such compounds, and therapeutic use of the same. Novel isoxazole compounds are disclosed as part of pharmaceutical compositions for the treatment of a condition mediated by decreased FXR activity, such as obesity, diabetes, cholestatic liver disease, liver fibrosis, and metabolic syndrome.

  本发明涉及法尼索德X受体（FXR，NR1H4）。FXR是配体激活转录因子的核受体类成员。更具体地，本发明涉及作为FXR激动剂有用的化合物，包含这些化合物的制药组合物以及其治疗用途。新型异唑咪唑化合物被揭示为用于治疗由FXR活性降低介导的疾病状态的制药组合物，例如肥胖症、糖尿病、胆汁淤积性肝病、肝纤维化和代谢综合征。
• FXR agonist activity of conformationally constrained analogs of GW 4064
  作者：Adwoa Akwabi-Ameyaw、Jonathan Y. Bass、Richard D. Caldwell、Justin A. Caravella、Lihong Chen、Katrina L. Creech、David N. Deaton、Kevin P. Madauss、Harry B. Marr、Robert B. McFadyen、Aaron B. Miller、Frank Navas、Derek J. Parks、Paul K. Spearing、Dan Todd、Shawn P. Williams、G. Bruce Wisely

  DOI：10.1016/j.bmcl.2009.06.062

  日期：2009.8

  Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.

  制备了两个系列的FXR激动剂GW 4064 1的构象约束类似物。用苯并噻吩或萘环取代代谢不稳定的二苯乙烯导致了强有力的全激动剂2a和2g的鉴定。