1,1,1,3,3,3-hexafluoro-2-[4-(2,2,2-trifluoro-ethylamino)-phenyl]-propan-2-ol | 609772-03-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1,1,1,3,3,3-hexafluoro-2-[4-(2,2,2-trifluoro-ethylamino)-phenyl]-propan-2-ol
• 英文别名: 1,1,1,3,3,3-hexafluoro-2-{4-[(2,2,2-trifluoroethyl)amino]phenyl}propan-2-ol；1,1,1,3,3,3-hexafluoro-2-[4-(2,2,2-trifluoroethylamino)phenyl]propan-2-ol
• CAS: 609772-03-4
• 化学式: C₁₁H₈F₉NO
• 分子量: 341.176
• InChiKey: VHDRSZOHKKZOQF-UHFFFAOYSA-N

物化性质

• 沸点：
  295.5±40.0 °C(Predicted)
• 密度：
  1.535±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  1,1,1,3,3,3-hexafluoro-2-[4-(2,2,2-trifluoro-ethylamino)-phenyl]-propan-2-ol 在 N-氯代丁二酰亚胺 作用下， 以 丙醇 为溶剂， 生成 2-{4-[benzyl-(2,2,2-trifluoro-ethyl)-amino]-3-chloro-phenyl}-1,1,1,3,3,3-hexafluoro-propan-2-ol
  参考文献：
  名称：

  Synthesis and evaluation of anilinohexafluoroisopropanols as activators/modulators of LXRα and β

  摘要：

  A series of branched and unbranched anilinohexafluoroisopropanols related to the known sulfonamide T0901317 were prepared and evaluated as activators/modulators of both LXR alpha and LXR beta. A structure-activity relationship was established and compounds with high potency on both the receptors were identified. Many compounds showed a tendency toward selectivity for LXR beta versus LXR alpha. Several analogues were evaluated for effects on plasma lipoprotein levels in mice. A few of these significantly raised HDL-cholesterol levels in plasma but showed markedly different effects on liver triglyceride content, suggesting that this series may yield candidates with improved efficacy/safety profiles compared to existing molecules. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.06.081
• 作为产物：
  描述：

  2-(4-氨基苯)-1,1,1,3,3,3-六氟-2-丙醇 在 硼烷四氢呋喃络合物 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 1,1,1,3,3,3-hexafluoro-2-[4-(2,2,2-trifluoro-ethylamino)-phenyl]-propan-2-ol
  参考文献：
  名称：

  Synthesis and evaluation of anilinohexafluoroisopropanols as activators/modulators of LXRα and β

  摘要：

  A series of branched and unbranched anilinohexafluoroisopropanols related to the known sulfonamide T0901317 were prepared and evaluated as activators/modulators of both LXR alpha and LXR beta. A structure-activity relationship was established and compounds with high potency on both the receptors were identified. Many compounds showed a tendency toward selectivity for LXR beta versus LXR alpha. Several analogues were evaluated for effects on plasma lipoprotein levels in mice. A few of these significantly raised HDL-cholesterol levels in plasma but showed markedly different effects on liver triglyceride content, suggesting that this series may yield candidates with improved efficacy/safety profiles compared to existing molecules. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.06.081

文献信息

• Discovery and Optimization of a Series of Sulfonamide Inverse Agonists for the Retinoic Acid Receptor-Related Orphan Receptor-α
  作者：Christelle Doebelin、Yuanjun He、Sean Campbell、Philippe Nuhant、Naresh Kumar、Marcel Koenig、Ruben Garcia-Ordonez、Mi Ra Chang、William R. Roush、Li Lin、Susan Kahn、Michael D. Cameron、Patrick R. Griffin、Laura A. Solt、Theodore M. Kamenecka

  DOI：10.2174/1573406415666190222124745

  日期：2019.8.26

  Structure-activity relationship studies led to potent dual RORα/RORγ inverse agonists as well as RORα-selective inverse agonists (20, 28). LXR activity could be reduced by removing the sulfonamide nitrogen substituent. Attempts to improve the potency of these selective leads by varying substitution patterns throughout the molecule proved challenging. Conclusion: The synthetic RORα-selective inverse agonists identified

  背景：尽管业界大力开发用于自身免疫性疾病的RORγ调节剂，但尚无迹象表明有努力将近亲RORα靶向类似适应症。这可能是由于误解认为RORα相对于RORγ是多余的，或者是为RORα培养易于处理的起始点固有的困难。RORα-选择性调节剂将是有用的工具，以询问这种被研究不足的孤儿核受体的生物学。 目的：这项研究工作的目的是从已知的LXR激动剂T0901317开始确定和优化RORα的合成配体。 方法：合成了45种磺酰胺铅（1）的类似物，并在基于细胞的测定中评估了其抑制RORα，RORγ和LXRα转录活性的能力。类似物通过1 H-NMR，13 C-NMR和LC-MS分析进行表征。在腹膜内（ip）和口服（po）给药的大鼠中评估了选择性最高的RORα反向激动剂的药代动力学特征。 结果：结构-活性关系研究导致了有效的双重RORα/RORγ反向激动剂以及RORα-选择性反向激动剂（20，28）。通过除去磺酰胺
• [EN] MODULATORS OF THE RETINOIC ACID RECEPTOR-RELATED ORPHAN RECEPTORS<br/>[FR] MODULATEURS DES RÉCEPTEURS ORPHELINS LIÉS AU RÉCEPTEUR DE L'ACIDE RÉTINOÏQUE
  申请人：GRIFFIN PATRICK R

  公开号：WO2011115892A1

  公开（公告）日：2011-09-22

  The invention provides small molecule modulators of retinoic acid receptor-related orphan receptors such as RORα RORβ, or RORγ. Compounds of the invention can be effective modulators at concentrations ineffective to act on LXR receptors, or on other nuclear receptors, or other biological targets. Methods of modulation the RORs and methods of treating metabolic disorders, immune disorders, cancer, and CNS disorders wherein modulation of an ROR is medically indicated are also provided.

  这项发明提供了调节视黄酸受体相关孤儿受体的小分子调节剂，如RORα、RORβ或RORγ。该发明的化合物可以在无法对LXR受体或其他核受体或其他生物靶点产生作用的浓度下起到有效的调节作用。还提供了调节RORs的方法以及治疗代谢紊乱、免疫紊乱、癌症和中枢神经系统紊乱的方法，其中调节ROR在医学上是指示的。
• [EN] ANILINO LIVER X-RECEPTOR MODULATORS<br/>[FR] MODULATEURS DES RECEPTEURS X DU FOIE A STRUCTURE ANILINO
  申请人：PHARMACIA CORP

  公开号：WO2003099769A1

  公开（公告）日：2003-12-04

  The present invention is directed to selective LXR modulators, small molecule compounds corresponding to Formula I and is further directed to a process of treating a condition in a mammal that is modulated by LXR using a therapeutically effective dose of a compound of Formula I.

  本发明涉及选择性LXR调节剂，对应于式I的小分子化合物，并进一步涉及利用式I化合物的治疗有效剂量来治疗受LXR调节的哺乳动物病症的方法。
• Novel hexafluoroisopropanol derivatives
  申请人：Dehmlow Henrietta

  公开号：US20060004068A1

  公开（公告）日：2006-01-05

  The invention is concerned with novel hexafluoroisopropanol derivatives of formula (I) wherein R 1 to R 6 , m and n are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds bind to LXR alpha and LXR beta and can be used as medicaments.

  这项发明涉及式(I)的新型六氟异丙醇衍生物，其中R1至R6，m和n如描述和索赔中所定义，以及其生理上可接受的盐和酯。这些化合物结合到LXR alpha和LXR beta，并可用作药物。
• Anilino liver X-receptor modulators
  申请人：Pharmacia Corporation

  公开号：US20040087632A1

  公开（公告）日：2004-05-06

  The present invention is directed to selective LXR modulators, small molecule compounds corresponding to Formula I and is further directed to a process of treating a condition in a mammal that is modulated by LXR using a therapeutically effective dose of a compound of Formula I.

  本发明涉及选择性LXR调节剂，对应于公式I的小分子化合物，同时还涉及使用公式I化合物的治疗有效剂量来治疗LXR调节的哺乳动物疾病的方法。