2-(4-(butylamino)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol | 449804-01-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-(4-(butylamino)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol
• 英文别名: 2-[4-(Butylamino)phenyl]-1,1,1,3,3,3-hexafluoro-2-propanol；2-[4-(butylamino)phenyl]-1,1,1,3,3,3-hexafluoropropan-2-ol
• CAS: 449804-01-7
• 化学式: C₁₃H₁₅F₆NO
• 分子量: 315.259
• InChiKey: FCRPOBIVQQWQPW-UHFFFAOYSA-N

物化性质

• 沸点：
  339.6±42.0 °C(Predicted)
• 密度：
  1.319±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(4-(butylamino)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol 在 (氯亚甲基)二甲基氯化铵 、 palladium diacetate 、 caesium carbonate 、 tricyclohexylphosphine tetrafluoroborate 作用下， 以 二氯甲烷 为溶剂， 反应 7.0h， 生成 5-butyl-2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-9-methylphenanthridin-6(5H)-one
  参考文献：
  名称：

  Structure–activity relationship-guided development of retinoic acid receptor-related orphan receptor gamma (RORγ)-selective inverse agonists with a phenanthridin-6(5H)-one skeleton from a liver X receptor ligand

  摘要：

  Retinoic acid receptor-related orphan receptors (RORs), which belong to the nuclear receptor superfamily, regulate many physiological processes, including hepatic gluconeogenesis, lipid metabolism, immune function and circadian rhythm. Since RORs resemble liver X receptors (LXRs) in the fold structure of their ligand-binding domains, we speculated that ROR-mediated transcription might be modulated by LXR ligands, in line with the multi-template hypothesis. Therefore, we screened our LXR ligand library for compounds with ROR ligand activity and identified a novel ROR ligand with a phenanthridin-6(5H)-one skeleton. Structure-activity relationship studies aimed at separating ROR inverse agonistic activity from LXR-agonistic activity enabled us to develop a series of ROR inverse agonists based on the phenanthridin-6(5H)-one skeleton, including a ROR gamma-selective inverse agonist. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.03.007
• 作为产物：
  描述：

  在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 4.0h， 以9.5 g的产率得到2-(4-(butylamino)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol
  参考文献：
  名称：

  Structure-Guided Design of N-Phenyl Tertiary Amines as Transrepression-Selective Liver X Receptor Modulators with Anti-Inflammatory Activity

  摘要：

  A cocrystal structure of T1317 (3) bound to hLXRbeta was utilized in the design of a series of substituted N-phenyl tertiary amines. Profiling in binding and functional assays led to the identification of LXR modulator GSK9772 ( 20) as a high-affinity LXRbeta ligand (IC 50 = 30 nM) that shows separation of anti-inflammatory and lipogenic activities in human macrophage and liver cell lines, respectively. A cocrystal structure of the structurally related analog 19 bound to LXRbeta reveals regions within the receptor that can affect receptor modulation through ligand modification. Mechanistic studies demonstrate that 20 is greater than 10-fold selective for LXR-mediated transrepression of proinflammatory gene expression versus transactivation of lipogenic signaling pathways, thus providing an opportunity for the identification of LXR modulators with improved therapeutic indexes.

  DOI：

  10.1021/jm800612u

文献信息

• Cobalt-Catalyzed Selective Functionalization of Aniline Derivatives with Hexafluoroisopropanol
  作者：He Zhao、Shuo Zhao、Xiu Li、Yinyue Deng、Huanfeng Jiang、Min Zhang

  DOI：10.1021/acs.orglett.8b03666

  日期：2019.1.4

  A cobalt-catalyzed site-selective functionalization of aniline derivatives with hexafluoroisopropanol, which enables the synthesis of a wide array of fluoroalkylated anilines, a class of highly valuable building blocks for further preparation of fluorinated functional products, is reported. The developed transformation proceeds with operational simplicity, use of earth-abundant metal catalyst, broad

  报道了用六氟异丙醇对苯胺衍生物进行钴催化的位点选择性官能化，这使得能够合成各种各样的氟代烷基化苯胺，这是一类非常有价值的用于进一步制备氟化功能产物的结构单元。所开发的转化过程将以操作简便，使用富含地球的金属催化剂，广泛的底物范围，良好的官能团耐受性和温和的反应条件进行。
• Copper(II)‐Catalysed Aerobic Oxidative Coupling of Arylamines with Hexafluoroisopropanol: An Alternative Methodology for Constructing Fluorinated Compounds
  作者：Liangying Wu、Yang Song、Zhanchong Li、Jiabao Guo、Xiaoquan Yao

  DOI：10.1002/adsc.202001048

  日期：2021.1.5

  The selective functionalisation of arylamine derivatives with hexafluoroisopropanol through copper(II)‐catalysed aerobic oxidative coupling was developed to generate various fluoroalkylated arylamines under mild conditions. This method has a wide substrate scope with excellent functional group tolerance and provides the fluorinated products in good to excellent yields. Furthermore, preliminary studies

  开发了在铜（II）催化的需氧氧化偶联作用下，六氟异丙醇对芳胺衍生物的选择性官能化反应，可在温和条件下生成各种氟代烷基化芳基胺。该方法具有广泛的底物范围，具有优异的官能团耐受性，并且以良好至优异的产率提供了氟化产物。此外，初步研究表明该反应是通过自由基机理发生的。该协议使用大气中的O 2作为氧化剂，为构建氟化化合物提供了另一种绿色途径。
• Synthesis and Structure−Activity Relationship of Small-Molecule Malonyl Coenzyme A Decarboxylase Inhibitors
  作者：Jie-Fei Cheng、Mi Chen、David Wallace、Souvothy Tith、Masayuki Haramura、Bin Liu、Chi Ching Mak、Thomas Arrhenius、Sean Reily、Steven Brown、Vicki Thorn、Charles Harmon、Rick Barr、Jason R. B. Dyck、Gary D. Lopaschuk、Alex M. Nadzan

  DOI：10.1021/jm050109n

  日期：2006.3.1

  discovery and structure-activity relationship of first-generation small-molecule malonyl-CoA decarboxylase (MCD; CoA = coenzyme A) inhibitors are reported. We demonstrated that MCD inhibitors increased malonyl-CoA concentration in the isolated working rat hearts. Malonyl-CoA is a potent, endogenous, and allosteric inhibitor of carnitine palmitoyltransferase-I (CPT-I), a key enzyme for mitochondrial fatty acid

  报道了第一代小分子丙二酰辅酶A脱羧酶（MCD； CoA =辅酶A）抑制剂的发现及其与构效关系。我们证明了MCD抑制剂增加了离体大鼠心脏中丙二酰辅酶A的浓度。丙二酰辅酶A是一种有效的，内源性的，变构的肉碱棕榈酰转移酶-I（CPT-1）抑制剂，CPT-1是线粒体脂肪酸氧化的关键酶。由于丙二酰辅酶A水平的增加，脂肪酸氧化速率降低并且葡萄糖氧化速率显着提高。证明5-（N-（4-（1,1,1,3,3,3-六氟-2-羟基丙烷-2-基）苯基）吗啉-4-羧氨基ido）戊酸甲酯（6u）的体内功效）在猪缺血模型中表明MCD抑制剂可能对治疗缺血性心脏病有用。
• Malonyl-coa decarboxylase inhibitors useful as metabolic modulators
  申请人：——

  公开号：US20040063671A1

  公开（公告）日：2004-04-01

  The present invention relates to novel compounds (I), their prodrugs, and the pharmaceutically acceptable salts as well as pharmaceutical compositions containing such compounds useful in treating certain metabolic diseases and diseases modulated by the inhibition of the enzyme malonyl-coenzyme A decarboxylase (malonyl-CoA decarboxylase, MCD). In particular, the invention relates to compounds and compositions and the methods for the prophylaxis, management and treatment of cardiovascular diseases, diabetes, acidosis, cancers, and obesity through the inhibition of malonyl-coenzyme A decarboxylase. 1

  本发明涉及新型化合物（I）、它们的前药和药物可接受的盐，以及包含这些化合物的药物组合物，用于治疗某些代谢性疾病和受酰辅酶A丙酮酸羧化酶（malonyl-CoA decarboxylase，MCD）抑制影响的疾病。特别是，本发明涉及化合物和组合物以及通过抑制受酰辅酶A丙酮酸羧化酶的方法进行心血管疾病、糖尿病、酸中毒、癌症和肥胖症的预防、管理和治疗。
• Chemical Compounds
  申请人：Collins John Loren

  公开号：US20080221176A1

  公开（公告）日：2008-09-11

  This invention relates to compounds that are modulators of the liver X receptors (LXRs), and also to the methods for the making and use of such compounds.

  本发明涉及调节肝X受体（LXR）的化合物，以及制备和使用这些化合物的方法。