5-butyl-2-(1',1',1',3',3',3'-hexafluoro-2'-hydroxypropan-2'-yl)-10-methoxy-phenanthridin-6(5H)-one | 1307740-67-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 5-butyl-2-(1',1',1',3',3',3'-hexafluoro-2'-hydroxypropan-2'-yl)-10-methoxy-phenanthridin-6(5H)-one
• 英文别名: 5-Butyl-10-methoxy-2-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenanthridin-6-one；5-butyl-2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-10-methoxyphenanthridin-6-one
• CAS: 1307740-67-5
• 化学式: C₂₁H₁₉F₆NO₃
• 分子量: 447.377
• InChiKey: KWIVMBACKDKFDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N-丁基苯胺 在 (氯亚甲基)二甲基氯化铵 、 palladium diacetate 、 caesium carbonate 、 对甲苯磺酸 、 tricyclohexylphosphine tetrafluoroborate 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 10.0h， 生成 5-butyl-2-(1',1',1',3',3',3'-hexafluoro-2'-hydroxypropan-2'-yl)-10-methoxy-phenanthridin-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

文献信息

• THERAPEUTIC AGENT FOR HEPATITIS C
  申请人：Baba Masanori

  公开号：US20120316342A1

  公开（公告）日：2012-12-13

  This invention provides a therapeutic agent for hepatitis C comprising, as an active ingredient, a compound having anti-HCV activity useful in treatment of hepatitis C. The therapeutic agent for hepatitis C comprises, as an active ingredient, a compound represented by formula (I) or a pharmaceutically acceptable salt thereof.

  这项发明提供了一种治疗丙型肝炎的药剂，其活性成分为具有抗丙型肝炎病毒活性的化合物，可用于治疗丙型肝炎。治疗丙型肝炎的药剂的活性成分包括由式（I）表示的化合物或其药用可接受的盐。
• Fused heterocyclic amido compounds as anti-hepatitis C virus agents
  作者：Hiroshi Aoyama、Kazuyuki Sugita、Masahiko Nakamura、Atsushi Aoyama、Mohammed T.A. Salim、Mika Okamoto、Masanori Baba、Yuichi Hashimoto

  DOI：10.1016/j.bmc.2011.03.002

  日期：2011.4

  We identified a fused heteroaromatic amido structure based on the phenanthridine skeleton as a superior scaffold for candidate drugs with potent anti-HCV activity. Among the compounds synthesized, a phenanthridine analogue with a 1,3-dioxolyl group (24) possessed the most potent anti-HCV activity (EC50 value: 50 nM), with acceptable cytotoxicity. The structural development and structure-activity relationships of these compounds are described. (C) 2011 Elsevier Ltd. All rights reserved.
• 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
  作者：Yuko Nishiyama、Masahiko Nakamura、Takashi Misawa、Madoka Nakagomi、Makoto Makishima、Minoru Ishikawa、Yuichi Hashimoto

  DOI：10.1016/j.bmc.2014.03.007

  日期：2014.5

  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.