(S)-5-(4-{1-ethyl-1-[3-methyl-4-(4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butynyl)phenyl]propyl}-2-methylphenoxymethyl)dihydrofuran-2-one | 865236-00-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-5-(4-{1-ethyl-1-[3-methyl-4-(4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butynyl)phenyl]propyl}-2-methylphenoxymethyl)dihydrofuran-2-one
• 英文别名: (S)-5-(4-{1-ethyl-1-[3-methyl-4-(4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-but-1-ynyl)-phenyl]-propyl}-2-methyl-phenoxymethyl)-dihydro-furan-2-one；(5S)-5-[[2-methyl-4-[3-[3-methyl-4-[4,4,4-trifluoro-3-hydroxy-3-(trifluoromethyl)but-1-ynyl]phenyl]pentan-3-yl]phenoxy]methyl]oxolan-2-one
• CAS: 865236-00-6
• 化学式: C₂₉H₃₀F₆O₄
• 分子量: 556.545
• InChiKey: IAAGRIPONPBEPI-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (S)-5-(4-{1-ethyl-1-[3-methyl-4-(4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butynyl)phenyl]propyl}-2-methylphenoxymethyl)dihydrofuran-2-one 在 palladium hydroxide, 20 wt% on carbon 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 以95%的产率得到(S)-5-(4-{1-ethyl-1-[3-methyl-4-(4,4,4-trifluoro-3-hydroxy-3-trifluoromethylbutyl)phenyl]propyl}-2-methylphenoxymethyl)dihydrofuran-2-one
  参考文献：
  名称：

  Effects of fluorines on nonsecosteroidal vitamin D receptor agonists

  摘要：

  From our research of nonsecosteroidal vitamin D-3 derivatives with gamma hydroxy carboxylic acid, we identified compound 6, with two CF3 groups in the side chain, as a most potent vitamin D receptor (VDR) agonist that shows superagonistic activity in VDRE reporter gene assay, MG-63 osteocalcin production assay and HL-60 cell differentiation assay. Compound 6 demonstrated that fluorination is as effective in the case of our nonsecosteroidal scaffold as in the case of secosteroidal VD3 analogs. X-ray analysis of the VDR with compound 6 revealed all of the six fluorine atoms of the hexafluoropropanol (HFP) moiety in the side chain effectively interacting with the VDR by both steric (van der Waals) and electrostatic (hydrogen bond, NH-F and CH-F) interactions. The HFP moiety of 6 effectively interacts with helix 12 (H12) of the VDR and stabilizes the position and the orientation of H12, which could result in stabilizing the coactivator and enhancing the VDR agonistic activity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.029
• 作为产物：
  描述：

  4-{1-ethyl-1-[3-methyl-4-(4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butynyl)phenyl]propyl}-2-methylphenol 在 盐酸 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.83h， 生成 (S)-5-(4-{1-ethyl-1-[3-methyl-4-(4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butynyl)phenyl]propyl}-2-methylphenoxymethyl)dihydrofuran-2-one
  参考文献：
  名称：

  Effects of fluorines on nonsecosteroidal vitamin D receptor agonists

  摘要：

  From our research of nonsecosteroidal vitamin D-3 derivatives with gamma hydroxy carboxylic acid, we identified compound 6, with two CF3 groups in the side chain, as a most potent vitamin D receptor (VDR) agonist that shows superagonistic activity in VDRE reporter gene assay, MG-63 osteocalcin production assay and HL-60 cell differentiation assay. Compound 6 demonstrated that fluorination is as effective in the case of our nonsecosteroidal scaffold as in the case of secosteroidal VD3 analogs. X-ray analysis of the VDR with compound 6 revealed all of the six fluorine atoms of the hexafluoropropanol (HFP) moiety in the side chain effectively interacting with the VDR by both steric (van der Waals) and electrostatic (hydrogen bond, NH-F and CH-F) interactions. The HFP moiety of 6 effectively interacts with helix 12 (H12) of the VDR and stabilizes the position and the orientation of H12, which could result in stabilizing the coactivator and enhancing the VDR agonistic activity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.029

文献信息

• Bisphenyl compounds useful as vitamin D3 receptor agonists
  申请人：Wallace David

  公开号：US20060025474A1

  公开（公告）日：2006-02-02

  The present invention discloses bisphenyl compounds of the formula: wherein R1, R2, R3, R4, R5, R6, X, Y, W are defined herein after. These compounds are useful as pharmaceuticals.

  本发明公开了以下式子的双苯基化合物：其中R1，R2，R3，R4，R5，R6，X，Y，W的定义见下文。这些化合物可用作药物。
• [EN] BISPHENYL COMPOUNDS USEFUL AS VITAMIN D3 RECEPTOR AGONISTS<br/>[FR] COMPOSES DE BISPHENYLE UTILES EN TANT QU'AGONISTES DE RECEPTEURS DE LA VITAMINE D3
  申请人：CHUGAI PHARMACEUTICAL CO LTD

  公开号：WO2005087700A3

  公开（公告）日：2006-10-19
• BISPHENYL COMPOUNDS USEFUL AS VITAMIN D SB 3 /SB RECEPTOR AGONISTS
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP1740522A2

  公开（公告）日：2007-01-10
• Effects of fluorines on nonsecosteroidal vitamin D receptor agonists
  作者：Hirotaka Kashiwagi、Masateru Ohta、Yoshiyuki Ono、Kenji Morikami、Susumu Itoh、Hideki Sato、Tadakatsu Takahashi

  DOI：10.1016/j.bmc.2012.11.029

  日期：2013.2

  From our research of nonsecosteroidal vitamin D-3 derivatives with gamma hydroxy carboxylic acid, we identified compound 6, with two CF3 groups in the side chain, as a most potent vitamin D receptor (VDR) agonist that shows superagonistic activity in VDRE reporter gene assay, MG-63 osteocalcin production assay and HL-60 cell differentiation assay. Compound 6 demonstrated that fluorination is as effective in the case of our nonsecosteroidal scaffold as in the case of secosteroidal VD3 analogs. X-ray analysis of the VDR with compound 6 revealed all of the six fluorine atoms of the hexafluoropropanol (HFP) moiety in the side chain effectively interacting with the VDR by both steric (van der Waals) and electrostatic (hydrogen bond, NH-F and CH-F) interactions. The HFP moiety of 6 effectively interacts with helix 12 (H12) of the VDR and stabilizes the position and the orientation of H12, which could result in stabilizing the coactivator and enhancing the VDR agonistic activity. (C) 2012 Elsevier Ltd. All rights reserved.