(S)-2-bromo-4-fluoro-1-(pent-4-en-2-yloxy)benzene | 1803595-86-9

• 英文名称: (S)-2-bromo-4-fluoro-1-(pent-4-en-2-yloxy)benzene
• 英文别名: 2-bromo-4-fluoro-1-[(2S)-pent-4-en-2-yl]oxybenzene
• CAS: 1803595-86-9
• 化学式: C₁₁H₁₂BrFO
• 分子量: 259.118
• InChiKey: MCCWGGQYADSVRD-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-2-bromo-4-fluoro-1-(pent-4-en-2-yloxy)benzene 在 四(三苯基膦)钯 、 正丁基锂 、 Hoveyda-Grubbs catalyst second generation 、 sodium carbonate 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.17h， 生成 methyl (2S)-2-(tert-butoxy)-2-[(22S)-17-fluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.1^6,9.1^10,14.0^2,7.0^15,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18,24-undecaen-3-yl]acetate
  参考文献：
  名称：

  Structure-based amelioration of PXR transactivation in a novel series of macrocyclic allosteric inhibitors of HIV-1 integrase

  摘要：

  Previous studies have identified a series of imidazo[1,2-a]pyridine (IZP) derivatives as potent allosteric inhibitors of HIV-1 integrase (ALLINIs) and virus infection in cell culture. However, IZPs were also found to be relatively potent activators of the pregnane-X receptor (PXR), raising the specter of induction of CYP-mediated drug disposition pathways. In an attempt to modify PXR activity without affecting anti-HIV-1 activity, rational structure-based design and modeling approaches were used. An X-ray cocrystal structure of (S,S)-1 in the PXR ligand binding domain (LBD) allowed an examination of the potential of rational structural modifications designed to abrogate PXR. The introduction of bulky basic amines at the C-8 position provided macrocyclic IZP derivatives that displayed potent HIV-1 inhibitory activity in cell culture with no detectable PXR transactivation at the highest concentration tested.

  DOI：

  10.1016/j.bmcl.2020.127531
• 作为产物：
  描述：

  (S)-(+)-4-戊烯-2-醇 、 2-溴-4-氟苯酚 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以92%的产率得到(S)-2-bromo-4-fluoro-1-(pent-4-en-2-yloxy)benzene
  参考文献：
  名称：

  Structure-based amelioration of PXR transactivation in a novel series of macrocyclic allosteric inhibitors of HIV-1 integrase

  摘要：

  Previous studies have identified a series of imidazo[1,2-a]pyridine (IZP) derivatives as potent allosteric inhibitors of HIV-1 integrase (ALLINIs) and virus infection in cell culture. However, IZPs were also found to be relatively potent activators of the pregnane-X receptor (PXR), raising the specter of induction of CYP-mediated drug disposition pathways. In an attempt to modify PXR activity without affecting anti-HIV-1 activity, rational structure-based design and modeling approaches were used. An X-ray cocrystal structure of (S,S)-1 in the PXR ligand binding domain (LBD) allowed an examination of the potential of rational structural modifications designed to abrogate PXR. The introduction of bulky basic amines at the C-8 position provided macrocyclic IZP derivatives that displayed potent HIV-1 inhibitory activity in cell culture with no detectable PXR transactivation at the highest concentration tested.

  DOI：

  10.1016/j.bmcl.2020.127531

文献信息

• [EN] IMIDAZOPYRIMIDINE MACROCYCLES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION<br/>[FR] MACROCYCLES D'IMIDAZOPYRIMIDINE UTILISÉS COMME INHIBITEURS DE LA RÉPLICATION DU VIRUS DE L'IMMUNODÉFICIENCE HUMAINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2015126758A1

  公开（公告）日：2015-08-27

  The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection. I

  该披露通常涉及到I式化合物，包括用于治疗人类免疫缺陷病毒（HIV）感染的组合物和方法。该披露提供了HIV的新型抑制剂，含有这些化合物的药物组合物，以及在治疗HIV感染中使用这些化合物的方法。
• Imidazopyridine Macrocycles as Inhibitors of Human Immunodeficiency Virus Replication
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20150232480A1

  公开（公告）日：2015-08-20

  The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.

  该披露通常涉及公式I的化合物，包括用于治疗人类免疫缺陷病毒（HIV）感染的组合物和方法。该披露提供了HIV的新型抑制剂，含有这些化合物的药物组合物，以及使用这些化合物治疗HIV感染的方法。
• Imidazopyridine macrocycles as inhibitors of human immunodeficiency virus replication
  申请人：Bristol-Myers Squibb Company

  公开号：US09409922B2

  公开（公告）日：2016-08-09

  The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.

  本公开涉及式I化合物，包括用于治疗人类免疫缺陷病毒（HIV）感染的组合物和方法。本公开提供了HIV的新型抑制剂，含有这些化合物的药物组合物以及使用这些化合物治疗HIV感染的方法。
• IMIDAZOPYRIDINE MACROCYCLES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
  申请人：VIIV Healthcare UK (No.5) Limited

  公开号：EP3114129A1

  公开（公告）日：2017-01-11
• IMIDAZOPYRIMIDINE MACROCYCLES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
  申请人：VIIV Healthcare UK (No.5) Limited

  公开号：EP3116879A1

  公开（公告）日：2017-01-18