tert-butyl 2-(3-(3-(3,4-dimethoxyphenyl)-1-((S)-1-(3,3-dimethyl-2-oxopentanoyl)piperidine-2-carboxamido)propyl)phenoxy)acetate | 1374119-30-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: tert-butyl 2-(3-(3-(3,4-dimethoxyphenyl)-1-((S)-1-(3,3-dimethyl-2-oxopentanoyl)piperidine-2-carboxamido)propyl)phenoxy)acetate
• CAS: 1374119-30-8
• 化学式: C₃₆H₅₀N₂O₈
• 分子量: 638.802
• InChiKey: JFJCYNWXIWPVSC-CPRJBALCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  46.0
• 可旋转键数：
  14.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  120.47
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-(3-(3-(3,4-dimethoxyphenyl)-1-((S)-1-(3,3-dimethyl-2-oxopentanoyl)piperidine-2-carboxamido)propyl)phenoxy)acetate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以40%的产率得到2-(3-(3-(3,4-dimethoxyphenyl)-1-((S)-1-(3,3-dimethyl-2-oxopentanoyl)piperidine-2-carboxamido)propyl)phenoxy)acetic acid
  参考文献：
  名称：

  Evaluation of Synthetic FK506 Analogues as Ligands for the FK506-Binding Proteins 51 and 52

  摘要：

  The FK506-binding proteins (FKBP) 51 and 52 are cochaperones that modulate the signal transduction of steroid hormone receptors. Both proteins have been implicated in prostate cancer. Furthermore, single nucleotide polymorphisms in the gene encoding FKBP51 have been associated with a variety of psychiatric disorders. Rapamycin and FK506 are two macrocyclic natural products that bind to these proteins indiscriminately but with nanomolar affinity. We here report the cocrystal structure of FKBP51 with a simplified alpha-ketoamide analogue derived from FK506 and the first structure-activity relationship analysis for FKBP51 and FKBP52 based on this compound. In particular, the tert-pentyl group of this ligand was systematically replaced by a cyclohexyl ring system, which more closely resembles the pyranose ring in the high-affinity ligands rapamycin and FK506. The interaction with FKBPs was found to be surprisingly tolerant to the stereochemistry of the attached cyclohexyl substituents. The molecular basis for this tolerance was elucidated by X-ray cocrystallography.

  DOI：

  10.1021/jm201746x
• 作为产物：
  描述：

  tert-butyl 2-(3-(3-(3,4-dimethoxyphenyl)-1-hydroxypropyl)phenoxy)acetate 在 4-二甲氨基吡啶 、 叠氮磷酸二苯酯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 20.0 ℃ 、100.0 kPa 条件下， 反应 12.0h， 生成 tert-butyl 2-(3-(3-(3,4-dimethoxyphenyl)-1-((S)-1-(3,3-dimethyl-2-oxopentanoyl)piperidine-2-carboxamido)propyl)phenoxy)acetate
  参考文献：
  名称：

  Evaluation of Synthetic FK506 Analogues as Ligands for the FK506-Binding Proteins 51 and 52

  摘要：

  The FK506-binding proteins (FKBP) 51 and 52 are cochaperones that modulate the signal transduction of steroid hormone receptors. Both proteins have been implicated in prostate cancer. Furthermore, single nucleotide polymorphisms in the gene encoding FKBP51 have been associated with a variety of psychiatric disorders. Rapamycin and FK506 are two macrocyclic natural products that bind to these proteins indiscriminately but with nanomolar affinity. We here report the cocrystal structure of FKBP51 with a simplified alpha-ketoamide analogue derived from FK506 and the first structure-activity relationship analysis for FKBP51 and FKBP52 based on this compound. In particular, the tert-pentyl group of this ligand was systematically replaced by a cyclohexyl ring system, which more closely resembles the pyranose ring in the high-affinity ligands rapamycin and FK506. The interaction with FKBPs was found to be surprisingly tolerant to the stereochemistry of the attached cyclohexyl substituents. The molecular basis for this tolerance was elucidated by X-ray cocrystallography.

  DOI：

  10.1021/jm201746x