(S)-1-(3,3-Dimethyl-2-oxo-pentanoyl)-pyrrolidine-2-carboxylic acid (R)-1-(3-tert-butoxycarbonylmethoxy-phenyl)-3-(3,4-dimethoxy-phenyl)-propyl ester | 215169-04-3

• 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: (S)-1-(3,3-Dimethyl-2-oxo-pentanoyl)-pyrrolidine-2-carboxylic acid (R)-1-(3-tert-butoxycarbonylmethoxy-phenyl)-3-(3,4-dimethoxy-phenyl)-propyl ester
• CAS: 215169-04-3
• 化学式: C₃₅H₄₇NO₉
• 分子量: 625.759
• InChiKey: HXXKIMGZDDNPEP-RRPNLBNLSA-N

物化性质

• 沸点：
  692.283±65.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.155±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.64
• 重原子数：
  45.0
• 可旋转键数：
  14.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  117.67
• 氢给体数：
  0.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  (S)-1-(3,3-Dimethyl-2-oxo-pentanoyl)-pyrrolidine-2-carboxylic acid (R)-1-(3-tert-butoxycarbonylmethoxy-phenyl)-3-(3,4-dimethoxy-phenyl)-propyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以22.6 mg的产率得到2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-(((S)-1-(3,3-dimethyl-2-oxopentanoyl)pyrrolidine-2-carbonyl)oxy)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：

  3-羟基苯乙酮 在 Lindlar's catalyst 4-二甲氨基吡啶 、 氢氧化钾 、 氢气 、 potassium carbonate 、 N,N'-二环己基碳二亚胺 、 (+)-二异松蒎基氯硼烷 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 丙酮 为溶剂， -20.0~20.0 ℃ 、344.74 kPa 条件下， 反应 44.0h， 生成 (S)-1-(3,3-Dimethyl-2-oxo-pentanoyl)-pyrrolidine-2-carboxylic acid (R)-1-(3-tert-butoxycarbonylmethoxy-phenyl)-3-(3,4-dimethoxy-phenyl)-propyl ester
  参考文献：
  名称：

  Synthesis and activity of bivalent FKBP12 ligands for the regulated dimerization of proteins

  摘要：

  The total synthesis and in vitro activities of a series of chemical inducers of dimerization (CIDs) is described. The use of small-molecule CIDs to control the dimerization of engineered FKBP12-containing fusion proteins has been demonstrated to have broad utility in biological research as well as potential medical applications in gene and cell therapies. The facility and flexibility of preparation make this new class of wholly synthetic compounds exceptionally versatile tools for the study of intracellular signaling events mediated by protein-protein interactions or protein localization. While some congeners possess potency comparable to or better than the first generation natural product-derived CID, FK1012, structure-activity relationships are complex and underscore the need for application-specific compound optimizations. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00125-4