(1S)-1,3-diphenyl-1-propyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-piperidinecarboxylate

• 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: (1S)-1,3-diphenyl-1-propyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-piperidinecarboxylate
• 英文别名: (1S)-1,3-diphenylpropyl (2S)-1-(3,3-dimethyl-2-oxopentanoyl)hexahydro-2-pyridinecarboxylate；[(1S)-1,3-diphenylpropyl] (2S)-1-(3,3-dimethyl-2-oxopentanoyl)piperidine-2-carboxylate
• 化学式: C₂₈H₃₅NO₄
• 分子量: 449.59
• InChiKey: WQTIHJORCCUQBO-ZEQRLZLVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  63.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  ω-苄基苯乙酮 在 4-二甲氨基吡啶 、 D(+)-10-樟脑磺酸 、 二乙醇胺 、 N,N'-二环己基碳二亚胺 、 (-)-diisopinocamphenylborane chloride 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 (1S)-1,3-diphenyl-1-propyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-piperidinecarboxylate
  参考文献：
  名称：

  Design, synthesis, and kinetic evaluation of high-affinity FKBP ligands and the X-ray crystal structures of their complexes with FKBP12

  摘要：

  The design and synthesis of high-affinity FKBP12 ligands is described. These compounds potently inhibit the cis-trans-peptidylprolyl isomerase (rotamase) activity catalyzed by FKBP12 with inhibition constants (K(i,app)) as low as 1 nM, yet they possess remarkable structural simplicity relative to FK506 and rapamycin, from which they are conceptually derived. The atomic structures of three FKBP12-ligand complexes and of one unbound ligand were determined by X-ray crystallography and are compared to the FKBP12-FK506 and FKBP12-rapamycin complexes.

  DOI：

  10.1021/ja00075a008

文献信息

• INHIBITORS OF ROTAMASE ENZYME ACTIVITY
  申请人：GUILFORD PHARMACEUTICALS INC.

  公开号：EP0777478B1

  公开（公告）日：2001-11-07
• NEUROPHILIN LIGANDS FOR TREATING OCULAR CONDITIONS
  申请人：Alcon, Inc.

  公开号：EP1227859B1

  公开（公告）日：2006-08-09
• US6187784B1
  申请人：——

  公开号：US6187784B1

  公开（公告）日：2001-02-13
• Design, synthesis, and kinetic evaluation of high-affinity FKBP ligands and the X-ray crystal structures of their complexes with FKBP12
  作者：Dennis A. Holt、Juan I. Luengo、Dennis S. Yamashita、Hye Ja Oh、Arda L. Konialian、Hwa Kwo Yen、Leonard W. Rozamus、Martin Brandt、Mary J. Bossard、Mark A. Levy、Drake S. Eggleston、Jun Liang、L. Wayne Schultz、Thomas J. Stout、Jon Clardy

  DOI：10.1021/ja00075a008

  日期：1993.11.1

  The design and synthesis of high-affinity FKBP12 ligands is described. These compounds potently inhibit the cis-trans-peptidylprolyl isomerase (rotamase) activity catalyzed by FKBP12 with inhibition constants (K(i,app)) as low as 1 nM, yet they possess remarkable structural simplicity relative to FK506 and rapamycin, from which they are conceptually derived. The atomic structures of three FKBP12-ligand complexes and of one unbound ligand were determined by X-ray crystallography and are compared to the FKBP12-FK506 and FKBP12-rapamycin complexes.