Fmoc-D-norleucinol | 1139710-53-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-D-norleucinol
• 英文别名: 9H-fluoren-9-ylmethyl N-[(2R)-1-hydroxyhexan-2-yl]carbamate
• CAS: 1139710-53-4
• 化学式: C₂₁H₂₅NO₃
• 分子量: 339.434
• InChiKey: YYQSZDIVCKUVDT-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Fmoc-D-norleucinol 在 草酰氯 、 二甲基亚砜 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 9H-fluoren-9-ylmethyl N-[(2R)-1-oxohexan-2-yl]carbamate
  参考文献：
  名称：

  Structure−Affinity Relationships of Glutamine Mimics Incorporated into Phosphopeptides Targeted to the SH2 Domain of Signal Transducer and Activator of Transcription 3

  摘要：

  In cancer cells, signal transducer and activator of transcription 3 (Stat3) participates in aberrant growth, survival, angiogenesis, and invasion signals and is a validated target for anticancer drug design. We are targeting its SH2 domain to prevent docking to cytokine and growth factor receptors and subsequent signaling. One of the important elements of the recognition sequence, pTyr-Xxx-Xxx-Gln, is glutamine. We incorporated novel Gin mimics into a lead peptide, pCinn-Leu-Pro-Gln-NHBn, and found that a linear, unconstrained side chain and carboxamide are necessary for high affinity, and the benzamide can be eliminated. Replacement of Gln-NHBn with (R)-4-aminopentanamide or 2-aminoethylurea produced inhibitors with equal or greater potency than that of the lead, as judged by fluorescence polarization (IC50 values were 110 and 130 nM, respectively). When Pro was replaced with cis-3,4-methanoproline, the glutamine mimic, (4R,5S)-4-amino-5-benzyloxyhexanamide resulted in an IC50 of 69 nM, the highest affinity Stat3 inhibitor reported to date.

  DOI：

  10.1021/jm901105k
• 作为产物：
  描述：

  在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 水 为溶剂， 以1.6 g的产率得到Fmoc-D-norleucinol
  参考文献：
  名称：

  Structure−Affinity Relationships of Glutamine Mimics Incorporated into Phosphopeptides Targeted to the SH2 Domain of Signal Transducer and Activator of Transcription 3

  摘要：

  In cancer cells, signal transducer and activator of transcription 3 (Stat3) participates in aberrant growth, survival, angiogenesis, and invasion signals and is a validated target for anticancer drug design. We are targeting its SH2 domain to prevent docking to cytokine and growth factor receptors and subsequent signaling. One of the important elements of the recognition sequence, pTyr-Xxx-Xxx-Gln, is glutamine. We incorporated novel Gin mimics into a lead peptide, pCinn-Leu-Pro-Gln-NHBn, and found that a linear, unconstrained side chain and carboxamide are necessary for high affinity, and the benzamide can be eliminated. Replacement of Gln-NHBn with (R)-4-aminopentanamide or 2-aminoethylurea produced inhibitors with equal or greater potency than that of the lead, as judged by fluorescence polarization (IC50 values were 110 and 130 nM, respectively). When Pro was replaced with cis-3,4-methanoproline, the glutamine mimic, (4R,5S)-4-amino-5-benzyloxyhexanamide resulted in an IC50 of 69 nM, the highest affinity Stat3 inhibitor reported to date.

  DOI：

  10.1021/jm901105k

文献信息

• Small Molecule Compositions for Sexual Dysfunction
  申请人：Sharma Shubh D.

  公开号：US20090253713A1

  公开（公告）日：2009-10-08

  Compounds of the general formula: or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , and X are as defined. Further provided are methods for treatment of sexual dysfunction, including erectile dysfunction and female sexual dysfunction, and combination drugs and method of use thereof, including a compound of the invention and one or more second sexual dysfunction pharmaceutical agents.
• US7550602B1
  申请人：——

  公开号：US7550602B1

  公开（公告）日：2009-06-23
• Structure−Affinity Relationships of Glutamine Mimics Incorporated into Phosphopeptides Targeted to the SH2 Domain of Signal Transducer and Activator of Transcription 3
  作者：Pijus K. Mandal、Zhiyong Ren、Xiaomin Chen、Chiyi Xiong、John S. McMurray

  DOI：10.1021/jm901105k

  日期：2009.10.8

  In cancer cells, signal transducer and activator of transcription 3 (Stat3) participates in aberrant growth, survival, angiogenesis, and invasion signals and is a validated target for anticancer drug design. We are targeting its SH2 domain to prevent docking to cytokine and growth factor receptors and subsequent signaling. One of the important elements of the recognition sequence, pTyr-Xxx-Xxx-Gln, is glutamine. We incorporated novel Gin mimics into a lead peptide, pCinn-Leu-Pro-Gln-NHBn, and found that a linear, unconstrained side chain and carboxamide are necessary for high affinity, and the benzamide can be eliminated. Replacement of Gln-NHBn with (R)-4-aminopentanamide or 2-aminoethylurea produced inhibitors with equal or greater potency than that of the lead, as judged by fluorescence polarization (IC50 values were 110 and 130 nM, respectively). When Pro was replaced with cis-3,4-methanoproline, the glutamine mimic, (4R,5S)-4-amino-5-benzyloxyhexanamide resulted in an IC50 of 69 nM, the highest affinity Stat3 inhibitor reported to date.