(2S)-Fmoc-4-phenylpyrrolidine-2-carboxylic acid | 316833-44-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (2S)-Fmoc-4-phenylpyrrolidine-2-carboxylic acid
• 英文别名: (2S)-1-(9H-fluoren-9-ylmethoxycarbonyl)-4-phenylpyrrolidine-2-carboxylic acid
• CAS: 316833-44-0
• 化学式: C₂₆H₂₃NO₄
• 分子量: 413.473
• InChiKey: YABZSVAQRSIEAZ-LUTIACGYSA-N

物化性质

• 沸点：
  626.3±55.0 °C(Predicted)
• 密度：
  1.299±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  、 (2S)-Fmoc-4-phenylpyrrolidine-2-carboxylic acid 、 FMOC-N-甲基-L-丙氨酸 、 Fmoc-L-叔亮氨酸 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成
  参考文献：
  名称：

  Solid phase synthesis of Smac/DIABLO-derived peptides using a ‘Safety-Catch’ resin: Identification of potent XIAP BIR3 antagonists

  摘要：

  The N-terminal sequence of the Smac/DIABLO protein is known to be involved in binding to the BIR3 domain of the anti-apoptotic proteins IAPs, antagonizing their action. Short peptides and peptide mimetics based on the first 4-residues of Smac/DIABLO have been demonstrated to re-sensitize resistant cancer cells, over-expressing IAPs, to apoptosis. Based on the well-defined structural basis for this interaction, a small focused library of C-terminal capped Smac/DIABLO-derived peptides was designed in silico using docking to the XIAP BIR3 domain. The top-ranked computational hits were conveniently synthesized employing Solid Phase Synthesis (SPS) on an alkane sulfonamide 'Safety-Catch' resin. This novel approach afforded the rapid synthesis of the target peptide library with high flexibility for the introduction of various C-terminal amide-capping groups. The library members were obtained in high yield (>65%) and purity (>85%), upon nucleophilic release from the activated resin by treatment with various amine nucleophiles. In vitro caspase-9 activity reconstitution assays of the peptides in the presence of the recombinant BIR3-domain of human XIAP (500 nM) revealed N-methylalanyl-tertiarybutylglycinyl-4-(R)-phenoxyprolyl-N-biphenylmethyl carboxamide (11a) to be the most potent XIAP BIR3 antagonist of the series synthesized inducing 93% recovery of caspase-9 activity, when used at 1 mu M concentration. Compound (11a) also demonstrated moderate cytotoxicity against the breast cancer cell lines MDA-MB-231 and MCF-7, compared to the Smac/DIABLO-derived wild-type peptide sequences that were totally inactive in the same cell lines. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.055

文献信息

• VLA-4 inhibitor compounds
  申请人：Daiichi Pharmaceutical Co., LTD.

  公开号：US20030078249A1

  公开（公告）日：2003-04-24

  Compounds that selectively inhibit the binding of ligands to &agr;4&bgr;1 integrin (VLA-4) and methods for their preparation are disclosed. In one embodiment, compounds of the invention are represented by Formula I: 1 As selective inhibitors of VLA-4 mediated cell adhesion, compounds of the present invention are useful in the treatment of conditions associated with such adhesion, including, but not limited to, such conditions as inflammatory and autoimmune responses, diabetes, asthma, psoriasis, inflammatory bowel disease, transplantation rejection, and tumor metastasis. Also disclosed are pharmaceutical compositions, methods of inhibiting VLA-4 mediated cell adhesion and methods of treating conditions associated with LA-4 mediated cell adhesion, which involve compounds of Formula I.

  本发明公开了选择性抑制配体与α4β1整合素（VLA-4）结合的化合物及其制备方法。在一个实施例中，本发明的化合物由式I表示： 1 作为VLA-4介导的细胞粘附的选择性抑制剂，本发明的化合物可用于治疗与该粘附相关的疾病，包括但不限于炎症和自身免疫反应、糖尿病、哮喘、银屑病、炎症性肠病、移植排斥和肿瘤转移。还公开了包含式I化合物的药物组合物、抑制VLA-4介导的细胞粘附的方法以及治疗与VLA-4介导的细胞粘附相关疾病的方法。
• VLA-4 INHIBITOR COMPOUNDS
  申请人：Daiichi Pharmaceutical Co., Ltd.

  公开号：EP1189612A1

  公开（公告）日：2002-03-27
• EP1189612A4
  申请人：——

  公开号：EP1189612A4

  公开（公告）日：2005-02-16
• US6756378B2
  申请人：——

  公开号：US6756378B2

  公开（公告）日：2004-06-29
• US7179819B2
  申请人：——

  公开号：US7179819B2

  公开（公告）日：2007-02-20