tert-butyl ((S)-3-((S)-2-amino-3-(3,4-difluorophenyl)propanamido)-4-(benzylamino)-4-oxobutyl)carbamate | 315203-40-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl ((S)-3-((S)-2-amino-3-(3,4-difluorophenyl)propanamido)-4-(benzylamino)-4-oxobutyl)carbamate
• 英文别名: H-Phe(3,4-diF)-Dab(Boc)-NHBn；tert-butyl N-[(3S)-3-[[(2S)-2-amino-3-(3,4-difluorophenyl)propanoyl]amino]-4-(benzylamino)-4-oxobutyl]carbamate
• CAS: 315203-40-8
• 化学式: C₂₅H₃₂F₂N₄O₄
• 分子量: 490.55
• InChiKey: WJYQQOJTCNXUPH-SFTDATJTSA-N

物化性质

• 沸点：
  742.6±60.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  123
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl ((S)-3-((S)-2-amino-3-(3,4-difluorophenyl)propanamido)-4-(benzylamino)-4-oxobutyl)carbamate 在 DIC urea 、 苯甲醚 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 10.5h， 生成 RWJ 58259
  参考文献：
  名称：

  发现和优化新型凝血酶受体（par-1）拮抗剂：基于吲哚和吲唑模板的有效选择性肽模拟物。

  摘要：

  DOI：

  10.1021/jm000506s
• 作为产物：
  描述：

  NAlpha-芴甲氧羰基-Nγ-羰-L-2,4-氨基丁酸 在 哌啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 7.5h， 生成 tert-butyl ((S)-3-((S)-2-amino-3-(3,4-difluorophenyl)propanamido)-4-(benzylamino)-4-oxobutyl)carbamate
  参考文献：
  名称：

  Characterization of Protease-Activated Receptor (PAR) ligands: Parmodulins are reversible allosteric inhibitors of PAR1-driven calcium mobilization in endothelial cells

  摘要：

  Several classes of ligands for Protease-Activated Receptors (PARs) have shown impressive anti-inflammatory and cytoprotective activities, including PAR2 antagonists and the PAR1-targeting parmodulins. In order to support medicinal chemistry studies with hundreds of compounds and to perform detailed mode-of-action studies, it became important to develop a reliable PAR assay that is operational with endothelial cells, which mediate the cytoprotective effects of interest. We report a detailed protocol for an intracellular calcium mobilization assay with adherent endothelial cells in multiwell plates that was used to study a number of known and new PAR1 and PAR2 ligands, including an alkynylated version of the PAR1 antagonist RWJ-58259 that is suitable for the preparation of tagged or conjugate compounds. Using the cell line EA. hy926, it was necessary to perform media exchanges with automated liquid handling equipment in order to obtain optimal and reproducible antagonist concentration-response curves. The assay is also suitable for study of PAR2 ligands; a peptide antagonist reported by Fairlie was synthesized and found to inhibit PAR2 in a manner consistent with reports using epithelial cells. The assay was used to confirm that vorapaxar acts as an irreversible antagonist of PAR1 in endothelium, and parmodulin 2 (ML161) and the related parmodulin RR-90 were found to inhibit PAR1 reversibly, in a manner consistent with negative allosteric modulation. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.04.016

文献信息

• US7417030B2
  申请人：——

  公开号：US7417030B2

  公开（公告）日：2008-08-26
• Characterization of Protease-Activated Receptor (PAR) ligands: Parmodulins are reversible allosteric inhibitors of PAR1-driven calcium mobilization in endothelial cells
  作者：Disha M. Gandhi、Mark W. Majewski、Ricardo Rosas、Kaitlin Kentala、Trevor J. Foster、Eric Greve、Chris Dockendorff

  DOI：10.1016/j.bmc.2018.04.016

  日期：2018.5

  Several classes of ligands for Protease-Activated Receptors (PARs) have shown impressive anti-inflammatory and cytoprotective activities, including PAR2 antagonists and the PAR1-targeting parmodulins. In order to support medicinal chemistry studies with hundreds of compounds and to perform detailed mode-of-action studies, it became important to develop a reliable PAR assay that is operational with endothelial cells, which mediate the cytoprotective effects of interest. We report a detailed protocol for an intracellular calcium mobilization assay with adherent endothelial cells in multiwell plates that was used to study a number of known and new PAR1 and PAR2 ligands, including an alkynylated version of the PAR1 antagonist RWJ-58259 that is suitable for the preparation of tagged or conjugate compounds. Using the cell line EA. hy926, it was necessary to perform media exchanges with automated liquid handling equipment in order to obtain optimal and reproducible antagonist concentration-response curves. The assay is also suitable for study of PAR2 ligands; a peptide antagonist reported by Fairlie was synthesized and found to inhibit PAR2 in a manner consistent with reports using epithelial cells. The assay was used to confirm that vorapaxar acts as an irreversible antagonist of PAR1 in endothelium, and parmodulin 2 (ML161) and the related parmodulin RR-90 were found to inhibit PAR1 reversibly, in a manner consistent with negative allosteric modulation. (C) 2018 Elsevier Ltd. All rights reserved.
• Discovery and Optimization of a Novel Series of Thrombin Receptor (PAR-1) Antagonists:  Potent, Selective Peptide Mimetics Based on Indole and Indazole Templates
  作者：Han-Cheng Zhang、Claudia K. Derian、Patricia Andrade-Gordon、William J. Hoekstra、David F. McComsey、Kimberly B. White、Brenda L. Poulter、Michael F. Addo、Wai-Man Cheung、Bruce P. Damiano、Donna Oksenberg、Elwood E. Reynolds、Anjali Pandey、Robert M. Scarborough、Bruce E. Maryanoff

  DOI：10.1021/jm000506s

  日期：2001.3.1