(S)-t-butyl 3-(4-(3-t-butoxycarbonylaminopropoxy)-3-nitrophenyl)-2-(3-(trifluoromethyl)phenylsulfonamido)propionate | 798567-32-5

• 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: (S)-t-butyl 3-(4-(3-t-butoxycarbonylaminopropoxy)-3-nitrophenyl)-2-(3-(trifluoromethyl)phenylsulfonamido)propionate
• 英文别名: t-butyl O-[N-(t-butoxycarbonyl)-3-aminopropyl]-meta-nitro-N-[3-(trifluoromethyl)phenylsulfonyl]-L-tyrosinate
• CAS: 798567-32-5
• 化学式: C₂₈H₃₆F₃N₃O₉S
• 分子量: 647.67
• InChiKey: TZYYRMCQOZQLAU-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.14
• 重原子数：
  44.0
• 可旋转键数：
  12.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  163.17
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  (S)-t-butyl 3-(4-(3-t-butoxycarbonylaminopropoxy)-3-nitrophenyl)-2-(3-(trifluoromethyl)phenylsulfonamido)propionate 在 platinum(IV) oxide benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、275.79 kPa 条件下， 反应 66.0h， 生成 t-butyl O-[N-(t-butoxycarbonyl)-3-aminopropyl]-meta-[N-(methyl)isonipecotyl]amino-N-[3-(trifluoromethyl)phenylsulfonyl]-L-tyrosinate
  参考文献：
  名称：

  Novel RGD-like molecules based on the tyrosine template: design, synthesis, and biological evaluation on isolated integrins αVβ3/αIIbβ3 and in cellular adhesion tests

  摘要：

  RGD (Arg-Gly-Asp) peptidomimetics have been designed for covalent anchorage on biomaterials. The tyrosine template was thus equipped with (i) a basic side chain of various flexibility, (ii) an acidic side chain, which incorporated the XPS fluorine tag, and (iii) a spacer-arm terminated by a primary amine for surface grafting. The most active compounds showed IC50 values in the nanomolar range versus isolated human integrins alpha(v)beta(3) and alpha(IIb)beta(3). Preincubation of CaCo2 cells with soluble peptidomimetics (2 and 19a) prevented cellular adhesion on culture plates coated with vitronectin. On the other hand, peptidomimetics (19a and 19b) immobilized on a poly(ethylene)terephthalate membrane (PET) promoted CaCo2 cells adhesion. A modeling study at the ab initio level in MINI-1' basis allowed to compare the various synthetic ligands of integrins and to propose novel pharmacophore structures. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.07.055
• 作为产物：
  描述：

  t-butyl N-[3-(trifluoromethyl)phenylsulfonyl]-L-tyrosinate 在 18-冠醚-6 、 硝酸 、 potassium carbonate 、 溶剂黄146 作用下， 以 乙腈 为溶剂， 反应 22.0h， 生成 (S)-t-butyl 3-(4-(3-t-butoxycarbonylaminopropoxy)-3-nitrophenyl)-2-(3-(trifluoromethyl)phenylsulfonamido)propionate
  参考文献：
  名称：

  Novel RGD-like molecules based on the tyrosine template: design, synthesis, and biological evaluation on isolated integrins αVβ3/αIIbβ3 and in cellular adhesion tests

  摘要：

  RGD (Arg-Gly-Asp) peptidomimetics have been designed for covalent anchorage on biomaterials. The tyrosine template was thus equipped with (i) a basic side chain of various flexibility, (ii) an acidic side chain, which incorporated the XPS fluorine tag, and (iii) a spacer-arm terminated by a primary amine for surface grafting. The most active compounds showed IC50 values in the nanomolar range versus isolated human integrins alpha(v)beta(3) and alpha(IIb)beta(3). Preincubation of CaCo2 cells with soluble peptidomimetics (2 and 19a) prevented cellular adhesion on culture plates coated with vitronectin. On the other hand, peptidomimetics (19a and 19b) immobilized on a poly(ethylene)terephthalate membrane (PET) promoted CaCo2 cells adhesion. A modeling study at the ab initio level in MINI-1' basis allowed to compare the various synthetic ligands of integrins and to propose novel pharmacophore structures. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.07.055

文献信息

• α_vβ₃ Integrin-Targeting Arg-Gly-Asp (RGD) Peptidomimetics Containing Oligoethylene Glycol (OEG) Spacers
  作者：Vincent Rerat、Georges Dive、Alex A. Cordi、Gordon C. Tucker、Reine Bareille、Joëlle Amédée、Laurence Bordenave、Jacqueline Marchand-Brynaert

  DOI：10.1021/jm901133z

  日期：2009.11.26

  RGD peptides are used in biomaterials science for surface modifications with a view to elicit selective cellular responses. Our objective is to replace peptides by small peptidomimetics acting similarly. We designed novel molecules targeting alpha(v)beta(3) integrin and featuring spacer-arms (for surface grafting), which do not disturb the biological activity, from (L) N-(3-(trifluoromethyl)benzenesulfonyl) tyrosine used as scaffold. Various Arg-mimics were fixed on the phenol function, and the ortho position was used for the Coupling of OEG spacers. All peptidomimetics were active in the nM range in a binding test toward human alpha(v)beta(3) integrin (IC50 = 0.1 to 1.7 nM) and selective versus platelet integrin alpha(IIb)beta(3) Selected compounds revealed excellent ability to inhibit bone cells adhesion on vitronectin. Modeling and docking studies were performed for comparing the most active RGD peptidomimetic to cilengitide, i.e., cyclo-[RGDfN(Me)V]-. Lastly, the adhesion of endothelial cells on a cultivation support grafted with RGD peptidomimetics was significantly improved.