RGD mimetics containing phthalimidine fragment as novel ligands of fibrinogen receptor

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• 作者：Andrei A.  ; Krysko^a ;   ; ^{peptides@paco.net} ;   ; ^{peptides@physchem.od.ua} ; Georgiy V.  ; Samoylenko^a ; Pavel G.  ; Polishchuk^a ;   ; ^b ; Sergei A.  ; Andronati^a ; Tatyana A.  ; Kabanova^a ; Tetiana M.  ; Khristova^a ;   ; ^b ; Victor E.  ; Kuz&rsquo ; min^a ; Vladimir M.  ; Kabanov^a ; Olga L.  ; Krysko^a ; Alexandre A.  ; Varnek^b ; Ruslan Ya.  ; Grygorash^a
• 关键词：Fibrinogen receptor antagonists ; ¦Á_IIb¦Â₃ ; RGD mimetics ; Phthalimidine ; Platelet aggregation
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2011
• 出版时间：1 October 2011
• 年：2011
• 卷：21
• 期：19
• 页码：5971-5974
• 全文大小：546 K

文摘

The novel RGD mimetics with phthalimidine central fragment were synthesized with the use of 4-piperidine-4-yl-butyric, 4-piperidine-4-yl-benzoic, 4-piperazine-4-yl-benzoic and 1,2,3,4-tetrahydroisoquinoline-7-carboxylic acids as surrogates of Arg motif. The synthesized compounds potently inhibited platelet aggregation in vitro and blocked FITC-Fg binding to ¦Á_IIb¦Â₃ integrin in a suspension of washed human platelets. The key ¦Á_IIb¦Â₃ protein¨Cligand interactions were determined in docking experiments.