RGD mimetics containing phthalimidine fragment as novel ligands of fibrinogen receptor

  • Bioorg Med Chem Lett. 2011 Oct 1;21(19):5971-4. doi: 10.1016/j.bmcl.2011.07.063.
Andrei A Krysko  1 ,  Georgiy V Samoylenko ,  Pavel G Polishchuk ,  Sergei A Andronati ,  Tatyana A Kabanova ,  Tetiana M Khristova ,  Victor E Kuz'min ,  Vladimir M Kabanov ,  Olga L Krysko ,  Alexandre A Varnek ,  Ruslan Ya Grygorash
Affiliations
  • 1. A.V. Bogatsky Physico-Chemical Institute of the National Academy of Sciences of Ukraine, Lustdorfskaya doroga 86, Odessa 65080, Ukraine. [email protected]
PMID: 21852128 DOI: 10.1016/j.bmcl.2011.07.063
Abstract

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 α(IIb)β(3) Integrin in a suspension of washed human platelets. The key α(IIb)β(3) protein-ligand interactions were determined in docking experiments.