Synthesis, biological evaluation, X-ray molecular structure and molecular docking studies of RGD mimetics containing 6-amino-2,3-dihydroisoindolin-1-one fragment as ligands of integrin αIIbβ3

• Published in: Bioorganic & medicinal chemistry Vol. 21; no. 15; pp. 4646 - 4661
• Main Authors: Krysko, Andrei A., Samoylenko, Georgiy V., Polishchuk, Pavel G., Fonari, Marina S., Kravtsov, Victor Ch, Andronati, Sergei A., Kabanova, Tatyana A., Lipkowski, Janusz, Khristova, Tetiana M., Kuz’min, Victor E., Kabanov, Vladimir M., Krysko, Olga L., Varnek, Alexandre A.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-08-2013; Elsevier
• Subjects: Chemical Sciences; Cristallography; Fibrinogen receptor antagonists; Medicinal Chemistry; Phthalimidine; Platelet aggregation; RGD mimetics; αIIbβ3; AIRUUOCOXXACEV-UHFFFAOYSA-N; CKECWRXYAMKFHV-UHFFFAOYSA-N; SSWSLPCUNMAUSZ-UHFFFAOYSA-N; DISRKAFSSZETAR-UHFFFAOYSA-N; UODRQLBFKVRYGW-UHFFFAOYSA-N; αIIbβ3; Phthalimidine; LRTORXSNRLEYOP-UHFFFAOYSA-N; IAOPHVMTJMMXJT-UHFFFAOYSA-N; QTBLXMNWHKBUMF-UHFFFAOYSA-N; MRNSUCVHUMPVKT-UHFFFAOYSA-N; QZWNWSOWJFXEMD-UHFFFAOYSA-N; RGD mimetics; ZLYJDZGAMYRBMF-UHFFFAOYSA-N; KRIJVAHTBHBBNQ-UHFFFAOYSA-N; FOOWPXAXLKCQAE-UHFFFAOYSA-N; Fibrinogen receptor antagonists; WJJJDVWSFABCPR-UHFFFAOYSA-N; DSAMJFLLUBEPQJ-UHFFFAOYSA-N; OVIDRTFSASUVLE-UHFFFAOYSA-N; POCHPFHVSXQHTE-UHFFFAOYSA-N; MVAPRARLGZLDBX-UHFFFAOYSA-N; BBWKZZPNNLEBAU-UHFFFAOYSA-N; PLPMPULYBOOXGU-UHFFFAOYSA-N; WGVJCXGTTUEXJS-UHFFFAOYSA-N; KLQFIRQJNLQJPX-UHFFFAOYSA-N; CZFIMBUKMXTYLV-UHFFFAOYSA-N; Platelet aggregation; JNAHDNDQSUGXPO-UHFFFAOYSA-N; PLPQUBBLGBDIKT-UHFFFAOYSA-N; LVUPQRKZRPJMPX-UHFFFAOYSA-N; HUGQZSJOLXZACT-UHFFFAOYSA-N; GDJMPHMKDCIYBS-UHFFFAOYSA-N
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2013.05.019

A series of novel RGD mimetics containing phthalimidine fragment was designed and synthesized. Their antiaggregative activity determined by Born’s method was shown to be due to inhibition of fibrinogen binding to αIIbβ3. Molecular docking of RGD mimetics to αIIbβ3 receptor showed the key interactions in this complex, and also some correlations have been observed between values of biological activity and docking scores. The single crystal X-ray data were obtained for five mimetics.