Derivatives of tetrahydroisoquinoline: synthesis and initial evaluation of novel non-peptide antagonists of the alpha(IIb)beta(3)-integrin.
The novel RGDF mimetics were synthesized with the use of 4-(1,2,3,4-tetrahydroisoquinoline-7-yl)amino-4-oxobutyric or 5-(1,2,3,4-tetrahydroisoquinoline-7-yl)amino-5-oxopentanoic acids as a surrogate of Arg-Gly motif. The synthesized compounds have demonstrated a high potency to inhibit platelet aggregation in vitro and to block FITC-Fg binding to alpha(IIb)beta(3) on washed human platelets.
Krysko
Andrei A
AA
Department of Medicinal Chemistry, A.V. Bogatsky Physico-Chemical Institute of the National Academy of Sciences of Ukraine, Odessa, Ukraine. peptides@physchem.od.ua
Krysko
Olga L
OL
Kabanova
Tatyana A
TA
Andronati
Sergei A
SA
Kabanov
Vladimir M
VM
D005340:Fibrinogen / Q000737:chemistry; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D044005:Tetrahydroisoquinolines; C084961:arginyl-glycyl-aspartyl-phenylalanine; C014843:1,2,3,4-tetrahydroisoquinoline; D005340:Fibrinogen; D016650:Fluorescein-5-isothiocyanate