Synthesis and evaluation of a small library of graftable thrombin inhibitors derived from (L)-arginine.
Novel piperazinyl-amide derivatives of N-alpha-(aryl-sulfonyl)-L-arginine were synthesized as graftable thrombin inhibitors, in the context of biomaterials' design. The possible disturbance of biological activity due to a variable spacer-arm fixed on the N-4 piperazinyl position and the introduction of a trifluoromethyl group as XPS (X-ray Photoelectron Spectroscopy) tag on the sulfonamide moiety were evaluated in vitro against human alpha-thrombin. All the compounds of the library were found to be active at the micromolar level, as the reference TAME (N-tosyl-L-arginine methyl ester). The blood compatibilization improvement of poly(ethylene terephthalate) (PET) membrane, coated or grafted by wet chemistry treatment with one representative inhibitor of the library, was also evaluated, showing interesting decrease in blood clot formation.
Salvagnini
Claudio
C
Unité de Chimie Organique et Médicinale, Université catholique de Louvain, Bâtiment Lavoisier, Place Louis Pasteur 1, B-1348 Louvain-la-Neuve, Belgium.
Gharbi
Sonia
S
Boxus
Thierry
T
Marchand-Brynaert
Jacqueline
J
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000925:Anticoagulants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008567:Membranes, Artificial; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011093:Polyethylene Terephthalates; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000737:chemistry
D000577:Amides; D000925:Anticoagulants; D008567:Membranes, Artificial; D010879:Piperazines; D011093:Polyethylene Terephthalates; D001120:Arginine; D013917:Thrombin