New tripeptidic thrombin inhibitors. Influence of P2 and P3 residues on activity and selectivity

Structural variations of P2 and P3 residues in tripeptidic boroarginine thrombin inhibitors led to compounds with similar potency than reference compound DuP 714, but with enhanced selectivity for thrombin compared to plasmin. Replacement of the P2 proline residue in tripeptidic thrombin inhibitors...

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Veröffentlicht in:	Bioorganic & medicinal chemistry 1995-08, Vol.3 (8), p.1019-1024
Hauptverfasser:	De Nanteuil, Guillaume, Gloanec, Philippe, Lila, Christine, Portevin, Bernard, Boudon, Alain, Rupin, Alain, Verbeuren, Tony J.
Format:	Artikel
Sprache:	eng
Schlagworte:	Amino Acid Sequence Antithrombins - chemical synthesis Antithrombins - chemistry Antithrombins - pharmacology Arginine - analogs & derivatives Binding Sites Boron Compounds - chemistry Boron Compounds - pharmacology Fibrinolysin - pharmacology Molecular Sequence Data Molecular Structure Oligopeptides - chemical synthesis Oligopeptides - chemistry Oligopeptides - pharmacology Structure-Activity Relationship Thrombin - antagonists & inhibitors
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Beschreibung
Zusammenfassung:	Structural variations of P2 and P3 residues in tripeptidic boroarginine thrombin inhibitors led to compounds with similar potency than reference compound DuP 714, but with enhanced selectivity for thrombin compared to plasmin. Replacement of the P2 proline residue in tripeptidic thrombin inhibitors by non natural amino acids (PHI, ABO, N-cycloalkyl glycines) afforded compounds with similar potency than reference compound DuP 714, but with enhanced selectivity for thrombin as compared to plasmin.
ISSN:	0968-0896 1464-3391
DOI:	10.1016/0968-0896(95)00107-R