Unexpected enhancement of thrombin inhibitor potency with o-aminoalkylbenzylamides in the P1 position

Thrombin inhibitors incorporating o-aminoalkylbenzylamides in the P1 position were designed, synthesized and found to have enhanced potency and selectivity in several different structural classes. X-ray crystallographic analysis of compound 24 bound in the alpha-thrombin-hirugen complex provides an...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2003-10, Vol.13 (20), p.3477-3482
Hauptverfasser:	RITTLE, Kenneth E, BARROW, James C, NANTERMET, Philippe G, NEWTON, Christina L, SANDERS, William M, YOUWEI YAN, VACCA, Joseph P, SELNICK, Harold G, CUTRONA, Kellie J, GLASS, Kristen L, KRUEGER, Julie A, KUO, Lawrence C, LEWIS, S. Dale, LUCAS, Bobby J, MCMASTERS, Daniel R, MORRISSETTE, Matthew M
Format:	Artikel
Sprache:	eng
Schlagworte:	Amides - chemistry Antithrombins - chemistry Antithrombins - pharmacology Biological and medical sciences Blood. Blood coagulation. Reticuloendothelial system Crystallography, X-Ray Medical sciences Molecular Structure Pharmacology. Drug treatments
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	Thrombin inhibitors incorporating o-aminoalkylbenzylamides in the P1 position were designed, synthesized and found to have enhanced potency and selectivity in several different structural classes. X-ray crystallographic analysis of compound 24 bound in the alpha-thrombin-hirugen complex provides an explanation for these unanticipated results.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/S0960-894X(03)00732-7