Abstract
Novel, potent, and highly selective classes of thrombin inhibitors were identified, which resulted from judicious combination of P4-aromatics and P2-P3-heterocyclic dipeptide surrogates with weakly basic (calcd pKa approximately non-basic-8.6) bicyclic P1-arginine mimics. The design, synthesis, and biological activity of achiral, non-covalent, orally bioavailable inhibitors NC1-NC44 featuring P1-indazoles, benzimidazoles, indoles, benzotriazoles, and aminobenzisoxazoles is disclosed.
MeSH terms
-
Animals
-
Area Under Curve
-
Biological Availability
-
Bridged Bicyclo Compounds / chemical synthesis*
-
Bridged Bicyclo Compounds / pharmacokinetics
-
Bridged Bicyclo Compounds / pharmacology*
-
Crystallography, X-Ray
-
Enzyme Inhibitors / chemical synthesis*
-
Enzyme Inhibitors / pharmacokinetics
-
Enzyme Inhibitors / pharmacology*
-
Heterocyclic Compounds, 3-Ring / chemical synthesis*
-
Heterocyclic Compounds, 3-Ring / pharmacokinetics
-
Heterocyclic Compounds, 3-Ring / pharmacology*
-
Indicators and Reagents
-
Rats
-
Structure-Activity Relationship
-
Thrombin / antagonists & inhibitors*
-
Tumor Cells, Cultured
Substances
-
Bridged Bicyclo Compounds
-
Enzyme Inhibitors
-
Heterocyclic Compounds, 3-Ring
-
Indicators and Reagents
-
Thrombin