Abstract
A metabolism study of FR181157 (1) led to the discovery of new oxazole derivatives as active metabolites. The metabolite 6 with an epoxy ring exhibited high anti-aggregative potency with an IC(50) of 5.8 nM and potent binding affinity for the human recombinant IP receptor with a K(i) value of 6.1 nM and selectivity for human IP receptor over all other members of the human prostanoid receptor family.
MeSH terms
-
Administration, Oral
-
Animals
-
Biological Availability
-
Biotransformation
-
Drug Design
-
Epoprostenol / agonists
-
Epoprostenol / antagonists & inhibitors*
-
Humans
-
Inhibitory Concentration 50
-
Microsomes, Liver / metabolism
-
Molecular Mimicry
-
Oxazoles / pharmacokinetics*
-
Oxazoles / pharmacology
-
Pharmacokinetics
-
Platelet Aggregation / drug effects
-
Rats
-
Receptors, Epoprostenol
-
Receptors, Prostaglandin / antagonists & inhibitors*
-
Structure-Activity Relationship
Substances
-
Oxazoles
-
PTGIR protein, human
-
Receptors, Epoprostenol
-
Receptors, Prostaglandin
-
Epoprostenol