Structure-activity relationships of pyrroloquinazolines as thrombin receptor antagonists.
A series of pyrroloquinazolines has been discovered that represent novel small molecule inhibitors of the intramolecular ligand of the thrombin receptor. Analogs were prepared to study the structure-activity relationships of substitution at the N 1, N3, and N7 positions of the heterocycle. Compounds 4e and 4f have been identified with IC50's of 56 and 52 nM, respectively.
Ahn
H S
HS
Schering-Plough Research Institute, Kenilworth, NJ 07033-0539, USA.
Arik
L
L
Boykow
G
G
Burnett
D A
DA
Caplen
M A
MA
Czarniecki
M
M
Domalski
M S
MS
Foster
C
C
Manna
M
M
Stamford
A W
AW
Wu
Y
Y
D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D011799:Quinazolines; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; D013917:Thrombin