Structure-activity relationships of pyrroloquinazolines as thrombin receptor antagonists

H S Ahn; L Arik; G Boykow; D A Burnett; M A Caplen; M Czarniecki; M S Domalski; C Foster; M Manna; A W Stamford; Y Wu

doi:10.1016/s0960-894x(99)00339-x

Structure-activity relationships of pyrroloquinazolines as thrombin receptor antagonists

Bioorg Med Chem Lett. 1999 Jul 19;9(14):2073-8. doi: 10.1016/s0960-894x(99)00339-x.

Authors

H S Ahn¹, L Arik, G Boykow, D A Burnett, M A Caplen, M Czarniecki, M S Domalski, C Foster, M Manna, A W Stamford, Y Wu

Affiliation

¹ Schering-Plough Research Institute, Kenilworth, NJ 07033-0539, USA.

PMID: 10450984
DOI: 10.1016/s0960-894x(99)00339-x

Abstract

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.

MeSH terms

Drug Evaluation, Preclinical
Humans
Inhibitory Concentration 50
Platelet Aggregation / drug effects
Platelet Aggregation Inhibitors / chemistry*
Platelet Aggregation Inhibitors / pharmacology*
Pyrroles / chemistry
Quinazolines / chemical synthesis*
Quinazolines / pharmacology*
Receptor, PAR-1
Receptors, Thrombin / antagonists & inhibitors*
Receptors, Thrombin / metabolism
Structure-Activity Relationship
Thrombin / pharmacology

Substances

Platelet Aggregation Inhibitors
Pyrroles
Quinazolines
Receptor, PAR-1
Receptors, Thrombin
Thrombin