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Structure−Activity Relationship Studies Leading to the Identification of (2E)-3-[l-[(2,4-Dichlorophenyl)methyl]-5-fluoro-3-methyl-lH-indol-7-yl]-N-[(4,5-dichloro-2-thienyl)sulfonyl]-2-propenamide (DG-041), a Potent and Selective Prostanoid EP3 Receptor Antagonist, as a Novel Antiplatelet Agent That Does Not Prolong Bleeding
- Source :
- Journal of Medicinal Chemistry. 53:18-36
- Publication Year :
- 2009
- Publisher :
- American Chemical Society (ACS), 2009.
-
Abstract
- The EP3 receptor on the platelet mediates prostaglandin E2 potentiation of thrombogenic coagonists including collagen and adenosine diphosphate (ADP). A pharmacophore driven approach led to the identification of diverse peri-substituted heterocycles as potent and selective EP3 receptor antagonists. A simultaneous chemical optimization and druglike assessment of prioritized molecules converged on a lead compound 50 (DG-041) that displayed favorable in vitro and functional activities as an inhibitor of human platelet aggregation. This agent is currently in human clinical trials for the treatment of atherothrombosis.
- Subjects :
- Sulfonyl
chemistry.chemical_classification
Stereochemistry
Antagonist
Prostanoid
Chemical synthesis
Adenosine diphosphate
chemistry.chemical_compound
chemistry
Drug Discovery
medicine
Molecular Medicine
Structure–activity relationship
lipids (amino acids, peptides, and proteins)
Prostaglandin E2
Pharmacophore
medicine.drug
Subjects
Details
- ISSN :
- 15204804 and 00222623
- Volume :
- 53
- Database :
- OpenAIRE
- Journal :
- Journal of Medicinal Chemistry
- Accession number :
- edsair.doi...........8ffeb661cb3b7e33e9675f1aaf6879c6