Discovery and preliminary evaluation of 5-(4-phenylbenzyl)oxazole-4-carboxamides as prostacyclin receptor antagonists

Marc-Raleigh Brescia; Laura L Rokosz; Andrew G Cole; Tara M Stauffer; John M Lehrach; Douglas S Auld; Ian Henderson; Maria L Webb

doi:10.1016/j.bmcl.2006.12.025

Discovery and preliminary evaluation of 5-(4-phenylbenzyl)oxazole-4-carboxamides as prostacyclin receptor antagonists

Bioorg Med Chem Lett. 2007 Mar 1;17(5):1211-5. doi: 10.1016/j.bmcl.2006.12.025. Epub 2006 Dec 12.

Authors

Marc-Raleigh Brescia¹, Laura L Rokosz, Andrew G Cole, Tara M Stauffer, John M Lehrach, Douglas S Auld, Ian Henderson, Maria L Webb

Affiliation

¹ Pharmacopeia Drug Discovery Inc., PO Box 5350, Princeton, NJ 08543, USA. mbrescia@pcop.com

PMID: 17239589
DOI: 10.1016/j.bmcl.2006.12.025

Abstract

The discovery and evaluation of 5-(4-phenylbenzyl)oxazole-4-carboxamides as prostacyclin (IP) receptor antagonists is described. Analogs disclosed showed high affinity for the IP receptor in human platelet membranes with IC50 values of 0.05-0.50 microM, demonstrated functional antagonism by inhibiting cAMP production in HEL cells with IC50 values of 0.016-0.070 microM, and exhibited significant selectivity versus other prostanoid receptors.

MeSH terms

Amides / chemical synthesis*
Amides / pharmacology*
Humans
Inhibitory Concentration 50
Oxazoles / chemical synthesis
Oxazoles / pharmacology
Polycyclic Aromatic Hydrocarbons / chemical synthesis
Polycyclic Aromatic Hydrocarbons / pharmacology
Receptors, Epoprostenol
Receptors, Prostaglandin / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Amides
Oxazoles
PTGIR protein, human
Polycyclic Aromatic Hydrocarbons
Receptors, Epoprostenol
Receptors, Prostaglandin