Discovery and preliminary evaluation of 5-(4-phenylbenzyl)oxazole-4-carboxamides as prostacyclin receptor antagonists.
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.
Brescia
Marc-Raleigh
MR
Pharmacopeia Drug Discovery Inc., PO Box 5350, Princeton, NJ 08543, USA. mbrescia@pcop.com
Rokosz
Laura L
LL
Cole
Andrew G
AG
Stauffer
Tara M
TM
Lehrach
John M
JM
Auld
Douglas S
DS
Henderson
Ian
I
Webb
Maria L
ML
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D010080:Oxazoles / Q000138:chemical synthesis / Q000494:pharmacology; D011084:Polycyclic Aromatic Hydrocarbons / Q000138:chemical synthesis / Q000494:pharmacology; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000577:Amides; D010080:Oxazoles; C113936:PTGIR protein, human; D011084:Polycyclic Aromatic Hydrocarbons; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin