title: Discovery and preliminary evaluation of 5-(4-phenylbenzyl)oxazole-4-carboxamides as prostacyclin receptor antagonists.
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.
authors.affiliation: Pharmacopeia Drug Discovery Inc., PO Box 5350, Princeton, NJ 08543, USA. mbrescia@pcop.com
authors.forename: Marc-Raleigh
authors.initials: MR
authors.lastname: Brescia
authors.forename: Laura L
authors.initials: LL
authors.lastname: Rokosz
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Cole
authors.forename: Tara M
authors.initials: TM
authors.lastname: Stauffer
authors.forename: John M
authors.initials: JM
authors.lastname: Lehrach
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Auld
authors.forename: Ian
authors.initials: I
authors.lastname: Henderson
authors.forename: Maria L
authors.initials: ML
authors.lastname: Webb
mesh_terms: 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
chemical_list: D000577:Amides; D010080:Oxazoles; C113936:PTGIR protein, human; D011084:Polycyclic Aromatic Hydrocarbons; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin