Discovery and SAR development of 2-(phenylamino) imidazolines as prostacyclin receptor antagonists [corrected].
On the basis of screening hits (1a,b), a series of selective, high affinity prostacyclin receptor antagonists was developed. The optimized lead compound 25d [(4,5-dihydro-1H-imidazol-2-yl)-[4-(4-isopropoxybenzyl)phenyl]amine] had analgesic activity in the rat.
Clark
Robin D
RD
Department of Medicinal Chemistry, Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. robin.clark5@verizon.net
Jahangir
Alam
A
Severance
Daniel
D
Salazar
Rick
R
Chang
Thomas
T
Chang
David
D
Jett
Mary Frances
MF
Smith
Steven
S
Bley
Keith
K
D000284:Administration, Oral; D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D001681:Biological Assay; D001682:Biological Availability; D002351:Carrageenan / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D051379:Mice; D051381:Rats; D044006:Receptors, Epoprostenol / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000814:Aniline Compounds; D007093:Imidazoles; D044006:Receptors, Epoprostenol; C000622556:Ro 1138452; D002351:Carrageenan