Discovery and SAR development of 2-(phenylamino) imidazolines as prostacyclin receptor antagonists [corrected]

Robin D Clark; Alam Jahangir; Daniel Severance; Rick Salazar; Thomas Chang; David Chang; Mary Frances Jett; Steven Smith; Keith Bley

doi:10.1016/j.bmcl.2003.10.070

Discovery and SAR development of 2-(phenylamino) imidazolines as prostacyclin receptor antagonists [corrected]

Bioorg Med Chem Lett. 2004 Feb 23;14(4):1053-6. doi: 10.1016/j.bmcl.2003.10.070.

Authors

Robin D Clark¹, Alam Jahangir, Daniel Severance, Rick Salazar, Thomas Chang, David Chang, Mary Frances Jett, Steven Smith, Keith Bley

Affiliation

¹ Department of Medicinal Chemistry, Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. robin.clark5@verizon.net

PMID: 15013022
DOI: 10.1016/j.bmcl.2003.10.070

Abstract

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.

MeSH terms

Administration, Oral
Aniline Compounds / chemical synthesis*
Aniline Compounds / pharmacology*
Animals
Binding, Competitive
Biological Assay
Biological Availability
Carrageenan / antagonists & inhibitors
Carrageenan / pharmacology
Humans
Hyperalgesia / chemically induced
Hyperalgesia / drug therapy
Imidazoles / chemical synthesis*
Imidazoles / pharmacology*
Mice
Rats
Receptors, Epoprostenol / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Aniline Compounds
Imidazoles
Receptors, Epoprostenol
Ro 1138452
Carrageenan