title: Selective angiotensin II AT2 receptor agonists: arylbenzylimidazole structure-activity relationships.
abstract: Structural alterations in the 2- and 5-positions of the first drug-like selective angiotensin II AT2 receptor agonist (1) have been performed. The imidazole ring system was proven to be a strong determinant for the AT2 selectivity, and with few exceptions all variations gave good AT2 receptor affinities and with retained high AT2/AT1 selectivities. On the contrary to the findings with AT1 receptor agonists, the impact of structural modifications in the 5-position of the AT2 selective compounds were less pronounced regarding activation of the AT2 receptor. The butyloxyphenyl (56) and the propylthienyl (50) derivatives were found to exert a high agonistic effect as deduced from their capacity to induce neurite elongation in neuronal cells, as does angiotensin II.
authors.affiliation: Department of Medicinal Chemistry, BMC, Uppsala University, P.O. Box 574, SE-751 23 Uppsala, Sweden.
authors.forename: Xiongyu
authors.initials: X
authors.lastname: Wu
authors.forename: Yiqian
authors.initials: Y
authors.lastname: Wan
authors.forename: A K
authors.initials: AK
authors.lastname: Mahalingam
authors.forename: A M S
authors.initials: AM
authors.lastname: Murugaiah
authors.forename: Bianca
authors.initials: B
authors.lastname: Plouffe
authors.forename: Milad
authors.initials: M
authors.lastname: Botros
authors.forename: Anders
authors.initials: A
authors.lastname: Karlén
authors.forename: Mathias
authors.initials: M
authors.lastname: Hallberg
authors.forename: Nicole
authors.initials: N
authors.lastname: Gallo-Payet
authors.forename: Mathias
authors.initials: M
authors.lastname: Alterman
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D008024:Ligands; D008099:Liver / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D011869:Radioligand Assay; D051381:Rats; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013552:Swine; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014599:Uterus / Q000378:metabolism; D000096926:Benzenesulfonamides
chemical_list: D001562:Benzimidazoles; D008024:Ligands; D044139:Receptor, Angiotensin, Type 2; D013449:Sulfonamides; D013876:Thiophenes; C517061:N-butyloxycarbonyl-2-(4-imidazol-1-ylmethylphenyl)-4-butoxybenzenesulfonamide; D000096926:Benzenesulfonamides; C517060:N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-propylthiophene-2-sulfonamide