title: Selective angiotensin II AT(2) receptor agonists devoid of the imidazole ring system.
abstract: A versatile parallel synthetic method to obtain three series of non-cyclic analogues of the first drug-like selective angiotensin II AT(2) receptor agonist (1) has been developed. In analogy with the transformation of losartan to valsartan it was demonstrated that a non-cyclic moiety could be employed as an imidazole replacement to obtain AT(2) selective compounds. In all the three series, AT(2) receptor ligands with affinities in the lower nanomolar range were found. None of the analogues exhibited any affinity for the AT(1) receptor. Four compounds, 17, 22, 39 and 51, were examined in a neurite outgrowth cell assay. All four compounds 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, PO Box 574, SE-751 23 Uppsala, Sweden.
authors.forename: A M S
authors.initials: AM
authors.lastname: Murugaiah
authors.forename: Chalotta
authors.initials: C
authors.lastname: Wallinder
authors.forename: A K
authors.initials: AK
authors.lastname: Mahalingam
authors.forename: Xiongyu
authors.initials: X
authors.lastname: Wu
authors.forename: Yiqian
authors.initials: Y
authors.lastname: Wan
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; D001665:Binding Sites; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D008024:Ligands; D015394:Molecular Structure; D009215:Myometrium / Q000737:chemistry; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013552:Swine