Selective angiotensin II AT(2) receptor agonists: Benzamide structure-activity relationships

ArticleinBioorganic & medicinal chemistry 16(14):6841-9 · August 2008with13 Reads
Impact Factor: 2.79 · DOI: 10.1016/j.bmc.2008.05.066 · Source: PubMed

    Abstract

    In the investigation of the structure-activity relationship of nonpeptide AT(2) receptor agonists, a series of substituted benzamide analogues of the selective nonpeptide AT(2) receptor agonist M024 have been synthesised. In a second series, the biphenyl scaffold was compared to the thienylphenyl scaffold and the impact of the isobutyl substituent and its position on AT(1)/AT(2) receptor selectivity was also investigated. Both series included several compounds with high affinity and selectivity for the AT(2) receptor. Three of the compounds were also proven to function as agonists at the AT(2) receptor, as deduced from a neurite outgrowth assay, conducted in NG108-15 cells.