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ID: ALA3259667

Journal: Bioorg Med Chem Lett

Title: Bis-aryloxadiazoles as effective activators of the aryl hydrocarbon receptor.

Authors: Basham KJ, Bhonde VR, Kieffer C, Mack JB, Hess M, Welm BE, Looper RE.

Abstract: Bis-aryloxadiazoles are common scaffolds in medicinal chemistry due to their wide range of biological activities. Previously, we identified a 1,2,4-bis-aryloxadiazole that blocks mammary branching morphogenesis through activation of the aryl hydrocarbon receptor (AHR). In addition to defects in mammary differentiation, AHR stimulation induces toxicity in many other tissues. We performed a structure activity relationship (SAR) study of 1,2,4-bis-aryloxadiazole to determine which moieties of the molecule are critical for AHR activation. We validated our results with a functional biological assay, using desmosome formation during mammary morphogenesis to indicate AHR activity. These findings will aid the design of oxadiazole derivative therapeutics with reduced off-target toxicity profiles.

CiteXplore: 24767852

DOI: 10.1016/j.bmcl.2014.04.013