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ChemInform Abstract

Different substitution patterns of the triazole ring are explored with preference of 2,4-disubstitution. The prepared compounds (IV) and (X), in which fluorinated aromatic rings are substituted for aliphatic side chains, are analogues of potent and selective β₃-adrenergic receptor agonists. The new agonists show markedly improved oral bioavailabilities while maintaining potency, selectivity, and in vivo efficacy. In particular, compound (X), which is an exceptionally selective human β₃-agonist, reveals 6500- and 1500-fold selectivity over binding to β₁ and β₂ receptors, respectively.