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Analogues of the kappa (κ) opioid receptor agonist, ICI 199441, were prepared. K i values for these analogues at the cloned human κ opioid receptor ranged from 0.058 to 25nM. Trifluoromethylaryl derivatives were potent analgesics when administered subcutaneously in the rat and were more peripherally restricted than the parent compound, ICI 199441.