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Upjohn looked for the key moieties which gave the greatest activity and posted over a dozen patents on related compounds, each optimizing one moiety until they discovered that U-47700 was the most active. U-47700 became the lead compound of selective kappa-opioid receptor ligands such as U-50488, U-51754 (containing a single methylene spacer difference) and U-69,593, which share very similar structures.