U-77891 is an opioid analgesic drug that was first synthesized in 1983 by the Upjohn company. It was originally synthesized to prove that the removal of a single methylene spacer of the benzamide would alter a ú-opioid receptor agonist such as U-50488 into an ü-opioid receptor agonist, as well as producing a semi-rigid derivative of U-47700. This would help elucidate the relative positions of the hydrogen-bond acceptors and substituted aromatic system to find the compound with the lowest K<sub>i</sub> value in a series of benzamide opioids dating back to the 1970s. The original work found a mixture of agonists and antagonists.
U-77891 acts as an agonist of the ü-opioid, ô-opioid and ú-opioid receptors with K<sub>i</sub> values of 2, 105, and 2300 nM, respectively. The compound has ED<sub>50</sub> values of 0.02 mg/kg and 0.21 mg/kg in mouse phenylquinone writhing and tail-flick assays. One reason for the high potency is the LogP of 4.57, allowing it to accumulate in fatty tissue such as the brain.