U-77891

{{Short description|Chemical compound}}

{{Drugbox

| IUPAC_name = 3,4-Dibromo-N-methyl-N-[(5S,6R)-1-methyl-1-azaspiro[4.5]decan-6-yl]benzamide

| image = U-77891.svg

| tradename =

| pregnancy_AU =

| pregnancy_category =

| legal_AU =

| legal_CA =

| legal_UK =

| legal_US =

| legal_status =

| routes_of_administration = By mouth, parenteral

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

| CAS_number = 119878-31-8

| CAS_number_Ref = {{cascite|correct|CAS}}

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 7P6974D7RX

| ATC_suffix =

| PubChem = 117071705

| DrugBank =

| ChemSpiderID = 23120785

| ChEMBL = 279065

| C=18 | H=24 | Br=2 | N=2 | O=1

| smiles = CN1CCC[C@]12CCCC[C@H]2N(C)C(=O)c3ccc(Br)c(Br)c3

| StdInChI = 1S/C18H24Br2N2O/c1-21-11-5-10-18(21)9-4-3-6-16(18)22(2)17(23)13-7-8-14(19)15(20)12-13/h7-8,12,16H,3-6,9-11H2,1-2H3/t16-,18+/m1/s1

| StdInChIKey = XHBTZWGPHRHWQZ-AEFFLSMTSA-N

}}

U-77891 is an opioid analgesic drug that was first synthesized in 1983 by the Upjohn company.{{cite web | url=https://patents.google.com/patent/US4598088 | title=US Patent 4598088 - 2-pyrrolyl-cycloalkyl-amide analgesics | work=The Upjohn Company | date=18 May 1983 | author=Jacob Szmuszkovicz, John M. McCall, Lester J. Kaplan, Moses W. McMillan}} It was originally synthesized to prove that the removal of a single methylene spacer of the benzamide would alter a κ-opioid receptor agonist such as U-50488 into an μ-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_i value in a series of benzamide opioids dating back to the 1970s.{{cite journal | vauthors = Fujimoto RA, Boxer J, Jackson RH, Simke JP, Neale RF, Snowhill EW, Barbaz BJ, Williams M, Sills MA | display-authors = 6 | title = Synthesis, opioid receptor binding profile, and antinociceptive activity of 1-azaspiro[4.5]decan-10-yl amides | journal = Journal of Medicinal Chemistry | volume = 32 | issue = 6 | pages = 1259–65 | date = June 1989 | pmid = 2542556 | doi = 10.1021/jm00126a019 }} The original work found a mixture of agonists and antagonists.{{cite web | url=https://patents.google.com/patent/US4466977 | title=US Patent 4466977 - N-[2-Amino(oxy- or thia- group-substituted-cycloaliphatic)]benzeneacetamides and -benzamide analgesics | work=The Upjohn Company | date=9 April 1981 | author=Moses W. McMillan, Jacob Szmuszkovicz}}

U-77891 acts as an agonist of the μ-opioid, δ-opioid and κ-opioid receptors with K_i values of 2, 105, and 2300 nM, respectively. The compound has ED₅₀ 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,{{cite web | url=http://www.chemicalize.org/structure/#!mol=3%2C4-dibromo-N-methyl-N-%5B%285S%2C6R%29-1-methyl-1-azaspiro%5B4.5%5Ddecan-6-yl%5Dbenzamide&source=fp | title=Properties Viewer | publisher=chemicalize.org}} allowing it to accumulate in fatty tissue such as the brain.