U-77891

U-77891 is an opioid analgesic drug that was first synthesized in 1983 by the Upjohn company.[1] 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 Ki value in a series of benzamide opioids dating back to the 1970s.[2] The original work found a mixture of agonists and antagonists.[3]

U-77891
Clinical data
Routes of
administration		By mouth, parenteral
Identifiers
IUPAC name
  • 3,4-dibromo-N-methyl-N-[(5S,6R)-1-methyl-1-azaspiro[4.5]decan-6-yl]benzamide
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC18H24Br2N2O
Molar mass444.211 g·mol−1
3D model (JSmol)
SMILES
  • CN1CCC[C@]12CCCC[C@H]2N(C)C(=O)c3ccc(Br)c(Br)c3
InChI
  • InChI=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
  • Key:XHBTZWGPHRHWQZ-AEFFLSMTSA-N

U-77891 acts as an agonist of the μ-opioid, δ-opioid and κ-opioid receptors with Ki values of 2, 105 and 2300 nM, respectively.[2] The compound has ED50 values of 0.02 mg/kg and 0.21 mg/kg in mouse phenylquinone writhing and tail-flick assays.[2] One reason for the high potency is the LogP of 4.57,[4] allowing it to accumulate in fatty tissue such as the brain.

See also

References
  1. Jacob Szmuszkovicz, John M. McCall, Lester J. Kaplan, Moses W. McMillan (18 May 1983). "US Patent 4598088 - 2-pyrrolyl-cycloalkyl-amide analgesics". The Upjohn Company.{{cite web}}: CS1 maint: multiple names: authors list (link)
  2. Fujimoto RA, Boxer J, Jackson RH, Simke JP, Neale RF, Snowhill EW, et al. (June 1989). "Synthesis, opioid receptor binding profile, and antinociceptive activity of 1-azaspiro[4.5]decan-10-yl amides". Journal of Medicinal Chemistry. 32 (6): 1259–65. doi:10.1021/jm00126a019. PMID 2542556.
  3. Moses W. McMillan, Jacob Szmuszkovicz (9 April 1981). "US Patent 4466977 - N-[2-Amino(oxy- or thia- group-substituted-cycloaliphatic)]benzeneacetamides and -benzamide analgesics". The Upjohn Company.
  4. "Properties Viewer". chemicalize.org.


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