U-77891

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	119878-31-8 ;
PubChem CID	117071705;
ChemSpider	23120785;
UNII	7P6974D7RX;
ChEMBL	ChEMBL279065;
Chemical and physical data
Formula	C18H24Br2N2O
Molar mass	444.211 g·mol−1
3D model (JSmol)	Interactive image;
	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 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 K_i 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 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.^[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.

References

^ 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)
^ ^a ^b ^c 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.
^ 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.
^ "Properties Viewer". chemicalize.org.

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[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)

[Fujimoto-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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See also

References