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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 23113403
| ChemSpiderID = 23113403
| ChEMBL = 2062161
| ChEMBL = 2311130
<!--Chemical data-->
<!--Chemical data-->
| C=16 | H=22 | Cl=2 | N=2 | O=1
| C=16 | H=22 | Cl=2 | N=2 | O=1

Revision as of 08:28, 1 June 2016

U-47700
Legal status
Legal status
  • Illegal in Finland, Sweden, Ohio
Identifiers
  • trans-3,4-dichloro-N-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide
CAS Number
PubChem CID
ChemSpider
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC16H22Cl2N2O
Molar mass329.27 g·mol−1
3D model (JSmol)
  • ClC1=C(C=CC(=C1)C(=O)N(C)[C@@H]2CCCC[C@H]2N(C)C)Cl
  • InChI=1S/C16H22Cl2N2O/c1-19(2)14-6-4-5-7-15(14)20(3)16(21)11-8-9-12(17)13(18)10-11/h8-10,14-15H,4-7H2,1-3H3/t14-,15-/m1/s1
  • Key:JGPNMZWFVRQNGU-HUUCEWRRSA-N
 ☒NcheckY (what is this?)  (verify)

U-47700[1] is an opioid analgesic drug developed by a team at Upjohn in the 1970s.[2] U-47700 was derived from an earlier opioid AH-7921. U-47700 is selective for the µ-opioid receptor with a Kd value of 5.3 nM compared to 910 nM for the κ-opioid receptor[3][4] and has around 7.5 x the potency of morphine in animal models.[5][6]

U-47700 is the result of a great deal of work elucidating the quantitative structure–activity relationship of the scaffold. The team looked for the key moieties which gave the greatest activity.[7] Upjohn posted over a dozen patents on related compounds, each optimizing one moiety[8][9][10][11][12][13][14] until they discovered that U-47700 was the most active.[15]

U-47700 became the lead compound of selective kappa-opioid receptor ligands such as U-50488 (containing a single methylene spacer difference) and U-69,593, which share very similar structures.[3] Its structure led to other chemists experimenting with it to see if rigid analogues would retain activity.[16] Although not used medically, the selective kappa ligands are used in research.[17]

Side effects

U-47700 has never been studied in humans, but would be expected to produce effects similar to those of other potent opioid agonists, including strong analgesia, sedation, euphoria, constipation, itching and respiratory depression which could be harmful or fatal.[18] Tolerance and dependence would be expected to develop.[original research?]

Combined consumption of U-47700 and fentanyl caused one fatality in Belgium.[19][20] At least 17 opioid overdoses and several deaths in the USA have been connected with the use of U-47700.[21]

Following its sale as a designer drug, U-47700 was made illegal in Sweden on 26 January 2016.[22]

U-47700 was emergency scheduled in Ohio on 3 May 2016.[23]

See also

References

  1. ^ U-47700 at DistilBio
  2. ^ Jacob Szmuszkovicz (4 July 1978). "Patent US4098904 - Analgesic n-(2-aminocycloaliphatic)benzamides".
  3. ^ a b G. Loew, J. Lawson, L. Toll, G. Frenking, IP. Berzetei-Gurske, W. Polgar (1988). "Structure activity studies of two classes of beta-amino-amides: the search for kappa-selective opioids" (PDF). NIDA Research Monograph. 90: 144–151.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Marta Filizola, Hugo O. Villar, Gilda H. Loew (April 2001). "Differentiation of δ, μ, and κ opioid receptor agonists based on pharmacophore development and computed physicochemical properties". Journal of Computer-Aided Molecular Design. 15 (4): 297–307. doi:10.1023/A:1011187320095. PMID 11349813.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ B. Vernon Cheney, Jacob Szmuszkovicz, Robert A. Lahti, Dominic A. Zichi (December 1985). "Factors affecting binding of trans-N-[2-(methylamino)cyclohexyl]benzamides at the primary morphine receptor". Journal of Medicinal Chemistry. 28 (12): 1853–1864. doi:10.1021/jm00150a017. PMID 2999404.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ N. J. Harper, G. B. A. Veitch, D. G. Wibberley (November 1974). "1-(3,4-Dichlorobenzamidomethyl)cyclohexyldimethylamine and related compounds as potential analgesics". Journal of Medicinal Chemistry. 17 (11): 1188–1193. doi:10.1021/jm00257a012. PMID 4416926.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ Erik T. Michalson, Jacob Szmuszkovicz (1989). "Medicinal agents incorporating the 1,2-diamine functionality". Progress in Drug Research. 33: 135–149. doi:10.1007/978-3-0348-9146-2_6. PMID 2687936.
  8. ^ Darrell D Mullins (28 June 1966). "Patent US US3258489 - N-(1-aminocyclohexylmethyl)anilines and n-(1-nitrocyclohexylmethyl)an-ilines".
  9. ^ Norman James Harper, George Bryan Austin Veitch (17 August 1976). "Patent US3975443 - 1-(3,4-dichlorobenzamidomethyl)-cyclohexyldimethylamine".
  10. ^ Jacob Szmuszkovicz Kalamazoo (3 March 1970). "Patent US3499033 - Ethers of alpha-phenyl-2-aminocycloalkanemethanols".
  11. ^ Jacob Szmuszkovicz (5 May 1970). "Patent US3510492 - 2-anilino and 2-anilinomethyl cycloalkylamines".
  12. ^ Ronald H Rynbrandt, Louis L Skaletzky (7 March 1972). "Patent US3647804 - Cycloalkanecarboxamides".
  13. ^ W. Roll (23 July 1974). "Patent US3825595 - N-cyclopentyl-n-2-hydroxyalkyl-ring-substituted benzamides".
  14. ^ Norman James Harper, George Bryan Austin Veitch (20 September 1977). "Patent US4049663 - Ethylene diamine derivatives".
  15. ^ Alan F. Casy, Robert T. Parfitt (1986). Opioid Analgesics, Chemistry and Receptors. Springer US. p. 395. ISBN 978-1-4899-0587-1.
  16. ^ Shikai Zhao, Michael J. Totleben, Stephen A. Mizsak, Jeremiah P. Freeman, Jacob Szmuszkovicz (2000). "Phenanthridone Analogs of the Opiate Agonist U-47,700 in the trans-1,2-Diaminocyclohexane Benzamide Series". Heterocycles. 52 (1): 325–332. doi:10.3987/COM-99-S27.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ^ Jacob Szmuszkovicz (1999). U-50,488 and the к receptor: A personalized account covering the period 1973 to 1990. Birkhäuser Basel. pp. 167–195. doi:10.1007/978-3-0348-8730-4_4. ISBN 978-3-0348-8730-4.
  18. ^ Todd L. Davis (9 March 2016). "New Synthetic Opioid Surfaces in North Texas". NBCDFW.
  19. ^ Vera Coopman, Peter Blanckaert, Geert Van Parys, Serge Van Calenbergh, Jan Cordonnier (2016). "A case of acute intoxication due to combined use of fentanyl and 3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700)". Forensic Science International. doi:10.1016/j.forsciint.2016.05.001.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  20. ^ "Twee doden in België door overdosis met fentanylpleisters" (in Dutch). Deredactie. 29 January 2016.
  21. ^ Susan Zalkind (11 April 2016). "Synthetic opiate makers stay step ahead of US drug laws as overdose cases rise". The Guardian.
  22. ^ "31 nya ämnen kan klassas som narkotika eller hälsofarlig vara" (in Swedish). Folkhälsomyndigheten. November 2015.
  23. ^ John R. Kasich (3 May 2016). "Executive Order 2016-01K" (PDF). Governor of Ohio.


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