U-47700

U-47700
Legal status
Legal status
Identifiers
  • 3,4-Dichloro-N-[(1R,2R)-2-(dimethylamino)cyclohexyl]-N-methylbenzamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
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, also known as U4, pink heroin, pinky, and pink, is an opioid analgesic drug developed by a team at Upjohn in the 1970s[1] which has around 7.5 times the potency of morphine in animal models.[2][3][4]

Physical Sample of U-47700[5]

U-47700 is a structural isomer of the earlier opioid AH-7921[6] and the result of a great deal of work elucidating the quantitative structure–activity relationship of the scaffold. Upjohn looked for the key moieties which gave the greatest activity[7] and posted over a dozen patents on related compounds, each optimizing one moiety[8][9][10][11][12][13][14][15] until they discovered that U-47700 was the most active.[16]

U-47700 became the lead compound of selective kappa-opioid receptor ligands such as U-50488, U-51754 (containing a pyrrolidine rather than a dimethylamine substituent) and U-69,593, which share very similar structures.[17][18] Although not used medically, the selective kappa ligands are used in research.[19][20]

  1. ^ Szmuszkovicz J (4 July 1978). "Patent US4098904 - Analgesic N-(2-aminocycloaliphatic)benzamides".
  2. ^ Cheney BV, Szmuszkovicz J, Lahti RA, Zichi DA (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.
  3. ^ Harper NJ, Veitch GB, Wibberley DG (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.
  4. ^ Szmuszkovicz J, Von Voigtlander PF (October 1982). "Benzeneacetamide amines: structurally novel non-m mu opioids". Journal of Medicinal Chemistry. 25 (10): 1125–1126. doi:10.1021/jm00352a005. PMID 6128415.
  5. ^ Alzghari SK, Fleming SW, Rambaran KA, Long JE, Burkhart S, An J, Furmaga J (October 2017). "U-47700: An Emerging Threat". Cureus. 9 (10): e1791. doi:10.7759/cureus.1791. PMC 5741271. PMID 29282436.
  6. ^ Brittain RT, Kellett DN, Neat ML, Stables R (September 1973). "Proceedings: Anti-nociceptive effects in N-substituted cyclohexylmethylbenzamides". British Journal of Pharmacology. 49 (1): 158P–159P. doi:10.1111/j.1476-5381.1973.tb08279.x. PMC 1776456. PMID 4207044.
  7. ^ Michalson ET, Szmuszkovicz J (1989). "Medicinal agents incorporating the 1,2-diamine functionality". Progress in Drug Research. Vol. 33. Birkhäuser Basel. pp. 135–149. doi:10.1007/978-3-0348-9146-2_6. ISBN 9783034891462. PMID 2687936. {{cite book}}: |journal= ignored (help)
  8. ^ Mullins DD (28 June 1966). "Patent US US3258489 - N-(1-aminocyclohexylmethyl)anilines and N-(1-nitrocyclohexylmethyl)anilines".
  9. ^ Harper NJ, Veitch GB (17 August 1976). "Patent US3975443 - 1-(3,4-dichlorobenzamidomethyl)-cyclohexyldimethylamine".
  10. ^ Szmuszkovicz J (3 March 1970). "Patent US3499033 - Ethers of α-phenyl-2-aminocycloalkanemethanols".
  11. ^ Szmuszkovicz J (5 May 1970). "Patent US3510492 - 2-anilino and 2-anilinomethyl cycloalkylamines".
  12. ^ Rynbrandt RH, Skaletzky LL (7 March 1972). "Patent US3647804 - Cycloalkanecarboxamides".
  13. ^ Roll W (23 July 1974). "Patent US3825595 - N-cyclopentyl-N-2-hydroxyalkyl-ring-substituted benzamides".
  14. ^ Harper NJ, Veitch GB (20 September 1977). "Patent US4049663 - Ethylene diamine derivatives".
  15. ^ Collins RJ, Kaplan LJ, Ludens JH, Von Voigtlander PF (9 April 1982). "Patent US4463013 - Oxygen substituted amino-cyclohexyl-benzeneacetamides and -benzamides as water diuretic drugs".
  16. ^ Casy AF, Parfitt RT (1986). "Miscellaneous Groups of Analgesics". Opioid Analgesics. Springer US. pp. 385–403. doi:10.1007/978-1-4899-0585-7_11. ISBN 9781489905857.
  17. ^ Szmuszkovicz J, Zhao S, Totleben MJ, Mizsak SA, Freeman JP (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.
  18. ^ Loew G, Lawson J, Toll L, Frenking G, Berzetei-Gurske I, Polgar W (1988). "Structure activity studies of two classes of beta-amino-amides: the search for kappa-selective opioids" (PDF). NIDA Research Monograph. 90: 144–151. PMID 2855852.
  19. ^ Szmuszkovicz J (1999). "U-50,488 and the к receptor: A personalized account covering the period 1973 to 1990". Progress in Drug Research. Vol. 52. Birkhäuser Basel. pp. 167–195. doi:10.1007/978-3-0348-8730-4_4. ISBN 9783034887304. PMID 10396128. {{cite book}}: |journal= ignored (help)
  20. ^ Tsibulnikov SY, Maslov LN, Mukhomedzyanov AV, Krylatov AV, Tsibulnikova MR, Lishmanov YB (October 2015). "Prospects of Using of κ-Opioid Receptor Agonists U-50,488 and ICI 199,441 for Improving Heart Resistance to Ischemia/Reperfusion". Bulletin of Experimental Biology and Medicine. 159 (6): 718–721. doi:10.1007/s10517-015-3057-8. PMID 26519268. S2CID 1046853.