Ohmefentanyl

Ohmefentanyl
Systematic (IUPAC) name
N-[(3R,4S)-1-[(2S)-2-hydroxy-2-phenyl-ethyl] -3-methyl-4-piperidyl]-N-phenyl-propanamide
Legal status
Legal status
Identifiers
CAS Number 78995-14-9 YesY
ATC code none
PubChem CID 10474095
ChemSpider 8649506 YesY
UNII Y8263089ZX YesY
Chemical data
Formula C23H30N2O2
Molar mass 366.497 g/mol
  (verify)

Ohmefentanyl (β-hydroxy-3-methylfentanyl, OMF, RTI-4614-4[1]) is an extremely potent opioid analgesic drug which selectively binds to the µ-opioid receptor.[2][3] The Chinese have recorded ohmefentanyl as having a potency that is 6,300 times morphine.[4][5][6][7]

Ohmefentanyl is one of the most potent μ -receptor agonists known, comparable to super-potent opioids such as carfentanil and etorphine which are used for tranquilizing large animals such as elephants in veterinary medicine. In mouse studies, the most active isomer 3R,4S,βS-ohmefentanyl was 28 times more powerful as a painkiller than fentanyl, the chemical from which it is derived, and 6300 times more effective than morphine.[8] Ohmefentanyl has three stereogenic centers and so has eight stereoisomers, which are named F9201–F9208. Researchers are studying the different pharmaceutical properties of these isomers.[9]

The 4"-fluoro analogue (i.e. substituted on the phenethyl ring) of the 3R,4S,βS isomer of ohmefentanyl is one of the most potent opioid agonists yet discovered, possessing an analgesic potency approximately 18,000-fold greater than morphine.[10] Other analogues with potency higher than that of ohmefentanyl itself include the 2'-fluoro derivative (i.e. substituted on the aniline phenyl ring), and derivatives where the N-propionyl group was replaced by N-methoxyacetyl or 2-furamide groups, or a carboethoxy group is added to the 4-position of the piperidine ring. The latter is listed as being up to 30,000 times more potent than morphine.[11]

Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear.[12]

Molecular structure of four ohmefentanyl isomers

See also

References

  1. ↑ Rothman, R. B.; Heng Xu; Seggel, M.; Jacobson, A. E.; Rice, K. C.; Brine, G. A.; Carroll, F. I. (1991). "RTI-4614-4: An analog of (+)-cis-3-methylfentanyl with a 27,000-fold binding selectivity for mu versus delta opioid binding sites". Life Sciences 48 (23): PL111. doi:10.1016/0024-3205(91)90346-D. PMID 1646357.
  2. ↑ Brine, G. A.; Stark, P. A.; Liu, Y.; Carroll, F. I.; Singh, P.; Xu, H.; Rothman, R. B. (1995). "Enantiomers of Diastereomeric cis-N-[1-(2-Hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamides: Synthesis, X-ray Analysis, and Biological Activities". Journal of Medicinal Chemistry 38 (9): 1547–1557. doi:10.1021/jm00009a015.
  3. ↑ Wang, Z. X.; Zhu, Y. C.; Jin, W. Q.; Chen, X. J.; Chen, J.; Ji, R. Y.; Chi, Z. Q. (1995). "Stereoisomers of N-[1-(2-Hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]- N-phenylpropanamide: Synthesis, Stereochemistry, Analgesic Activity, and Opioid Receptor Binding Characteristics". Journal of Medicinal Chemistry 38 (18): 3652–9. doi:10.1021/jm00018a026. PMID 7658453.
  4. ↑ http://www.dtic.mil/dtic/tr/fulltext/u2/a199595.pdf
  5. ↑ Jin, W. Q.; Xu, H.; Zhu, Y. C.; Fang, S. N.; Xia, X. L.; Huang, Z. M.; Ge, B. L.; Chi, Z. Q. (1981). "Studies on synthesis and relationship between analgesic activity and receptor affinity for 3-methyl fentanyl derivatives". Scientia Sinica 24 (5): 710–720. PMID 6264594.
  6. ↑ Zhu, Y. C.; Wu, R. Q.; Chou, D. P.; Huang, Z. M. (1983). "Studies on potent analgesics. VII. Synthesis and analgesic activity of diastereoisomers of 1-beta-hydroxy-3-methylfentanyl (7302) and related compounds". Yao xue xue bao = Acta pharmaceutica Sinica 18 (12): 900–4. PMID 6679170.
  7. ↑ Xu, H., Chen, .1., and Chi, Z., "Studies in Synthesis and Relationship Between Analgesic Activity and Receptor Affinity for 3-Methylfentanyl Derivatives," Scientia Sinica (Series B , Vol.28, pp 504 - 511 (1985).
  8. ↑ Guo, G. W.; He, Y.; Jin, W. Q.; Zou, Y.; Zhu, Y. C.; Chi, Z. Q. (2000). "Comparison of physical dependence of ohmefentanyl stereoisomers in mice". Life Sciences 67 (2): 113–120. doi:10.1016/S0024-3205(00)00617-2. PMID 10901279.
  9. ↑ Liu, Z.; He, Y.; Jin, W.; Chen, X.; Shen, Q.; Chi, Z. (2004). "Effect of chronic treatment of ohmefentanyl stereoisomers on cyclic AMP formation in Sf9 insect cells expressing human mu-opioid receptors". Life Sciences 74 (24): 3001–3008. doi:10.1016/j.lfs.2003.10.027. PMID 15051423.
  10. ↑ Yong, Z.; Hao, W.; Weifang, Y.; Qiyuan, D.; Xinjian, C.; Wenqiao, J.; Youcheng, Z. (2003). "Synthesis and analgesic activity of stereoisomers of cis-fluoro-ohmefentanyl". Die Pharmazie 58 (5): 300–302. PMID 12779044.
  11. ↑ Brine GA, Carroll FI, Richardson-Leibert TM, Xu H, Rothman RB. Ohmefentanyl and its stereoisomers: Chemistry and Pharmacology. Current Medicinal Chemistry. 1997; 4(4):247-270. http://books.google.co.uk/books?id=wufUIdeynGsC
  12. ↑ Jane Mounteney, Isabelle Giraudon, Gleb Denissov, Paul Griffiths (July 2015). "Fentanyls: Are we missing the signs? Highly potent and on the rise in Europe.". The international journal of drug policy. 26 (7): 626–631. doi:10.1016/j.drugpo.2015.04.003. PMID 25976511.

External links


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