Ohmefentanyl

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Ohmefentanyl
Ohmefentanyl.svg
Systematic (IUPAC) name
N-[(3R,4S)-1-[(2S)-2-hydroxy-2-phenyl-ethyl] -3-methyl-4-piperidyl]-N-phenyl-propanamide
Clinical data
Legal status
?
Identifiers
CAS number 78995-14-9 YesY
ATC code None
PubChem CID 10474095
ChemSpider 8649506 YesY
Chemical data
Formula C23H30N2O2 
Mol. mass 366.497 g/mol
 YesY (what is this?)  (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]

Molecular structure of four ohmefentanyl isomers

See also[edit]

References[edit]

  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.  edit
  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. doi:10.1021/jm00009a015.  edit
  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.  edit
  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.  edit
  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.  edit
  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.  edit
  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.  edit
  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.  edit
  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

External links[edit]