Ciprefadol Explained

Ciprefadol is an opioid analgesic that is an isoquinoline derivative most closely related to cyclazocine and picenadol,^[1] with a number of other related compounds known.^{[2] [3] [4] [5]} Ciprefadol is a mixed agonist–antagonist at μ-opioid receptors and can partly block the effects of morphine at low doses, though at higher doses it acts more like a full agonist. It is also a potent κ-opioid agonist, unlike the corresponding N-methyl and N-phenethyl derivatives which are reasonably μ-selective agonists.^[6]

Notes and References

1. https://patents.google.com/patent/US4001248 Dennis M. Zimmerman et al. N-cycloalkylmethyl decahydroisoquinolines. US Patent 4001248, Jun 7, 1974
2. https://patents.google.com/patent/US4419517 David R. Brittelli et al. 4a-Aryl-trans-decahydroisoquinolines. US Patent 4419517, Apr 8, 1975
3. https://patents.google.com/patent/US4189583 Henry Rapoport et al. Synthesis of 4A-aryl-decahydroisoquinolines. US Patent 4189583, Apr 26, 1978
4. Judd DB, Brown DS, Lloyd JE, McElroy AB, Scopes DI, Birch PJ, Hayes AG, Sheehan MJ . 6 . Synthesis, antinociceptive activity, and opioid receptor profiles of substituted trans-3-(decahydro- and octahydro-4a-isoquinolinyl)phenols . Journal of Medicinal Chemistry . 35 . 1 . 48–56 . January 1992 . 1310115 . 10.1021/jm00079a005 .
5. Carroll FI, Chaudhari S, Thomas JB, Mascarella SW, Gigstad KM, Deschamps J, Navarro HA . N-substituted cis-4a-(3-hydroxyphenyl)-8a-methyloctahydroisoquinolines are opioid receptor pure antagonists . Journal of Medicinal Chemistry . 48 . 26 . 8182–93 . December 2005 . 16366600 . 10.1021/jm058261c . 2585695 .
6. Zimmerman DM, Cantrell BE, Swartzendruber JK, Jones ND, Mendelsohn LG, Leander JD, Nickander RC . Synthesis and analgesic properties of N-substituted trans-4a-aryldecahydroisoquinolines . Journal of Medicinal Chemistry . 31 . 3 . 555–60 . March 1988 . 2831363 . 10.1021/jm00398a011 .