AM-4030 explained
AM-4030 is an analgesic drug which is a cannabinoid receptor agonist. It is a derivative of HU-210 which has been substituted with a 6β-((E)-3-hydroxyprop-1-enyl) group. This adds a "southern" aliphatic hydroxyl group to the molecule as seen in the CP-series of nonclassical cannabinoid drugs, and so AM-4030 represents a hybrid structure between the classical and nonclassical cannabinoid families,[1] with the 6-hydroxyalkyl chain rigidified with a double bond with defined stereochemistry. This gives AM-4030 a greater degree of selectivity, so while it is still a potent agonist at both CB1 and CB2, it is reasonably selective for CB1, with a Ki of 0.7nM at CB1 and 8.6nM at CB2, a selectivity of around 12x.[2] [3] Resolution of the enantiomers of AM-4030 yields an even more potent compound, although with less selectivity, with the (−) enantiomer AM-4030a having a Ki of 0.6nM at CB1 and 1.1nM at CB2.[4]
See also
Notes and References
- Book: Pertwee, Roger . vanc . Cannabinoids . Handbook of Experimental Pharmacology . 168 . 269 . Springer . 3-540-22565-X .
- Tius MA, Hill WA, Zou XL, Busch-Petersen J, Kawakami JK, Fernandez-Garcia MC, Drake DJ, Abadji V, Makriyannis A . 6 . Classical/non-classical cannabinoid hybrids; stereochemical requirements for the southern hydroxyalkyl chain . Life Sciences . 1995 . 56 . 23–24 . 2007–12 . 7776825 . 10.1016/0024-3205(95)00182-6 .
- Drake DJ, Jensen RS, Busch-Petersen J, Kawakami JK, Concepcion Fernandez-Garcia M, Fan P, Makriyannis A, Tius MA . 6 . Classical/nonclassical hybrid cannabinoids: southern aliphatic chain-functionalized C-6beta methyl, ethyl, and propyl analogues . Journal of Medicinal Chemistry . 41 . 19 . 3596–608 . September 1998 . 9733485 . 10.1021/jm960677q .
- Thakur GA, Palmer SL, Harrington PE, Stergiades IA, Tius MA, Makriyannis A . Enantiomeric resolution of a novel chiral cannabinoid receptor ligand . Journal of Biochemical and Biophysical Methods . 54 . 1–3 . 415–22 . December 2002 . 12543516 . 10.1016/s0165-022x(02)00144-6 .
