AM-4030

Drugbox
IUPAC_name = (6S,6aR,9R,10aR)-9-(hydroxymethyl)-6-((E)-3-hydroxyprop-1-enyl)-6-methyl-3-(2-methyloctan-2-yl)-6a,7,8,9,10,10a-hexahydrobenzo [c] chromen-1-ol

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PubChem= 10550598
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C=27 | H=42 | O=4
molecular_weight = 430.618 g/mol
smiles = OCC=CC3(C)C1CCC(CO)CC1c2c(O3)cc(cc2O)C(C)(C)CCCCCC
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AM-4030 is an analgesic drug which is a cannabinoid 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, [Roger Pertwee. Cannabinoids. Handbook of Experimental Pharmacology Volume 168, p 269. Springer. ISBN 3-540-22565-X] 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 vs 8.6nM at CB₂, a selectivity of around 12x. [Tius MA, Hill WA, Zou XL, Busch-Petersen J, Kawakami JK, Fernandez-Garcia MC, Drake DJ, Abadji V, Makriyannis A. Classical/non-classical cannabinoid hybrids; stereochemical requirements for the southern hydroxyalkyl chain. "Life Sciences". 1995;56(23-24):2007-12. PMID 7776825] [Drake DJ, Jensen RS, Busch-Petersen J, Kawakami JK, Concepcion Fernandez-Garcia M, Fan P, Makriyannis A, Tius MA. Classical/nonclassical hybrid cannabinoids: southern aliphatic chain-functionalized C-6beta methyl, ethyl, and propyl analogues. "Journal of Medicinal Chemistry". 1998 Sep 10;41(19):3596-608. PMID 9733485] 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. [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". 2002 Dec 31;54(1-3):415-22. PMID 12543516]

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