AM-2389

AM-2389

Identifiers
IUPAC name (6aR,9R,10aR)-3-(1-hexylcyclobut-1-yl)-6a,7,8,9,10,10a-hexahydro-6,6-dimethyl-6H-dibenzo[b,d]pyran-1,9 diol
CAS Number	1256842-49-5
PubChem (CID)	49783410
ChemSpider	26333264
Chemical and physical data
Formula	C25H38O3
Molar mass	386.566 g/mol
3D model (Jmol)	Interactive image
SMILES OC1=C([C@@H]2C[C@@H](CC[C@H]2C(C)(O3)C)O)C3=CC(C4(CCC4)CCCCCC)=C1
InChI InChI=1S/C25H38O3/c1-4-5-6-7-11-25(12-8-13-25)17-14-21(27)23-19-16-18(26)9-10-20(19)24(2,3)28-22(23)15-17/h14-15,18-20,26-27H,4-13,16H2,1-3H3/t18-,19-,20-/m1/s1 Key:CSXKNESDVLECTJ-VAMGGRTRSA-N
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AM-2389 is a classical cannabinoid derivative which acts as a potent and reasonably selective agonist for the CB₁ receptor, with a K_i of 0.16 nM, and 26x selectivity over the related CB₂ receptor. It has high potency in animal tests of cannabinoid activity, and a medium duration of action.^[1][2] Replacing the 1',1'-dimethyl substitution of the dimethylheptyl side chain of classical cannabinoids with cyclopropyl or cyclopentyl results in higher potency than cyclobutyl, but only the cyclobutyl derivatives show selectivity for CB₁ over CB₂.^[3] High selectivity for CB₁ over CB₂ is difficult to achieve (cf. AM-906, AM-1235), as almost all commonly used CB₁ agonists have similar or greater affinity for CB₂ than CB₁, and the only truly highly selective CB₁ agonists known as of 2012 are eicosanoid derivatives such as O-1812.

See also

• HHC
• AMG-36
• AMG-41

References

1. Nikas SP, et al. Novel 1',1'-chain substituted hexahydrocannabinols: 9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol (AM2389) a highly potent cannabinoid receptor 1 (CB1) agonist. Journal of Medicinal Chemistry. 2010 Oct 14;53(19):6996-7010. PMID 20925434
2. Järbe TU, et al. AM2389, a high-affinity, in vivo potent CB(1)-receptor-selective cannabinergic ligand as evidenced by drug discrimination in rats and hypothermia testing in mice. Psychopharmacology (Berlin). 2011 Oct 12. PMID 21989802
3. Papahatjis DP, et al. C1'-cycloalkyl side chain pharmacophore in tetrahydrocannabinols. Journal of Medicinal Chemistry. 2007 Aug 23;50(17):4048-60. PMID 17672444