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 ;
UNII	GGT8LM8A2O;
CompTox Dashboard (EPA)	DTXSID70678538 ;
Chemical and physical data
Formula	C25H38O3
Molar mass	386.576 g·mol−1
3D model (JSmol)	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 ;
	(what is this?)

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 26× 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.^{[citation needed]}

References

^ Nikas SP, Alapafuja SO, Papanastasiou I, Paronis CA, Shukla VG, Papahatjis DP, et al. (October 2010). "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. 53 (19): 6996–7010. doi:10.1021/jm100641g. PMC 3650853. PMID 20925434.
^ Järbe TU, Tai S, LeMay BJ, Nikas SP, Shukla VG, Zvonok A, Makriyannis A (March 2012). "AM2389, a high-affinity, in vivo potent CB1-receptor-selective cannabinergic ligand as evidenced by drug discrimination in rats and hypothermia testing in mice". Psychopharmacology. 220 (2): 417–26. doi:10.1007/s00213-011-2491-1. PMC 3291515. PMID 21989802.
^ Papahatjis DP, Nahmias VR, Nikas SP, Andreou T, Alapafuja SO, Tsotinis A, et al. (August 2007). "C1'-cycloalkyl side chain pharmacophore in tetrahydrocannabinols". Journal of Medicinal Chemistry. 50 (17): 4048–60. doi:10.1021/jm070121a. PMID 17672444.

[1] Nikas SP, Alapafuja SO, Papanastasiou I, Paronis CA, Shukla VG, Papahatjis DP, et al. (October 2010). "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. 53 (19): 6996–7010. doi:10.1021/jm100641g. PMC 3650853. PMID 20925434.

[2] Järbe TU, Tai S, LeMay BJ, Nikas SP, Shukla VG, Zvonok A, Makriyannis A (March 2012). "AM2389, a high-affinity, in vivo potent CB1-receptor-selective cannabinergic ligand as evidenced by drug discrimination in rats and hypothermia testing in mice". Psychopharmacology. 220 (2): 417–26. doi:10.1007/s00213-011-2491-1. PMC 3291515. PMID 21989802.

[3] Papahatjis DP, Nahmias VR, Nikas SP, Andreou T, Alapafuja SO, Tsotinis A, et al. (August 2007). "C1'-cycloalkyl side chain pharmacophore in tetrahydrocannabinols". Journal of Medicinal Chemistry. 50 (17): 4048–60. doi:10.1021/jm070121a. PMID 17672444.

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See also

References