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Chemical compound
AM-2389
(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
PubChem
CID
ChemSpider
UNII
CompTox Dashboard (
EPA )
Formula C 25 H 38 O 3
Molar mass 386.576 g·mol−1 3D model (
JSmol )
OC1=C([C@@H]2C[C@@H](CC[C@H]2C(C)(O3)C)O)C3=CC(C4(CCC4)CCCCCC)=C1
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
Y Key:CSXKNESDVLECTJ-VAMGGRTRSA-N
Y
N Y
(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 ]
See also
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 .
Phytocannabinoids (
comparison )
Cannabibutols Cannabichromenes Cannabicyclols Cannabidiols Cannabielsoins Cannabigerols Cannabiphorols Cannabinols Cannabitriols Cannabivarins Delta-8-tetrahydrocannabinols Delta-9-tetrahydrocannabinols Delta-10-Tetrahydrocannabinols Miscellaneous cannabinoids Active metabolites
Endocannabinoids
Synthetic cannabinoid receptor agonists / neocannabinoids
Classical cannabinoids (dibenzopyrans) Non-classical cannabinoids Adamantoylindoles Benzimidazoles Benzoylindoles Cyclohexylphenols
Eicosanoids
Hydrocarbons Indazole carboxamides Indazole-3- carboxamides Indole-3-carboxamides Indole-3-carboxylates Naphthoylindazoles
Naphthoylindoles Naphthoylpyrroles Naphthylmethylindenes Naphthylmethylindoles Phenylacetylindoles Pyrazolecarboxamides Pyrrolobenzoxazines Quinolinyl esters Tetramethylcyclo- propanoylindazoles Tetramethylcyclo- propanoylindoles Tetramethylcyclo- propylindoles Others
Allosteric
CBR Tooltip Cannabinoid receptor
ligands
Endocannabinoid enhancers (inactivation inhibitors)
Anticannabinoids (antagonists/inverse agonists/antibodies)