View source for AM-2389

{{Short description|Chemical compound}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid =
| IUPAC_name = (6a''R'',9''R'',10a''R'')-3-(1-hexylcyclobut-1-yl)-6a,7,8,9,10,10a-hexahydro-6,6-dimethyl-6''H''-dibenzo[''b'',''d'']pyran-1,9 diol
| image = AM-2389 Structure.svg
| width = 260
<!--Clinical data-->
| pregnancy_category =
| legal_status =
<!--Identifiers-->
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 1256842-49-5
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = GGT8LM8A2O
| ATC_prefix =
| ATC_suffix =
| PubChem = 49783410
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank =
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 26333264
<!--Chemical data-->
| C=25|H=38|O=3
| smiles = OC1=C([C@@H]2C[C@@H](CC[C@H]2C(C)(O3)C)O)C3=CC(C4(CCC4)CCCCCC)=C1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = CSXKNESDVLECTJ-VAMGGRTRSA-N
}}
'''AM-2389''' is a classical [[cannabinoid]] derivative which acts as a potent and reasonably selective [[agonist]] for the [[Cannabinoid receptor 1|CB<sub>1</sub>]] [[Receptor (biochemistry)|receptor]], with a ''K''<sub>i</sub> of 0.16&nbsp;nM, and 26× selectivity over the related [[Cannabinoid receptor 2|CB<sub>2</sub>]] receptor. It has high potency in animal tests of cannabinoid activity, and a medium duration of action.<ref>{{cite journal | vauthors = Nikas SP, Alapafuja SO, Papanastasiou I, Paronis CA, Shukla VG, Papahatjis DP, Bowman AL, Halikhedkar A, Han X, Makriyannis A | display-authors = 6 | title = 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 = Journal of Medicinal Chemistry | volume = 53 | issue = 19 | pages = 6996–7010 | date = October 2010 | pmid = 20925434 | doi = 10.1021/jm100641g | pmc = 3650853 }}</ref><ref>{{cite journal | vauthors = Järbe TU, Tai S, LeMay BJ, Nikas SP, Shukla VG, Zvonok A, Makriyannis A | title = AM2389, a high-affinity, in vivo potent CB1-receptor-selective cannabinergic ligand as evidenced by drug discrimination in rats and hypothermia testing in mice | journal = Psychopharmacology | volume = 220 | issue = 2 | pages = 417–26 | date = March 2012 | pmid = 21989802 | doi = 10.1007/s00213-011-2491-1 | pmc = 3291515 }}</ref> 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 CB<sub>1</sub> over CB<sub>2</sub>.<ref>{{cite journal | vauthors = Papahatjis DP, Nahmias VR, Nikas SP, Andreou T, Alapafuja SO, Tsotinis A, Guo J, Fan P, Makriyannis A | display-authors = 6 | title = C1'-cycloalkyl side chain pharmacophore in tetrahydrocannabinols | journal = Journal of Medicinal Chemistry | volume = 50 | issue = 17 | pages = 4048–60 | date = August 2007 | pmid = 17672444 | doi = 10.1021/jm070121a }}</ref> High selectivity for CB<sub>1</sub> over CB<sub>2</sub> is difficult to achieve (cf. [[AM-906]], [[AM-1235]]), as almost all commonly used CB<sub>1</sub> agonists have similar or greater affinity for CB<sub>2</sub> than CB<sub>1</sub>, and the only truly highly selective CB<sub>1</sub> agonists known as of 2012 are eicosanoid derivatives such as [[O-1812]].{{cn|date=December 2023}}
== See also ==
* [[9-nor-9β-Hydroxyhexahydrocannabinol|HHC]]
* [[AMG-36]]
* [[AMG-41]]
== References ==
{{reflist}}
{{Cannabinoids}}
[[Category:AM cannabinoids]]
[[Category:Benzochromenes]]
[[Category:Cyclobutanes]]