The new synthetic cannabinoids on the block

Since approximately 2007, quinoline cannabinoid derivatives have been evaluated for cannabinoid receptor affinity.  A few studies have demonstrated a handful of compounds with the quinoline structure to be highly selective for the CB2 receptor over the CB1 receptor.

PB-22 and 5F-PB-22 are two emerging synthetic cannabinoid substances of this quinoline class.  They have been analytically confirmed as adulterants in herbal incense blends in the USA.

PB-22’s chemical name is 1-pentyl-8-quinolinyl ester-1H-indole-3-carboxylic acid.  Its molecular formula is C23H22N2O2 and formula weight is 358.4 g/mol.  The chemical structure features an indole group, a pentyl alkyl chain, a carbonyl group and a 8-hydroxyquinoline moiety.

5F-PB-22’s chemical name is 1-(5-fluoropentyl)-8-quinolinyl ester-1H-indole-3-carboxylic acid.  Its molecular formula is C23H21FN2O2 and formula weight is 376.4 g/mol.  It features the same chemical structure as PB-22 with the exception of a single fluorine atom at the terminal carbon of the pentyl chain.

BB-22’s chemical name is 1-(cyclohexylmethyl)-8-quinolinyl ester-1H-indole-3-carboxylic acid.  Its molecular formula is C25H24N2O2 and formula weight is 384.5 g/mol.  It features the same chemical structure as PB-22 with the exception of the replacement of the pentyl alkyl chain with a cyclohexylmethyl moiety.

I am currently in the midwest traveling, so I thought I would look up these substances and see if they are controlled at the state level.  They are not controlled in any of the several midwestern states as schedule I drugs.  They are also not included in the updated list of controlled compounds in the legislation pending in any midwestern state.  In fact, I do not know of any location in the USA (state and/or federal) in which they are controlled explicitly.  It would also prove difficult to make these an analog case as they are significantly different (my scientific opinion) than JWH-018 or other controlled synthetic cannabinoids.   It is also of importance that these substances have no published in vitro or animal modeling data regarding their pharmacological activity at the receptor. 

Goodbye UR-144 and XLR-11.  Welcome the next wave of synthetic cannabinoids…the quinoline derivatives.  Meet the new boss, same as the old boss - more unknown than the preceding generations.

PS. Note reference 4 – not only the quinoline derivatives are listed, but also isoquinoline, quinoxaline, and quinazoline derivaties exist as well.

The cat and mouse games will continue!

References

1.    C Manera, V Benetti, MP Castelli et al. Design, synthesis, and biological evaluation of new 1,8-naphthyridin-4(1H)-on-3-carboxamide and quinolin-4(1H)-on-3-carboxamide derivatives as CB2 selective agonists. J Med Chem (2006) 49(20):  5947-5957.  PMID:  17004710

2.    C Manera, MG Cascio, V Benetti et al. New 1,8-naphthyridine and quinoline derivatives as CB2 selective agonists. Bioorg Med Chem Lett (2007) 17(23): 6505-6510.  PMID: 17942307

3.    R Saari, JC Torma, T Nevalainen. Microwave-assisted synthesis of quinoline, isoquinoline, quinoxaline and quinazoline derivatives as CB2 receptor agonists. Bioorg Med Chem (2011) 19(2): 939-950. PMID: 21215643

4.    PG Baraldi, G Saponaro, AR Moorman et al. 7-Oxo-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamides as selective CB(2) cannabinoid receptor ligands: structural investigations around a novel class of full agonists. J Med Chem (2012) 55(14): 6608-6623.  PMID 22738271