137642-54-7 (racemic) |
134959-64-1 ((R) enantiomer)
|Chemical and physical data|
|Molar mass||382.497 g/mol|
|3D model (Jmol)||Interactive image|
AM-1220 is a drug that acts as a potent and moderately selective agonist for the cannabinoid receptor CB1, with around 19x selectivity for CB1 over the related CB2 receptor. It was originally invented in the early 1990s by a team led by Thomas D'Ambra at Sterling Winthrop, but has subsequently been researched by many others, most notably the team led by Alexandros Makriyannis at the University of Connecticut. The (piperidin-2-yl)methyl side chain of AM-1220 contains a stereocenter, so there are two enantiomers with quite different potency, the (R) enantiomer having a Ki of 0.27nM at CB1 while the (S) enantiomer has a much weaker Ki of 217nM. A number of related compounds are known with similar potent cannabinoid activity, with modifications such as substitution of the indole ring at the 2- or 6- positions, the naphthoyl ring substituted at the 4- position or replaced by substituted benzoyl rings or other groups, or the 1-(N-methylpiperidin-2-ylmethyl) group replaced by similar heterocyclic groups such as N-methylpyrrolidin-2-ylmethyl or N-methylmorpholin-3-ylmethyl. AM-1220 was first detected as an ingredient of synthetic cannabis smoking blends in 2010.
- WO patent 200128557, Makriyannis A, Deng H, "Cannabimimetic indole derivatives", granted 2001-06-07
- US patent 5068234, Thomas E. D'Ambra et al., "3-arylcarbonyl-1-(C-attached-N-heteryl)-1H-indoles", granted 1991-11-26
- D'ambra, T. (1996). "C-Attached aminoalkylindoles: potent cannabinoid mimetics". Bioorganic & Medicinal Chemistry Letters. 6: 17–14. doi:10.1016/0960-894X(95)00560-G.
- Hongfeng Deng (2000). Design and synthesis of selective cannabinoid receptor ligands: Aminoalkylindole and other heterocyclic analogs (PhD. Dissertation). University of Connecticut.
- Willis, P. G.; Pavlova, O. A.; Chefer, S. I.; Vaupel, D. B.; Mukhin, A. G.; Horti, A. G. (2005). "Synthesis and Structure−Activity Relationship of a Novel Series of Aminoalkylindoles with Potential for Imaging the Neuronal Cannabinoid Receptor by Positron Emission Tomography". Journal of Medicinal Chemistry. 48 (18): 5813–22. doi:10.1021/jm0502743. PMID 16134948.
- US patent 7820144, Alexandros Makriyannis, et al., "Receptor selective cannabimimetic aminoalkylindoles", granted 2010-10-26
- Head Shop ‘Legal Highs’ Active Constituents Identification Chart (July - August 2010)
- "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Retrieved 1 October 2015.