AM-1220

AM-1220
Legal status
Legal status	AU: S9 (Prohibited substance); CA: Schedule II; DE: Anlage II (Authorized trade only, not prescriptible); NZ: Temporary Class; UK: Class B; US: Schedule I;
Identifiers
	IUPAC name (R)-(1-((1-Methylpiperidin-2-yl)methyl)-1H-indol-3-yl)(naphthalen-1-yl)methanone;
CAS Number	137642-54-7 (racemic) ; 134959-64-1 ((R)-enantiomer);
PubChem CID	9929889;
ChemSpider	26231035 ;
UNII	05850M72P2; (R)-enantiomer: 44NQ9RBE1B ;
CompTox Dashboard (EPA)	DTXSID50433001 ;
Chemical and physical data
Formula	C26H26N2O
Molar mass	382.507 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(C1=CC=CC2=C1C=CC=C2)C3=CN(C[C@@H]4N(C)CCCC4)C5=CC=CC=C53;
	InChI InChI=1S/C26H26N2O/c1-27-16-7-6-11-20(27)17-28-18-24(22-13-4-5-15-25(22)28)26(29)23-14-8-10-19-9-2-3-12-21(19)23/h2-5,8-10,12-15,18,20H,6-7,11,16-17H2,1H3/t20-/m1/s1 ; Key:URKVBEKZCMUTQC-HXUWFJFHSA-N ;
	(verify)

AM-1220 is a drug that acts as a potent and moderately selective agonist for the cannabinoid receptor CB₁, with around 19 times selectivity for CB₁ over the related CB₂ receptor.^[1] It was originally invented in the early 1990s by a team led by Thomas D'Ambra at Sterling Winthrop,^[2] 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 K_i of 0.27 nM at CB₁ while the (S)-enantiomer has a much weaker K_i of 217 nM.^[3]

Related compounds

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.^[4]^[5]^[6] AM-1220 was first detected as an ingredient of synthetic cannabis smoking blends in 2010.^[7]

Related 1-(N-methylpyrrolidin-2-ylmethyl) and 1-(N-methylmorpholin-3-ylmethyl) derivatives

Legal status

United States

in the United States of America all CB₁ receptor agonists of the 3-(1-naphthoyl)indole class such as AM-1220 are Schedule I Controlled Substances under the Controlled Substances Act s.^[8]

United Kingdom

it's illegal to supply, smuggle, distribute, transport, sell or trade the pharmaceutical drug under the Psychoactive Substances Act 2016 which was enforced on May26th 2016.

China

As of October 2015, AM-1220 is a controlled substance in China.^[9]

References

^ WO patent 200128557, Makriyannis A, Deng H, "Cannabimimetic indole derivatives", granted 2001-06-07
^ US patent 5068234, D'Ambra TE, 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 (1): 17–22. doi:10.1016/0960-894X(95)00560-G.
^ Deng H (2000). Design and synthesis of selective cannabinoid receptor ligands: Aminoalkylindole and other heterocyclic analogs (PhD. Dissertation). University of Connecticut. ProQuest 304624325.
^ Willis PG, Pavlova OA, Chefer SI, Vaupel DB, Mukhin AG, Horti AG (September 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, Makriyannis A, et al., "Receptor selective cannabimimetic aminoalkylindoles", granted 2010-10-26
^ Head Shop ‘Legal Highs’ Active Constituents Identification Chart (July - August 2010)
^ 21 U.S.C. § 812: Schedules of controlled substances
^ "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. Archived from the original on 1 October 2015. Retrieved 1 October 2015.

[WO_2001_28557_A1-1] WO patent 200128557, Makriyannis A, Deng H, "Cannabimimetic indole derivatives", granted 2001-06-07

[US_5068234-2] US patent 5068234, D'Ambra TE, et al., "3-arylcarbonyl-1-(C-attached-N-heteryl)-1H-indoles", granted 1991-11-26

[3] D'ambra, T. (1996). "C-Attached aminoalkylindoles: potent cannabinoid mimetics". Bioorganic & Medicinal Chemistry Letters. 6 (1): 17–22. doi:10.1016/0960-894X(95)00560-G.

[liganDesign-4] Deng H (2000). Design and synthesis of selective cannabinoid receptor ligands: Aminoalkylindole and other heterocyclic analogs (PhD. Dissertation). University of Connecticut. ProQuest 304624325.

[5] Willis PG, Pavlova OA, Chefer SI, Vaupel DB, Mukhin AG, Horti AG (September 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_7820144-6] US patent 7820144, Makriyannis A, et al., "Receptor selective cannabimimetic aminoalkylindoles", granted 2010-10-26

[7] Head Shop ‘Legal Highs’ Active Constituents Identification Chart (July - August 2010)

[8] 21 U.S.C. § 812: Schedules of controlled substances

[9] "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. Archived from the original on 1 October 2015. Retrieved 1 October 2015.

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