AM-1235

AM-1235
Legal status
Legal status	CA: Schedule II; DE: NpSG (Industrial and scientific use only); UK: Under Psychoactive Substances Act; US: Schedule I;
Identifiers
	IUPAC name 1-[(5-Fluoropentyl)-6-nitro-1H-indol-3-yl]-(naphthalen-1-yl)methanone;
CAS Number	335161-27-8 ;
ChemSpider	26633899 ;
UNII	2HV9AH611M;
CompTox Dashboard (EPA)	DTXSID10187159 ;
Chemical and physical data
Formula	C24H21FN2O3
Molar mass	404.441 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES c24ccccc2cccc4C(=O)c(c3)c1ccc([N](=O)=O)cc1n3CCCCCF;
	InChI InChI=1S/C24H21FN2O3/c25-13-4-1-5-14-26-16-22(20-12-11-18(27(29)30)15-23(20)26)24(28)21-10-6-8-17-7-2-3-9-19(17)21/h2-3,6-12,15-16H,1,4-5,13-14H2 ; Key:LNGVQORPSNNMSZ-UHFFFAOYSA-N ;
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AM-1235 (1-(5-fluoropentyl)-3-(naphthalen-1-oyl)-6-nitroindole) is a drug that acts as a potent and reasonably selective agonist for the cannabinoid receptor CB₁.

Pharmacology

Pharmacodynamics

AM-1235 is a cannabinoid receptor agonist with K_i of 1.5 nM at CB₁ compared to 20.4 nM at CB₂.^[1] While the 6-nitro substitution on the indole ring reduces affinity for both CB₁ and CB₂ relative to the unsubstituted parent compound AM-2201, CB₂ affinity is reduced much more, resulting in a CB₁ selectivity of around 13 times.^[2] This is in contrast to other related compounds such as AM-1221 where a 6-nitro substitution instead confers significant selectivity for CB₂.^[3]

Pharmacokinetics

AM-1235 metabolism differs only slightly from that of JWH-018. AM-1235 N-dealkylation produces fluoropentane instead of pentane (or plain alkanes in general). It has been speculated that the fluoropentane might function as an alkylating agent or is further metabolized into toxic fluoroacetic acid. This is not true since fluoroalkanes do not act as alkylating agents under normal conditions and uneven fluoroalkane chains metabolize into substantially less toxic fluoropropanoic acid.^[4]^[5]

Legal status

In the United States, all CB₁ receptor agonists of the 3-(1-naphthoyl)indole class such as AM-1235 are Schedule I Controlled Substances.^[6]

References

^ US granted 7241799, Makriyannis A, Deng H, "Cannabimimetic indole derivatives", published 2004-11-05, issued 2007-07-10
^ Deng H (2000). Design and synthesis of selective cannabinoid receptor ligands: Aminoalkylindole and other heterocyclic analogs (PhD. Dissertation). University of Connecticut. ProQuest 304624325.
^ WO granted 200128557, Makriyannis A, Deng H, "Cannabimimetic indole derivatives", published 2001-04-26, issued 2001-06-07
^ Millington JE, Pattison FL (November 1956). "Toxic fluorine compounds: XII. Esters of ω-fluoroalcohols". Canadian Journal of Chemistry. 34 (11): 1532–1541. doi:10.1139/v56-200.
^ Pattison FL, Howell WC, Woolford RG (February 1957). "Toxic fluorine compounds: XIII. ω-Fluoroalkyl ethers". Canadian Journal of Chemistry. 35 (2): 141–148. doi:10.1139/v57-021.
^ 21 U.S.C. § 812: Schedules of controlled substances

[US_7241799-1] US granted 7241799, Makriyannis A, Deng H, "Cannabimimetic indole derivatives", published 2004-11-05, issued 2007-07-10

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

[WO_2001_28557_A1-3] WO granted 200128557, Makriyannis A, Deng H, "Cannabimimetic indole derivatives", published 2001-04-26, issued 2001-06-07

[4] Millington JE, Pattison FL (November 1956). "Toxic fluorine compounds: XII. Esters of ω-fluoroalcohols". Canadian Journal of Chemistry. 34 (11): 1532–1541. doi:10.1139/v56-200.

[5] Pattison FL, Howell WC, Woolford RG (February 1957). "Toxic fluorine compounds: XIII. ω-Fluoroalkyl ethers". Canadian Journal of Chemistry. 35 (2): 141–148. doi:10.1139/v57-021.

[6] 21 U.S.C. § 812: Schedules of controlled substances

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