AM-1235

AM-1235

Systematic (IUPAC) name
1-[(5-fluoropentyl)-6-nitro-1H-indol-3-yl]-(naphthalen-1-yl)methanone
Clinical data
Legal status	CA: Schedule II
Identifiers
CAS Number	335161-27-8
ChemSpider	26633899
UNII	2HV9AH611M
Chemical data
Formula	C24H21FN2O3
Molar mass	404.433 g/mol
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 1.5nM at CB₁ compared to 20.4nM 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 13x.^[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]

See also

• AM-694
• AM-906
• AM-1235
• AM-2232
• AM-2233
• AM-2389
• JWH-018
• List of AM cannabinoids
• List of JWH cannabinoids
• O-1812
• THJ-2201

References

1. US patent 7241799, Makriyannis A, Deng H, "Cannabimimetic indole derivatives", granted 2007-07-10 
2. Deng, Hongfeng (2000). Design and synthesis of selective cannabinoid receptor ligands: Aminoalkylindole and other heterocyclic analogs (PhD. Dissertation). University of Connecticut.
3. WO patent 200128557, Makriyannis A, Deng H, "Cannabimimetic indole derivatives", granted 2001-06-07 
4. Millington JE, Pattison FLM. TOXIC FLUORINE COMPOUNDS: XII. ESTERS OF ω-FLUOROALCOHOLS. Canadian Journal of Chemistry. 1956 Nov;34(11):1532-1541.
5. Pattison FLM, Howell WC, Woolford RG. TOXIC FLUORINE COMPOUNDS: XIII. ω-FLUOROALKYL ETHERS. Canadian Journal of Chemistry. 1957 Feb;35(2):141-148.