List of AM cannabinoids

Alexandros Makriyannis is a professor in the Department of Medicinal Chemistry at Northeastern University, where his research group has synthesized many new compounds with cannabinoid activity. Some of those are:

• AM-087 — an analgesic CB₁ agonist derived from Δ⁸THC substituted with a side chain on the 3-position, it has a K_i of 0.43nM making it roughly 100x as potent as THC.
• AM-251 — an inverse agonist at the CB₁ cannabinoid receptor that is structurally related to SR141716A (rimonabant), but has a higher binding affinity with a K_i value of 7.5nM.^[1]
• AM-279 — a Schedule I substance in Alabama.^[2]
• AM-281 — N-(morpholin-4-yl)-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-1H-pyrazole-3-carboxamide^[1]
• AM-356 — a synthetically created stable chiral analog of anandamide, it acts on the cannabinoid receptors with a K_i of 17.9nM at CB₁ and 868nM at CB₂.^[3]
• AM-374 — palmitylsulfonyl fluoride^[4]
• AM-381 — stearylsulfonyl fluoride
• AM-404 — an active metabolite of paracetamol (acetaminophen) and a likely inhibitor of fatty acid amide hydrolase (FAAH)
• AM-411 — an adamantyl-substituted derivative of Δ⁸THC, it is a potent and fairly selective CB₁ full agonist with a K_i of 6.80nM. It is also a moderately potent CB₂ agonist with a K_i of 52.0nM.
• AM-630 — a potent and selective inverse agonist for the cannabinoid receptor CB₂, with a K_i of 32.1nM at CB₂ and 165x selectivity over CB₁, at which it acts as a weak partial agonist.
• AM-661 — 1-(N-methyl-2-piperidine)methyl-2-methyl-3-(2-iodo)benzoylindole^[5]
• AM-678 — another name for JWH-018, it is a full agonist at both cannabinoid receptors with some selectivity for CB₂.
• AM-679 — an iodobenzoylindole which acts as a moderately potent agonist for the cannabinoid receptors, with a K_i of 13.5nM at CB₁ and 49.5nM at CB₂.
• AM-694 — an iodobenzoylindole which acts as a potent and selective agonist for the CB₁ cannabinoid receptor, with a K_i of 0.08nM at CB₁ and 18x selectivity over the related CB₂ receptor (1.44nM).^[6]
• AM-735 — 3-bornyl-Δ8-THC, a mixed CB₁ / CB₂ agonist with K_i of 8.9nM at CB₁ and 7.4nM at CB₂.^[7]
• AM-855 — an analgesic derivative of Δ⁸tetrahydrocannabinol, it is an agonist at both CB₁ and CB₂ with moderate selectivity for CB₁, with a K_i of 22.3nM at CB₁ and 58.6nM at CB₂.
• AM-881 — a chlorine-substituted stereoisomer of anandamide whose K_i = 5.3nM at CB₁ and 95nM at CB₂.^[3]
• AM-883 — an allyl-substituted stereoisomer of anandamide whose K_i = 9.9nM at CB₁ and 226nM at CB₂.^[3]
• AM-905 — a potent and reasonably selective agonist for the CB₁ cannabinoid receptor, with a K_i of 1.2nM at CB₁ and 5.3nM at CB₂.
• AM-906 — a potent and dodecally selective agonist for the CB₁ cannabinoid receptor, with a K_i of 0.8nM at CB₁ and 9.5nM at CB₂.
• AM-919 — a potent agonist at both CB₁ and CB₂ with moderate selectivity for CB₁, with a K_i of 2.2nM at CB₁ and 3.4nM at CB₂. It is a derivative of HU-210 and represents a hybrid structure between the classical and nonclassical cannabinoid families.
• AM-926 — a potent agonist at both CB₁ and CB₂ with moderate selectivity for CB₁, with a K_i of 2.2nM at CB₁ and 4.3nM at CB₂. It is a derivative of HU-210 and represents a hybrid structure between the classical and nonclassical cannabinoid families.
• AM-938 — a potent agonist at both CB₁ and CB₂ with quadruple selectivity for CB₂, with a K_i of 1.2nM at CB₁ and 0.3nM at CB₂. It is a derivative of HU-210 and represents a hybrid structure between the classical and nonclassical cannabinoid families.
• AM-1116 — a dimethylated stereoisomer of anandamide whose K_i = 7.4nM at CB₁.^[3]
• AM-1172 — an endocannabinoid analog specifically designed to be a potent and selective inhibitor of AEA uptake that is resistant to FAAH hydrolysis.
• AM-1220 — a potent and selective analgesic CB₁ agonist (as racemate) with a K_i of 3.88nM at CB₁ and 73.4nM at CB₂, giving it 19x selectivity for CB₁. (R) enantiomer has around 1000x higher affinity for CB₁ than (S) enantiomer.^[8][9]
• AM-1221 — a potent and selective CB₂ agonist with a K_i of 0.28nM at CB₂ and 52.3nM at CB₁, giving it a selectivity of almost 187x.
• AM-1235 — a moderately CB₁ selective agonist, with a K_i of 1.5nM at CB₁ and 20.4nM at CB₂, giving it a selectivity of around 13x.^[10]
• AM-1241 — a potent and selective analgesic CB₂ agonist with a K_i of 3.4nM at CB₂ and 80x selectivity over CB₁.^[11]
• AM-1248 — a moderately potent agonist with some selectivity for CB₁, containing an unusual 3-(adamant-1-oyl) substitution on the indole ring.
• AM-1710 — a CB₂ selective cannabilactone with 54x selectivity over CB₁.^[12]
• AM-1714 — a CB₂ selective cannabilactone with 490x selectivity over CB₁.^[12]
• AM-2201 — a potent agonist at both CB₁ and CB₂ with moderate selectivity for CB₁, with a K_i of 1.0nM at CB₁ and 2.6nM at CB₂.
• AM-2212 — a potent agonist at both CB₁ and CB₂ with dodecal selectivity for CB₁, with a K_i of 1.4nM at CB₁ and 18.9nM at CB₂.^[5]
• AM-2213 — a potent agonist at both CB₁ and CB₂ with 10x selectivity for CB₁, with a K_i of 3.0M at CB₁ and 30nM at CB₂.^[5]
• AM-2232 — a potent agonist at both CB₁ and CB₂, with a K_i of 0.28nM at CB₁ and 1.48nM at CB₂.^[10]
• AM-2233 — (R) enantiomer is potent and selective CB₁ agonist used in ¹³¹I radiolabelled form to map distribution of CB₁ receptors in brain.^{[13][14][15][16][17][18]}
• AM-2389 — classical cannabinoid derivative with 26x selectivity for CB₁.
• AM-3102 — an analog of oleoylethanolamide, the endogenous agonist for proliferator-activated receptor α (PPARα). It also acts as a weak cannabinoid agonist with K_i values of 33µM at CB₁ and 26µM at CB₂.
• AM-4030 — a potent agonist at both CB₁ and CB₂, it is dodecally selective for CB₁, with a K_i of 0.7nM at CB₁ and 8.6nM at CB₂. It is a derivative of HU-210 and represents a hybrid structure between the classical and nonclassical cannabinoid families.
• AM-4054 — a potent but slow-onset agonist with CB₁ affinity of 2.2nM and a 40x selectivity for CB₁ over CB₂.^[19][20]
• AM-4054 —
• AM-4113 — a CB₁ selective neutral antagonist.^[21]
• AM-6545 — a peripherally selective silent antagonist of CB₁ receptors.

See also

• List of CP cannabinoids
• List of JWH cannabinoids
• List of HU cannabinoids
• List of miscellaneous designer cannabinoids

References

1. 1 2 Lan, Ruoxi; Lu, Qian; Fan, Pusheng; Gatley, John; Volkow, Nora D.; Fernando, Susanthi R.; Pertwee, Roger; Makriyannis, Alexandros (1999). "Design and synthesis of the CB1 selective cannabinoid antagonist AM281: A potential human SPECT ligand". AAPS PharmSci. 1 (2): 39–45. doi:10.1208/ps010204. 
2. ↑ "Alabama Senate Bill 333 - Controlled substances, Schedule I, additional synthetic controlled substances and analogue substances included in, trafficking in controlled substance analogues, requisite weight increased, Secs. 13A-12-231, 20-2-23 am'd.". March 2014. Retrieved 28 September 2015. 
3. 1 2 3 4 Selwood, D. (2009). "The Cannabinoid Receptors. Edited by Patricia H. Reggio". ChemMedChem. 4: 1949. doi:10.1002/cmdc.200900286. 
4. ↑ Pacher, P.; Bátkai, S; Kunos, G (2006). "The Endocannabinoid System as an Emerging Target of Pharmacotherapy". Pharmacological Reviews. 58 (3): 389–462. doi:10.1124/pr.58.3.2. PMC 2241751. PMID 16968947. 
5. 1 2 3 Hongfeng Deng. Design and synthesis of selective cannabinoid receptor ligands: Aminoalkylindole and other heterocyclic analogs. PhD Dissertation, University of Connecticut, 2000.
6. ↑ WO patent 200128557, Makriyannis A, Deng H, "Cannabimimetic indole derivatives", granted 2001-06-07 
7. ↑ Lu, D; Guo, J; Duclos, RI Jr; Bowman, AL; Makriyannis, A (Oct 2008). "Bornyl- and isobornyl-Delta8-tetrahydrocannabinols: a novel class of cannabinergic ligands". Journal of Medicinal Chemistry. 51 (20): 6393–9. doi:10.1021/jm8005299. PMID 18826296. 
8. ↑ 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. 
9. ↑ 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. 
10. 1 2 US patent 7241799, Makriyannis A, Deng H, "Cannabimimetic indole derivatives", granted 2007-07-10 
11. ↑ Poso, A.; Huffman, J. W. (2008). "Targeting the cannabinoid CB2 receptor: modelling and structural determinants of CB2 selective ligands". British Journal of Pharmacology. 153 (2): 335–46. doi:10.1038/sj.bjp.0707567. PMC 2219524. PMID 17982473. 
12. 1 2 Khanolkar, AD; Lu, D; Ibrahim, M; Duclos, RI Jr; Thakur, GA; Malan, TP; Porreca, F; Veerappan, V; Tian, X; George, C; Parrish, DA; Papahatjis, DP; Makriyannis, A (Dec 2007). "Cannabilactones: a novel class of CB2 selective agonists with peripheral analgesic activity". Journal of Medicinal Chemistry. 50 (26): 6493–500. doi:10.1021/jm070441u. PMID 18038967. 
13. ↑ Deng H, Gifford AN, Zvonok AM, Cui G, Li X, Fan P, Deschamps JR, Flippen-Anderson JL, Gatley SJ, Makriyannis A (October 2005). "Potent cannabinergic indole analogues as radioiodinatable brain imaging agents for the CB1 cannabinoid receptor". Journal of Medicinal Chemistry. 48 (20): 6386–92. doi:10.1021/jm050135l. PMID 16190764. 
14. ↑ Hanuš, L. R. O.; Mechoulam, R. (2005). "Cannabinoid chemistry: an overview". Cannabinoids as Therapeutics. Milestones in Drug Therapy MDT. p. 23. doi:10.1007/3-7643-7358-X_2. ISBN 3-7643-7055-6. 
15. ↑ Shen CP, Xiao JC, Armstrong H, Hagmann W, Fong TM (February 2006). "F200A substitution in the third transmembrane helix of human cannabinoid CB1 receptor converts AM2233 from receptor agonist to inverse agonist". European Journal of Pharmacology. 531 (1–3): 41–6. doi:10.1016/j.ejphar.2005.12.026. PMID 16438957. 
16. ↑ Dhawan, J.; Deng, H.; Gatley, S. J.; Makriyannis, A.; Akinfeleye, T.; Bruneus, M.; Dimaio, A. A.; Gifford, A. N. (2006). "Evaluation of the in vivo receptor occupancy for the behavioral effects of cannabinoids using a radiolabeled cannabinoid receptor agonist, R-[125/131I]AM2233". Synapse. 60 (2): 93–101. doi:10.1002/syn.20277. PMID 16715483. 
17. ↑ Leung K (Dec 12, 2006). "R-2-[131I]Iodophenyl-(1-(1-methylpiperidin-2-ylmethyl)-1H-indol-3-yl)methanone". Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. PMID 20641836. 
18. ↑ Pei, Y.; et al. (2008). "Ligand-Binding Architecture of Human CB2 Cannabinoid Receptor: Evidence for Receptor Subtype-Specific Binding Motif and Modeling GPCR Activation". Chemistry & Biology. 15: 1207. doi:10.1016/j.chembiol.2008.10.011. 
19. ↑ [Paronis CA, Thakur GA, Vemuri K, Makriyannis A, Bergman J. Effects of a Selective Cannabinoid Agonist and Antagonist on Body Temperature in Rats. The FASEB Journal. April 2007 21 (Meeting Abstract Supplement) A409. http://www.fasebj.org/cgi/content/meeting_abstract/21/5/A409]
20. ↑ Paronis, C. A.; Thakur, G. A.; Bajaj, S.; Nikas, S. P.; Vemuri, V. K.; Makriyannis, A.; Bergman, J. (2012). "Diuretic effects of cannabinoids". Journal of Pharmacology and Experimental Therapeutics. 344 (1): 8–14. doi:10.1124/jpet.112.199331. PMID 23019138. 
21. ↑ Seely, KA; Prather, PL; James, LP; Moran, JH (Feb 2011). "Marijuana-based drugs: innovative therapeutics or designer drugs of abuse?". Molecular Interventions. 11 (1): 36–51. doi:10.1124/mi.11.1.6. PMC 3139381. PMID 21441120.