AM-630

AM-630 (6-Iodopravadoline) is a drug that acts as a potent and selective inverse agonist for the cannabinoid receptor CB₂, with a K_i of 32.1 nM at CB₂ and 165x selectivity over CB₁, at which it acted as a weak partial agonist.^[1][2] It is used in the study of CB₂ mediated responses and has been used to investigate the possible role of CB₂ receptors in the brain.^[3][4] AM-630 is significant as one of the first indole derived cannabinoid ligands substituted on the 6-position of the indole ring, a position that has subsequently been found to be important in determining affinity and efficacy at both the CB₁ and CB₂ receptors, and has led to the development of many related derivatives.^{[5][6][7][8][9]}

AM-630

Legal status
Legal status	CA: Schedule II DE: NpSG (Industrial and scientific use only) UK: Under Psychoactive Substances Act
Identifiers
IUPAC name 1-[2-(Morpholin-4-yl)ethyl]-2-methyl-3-(4-methoxybenzoyl)-6-iodoindole
CAS Number	164178-33-0 N
PubChem CID	4302963
IUPHAR/BPS	750
ChemSpider	3508738 Y
UNII	U1LNJ6NBKA
ChEMBL	ChEMBL181633 Y
CompTox Dashboard (EPA)	DTXSID10167719
ECHA InfoCard	100.229.964
Chemical and physical data
Formula	C23H25IN2O3
Molar mass	504.368 g·mol−1
3D model (JSmol)	Interactive image
SMILES C4COCCN4CCn(c1C)c2cc(I)ccc2c1C(=O)c3ccc(OC)cc3
InChI InChI=1S/C23H25IN2O3/c1-16-22(23(27)17-3-6-19(28-2)7-4-17)20-8-5-18(24)15-21(20)26(16)10-9-25-11-13-29-14-12-25/h3-8,15H,9-14H2,1-2H3 Y Key:JHOTYHDSLIUKCJ-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

See also

• AM-1221
• Pravadoline
• WIN 54,461 (6-Bromopravadoline)

References

1. Ross RA, Brockie HC, Stevenson LA, Murphy VL, Templeton F, Makriyannis A, Pertwee RG (February 1999). "Agonist-inverse agonist characterization at CB1 and CB2 cannabinoid receptors of L759633, L759656, and AM630". British Journal of Pharmacology. 126 (3): 665–672. doi:10.1038/sj.bjp.0702351. PMC 1565857. PMID 10188977.
2. Murataeva N, Mackie K, Straiker A (November 2012). "The CB2-preferring agonist JWH015 also potently and efficaciously activates CB1 in autaptic hippocampal neurons". Pharmacological Research. 66 (5): 437–442. doi:10.1016/j.phrs.2012.08.002. PMC 3601544. PMID 22921769.
3. Morgan NH, Stanford IM, Woodhall GL (September 2009). "Functional CB2 type cannabinoid receptors at CNS synapses". Neuropharmacology. 57 (4): 356–368. doi:10.1016/j.neuropharm.2009.07.017. PMID 19616018. S2CID 207224823.
4. Ishiguro H, Horiuchi Y, Ishikawa M, Koga M, Imai K, Suzuki Y, et al. (May 2010). "Brain cannabinoid CB2 receptor in schizophrenia". Biological Psychiatry. 67 (10): 974–982. doi:10.1016/j.biopsych.2009.09.024. PMID 19931854. S2CID 14222913.
5. Eissenstat MA, Bell MR, D'Ambra TE, Alexander EJ, Daum SJ, Ackerman JH, et al. (August 1995). "Aminoalkylindoles: structure-activity relationships of novel cannabinoid mimetics". Journal of Medicinal Chemistry. 38 (16): 3094–3105. doi:10.1021/jm00016a013. PMID 7636873.
6. Hongfeng Deng. Design and synthesis of selective cannabinoid receptor ligands: Aminoalkylindole and other heterocyclic analogs. PhD Dissertation, University of Connecticut, 2000.
7. Hynes J, Leftheris K, Wu H, Pandit C, Chen P, Norris DJ, et al. (September 2002). "C-3 Amido-indole cannabinoid receptor modulators". Bioorganic & Medicinal Chemistry Letters. 12 (17): 2399–2402. doi:10.1016/S0960-894X(02)00466-3. PMID 12161142.
8. Frost JM, Dart MJ, Tietje KR, Garrison TR, Grayson GK, Daza AV, et al. (March 2008). "Indol-3-yl-tetramethylcyclopropyl ketones: effects of indole ring substitution on CB2 cannabinoid receptor activity". Journal of Medicinal Chemistry. 51 (6): 1904–1912. doi:10.1021/jm7011613. PMID 18311894.
9. Adam, J. M.; et al. (2010). "Design, synthesis, and structure–activity relationships of indole-3-carboxamides as novel water soluble cannabinoid CB1 receptor agonists". MedChemComm. 1: 54. doi:10.1039/c0md00022a.