A-834,735

A-834,735

Identifiers
IUPAC name {1-[(tetrahydro-2H-pyran-4-yl)methyl]-1H-indol-3-yl}-(2,2,3,3-tetramethylcyclopropyl)methanone
CAS Number	895155-57-4
PubChem (CID)	11544639
ChemSpider	9719418
ChEMBL	CHEMBL271158
Chemical and physical data
Formula	C22H29NO2
Molar mass	339.48 g·mol^−1
3D model (Jmol)	Interactive image
SMILES C4COCCC4Cn(c3)c2ccccc2c3C(=O)C1C(C)(C)C1(C)C
InChI InChI=1S/C22H29NO2/c1-21(2)20(22(21,3)4)19(24)17-14-23(13-15-9-11-25-12-10-15)18-8-6-5-7-16(17)18/h5-8,14-15,20H,9-13H2,1-4H3 Key:NQTMRZNYLIGQCF-UHFFFAOYSA-N
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A-834,735 is a drug developed by Abbott Laboratories that acts as a potent cannabinoid receptor full agonist at both the CB₁ and CB₂ receptors, with a K_i of 12 nM at CB₁ and 0.21 nM at CB₂. Replacing the aromatic 3-benzoyl or 3-naphthoyl group found in most indole derived cannabinoids, with the 3-tetramethylcyclopropylmethanone group of A-834,735 and related compounds, imparts significant selectivity for CB₂, with most compounds from this group found to be highly selective CB₂ agonists with little affinity for CB₁. However low nanomolar CB₁ binding affinity is retained with certain heterocyclic 1-position substituents such as (N-methylpiperidin-2-yl)methyl (cf. AM-1220, AM-1248), or the (tetrahydropyran-4-yl)methyl substituent of A-834,735, resulting in compounds that still show significant affinity and efficacy at both receptors despite being CB₂ selective overall.^{[1][2][3][4][5]}

Legal Status

As of October 2015 A-834,735 is a controlled substance in China.^[6]

See also

• A-796,260
• AB-001
• AB-005
• FUB-144
• JTE 7-31
• UR-144
• XLR-11

References

1. Dart M, et al. (2006). 1-Alkyl-3-keto-indoles: identification and in vitro characterization of a series of potent cannabinoid ligands. In 2006 Symposium on the Cannabinoids. International Cannabinoid Research Society: Burlington, VT.
2. 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.
3. Chin CL; et al. (January 2008). "Differential effects of cannabinoid receptor agonists on regional brain activity using pharmacological MRI". British Journal of Pharmacology. 153 (2): 367–79. doi:10.1038/sj.bjp.0707506. PMC 2219521. PMID 17965748.
4. Frost, J. M.; et al. (2008). "Indol-3-yl-tetramethylcyclopropyl Ketones: Effects of Indole Ring Substitution on CB2 Cannabinoid Receptor Activity". Journal of Medicinal Chemistry. 51 (6): 1904–12. doi:10.1021/jm7011613. PMID 18311894.
5. Frost, J. M.; et al. (2010). "Indol-3-ylcycloalkyl Ketones: Effects of N1 Substituted Indole Side Chain Variations on CB2 Cannabinoid Receptor Activity". Journal of Medicinal Chemistry. 53 (1): 295–315. doi:10.1021/jm901214q. PMID 19921781.
6. "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. Retrieved 1 October 2015.