A-834,735

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]

A-834,735

Legal status
Legal status	UK: Class B
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
UNII	XE27L67C93
ChEMBL	ChEMBL271158
CompTox Dashboard (EPA)	DTXSID60468349
Chemical and physical data
Formula	C22H29NO2
Molar mass	339.479 g·mol^−1
3D model (JSmol)	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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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, Frost J, Tietje K, Daza A, Grayson G, Fan Y, et al. (2006). "1-Alkyl-3-keto-indoles: identification and in vitro characterization of a series of potent cannabinoid ligands". 2006 Symposium on the Cannabinoids. Burlington, VT: International Cannabinoid Research Society.
2. Poso A, Huffman JW (January 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, Tovcimak AE, Hradil VP, Seifert TR, Hollingsworth PR, Chandran P, 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 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): 1904–12. doi:10.1021/jm7011613. PMID 18311894.
5. Frost JM, Dart MJ, Tietje KR, Garrison TR, Grayson GK, Daza AV, et al. (January 2010). "Indol-3-ylcycloalkyl ketones: effects of N1 substituted indole side chain variations on CB(2) 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. Archived from the original on 1 October 2015. Retrieved 1 October 2015.