A-834,735

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A-834,735
A-834735 structure.png
Systematic (IUPAC) name
1-(tetrahydropyran-4-ylmethyl)-1H-indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone
Clinical data
Legal status
?
Identifiers
CAS number 895155-57-4 N
ATC code ?
PubChem CID 11544639
ChemSpider 9719418 YesY
ChEMBL CHEMBL271158 YesY
Chemical data
Formula C22H29NO2 
Mol. mass 339.470 g/mol
 N (what is this?)  (verify)

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 Ki of 12nM at CB1 and 0.21nM 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]

See also[edit]

References[edit]

  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.  edit
  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.  edit
  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.  edit