SB-271046

SB-271046
Identifiers
IUPAC name
  • 5-chloro-N-(4-methoxy-3-piperazin-1-ylphenyl)-3-methyl-1-benzothiophene-2-sulfonamide
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC20H22ClN3O3S2
Molar mass451.98 g·mol−1
3D model (JSmol)
SMILES
  • C4CNCCN4c3cc(ccc3OC)NS(=O)(=O)c1sc2ccc(Cl)cc2c1C
InChI
  • InChI=1S/C20H22ClN3O3S2/c1-13-16-11-14(21)3-6-19(16)28-20(13)29(25,26)23-15-4-5-18(27-2)17(12-15)24-9-7-22-8-10-24/h3-6,11-12,22-23H,7-10H2,1-2H3 ☒N
  • Key:LOCQRDBFWSXQQI-UHFFFAOYSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

SB-271046 is a drug which is used in scientific research. It was one of the first selective 5-HT6 receptor antagonists to be discovered, and was found through high-throughput screening of the SmithKline Beecham Compound Bank using cloned 5-HT6 receptors as a target, with an initial lead compound being developed into SB-271046 through a structure-activity relationship (SAR) study.[1] SB-271046 was found to be potent and selective in vitro and had good oral bioavailability in vivo, but had poor penetration across the blood–brain barrier, so further SAR work was then conducted, which led to improved 5-HT6 antagonists such as SB-357,134 and SB-399,885.[2]

SB-271046 was found to increase levels of the excitatory amino acid neurotransmitters glutamate and aspartate,[3] as well as dopamine and noradrenaline[4] in the frontal cortex and hippocampus of rats,[5] and 5-HT6 antagonists have been shown to produce nootropic effects in a variety of animal studies.[6][7][8] Suggested applications of these drugs include treatment of schizophrenia and other psychiatric disorders.[9][10][11][12]

References

  1. ↑ Bromidge SM, Brown AM, Clarke SE, Dodgson K, Gager T, Grassam HL, et al. (January 1999). "5-Chloro-N-(4-methoxy-3-piperazin-1-yl- phenyl)-3-methyl-2-benzothiophenesulfon- amide (SB-271046): a potent, selective, and orally bioavailable 5-HT6 receptor antagonist". Journal of Medicinal Chemistry. 42 (2): 202–5. doi:10.1021/jm980532e. PMID 9925723.
  2. ↑ Ahmed M, Briggs MA, Bromidge SM, Buck T, Campbell L, Deeks NJ, et al. (November 2005). "Bicyclic heteroarylpiperazines as selective brain penetrant 5-HT6 receptor antagonists". Bioorganic & Medicinal Chemistry Letters. 15 (21): 4867–71. doi:10.1016/j.bmcl.2005.06.107. PMID 16143522.
  3. ↑ Dawson LA, Nguyen HQ, Li P (May 2000). "In vivo effects of the 5-HT(6) antagonist SB-271046 on striatal and frontal cortex extracellular concentrations of noradrenaline, dopamine, 5-HT, glutamate and aspartate". British Journal of Pharmacology. 130 (1): 23–6. doi:10.1038/sj.bjp.0703288. PMC 1572041. PMID 10780993.
  4. ↑ Lacroix LP, Dawson LA, Hagan JJ, Heidbreder CA (February 2004). "5-HT6 receptor antagonist SB-271046 enhances extracellular levels of monoamines in the rat medial prefrontal cortex". Synapse. 51 (2): 158–64. doi:10.1002/syn.10288. PMID 14618683. S2CID 6539467.
  5. ↑ Dawson LA, Nguyen HQ, Li P (November 2001). "The 5-HT(6) receptor antagonist SB-271046 selectively enhances excitatory neurotransmission in the rat frontal cortex and hippocampus". Neuropsychopharmacology. 25 (5): 662–8. doi:10.1016/S0893-133X(01)00265-2. PMID 11682249.
  6. ↑ Rogers DC, Hagan JJ (November 2001). "5-HT6 receptor antagonists enhance retention of a water maze task in the rat". Psychopharmacology. 158 (2): 114–9. doi:10.1007/s002130100840. PMID 11702084. S2CID 29472459.
  7. ↑ Foley AG, Murphy KJ, Hirst WD, Gallagher HC, Hagan JJ, Upton N, et al. (January 2004). "The 5-HT(6) receptor antagonist SB-271046 reverses scopolamine-disrupted consolidation of a passive avoidance task and ameliorates spatial task deficits in aged rats". Neuropsychopharmacology. 29 (1): 93–100. doi:10.1038/sj.npp.1300332. PMID 14571256.
  8. ↑ Marcos B, Chuang TT, Gil-Bea FJ, Ramirez MJ (October 2008). "Effects of 5-HT6 receptor antagonism and cholinesterase inhibition in models of cognitive impairment in the rat". British Journal of Pharmacology. 155 (3): 434–40. doi:10.1038/bjp.2008.281. PMC 2567877. PMID 18622410.
  9. ↑ Minabe Y, Shirayama Y, Hashimoto K, Routledge C, Hagan JJ, Ashby CR (April 2004). "Effect of the acute and chronic administration of the selective 5-HT6 receptor antagonist SB-271046 on the activity of midbrain dopamine neurons in rats: an in vivo electrophysiological study". Synapse. 52 (1): 20–8. doi:10.1002/syn.20002. PMID 14755629. S2CID 25687099.
  10. ↑ de Foubert G, O'Neill MJ, Zetterström TS (July 2007). "Acute onset by 5-HT(6)-receptor activation on rat brain brain-derived neurotrophic factor and activity-regulated cytoskeletal-associated protein mRNA expression". Neuroscience. 147 (3): 778–85. doi:10.1016/j.neuroscience.2007.04.045. PMID 17560041. S2CID 37184427.
  11. ↑ Marcos B, Aisa B, Ramírez MJ (March 2008). "Functional interaction between 5-HT(6) receptors and hypothalamic-pituitary-adrenal axis: cognitive implications". Neuropharmacology. 54 (4): 708–14. doi:10.1016/j.neuropharm.2007.11.019. PMID 18206183. S2CID 21417069.
  12. ↑ Loiseau F, Dekeyne A, Millan MJ (January 2008). "Pro-cognitive effects of 5-HT6 receptor antagonists in the social recognition procedure in rats: implication of the frontal cortex". Psychopharmacology. 196 (1): 93–104. doi:10.1007/s00213-007-0934-5. PMID 17922111. S2CID 35795618.
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