SB-271046

SB-271046

Systematic (IUPAC) name
5-chloro-N-(4-methoxy-3-piperazin-1-ylphenyl)-3-methyl-1-benzothiophene-2-sulfonamide
Identifiers
PubChem	CID 5312149
IUPHAR/BPS	276
ChemSpider	4471579
ChEMBL	CHEMBL431298
Chemical data
Formula	C20H22ClN3O3S2
Molar mass	451.989 g/mol
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 Key:LOCQRDBFWSXQQI-UHFFFAOYSA-N
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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; Jeffrey, PM; Joiner, GF; et al. (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; Garner, A; Gordon, L; et al. (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 (2000). "In vivo effects of the 5-HT6 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 (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.
5. Dawson, LA; Nguyen, HQ; Li, P (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 (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.
7. Foley, AG; Murphy, KJ; Hirst, WD; Gallagher, HC; Hagan, JJ; Upton, N; Walsh, FS; Regan, CM (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 (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 Jr, CR (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.
10. De Foubert, G; O'Neill, MJ; Zetterström, TS (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.
11. Marcos, B; Aisa, B; Ramírez, MJ (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.
12. Loiseau, F; Dekeyne, A; Millan, MJ (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.