SB-271046

SB-271046

Identifiers
IUPAC name 5-chloro-N-(4-methoxy-3-piperazin-1-ylphenyl)-3-methyl-1-benzothiophene-2-sulfonamide
CAS Number	209481-20-9  Y[ ChemSpider ]
PubChem CID	5312149
IUPHAR/BPS	276
ChemSpider	4471579  Y
UNII	L3SK5KX24S
ChEMBL	ChEMBL431298  Y
CompTox Dashboard (EPA)	DTXSID301026006
Chemical and physical data
Formula	C20H22ClN3O3S2
Molar mass	451.98 g·mol−1
3D model (JSmol)	Interactive image
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
NY  (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]

Usages

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.