Chemistry:SB-247853

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SB-247853 is a highly selective serotonin 5-HT2C receptor inverse agonist which was under development for the treatment of major depressive disorder but was never marketed.[1][2][3][4][5][6]

Its affinities (Ki) were found to be 0.50 nM for the serotonin 5-HT2C receptor, 60 nM for the serotonin 5-HT2B receptor, and 1,300 nM for the serotonin 5-HT2A receptor.[3][5] Hence, it shows 120-fold selectivity for the serotonin 5-HT2C receptor over the serotonin 5-HT2B receptor and 2,600-fold selectivity for the serotonin 5-HT2C receptor over the serotonin 5-HT2A receptor.[3][5] The drug reverses the hypolocomotion induced by the serotonin 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) in rodents.[3][5] It is orally active.[5][7]

The drug produced orthostatic intolerance in healthy human volunteers during the first dose-escalation clinical study.[7] Subsequently, it was found to cause substantial hypotension (low blood pressure) and presyncope (pre-fainting symptoms) in the tilt table test.[7] It was concluded based on these findings that the serotonin 5-HT2C receptor is involved in regulating the cardiovascular system.[7]

SB-247853 was first described in the scientific literature by 2000.[5] It was developed by GlaxoSmithKline.[1][2][3] The drug reached phase 1 clinical trials prior to the discontinuation of its development in 2005.[1][2]

See also

References

  1. ↑ 1.0 1.1 1.2 "SB 247853". 17 March 2005. https://adisinsight.springer.com/drugs/800016366. 
  2. ↑ 2.0 2.1 2.2 "Delving into the Latest Updates on SB-247853 with Synapse". 24 January 2026. https://synapse.patsnap.com/drug/a8fc9e7aff1d4b8995a807dec298d9ed. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 "5-HT2C receptor modulators: a patent survey". Expert Opinion on Therapeutic Patents 20 (11): 1429–1455. November 2010. doi:10.1517/13543776.2010.518956. PMID 20849206. "GlaxoSmithKline had also investigated SB-247853 (77, Figure 5), an orally active 5-HT2C receptor inverse agonist, for the potential treatment of CNS disorders such as anxiety and depression. However, no development has been reported since 2000. SB-247853 (77) has a pKi value of 9.3 at 5-HT2C receptor and 1300- and 60-fold selectivity over 5-HT2A and 5-HT2B, respectively. It showed an ID50 value for the inhibition of m-CPP induced hyperlocomotion in rat of 1 mg/kg p.o. Although compound 77 has good overall pharmacological profiles, it has also poor solubility (0.014 mg/ml in 0.1 N HCl for the monohydrochloride salt) [162,163]. [...] Through a series of structural optimization process, GlaxoSmithKline developed the selective 5-HT2C inverse agonist SB-243213 (76) and SB-247853 (77), both of which progressed to clinical developments. These compounds appear to have good target product profiles except for their relatively poor solubility.". 
  4. ↑ "Selective agents for serotonin2C (5-HT2C) receptor". Current Topics in Medicinal Chemistry 6 (18): 1927–1970. 2006. doi:10.2174/156802606778522168. PMID 17017967. 
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 "1-[2-[(Heteroarylmethoxy)aryl]carbamoyl]indolines are selective and orally active 5-HT2C receptor inverse agonists". Bioorganic & Medicinal Chemistry Letters 10 (16): 1867–1870. August 2000. doi:10.1016/s0960-894x(00)00365-6. PMID 10969987. 
  6. ↑ "A series of bisaryl imidazolidin-2-ones has shown to be selective and orally active 5-HT2C receptor antagonists". Bioorganic & Medicinal Chemistry Letters 15 (22): 4989–4993. November 2005. doi:10.1016/j.bmcl.2005.08.004. PMID 16168649. 
  7. ↑ 7.0 7.1 7.2 7.3 "Orthostatic intolerance induced by the 5-HT2C antagonist SB-247853 in healthy volunteers during head-up tilting". Clinical Pharmacology & Therapeutics 77 (2): P66. 2005. doi:10.1016/j.clpt.2004.12.143. 



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