SB-247853

Last updated
SB-247853
SB-247853.svg
Clinical data
Other namesSB247853
Routes of
administration 		Unknown/unspecified (but orally active) [1] [2] [3]
Drug class Serotonin 5-HT2C receptor inverse agonist
ATC code
  • None
Identifiers
  • 5-methyl-N-[6-(pyridin-2-ylmethoxy)-3-pyridinyl]-6-(trifluoromethyl)-2,3-dihydroindole-1-carboxamide
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
Formula C22H19F3N4O2
Molar mass 428.415 g·mol−1
3D model (JSmol)
  • CC1=CC2=C(C=C1C(F)(F)F)N(CC2)C(=O)NC3=CN=C(C=C3)OCC4=CC=CC=N4
  • InChI=1S/C22H19F3N4O2/c1-14-10-15-7-9-29(19(15)11-18(14)22(23,24)25)21(30)28-16-5-6-20(27-12-16)31-13-17-4-2-3-8-26-17/h2-6,8,10-12H,7,9,13H2,1H3,(H,28,30)
  • Key:KLAHZRONIHBPPB-UHFFFAOYSA-N

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] [4] [5] [6] [2] [7]

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. [5] [2] 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. [5] [2] The drug reverses the hypolocomotion induced by the serotonin 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) in rodents. [5] [2] It is orally active. [2] [3]

The drug produced orthostatic intolerance in healthy human volunteers during the first dose-escalation clinical study. [3] Subsequently, it was found to cause substantial hypotension (low blood pressure) and presyncope (pre-fainting symptoms) in the tilt table test. [3] It was concluded based on these findings that the serotonin 5-HT2C receptor is involved in regulating the cardiovascular system. [3]

SB-247853 was first described in the scientific literature by 2000. [2] It was developed by GlaxoSmithKline. [1] [4] [5] The drug reached phase 1 clinical trials prior to the discontinuation of its development in 2005. [1] [4]

See also

References

  1. 1 2 3 4 "SB 247853". AdisInsight. 17 March 2005. Retrieved 26 January 2026.
  2. 1 2 3 4 5 6 7 Bromidge SM, Davies S, Duckworth DM, Forbes IT, Jones GE, Jones J, King FD, Blackburn TP, Holland V, Kennett GA, Lightowler S, Middlemiss DN, Riley GJ, Trail B, Wood MD (August 2000). "1-[2-[(Heteroarylmethoxy)aryl]carbamoyl]indolines are selective and orally active 5-HT2C receptor inverse agonists". Bioorg Med Chem Lett. 10 (16): 1867–1870. doi:10.1016/s0960-894x(00)00365-6. PMID   10969987.
  3. 1 2 3 4 5 Theis, J; Mceniery, C; Maltby, K; Overend, P; Price, J; Smith, T; Ostenfeld, T; Wilkinson, I; Brown, J (2005). "Orthostatic intolerance induced by the 5-HT2C antagonist SB-247853 in healthy volunteers during head-up tilting". Clinical Pharmacology & Therapeutics. 77 (2): P66. doi:10.1016/j.clpt.2004.12.143 . Retrieved 26 January 2026.
  4. 1 2 3 "Delving into the Latest Updates on SB-247853 with Synapse". Synapse. 24 January 2026. Retrieved 26 January 2026.
  5. 1 2 3 4 5 Lee J, Jung ME, Lee J (November 2010). "5-HT2C receptor modulators: a patent survey". Expert Opin Ther Pat. 20 (11): 1429–1455. 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.
  6. ↑ Lacivita E, Leopoldo M (2006). "Selective agents for serotonin2C (5-HT2C) receptor". Curr Top Med Chem. 6 (18): 1927–1970. doi:10.2174/156802606778522168. PMID   17017967.
  7. ↑ Goodacre CJ, Bromidge SM, Clapham D, King FD, Lovell PJ, Allen M, Campbell LP, Holland V, Riley GJ, Starr KR, Trail BK, Wood MD (November 2005). "A series of bisaryl imidazolidin-2-ones has shown to be selective and orally active 5-HT2C receptor antagonists". Bioorg Med Chem Lett. 15 (22): 4989–93. doi:10.1016/j.bmcl.2005.08.004. PMID   16168649.
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