SB-247853

SB-247853
Clinical data
Other namesSB247853
Routes of
administration		Unknown/unspecified (but orally active)[1][2][3]
Drug classSerotonin 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
FormulaC22H19F3N4O2
Molar mass428.415 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. ^ a b c d "SB 247853". AdisInsight. 17 March 2005. Retrieved 26 January 2026.
  2. ^ a b c d e f g Bromidge SM, Davies S, Duckworth DM, Forbes IT, Jones GE, Jones J, et al. (August 2000). "1-[2-[(Heteroarylmethoxy)aryl]carbamoyl]indolines are selective and orally active 5-HT2C receptor inverse agonists". Bioorganic & Medicinal Chemistry Letters. 10 (16): 1867–1870. doi:10.1016/s0960-894x(00)00365-6. PMID 10969987.
  3. ^ a b c d e Theis J, Mceniery C, Maltby K, Overend P, Price J, Smith T, et al. (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.
  4. ^ a b c "Delving into the Latest Updates on SB-247853 with Synapse". Synapse. 24 January 2026. Retrieved 26 January 2026.
  5. ^ a b c d e Lee J, Jung ME, Lee J (November 2010). "5-HT2C receptor modulators: a patent survey". Expert Opinion on Therapeutic Patents. 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". Current Topics in Medicinal Chemistry. 6 (18): 1927–1970. doi:10.2174/156802606778522168. PMID 17017967.
  7. ^ Goodacre CJ, Bromidge SM, Clapham D, King FD, Lovell PJ, Allen M, et al. (November 2005). "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. doi:10.1016/j.bmcl.2005.08.004. PMID 16168649.
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