BRL 54443 Chemical Properties

Boiling point:

431.5±45.0 °C(Predicted)

Density 

1.196

storage temp. 

Inert atmosphere,2-8°C

solubility 

H₂O: 50 mg/mL

form 

solid

pka

10.08±0.40(Predicted)

color 

white

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36

WGK Germany 

3

BRL 54443 Usage And Synthesis

Uses

BRL-53443 is a potent 5-HT and dopamine receptor agonist. Neuroresearch product.

Definition

ChEBI: 3-(1-methyl-4-piperidinyl)-1H-indol-5-ol is a member of hydroxyindoles.

Biological Activity

A potent 5-ht 1E/1F receptor agonist (pEC 50 values are 8.5 and 8.6 respectively). Displays > 30-fold selectivity over other 5-HT and dopamine receptors (pK i values are 8.7. 8.9, 7.2, 6.9, 7.2, 5.9, 7.0, 6.5, < 6, < 6, 6.3 and 6.2 for human 5-HT 1E , 1F , 1A , 1B , 1D , 2A , 2B , 2C , 4 , 7 , D 2 and D 3 receptors respectively). Induces 5-HT 2A receptor-mediated mouse aortic contraction in vitro (pEC 50 = 6.52). Active in vivo .

Synthesis

1. 5-methoxy-3-(1-methyl-4-piperidinyl)indole (2.30 g, 9.4 mmol) was dissolved in 30 mL of 30% hydrobromic acid acetic acid solution. 2. The reaction mixture was placed in a sealed tube and heated at 105 °C for 72 hours. 3. Upon completion of the reaction, it was cooled to room temperature and concentrated under vacuum to remove the solvent. 4. the concentrated residue was dissolved in water and the pH was adjusted to about 13 with 5N aqueous sodium hydroxide solution. 5. Vacuum concentration is performed again and the residue is purified by silica gel column chromatography using a methanol/dichloromethane solution of 20% 2M ammonia as eluent. 6. The target fraction was collected, concentrated under vacuum and the residue was dissolved in methanol. 7. Dowex? 50X8-200 ion exchange resin (25 g) was added and stirred overnight at room temperature. 8. Filter the mixture and wash the resin sequentially with water and methanol. 9. Mix the resin with 100 mL of 2 M ammonia in methanol, stir overnight and filter. 10. The filtrate was concentrated in vacuum to give 1.84 g (85% yield) of 3-(1-methylpiperidin-4-yl)-1H-indol-5-ol, which could be used in subsequent steps without further purification. 11. Elemental analysis results: For C13H17N3O, calculated values: C, 67.53; H, 7.36; N, 18.18. measured values: C, 67.24; H, 7.37; N, 18.38.

in vivo

IC 50

5-HT_1E Receptor: 1.1 nM (Ki); 5-HT_1F Receptor: 0.7 nM (Ki); 5-HT_1A Receptor: 63 nM (Ki); 5-HT_1B Receptor: 126 nM (Ki); 5-HT_1D Receptor: 63 nM (Ki); 5-HT_2A Receptor: 1259 nM (Ki); 5-HT_2B Receptor: 100 nM (Ki); 5-HT_2C Receptor: 316 nM (Ki); 5-HT₆ Receptor: >10,000 nM (Ki); 5-HT₇ Receptor: >10,000 nM (Ki)

storage

+4°C (desiccate)

References

1. a.m. brown, k. avenell, t j. young et al. brl 54443, a potent agonist with selectivity for human cloned 5-ht1e and 5-ht1f receptors. 1998. br.j.pharmacol. 123 233p.2. s. lightowler, t. stean, n. upton et al. effect of brl 54443 (3-(1-methylpiperidin-4-yl)-1h-indol-5-ol), a 5-ht1e/1f receptor agonist, on general behaviour and maximal electroshock seizure threshold in the rat. 1998. br.j.pharmacol. 123 237p.3. mckune cm, watts sw. characterization of the serotonin receptor mediating contraction in the mouse thoracic aorta and signal pathway coupling. j pharmacol exp ther. 2001 apr;297(1):88-95.4. janssen p, tack j, sifrim d et al. influence of 5-ht1 receptor agonists on feline stomach relaxation. eur j pharmacol. 2004 may 25;492(2-3):259-67.

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