| Identification | Back Directory | [Name]
BRL 54443 | [CAS]
57477-39-1 | [Synonyms]
CS-1781
BRL 54443
BRL 54443 HCl
BRL 54443, >=98%
BRL-54443;BRL54443
BRL 54443 USP/EP/BP
BRL54443;BRL 54443;BRL-54443
3-(1-methylpiperidin-4-yl)-1H-indol-5-ol
3-(1-Methyl-4-piperidinyl)-1H-indol-5-ol
1H-Indol-5-ol, 3-(1-Methyl-4-piperidinyl)-
5-HYDROXY-3-(1-METHYLPIPERIDIN-4-YL)-1H-INDOLE
3-(1-Methyl-4-piperidinyl)-1H-indol-5-ol BRL 54443 | [Molecular Formula]
C14H18N2O | [MDL Number]
MFCD01861184 | [MOL File]
57477-39-1.mol | [Molecular Weight]
230.31 |
| Chemical Properties | Back Directory | [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
|
| Hazard Information | Back Directory | [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]
Reduction of flinching was considered as antinociception. Ipsilateral, but not contralateral, peripheral administration of BRL54443 (5-HT(1E/1F); 3-300 microg/paw) significantly reduced formalin-induced flinching in rats[3].
| [IC 50]
5-HT1E Receptor: 1.1 nM (Ki); 5-HT1F Receptor: 0.7 nM (Ki); 5-HT1A Receptor: 63 nM (Ki); 5-HT1B Receptor: 126 nM (Ki); 5-HT1D Receptor: 63 nM (Ki); 5-HT2A Receptor: 1259 nM (Ki); 5-HT2B Receptor: 100 nM (Ki); 5-HT2C Receptor: 316 nM (Ki); 5-HT6 Receptor: >10,000 nM (Ki); 5-HT7 Receptor: >10,000 nM (Ki) | [storage]
Store at -20°C | [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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