1-[3-(4-Bromo-1-methyl-1H-pyrazol-5-yl)-4-methoxyphenyl]-3-(2,4-difluorophenyl)urea Chemical Properties

Boiling point:

425.9±45.0 °C(Predicted)

Density 

1.55±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMSO:32.0(Max Conc. mg/mL);73.2(Max Conc. mM)

form 

Solid

pka

12.29±0.70(Predicted)

color 

White to off-white

1-[3-(4-Bromo-1-methyl-1H-pyrazol-5-yl)-4-methoxyphenyl]-3-(2,4-difluorophenyl)urea Usage And Synthesis

Uses

Nelotanserin is a potent selective 5-HT2A inverse agonist, nelotanserin has low nanomolar potency on the 5-HT2A receptor with at least 30- and 5000-fold selectivity compared with 5-HT2C and 5-HT2B receptors.

Definition

ChEBI: Nelotanserin is a member of pyrazoles and a ring assembly.

Synthesis

3-(4-bromo-1-methyl-1H-pyrazol-5-yl)-4-methoxyaniline (16.7 kg) was dissolved in acetonitrile (78.6 kg) in a 200 liter glass jacketed reactor under nitrogen protection. Top stirring was turned on and the internal temperature was controlled within the specified range. Subsequently, 2,4-difluorophenyl isocyanate was slowly added to keep the temperature of the reaction system stable. Upon completion of the reaction, the target product 1-(3-(4-bromo-1-methyl-1H-pyrazol-5-yl)-4-methoxyphenyl)-3-(2,4-difluorophenyl)urea was isolated and purified by appropriate post-treatment steps.

in vivo

IC 50

5-HT_2A Receptor: 1.7 nM (IC₅₀); 5-HT_2C Receptor: 79 nM (IC₅₀); 5-HT_2B Receptor: 791 nM (IC₅₀)

References

[1] Patent: US2016/67216, 2016, A1. Location in patent: Paragraph 0834; 0835
[2] Patent: WO2010/62321, 2010, A1. Location in patent: Page/Page column 75-76
[3] Journal of Medicinal Chemistry, 2010, vol. 53, # 5, p. 1923 - 1936
[4] Patent: WO2006/81335, 2006, A2. Location in patent: Page/Page column 34-37