ChemicalBook Product Catalog Biochemical Engineering Biochemical Reagents Agonist Inhibitors 1-[3-(4-Bromo-1-methyl-1H-pyrazol-5-yl)-4-methoxyphenyl]-3-(2,4-difluorophenyl)urea

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

Product Name1-[3-(4-Bromo-1-methyl-1H-pyrazol-5-yl)-4-methoxyphenyl]-3-(2,4-difluorophenyl)urea
CAS839713-36-9
MFC18H15BrF2N4O2
MW437.24
EINECS
MOL File839713-36-9.mol

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

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

Benzenamine, 3-(4-bromo-1-methyl-1H-pyrazol-5-yl)-4-methoxy-

720702-45-4

59025-55-7

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

839713-36-9

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

Each compound is tested in a minimum of five rats by oral gavage with administration occurring in the middle of the inactive period, 6 h after light onset. The delta power during non-REM sleep (NREMS) is significantly different between all the analogues tested and the vehicle control. Nelotanserin (Compound 39) produces significant increases in delta power that persist for the first 4 h following dosing. Significant differences are found, however, in NREMS bout length. Nelotanserin significantly increases NREMS bout length during the first hour following dosing, and 3 does so during the second hour. In conjunction with this increased NREM bout duration, the number of NREM bouts decrease during the first hour for Nelotanserin (p<0.01) as well as for compound 15 (p<0.05)^[2].

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

Preparation Products And Raw materials

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