199864-87-4

Basic information

• Product Name: 4-(4-FLUORO-1-NAPHTHALENYL)-6-(1-METHYLETHYL)-2-PYRIMIDINAMINE HYDROCHLORIDE
• Synonyms: 4-(4-FLUORO-1-NAPHTHALENYL)-6-(1-METHYLETHYL)-2-PYRIMIDINAMINE HYDROCHLORIDE;RS 127445 HYDROCHLORIDE;2-Amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine;4-(4-Fluoro-1-naphthalenyl)-6-(1-methylethyl)-2-pyrimidinamine;MT500;RS127445;2-PyriMidinaMine, 4-(4-fluoro-1-naphthalenyl)-6-(1-Methylethyl)-;4-(4-Fluoronaphthalen-1-yl)-6-isopropylpyriMidin-2-aMine hydrochloride
• CAS NO: 199864-87-4
• Molecular Formula: C17H17ClFN3
• Molecular Weight: 317.8
• Product Categories: Inhibitors
• Mol File: 199864-87-4.mol
• Article Data: 0

Chemical Properties

• Boiling Point: 472.8°C at 760 mmHg
• Flash Point: 239.8°C
• Appearance: /
• Density: 1.213
• Vapor Pressure: 4.13E-09mmHg at 25°C
• Refractive Index: 1.637
• Storage Temp.: Desiccate at +4°C
• Solubility: ≥31.8 mg/mL in DMSO; insoluble in H2O; ≥33.15 mg/mL in EtOH
• CAS DataBase Reference: 4-(4-FLUORO-1-NAPHTHALENYL)-6-(1-METHYLETHYL)-2-PYRIMIDINAMINE HYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(4-FLUORO-1-NAPHTHALENYL)-6-(1-METHYLETHYL)-2-PYRIMIDINAMINE HYDROCHLORIDE(199864-87-4)
• EPA Substance Registry System: 4-(4-FLUORO-1-NAPHTHALENYL)-6-(1-METHYLETHYL)-2-PYRIMIDINAMINE HYDROCHLORIDE(199864-87-4)

Safety Data

• Hazardous Substances Data: 199864-87-4(Hazardous Substances Data)

Usage

Description

4-(4-FLUORO-1-NAPHTHALENYL)-6-(1-METHYLETHYL)-2-PYRIMIDINAMINE HYDROCHLORIDE, also known as RS 127445, is an orally bioavailable and potent antagonist of the serotonin (5-HT) receptor subtype 5-HT2B. It exhibits high selectivity for the 5-HT2B receptor over other 5-HT receptor subtypes, making it a valuable compound for various applications in the pharmaceutical and medical fields.

Uses

Used in Pharmaceutical Industry:
RS 127445 is used as a selective 5-HT2B receptor antagonist for its ability to modulate serotonin receptor activity. This makes it a potential candidate for the treatment of various conditions related to serotonin dysregulation.
Used in Gastrointestinal Applications:
In the gastrointestinal field, RS 127445 is used to reduce contraction of the rat isolated stomach fundus and lower intracellular increases in calcium induced by 5-HT. This suggests its potential use in treating gastrointestinal disorders related to serotonin receptor activity.
Used in Cardiovascular Applications:
RS 127445 is used to block the relaxation of isolated rat jugular veins induced by (±)-α-methyl-5-HT. This indicates its potential application in the treatment of cardiovascular conditions where serotonin receptor modulation is beneficial.
Used in Neurological Applications:
RS 127445 is used to reduce basal dopamine outflow in the nucleus accumbens of rats and decrease hyperlocomotion induced by cocaine or quinpirole. This suggests its potential use in the treatment of neurological disorders related to dopamine dysregulation, such as addiction or movement disorders.
Used in Preclinical Research:
RS 127445 is used in preclinical research to study the effects of 5-HT2B receptor antagonism on various physiological processes and to develop a better understanding of the role of serotonin in different conditions. This helps in the development of new therapeutic strategies and drugs targeting the serotonin system.

Biological Activity

High affinity 5-HT 2B receptor antagonist (pK i = 9.5). Displays 1000-fold selectivity for 5-HT 2B with good bioavailability.

in vitro

RS-127445 is a novel high affinity, selective 5-HT2B receptor antagonist devoid of detectable intrinsic activity. RS-127445 is found to have nM affinity and 1000 fold selectivity for the 5-HT2B receptor. RS-127445 is thus among the highest affinity, most selective 5- HT2B receptor ligands. RS-127445 potently blocks the 5-HT evoked increase in inositol phosphate formation and blocks the 5-HT evoked increases in intracellular calcium concentrations with a potency 1000 times greater than that of yohimbine.

in vivo

RS-127445 is readily absorbed with no obvious dose or route-dependent limitations and rapidly absorbed following both oral and intraperitoneal administration with peak plasma concentrations being achieved within 15 min of dosing. RS-127445 concentration in the plasma are achieved are proportional to the administered dose. RS-127445 administrated at dose of 5 mg/kg with approximately 60% of an intraperitoneal dose and 14% of the oral dose is bioavailable. RS-127445 concentration in the plasma is predicted to fully saturate accessible 5-HT2B receptors can be readily achieved and maintained in the rat. RS-127445 administered at 1 to 10 mg/kg with oral significantly inhibits visceral hypersensitivity up to 35 to 74% provoked by restraint stress. Oral RS-127445 produces a significant suppression of TNBS-induced visceral hypersensitivity (15 to 62% inhibition at 3 to 30 mg/ kg), although RS-127445 has no significant effect on the visceral nociceptive threshold of native rats. RS-127445 administrated orally with 1 to 30 mg/kg also dose -dependently reduce the restraint stress-induced defecation in native and TNBS-treated rats. . RS-127445 inhibits colonic motility and defecation.

references

[1] bonhaus d w, flippin l a, greenhouse r j, et al. rs‐127445: a selective, high affinity, orally bioavailable 5‐ht2b receptor antagonist[j]. british journal of pharmacology, 1999, 127(5): 1075-1082.

InChI:InChI=1/C17H16FN3/c1-10(2)15-9-16(21-17(19)20-15)13-7-8-14(18)12-6-4-3-5-11(12)13/h3-10H,1-2H3,(H2,19,20,21)