Urea, N-[5-chloro-2-[2-[(2R)-4-[(4-fluorophenyl)Methyl]-2-Methyl-1-piperazinyl]-2-oxoethoxy]phenyl]- Property

Boiling point:

593.5±50.0 °C(Predicted)

Density 

1.346±0.06 g/cm3(Predicted)

storage temp. 

Inert atmosphere,2-8°C

solubility 

DMSO: ≥25mg/mL

pka

13.66±0.70(Predicted)

form 

White powder

color 

white to tan

Safety

Hazard Codes 

Xn,N

Risk Statements 

22-50

Safety Statements 

61

WGK Germany 

3

HS Code 

2933.59.8000

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H312Harmful in contact with skin

H315Causes skin irritation

H319Causes serious eye irritation

H332Harmful if inhaled

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P330Rinse mouth.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

P362Take off contaminated clothing and wash before reuse.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P405Store locked up.

P501Dispose of contents/container to..…

Urea, N-[5-chloro-2-[2-[(2R)-4-[(4-fluorophenyl)Methyl]-2-Methyl-1-piperazinyl]-2-oxoethoxy]phenyl]- Chemical Properties,Usage,Production

Description

The CC chemokine receptor-1 (CCR1), whose ligands include macrophage inflammatory protein-1α (MIP-1α), RANTES, and monocyte chemotactic protein-3 (MCP-3), has a central role in leukocyte trafficking and is highly expressed in certain autoimmune diseases. BX 471 is a nonpeptide CCR1 antagonist that has been shown to displace MIP-1α, RANTES, and MCP-3 with K_i values of 1, 2.8, and 5.5 nM, respectively. It demonstrates >10,000-fold selectivity for CCR1 over 28 additional G protein-coupled receptors, including related chemokine receptors. In a rat experimental allergic encephalomyelitis model of multiple sclerosis, BX 471 at 50 mg/kg was shown to significantly reduce the severity of the disease. BX 471 also decreases the inflammatory response during sepsis, blocks migration of monocytes isolated from rheumatoid arthritis patients, and prevents macrophage and T-cell recruitment in a mouse model of lupus nephritis.

Uses

BX471 has been used in chemotaxis assay to study the responses of HEK293 cells expressing human C-C motif chemokine receptor 1 (CCR1) to CC motif ligand 3 (CCL3)-induced cell migration. It has also been used as a CCR1 inhibitor to assess the effects of CCR1 on the migration and epithelial-mesenchymal transition (EMT).

Biochem/physiol Actions

BX471 blocks CCR1 and downregulates the mRNA expression of ICAM-1, P-selectin and E-selectin. It decreases the inflammatory responses in sepsis, prevents monocyte recruitment in inflammation sites in rheumatoid arthritis patients and inhibits interstitial leukocyte recruitment and fibrosis in mouse model of lupus nephritis.

in vitro

competition binding studies revealed that bx 471 was able to displace the ccr1 ligands macrophage inflammatory protein-1a, rantes, and monocyte chemotactic protein-3 with high affinity. bx 471 was a potent functional antagonist based on its ability to inhibit plenty of ccr1-mediated effects. bx 471 also demonstrated a greater than 10,000-fold selectivity for ccr1 compared with 28 g-protein-coupled receptors [1].

in vivo

pharmacokinetic studies demonstrated that bx 471 was orally active with a 60% bioavailability in dogs. furthermore, in a rat experimental allergic encephalomyelitis model of multiple sclerosis, bx 471 effectively reduces disease [1].

storage

Store at +4°C

References

[1] liang m, mallari c, rosser m, ng hp, may k, monahan s, bauman jg, islam i, ghannam a, buckman b, shaw k, wei gp, xu w, zhao z, ho e, shen j, oanh h, subramanyam b, vergona r, taub d, dunning l, harvey s, snider rm, hesselgesser j, morrissey mm, perez hd. identification and characterization of a potent, selective, and orally active antagonist of the cc chemokine receptor-1. j biol chem. 2000 jun 23;275(25):19000-8.