1228690-19-4

Basic information

• Product Name: (R)-2-(4'-(4-(((1-(2-chlorophenyl)ethoxy)carbonyl)aMino)-3-Methylisoxazol-5-yl)-[1,1'-biphenyl]-4-yl)acetic acid
• Synonyms: (R)-2-(4'-(4-(((1-(2-chlorophenyl)ethoxy)carbonyl)aMino)-3-Methylisoxazol-5-yl)-[1,1'-biphenyl]-4-yl)acetic acid;AM 966;4'-[4-[[[(1R)-1-(2-Chlorophenyl)ethoxy]carbonyl]amino]-3-methyl-5-isoxazolyl]-[1,1'-biphenyl]-4-acetic acid
• CAS NO: 1228690-19-4
• Molecular Formula: C₂₇H₂₃ClN₂O₅
• Molecular Weight: 490.93492
• Mol File: 1228690-19-4.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 659.4±55.0 °C(Predicted)
• Appearance: /
• Density: 1.330±0.06 g/cm3 (20 ºC 760 Torr)
• Solubility: ≥24.55 mg/mL in DMSO; insoluble in H2O; ≥2.24 mg/mL in EtOH with gentle warming and ultrasonic
• PKA: 4.21±0.10(Predicted)
• CAS DataBase Reference: (R)-2-(4'-(4-(((1-(2-chlorophenyl)ethoxy)carbonyl)aMino)-3-Methylisoxazol-5-yl)-[1,1'-biphenyl]-4-yl)acetic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-2-(4'-(4-(((1-(2-chlorophenyl)ethoxy)carbonyl)aMino)-3-Methylisoxazol-5-yl)-[1,1'-biphenyl]-4-yl)acetic acid(1228690-19-4)
• EPA Substance Registry System: (R)-2-(4'-(4-(((1-(2-chlorophenyl)ethoxy)carbonyl)aMino)-3-Methylisoxazol-5-yl)-[1,1'-biphenyl]-4-yl)acetic acid(1228690-19-4)

Safety Data

• Hazardous Substances Data: 1228690-19-4(Hazardous Substances Data)

Usage

Biological Activity

am966 is a selective, potent and orally bioavailable antagonist of lysophosphatidic acid type 1 receptor (lpa1) with ic50 values of 17 and 19 nm for human or mouse lpa1, respectively [1]. relative to lpa2, 3, 4, 5 receptors, am966 shows 10-fold and 100-fold more selective in mouse and human cell lines for lpa1, respectively [1].

in vitro

am966 shows to inhibit lpa-induced chemotaxis in imr-90 human lung fibroblasts, a2058 human melanoma cells and cho cells expressing lpa1 receptors [1].

in vivo

am966 has been demonstrated to reduce total balf cells, ldh activity, balf collagen and total tgfβ concentrations in bleomycin-induced mice. moreover, am966 has been reported to block lung fibrosis, reduce lung inflammation and maintain body weight in mice induced by bleomycin [1].

references

[1] swaney js1, chapman c, correa ld, stebbins kj, bundey ra, prodanovich pc, fagan p, baccei cs, santini am, hutchinson jh, seiders tj,parr ta, prasit p, evans jf, lorrain ds. a novel, orally active lpa(1) receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. br j pharmacol. 2010 aug;160(7):1699-713.

Upstream product

• 1228690-21-8 (4'-{4-[(R)-1-(2-Chloro-phenyl)-ethoxycarbonylamino]-3-methyl-isoxazol-5-yl}-biphenyl-4-yl)-acetic acid ethyl ester 

Relevant articles and documents

ANTAGONISTS OF LYSOPHOSPHATIDIC ACID RECEPTORS

Described herein are compounds that are antagonists of lysophosphatidic receptor(s). Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such antagonists, alone and in combination with other compounds, for treating LPA-dependent or LPA-mediated conditions or diseases.