209410-46-8

Basic information

• Product Name: VX-745
• Synonyms: 5-(2,6-Dichlorophenyl)-2-(2,4-difluorophenylthio)-6H-pyrimido[1,6-b]pyridazin-6-one;5-(2,6-Dichlorophenyl)-2-(2,4-difluorophenyl)sulfanylpyridazino[6,1-f]pyrimidin-6-one;5-(2,6-Dichlorophenyl)-2-(2,4-difluorophenylsulfanyl)-6H-pyriMido[3,4-b]pyridazin-6-one;VX-745(VX 745);5-(2,6-Dichloro-phenyl)-2-(2,4-difluoro-phenylsulfanyl)-1,7,8a-triaza-naphthalen-6-one;5-(2,6-Dichlorophenyl)-2-(2,4-difluorophenyl)sulfanylpyridazino[6,1-f]pyrimidin-6-one VX-745;VX-745 5-(2,6-Dichlorophenyl)-2-((2,4-difluorophenyl)thio)-6H-pyrimido[1,6-b]pyridazin-6-one;VX-745, >=96%
• CAS NO: 209410-46-8
• Molecular Formula: C19H9Cl2F2N3OS
• Molecular Weight: 436.26
• Product Categories: Aromatics;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;MAPK
• Mol File: 209410-46-8.mol
• Article Data: 0

Chemical Properties

• Melting Point: 261-264 °C
• Boiling Point: 578.9 °C at 760 mmHg
• Flash Point: 303.9 °C
• Appearance: /
• Density: 1.55g/cm³
• Vapor Pressure: 2.13E-13mmHg at 25°C
• Refractive Index: 1.692
• Storage Temp.: Store at -20°C
• Solubility: ≥21.8 mg/mL in DMSO; insoluble in H2O; ≥2.1 mg/mL in EtOH with gentle warming and ultrasonic
• PKA: -0.97±0.40(Predicted)
• CAS DataBase Reference: VX-745(CAS DataBase Reference)
• NIST Chemistry Reference: VX-745(209410-46-8)
• EPA Substance Registry System: VX-745(209410-46-8)

Safety Data

• Hazardous Substances Data: 209410-46-8(Hazardous Substances Data)

Usage

Description

VX-745 is an inhibitor of p38α MAPK (IC50 = 9 nM). It is selective for p38α over p38β MAPK (Ki = 220 nM) as well as ERK, JNK, and a panel of 50 kinases when used at a concentration of 2 μM. VX-745 inhibits LPS-induced production of IL-1β and TNF-α in isolated human peripheral blood mononuclear cells (PBMCs; IC50s = 45 and 51 nM, respectively). It reduces disease severity in a type II collagen-induced mouse model of arthritis when administered at a dose of 10 mg/kg.

Chemical Properties

Pale Yellow Solid

Uses

Different sources of media describe the Uses of 209410-46-8 differently. You can refer to the following data:
1. VX 745 is a potent and selective inhibitor of p38α mitogen-activated protein (MAP) kinase. VX 745 is a potential anti-inflammatory agents. Studies suggest that VX 745 may be useful in the treatment of Werner syndrome.
2. VX 745 is a potent and selective inhibitor of p38α mitogen-activated protein (MAP) kinase. VX 745 is a potential anti-inflammatory agents. Studies suggest that VX 745 may be useful in the treatment of Werner syndrome.

Definition

ChEBI: A member of the class of pyrimidopyridazines that is 6H-pyrimido[1,6-b]pyridazin-6-one substituted at positions 2 and 5 by (2,4-difluorophenyl)sulfanyl and 2,6-dichlorophenyl groups respectively

Biochem/physiol Actions

VX-745 is a selective blood-brain barrier penetrant inhibitor of p38 MAPKα. VX-745 showed 20-fold selectivity for p38α over p38β and a Ki value of 220 nM. VX-745 has been shown to reduce inflammation in an arthritic (AIA) mouse model and to improve performance in aged rats.

references

[1]. bagley, m.c., et al., microwave-assisted ullmann c-s bond formation: synthesis of the p38alpha mapk clinical candidate vx-745. j org chem, 2009. 74(21): p. 8336-42.[2]. dent, p., et al., mapk pathways in radiation responses. oncogene, 2003. 22(37): p. 5885-96.[3]. dominguez, c., d.a. powers, and n. tamayo, p38 map kinase inhibitors: many are made, but few are chosen. curr opin drug discov devel, 2005. 8(4): p. 421-30.[4]. duffy, j.p., et al., the discovery of vx-745: a novel and selective p38alpha kinase inhibitor. acs med chem lett, 2011. 2(10): p. 758-63.[5]. bagley, m.c., et al., gram-scale synthesis of the p38alpha mapk-inhibitor vx-745 for preclinical studies into werner syndrome. future med chem, 2010. 2(9): p. 1417-27.

InChI:InChI=1/C19H9Cl2F2N3OS/c20-11-2-1-3-12(21)17(11)18-14-5-7-16(25-26(14)9-24-19(18)27)28-15-6-4-10(22)8-13(15)23/h1-9H