2-(2,4-difluorophenyl)-6-[1-(2,6-difluorophenyl)carbamoylamino]pyridine-3-carboxamide

• ChemBase ID: 73079
• Molecular Formular: C19H12F4N4O2
• Molecular Mass: 404.3177928
• Monoisotopic Mass: 404.08963852
• SMILES: c1cc(c(c(c1)F)N(c1nc(c(cc1)C(=O)N)c1c(cc(cc1)F)F)C(=O)N)F
• Canonical SMILES: Fc1ccc(c(c1)F)c1nc(ccc1C(=O)N)N(c1c(F)cccc1F)C(=O)N
• InChI: InChI=1S/C19H12F4N4O2/c20-9-4-5-10(14(23)8-9)16-11(18(24)28)6-7-15(26-16)27(19(25)29)17-12(21)2-1-3-13(17)22/h1-8H,(H2,24,28)(H2,25,29)
• InChIKey: FYSRKRZDBHOFAY-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-(2,4-difluorophenyl)-6-[1-(2,6-difluorophenyl)carbamoylamino]pyridine-3-carboxamide
• IUPAC Traditional name: 2-(2,4-difluorophenyl)-6-[1-(2,6-difluorophenyl)carbamoylamino]pyridine-3-carboxamide
• Synonyms: 6-[(Aminocarbonyl)(2,6-difluorophenyl)amino]-2-(2,4-difluorophenyl)-3-pyridinecarboxamide; VX-702

Database IDs

• CAS Number: 745833-23-2; 479543-46-9
• PubChem SID: 162037999
• PubChem CID: 10341154

CALCULATED PROPERTIES

• Acid pKa: 13.950963
• H Acceptors: 3
• H Donor: 2
• LogD (pH = 5.5): 3.230744
• LogD (pH = 7.4): 3.2307441
• Log P: 3.230744
• Molar Refractivity: 95.356 cm^3
• Polarizability: 35.85767 Å^3
• Polar Surface Area: 102.31 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: DMSO

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: p38 MAPK

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S6005

Research Area

• Description: Inflammation

Biological Activity

• Description: VX-702 is a highly selective inhibitor of p38 MAPKα with IC50 of 4-20 nM.
• Targets: p38 MAPKα
• IC50: 4 - 20 nM ^[1]
• In Vitro: Pre-incubation of platelets with VX-702 (1 μM) completely or partially inhibits p38 activation (IC50 4 to 20 nM) induced by platelet agonists including thrombin, SFLLRN, AYPGKF, U46619 and collagen. VX-702 shows no effect on platelet aggregation induced by any of the p38 MAPK agonists in the presence or absence of anti-platelet therapies. ^[1] VX-702 inhibits the production of IL-6, IL-1β and TNFα (IC50 = 59, 122 and 99 ng/mL, respectively) in a dose-dependent manner. ^[2]
• In Vivo: The half-life of VX-702 is 16 to 20 hours, with a median clearance of 3.75 L/h and a volume of distribution of 73 L/kg. Both AUC and C_max values are dose proportional for VX-702, which is predominantly cleared renally. ^[2] VX-702 (at a dose of 0.1 mg/kg twice daily) has an equivalent effect as that of methotrexate (0.1 mg/kg). In addition, VX-702 (5 mg/kg twice daily) also has an equivalent effect as prednisolone (10 mg/kg once daily), as measured by percentage inhibition of wrist joint erosion and inflammation score. ^[3] VX-702 selectively inhibits activation of p38 MAPK after ischemia with no effects on ERKs and JNKs. The MI/AAR ratio is significantly reduced in the 50 mg/kg group compared with the 5 mg/kg and vehicle groups.^[4]
• Clinical Trials: VX-702 is currently in Phase II clinical trial in patients with rheumatoid arthritis.
• Features: VX-702 is a highly selective, orally active inhibitor of p38 MAPK

Protocol

• Protocol: Animal Study ^[3]
• Animal Models: Mouse with collagen-induced arthritis
• Doses: ≤10 mg/kg
• Administration: Administered via p.o.

References

• References: [1] Kuliopulos A, et al. Thromb Haemost, 2004, 92(6), 1387-1393.
• References: [2] Braddock M, IDDB Meeting Report, 2005, March 14-15.
• References: [3] Gill A, IDDB Meeing Report, 2002, March 06-08.
• References: [4] Bhattacharya K, et al. Circulation, 2003, 108(17), 882.

Toronto Research Chemicals - V900250

VX-702 is a p38 mitogen-activated protein kinase (MAPK) inhibitor. VX-702 had no effect on platelet aggregation induced by any of the p38 MAPK agonists. VX-702 has potential use in the treatment of inflammation, rheumatoid arthritis and cardiovascular dis

REFERENCES

• Kuliopulos A, et al. Thromb Haemost, 2004, 92(6), 1387-1393.
• Braddock M, IDDB Meeting Report, 2005, March 14-15.
• Gill A, IDDB Meeing Report, 2002, March 06-08.
• Bhattacharya K, et al. Circulation, 2003, 108(17), 882.
• Kuliopulos, A. et al.: Thromb. Haemost., 92, 1387 (2004)
• Ding, C.: Curr. Opin. Invest. Drug, 7, 1020 (2004)
• Cohen, S. et al.: Curr. Opin. Rheumatol., 22, 330 (2004)