N-{3-[(4-chloro-2-fluorophenyl)methyl]-2-methyl-8-(morpholin-4-ylmethyl)imidazo[1,2-b]pyridazin-6-yl}-3-methyl-1H-pyrazol-5-amine

• ChemBase ID: 72876
• Molecular Formular: C23H25ClFN7O
• Molecular Mass: 469.9423032
• Monoisotopic Mass: 469.17931436
• SMILES: c1c(nn2c(c1CN1CCOCC1)nc(c2Cc1ccc(cc1F)Cl)C)Nc1[nH]nc(c1)C
• Canonical SMILES: Clc1ccc(c(c1)F)Cc1c(C)nc2n1nc(Nc1[nH]nc(c1)C)cc2CN1CCOCC1
• InChI: InChI=1S/C23H25ClFN7O/c1-14-9-21(29-28-14)27-22-11-17(13-31-5-7-33-8-6-31)23-26-15(2)20(32(23)30-22)10-16-3-4-18(24)12-19(16)25/h3-4,9,11-12H,5-8,10,13H2,1-2H3,(H2,27,28,29,30)
• InChIKey: SQSZANZGUXWJEA-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-{3-[(4-chloro-2-fluorophenyl)methyl]-2-methyl-8-(morpholin-4-ylmethyl)imidazo[1,2-b]pyridazin-6-yl}-3-methyl-1H-pyrazol-5-amine
• IUPAC Traditional name: N-{3-[(4-chloro-2-fluorophenyl)methyl]-2-methyl-8-(morpholin-4-ylmethyl)imidazo[1,2-b]pyridazin-6-yl}-5-methyl-2H-pyrazol-3-amine
• Synonyms: LY2784544

Database IDs

• CAS Number: 1229236-86-5
• PubChem SID: 162037797
• PubChem CID: 46213929

CALCULATED PROPERTIES

• Acid pKa: 14.144992
• H Acceptors: 6
• H Donor: 2
• LogD (pH = 5.5): 2.6034193
• LogD (pH = 7.4): 3.6270852
• Log P: 3.669102
• Molar Refractivity: 137.1041 cm^3
• Polarizability: 47.083466 Å^3
• Polar Surface Area: 83.37 Å^2
• Rotatable Bonds: 6
• Lipinski's Rule of Five: true

PROPERTIES

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: JAK

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S2179

Research Area

• Description: Myeloproliferative disorders

Biological Activity

• Description: LY2784544 is selective to V617F mutant JAK2 with IC50 of 55 nM in Ba/F3 cells.
• Targets: JAK2 V617F mutant
• IC50: 55 nM ^[1]
• In Vitro: LY2784544 also inhibits IL-3-activated wild type JAK2 with IC50 of 2.26 μM. Similarly in the proliferation assay, LY2784544 shows antiproliferation activity in JAK2 V617F-driven cells with IC50 of 68 nM, compared to 1.36 μM in wild type JAK2-driven cells and 0.94 μM in JAK3-driven cells. ^[1]
• In Vivo: LY2784544 significantly inhibits STAT5 phosphorylation in Ba/F3-JAK2 V617F-GFP xenografts with a Threshold Effective Dose 50 (TED50) of 12.7 mg/kg. LY2784544 also reduces Ba/F3-JAK2 V617F-GFP tumor burden in the JAK2 V617F-induced MPN model with a TED50 of 13.7 mg/kg after oral treatment. LY2784544 has no effect on CD71/Ter119 positive erythroid progenitors in spleens of SCID mice after oral treatment. ^[1]
• Clinical Trials: Currently in Phase I clinical trial in patients with JAK2 V617F-positive myeloproliferative disorders.

References

• References: [1] Ma L, et al. 53rd ASH Annual Meeting and Exposition, 2011, Abstract 4087.

REFERENCES

• Ma L, et al. 53rd ASH Annual Meeting and Exposition, 2011, Abstract 4087.