4-fluoro-N-methyl-N-{1-[4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl]piperidin-4-yl}-2-(trifluoromethyl)benzamide

• ChemBase ID: 73133
• Molecular Formular: C26H24F4N6O
• Molecular Mass: 512.5019728
• Monoisotopic Mass: 512.1947723
• SMILES: c1(nnc(c2c1cccc2)N1CCC(CC1)N(C)C(=O)c1c(cc(cc1)F)C(F)(F)F)c1ccnn1C
• Canonical SMILES: Fc1ccc(c(c1)C(F)(F)F)C(=O)N(C1CCN(CC1)c1nnc(c2c1cccc2)c1ccnn1C)C
• InChI: InChI=1S/C26H24F4N6O/c1-34(25(37)20-8-7-16(27)15-21(20)26(28,29)30)17-10-13-36(14-11-17)24-19-6-4-3-5-18(19)23(32-33-24)22-9-12-31-35(22)2/h3-9,12,15,17H,10-11,13-14H2,1-2H3
• InChIKey: SZBGQDXLNMELTB-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 4-fluoro-N-methyl-N-{1-[4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl]piperidin-4-yl}-2-(trifluoromethyl)benzamide
• IUPAC Traditional name: 4-fluoro-N-methyl-N-{1-[4-(2-methylpyrazol-3-yl)phthalazin-1-yl]piperidin-4-yl}-2-(trifluoromethyl)benzamide
• Synonyms: LY2940680

Database IDs

• CAS Number: 1258861-20-9
• PubChem SID: 162038053
• PubChem CID: 49848070

CALCULATED PROPERTIES

• H Acceptors: 5
• H Donor: 0
• LogD (pH = 5.5): 3.970506
• LogD (pH = 7.4): 3.9770596
• Log P: 3.9771438
• Molar Refractivity: 145.0847 cm^3
• Polarizability: 50.097492 Å^3
• Polar Surface Area: 67.15 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: false

PROPERTIES

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: Hedgehog

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S2157

Biological Activity

• Description: LY2940680 binds to the Smo receptor and potently inhibits Hh signaling.
• Targets: Smo
• In Vitro: LY2940680 inhibits cancer growth in cell lines containing a mutation in the gene encoding Smoothened that researchers had previously observed in patient with cancer who developed resistance to vismodegib. ^[1]
• In Vivo: LY2940680 has excellent pharmacokinetic properties in rodent and non-rodent species. LY2940680 administrated orally treats Ptch^+/- p53^-/- transgenic mice which spontaneously develop medulloblastoma, produces remarkable efficacy and significantly improves their survival. LY2940680 reveals rapid kinetics of anti-tumor activity through magnetic resonance imaging of these mice, and LY2940680 induces Caspase-3 activity and reduces proliferation by immunohistochemistry analysis of medulloblastoma tumors. LY2940680 inhibits Hh regulated gene expression in the subcutaneous xenograft tumor stroma and produces significant anti-tumor activity. ^[2]
• Clinical Trials: LY2940680 is currently being tested in phase 1 trials for people with a range of solid tumors.

Combination Therapy

• Description: LY2940680 inhibits the functional activity of resistant Smo mutant (D473H) produced by treatment with GDC-0449 (a Smo antagonist). sup>[2]

References

• References: [1] Redmond EM et al. Expert Opin Investig Drugs, 2011, 20(12),1649-1664.
• References: [2] Mark H. Bender, Cancer Research, 2011, Volume 71, Issue 8, Supplement1

REFERENCES

• Redmond EM et al. Expert Opin Investig Drugs, 2011, 20(12),1649-1664.
• Mark H. Bender, Cancer Research, 2011, Volume 71, Issue 8, Supplement1