5-fluoro-3-phenyl-2-[(1S)-1-[(9H-purin-6-yl)amino]propyl]-3,4-dihydroquinazolin-4-one

• ChemBase ID: 73082
• Molecular Formular: C22H18FN7O
• Molecular Mass: 415.4230232
• Monoisotopic Mass: 415.15568645
• SMILES: c1ccc2c(c1F)c(=O)n(c(n2)[C@@H](Nc1c2c(ncn1)[nH]cn2)CC)c1ccccc1
• Canonical SMILES: CC[C@@H](c1nc2cccc(c2c(=O)n1c1ccccc1)F)Nc1ncnc2c1nc[nH]2
• InChI: InChI=1S/C22H18FN7O/c1-2-15(28-20-18-19(25-11-24-18)26-12-27-20)21-29-16-10-6-9-14(23)17(16)22(31)30(21)13-7-4-3-5-8-13/h3-12,15H,2H2,1H3,(H2,24,25,26,27,28)/t15-/m0/s1
• InChIKey: IFSDAJWBUCMOAH-HNNXBMFYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 5-fluoro-3-phenyl-2-[(1S)-1-[(9H-purin-6-yl)amino]propyl]-3,4-dihydroquinazolin-4-one
• IUPAC Traditional name: 5-fluoro-3-phenyl-2-[(1S)-1-(9H-purin-6-ylamino)propyl]quinazolin-4-one
• Synonyms: CAL101; CAL-101

Database IDs

• CAS Number: 870281-82-6
• PubChem SID: 162038002
• PubChem CID: 11625818

CALCULATED PROPERTIES

• Acid pKa: 9.863462
• H Acceptors: 6
• H Donor: 2
• LogD (pH = 5.5): 3.2383378
• LogD (pH = 7.4): 3.3557765
• Log P: 3.361084
• Molar Refractivity: 116.8321 cm^3
• Polarizability: 42.556435 Å^3
• Polar Surface Area: 99.16 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

PROPERTIES

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: PI3K

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S2226

Research Area

• Description: Non-Hodgkin's lymphoma, Multiple myeloma ,Chronic lymphocytic leukaemia ,Acute myeloid leukaemia

Protocol

• Protocol: Kinase Assay ^[2]
• PI3K assay: PI3K assay is preformed on whole-cell lysates from CLL or normal B cells. A PI3K ELISA assay is performed. Briefly, whole-cell extracts are added to a mixture of PI(4,5)P2 substrate and reaction buffer containing adenosine triphosphate (ATP) and allowed to incubate at room temperature. The reaction is stopped by adding PI(3,4,5)P3 detector mixed with EDTA (ethylenediaminetetraacetic acid) and allowed to incubate at room temperature for 1 hour. After this time, the mixture is transferred from each well to a PI3K ELISA plate and allowed to incubate 1 hour. Plates are washed and then incubated with secondary detector for 30 minutes. Plates are washed again, and 3,3′,5,5′-tetramethylbenzidine solution is added for 5 minutes at which time H2SO4 is added to stop all reactions. Plates are read at 450 nm on a Labsystems 96-well plate reader.
• Protocol: Cell Assay ^[2]
• Cell Lines: CLL B cells or healthy volunteer T cells or NK cells
• Concentrations: 0.01-100 μM
• Incubation Time: 48 hours
• Methods: MTT assays are performed to determine cytotoxicity. 1 × 10^5 cells are incubated with CAL-101. MTT reagent is then added, and plates are incubated for an additional 20 hours before washing with protamine sulfate in phosphate-buffered saline. DMSO is added, and absorbance is measured by spectrophotometry at 540 nm in a Labsystems plate reader. Cell viability is also measured at various time points with the use of annexin/PI flow cytometry. Data are analyzed. At least 104 cells are counted for each sample. Results are expressed as the percentage of total positive cells over untreated control. Experiments examining caspase-dependent apoptosis included the addition of 100 μM Z-VAD. Experiments examining survival signals include the addition of 1 μg/mL CD40L, 800 U/mL IL-4, 50 ng/mL BAFF, 20 ng/mL TNF-α, or coculturing on fibronectin or stromal (HS-5 cell line) coated plates. Stromal coculture is done by plating a 75-cm^2 flask (80%-100% confluent) per 6-well plate 24 hours before the addition of CLL cells.

References

• References: [1] Lannutti BJ, et al. Blood, 2011, 117(2), 591-594.
• References: [2] Herman SE, et al. Blood, 2010, 116(12), 2078-2088.
• References: [3] Meadows SA, et al. Blood, 2011 Dec 30.

REFERENCES

• Lannutti BJ, et al. Blood, 2011, 117(2), 591-594.
• Herman SE, et al. Blood, 2010, 116(12), 2078-2088.
• Meadows SA, et al. Blood, 2011 Dec 30.