4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl}-2-fluoro-N-methylbenzamide

• ChemBase ID: 70492
• Molecular Formular: C21H16F4N4O2S
• Molecular Mass: 464.4359528
• Monoisotopic Mass: 464.09300965
• SMILES: C(=O)(c1c(cc(cc1)N1C(=S)N(C(=O)C1(C)C)c1cc(c(cc1)C#N)C(F)(F)F)F)NC
• Canonical SMILES: CNC(=O)c1ccc(cc1F)N1C(=S)N(C(=O)C1(C)C)c1ccc(c(c1)C(F)(F)F)C#N
• InChI: InChI=1S/C21H16F4N4O2S/c1-20(2)18(31)28(12-5-4-11(10-26)15(8-12)21(23,24)25)19(32)29(20)13-6-7-14(16(22)9-13)17(30)27-3/h4-9H,1-3H3,(H,27,30)
• InChIKey: WXCXUHSOUPDCQV-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl}-2-fluoro-N-methylbenzamide
• IUPAC Traditional name: 4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl}-2-fluoro-N-methylbenzamide
• Synonyms: 4-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide; 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxo-1-imidazolidinyl)-2-fluoro-n-methylbenzamide; MDV3100

Database IDs

• CAS Number: 915087-33-1
• MDL Number: MFCD14155804
• PubChem SID: 162036208
• PubChem CID: 15951529

CALCULATED PROPERTIES

• Acid pKa: 13.054718
• H Acceptors: 3
• H Donor: 1
• LogD (pH = 5.5): 4.1554112
• LogD (pH = 7.4): 4.1554103
• Log P: 4.1554112
• Molar Refractivity: 113.4796 cm^3
• Polarizability: 41.52869 Å^3
• Polar Surface Area: 76.44 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: DMSO

Safety Information

• Storage Condition: -20°C
• Storage Warning: IRRITANT
• TSCA Listed: false

Pharmacology Properties

• Target: Androgen receptor

Product Information

• Purity: 95+%; 97%
• Salt Data: Free Base

DETAILS

Selleck Chemicals - S1250

Research Area

• Description: Prostate cancer

Protocol

• Protocol: Kinase Assay ^[3]
• AR reporter assay: MDV3100 is evaluated by an artificial AR response reporter system in a hormone refractory prostate cancer cell line. In this system, the prostate cancer LNCaP cells are engineered to stably express about 5-fold higher level of AR than endogenous level. The exogenous AR has similar properties to endogenous AR in that both are stabilized by a synthetic androgen R1881. The AR-over expressed cells are also engineered to stably incorporate an AR response reporter and the reporter activity of these cells shows features of hormone refractory prostate cancer. The antagonistic activity of MDV3100 is tested in the presence of 100 pM of R1881. Engineered LNCaP cells are maintained in Iscove's medium containing 10% fetal bovine serum (FBS). Two days prior to MDV3100 treatment, the cells are grown in Iscove's medium containing 10% charcoal-stripped FBS (CS-FBS) to deprive of androgens. The cells are split and grown in Iscove's medium containing 10% CS-FBS with 100 pM of R1881 and increasing concentrations of MDV3100. After two days of incubation, reporter activities are assayed.
• Protocol: Cell Assay ^[1]
• Cell Lines: LNCaP or LNCaP/AR cells
• Concentrations: 0-10 μM
• Incubation Time: 1-4 days
• Methods: MDV3100 is diluted in DMSO. LNCaP or LNCaP/AR cells (10^4 cells/well) are androgen-starved by growth in media containing 5-10% charcoal-stripped serum for 3-5 days. Then the cells are challenged with various concentrations of MDV3100 in media containing 5-10% charcoal-stripped serum.
• Protocol: Animal Study ^[1]
• Animal Models: Castration-resistant LNCaP/HR xenografts in male SCID mice
• Formulation: Formulated in 1% carboxymethyl cellulose, 0.1% Tween-80, 5% DMSO
• Doses: 10 mg/kg
• Administration: Administered via gavage daily

References

• References: [1] Tran C, et al, Science, 2009, 324 (5928), 787-790.
• References: [2] Scher HI, et al, Lancet, 2010, 375(9724), 1437-1446.
• References: [3] US2007254933 (A1)

REFERENCES

• Tran C, et al, Science, 2009, 324 (5928), 787-790.
• Scher HI, et al, Lancet, 2010, 375(9724), 1437-1446.
• US2007254933  (A1)