6-[(3-chloro-2-fluorophenyl)methyl]-1-[(2S)-1-hydroxy-3-methylbutan-2-yl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

• ChemBase ID: 72835
• Molecular Formular: C23H23ClFNO5
• Molecular Mass: 447.8838232
• Monoisotopic Mass: 447.12487874
• SMILES: c1cc(c(c(c1)Cl)F)Cc1cc2c(cc1OC)n(cc(c2=O)C(=O)O)[C@@H](C(C)C)CO
• Canonical SMILES: OC[C@@H](n1cc(C(=O)O)c(=O)c2c1cc(OC)c(c2)Cc1cccc(c1F)Cl)C(C)C
• InChI: InChI=1S/C23H23ClFNO5/c1-12(2)19(11-27)26-10-16(23(29)30)22(28)15-8-14(20(31-3)9-18(15)26)7-13-5-4-6-17(24)21(13)25/h4-6,8-10,12,19,27H,7,11H2,1-3H3,(H,29,30)/t19-/m1/s1
• InChIKey: JUZYLCPPVHEVSV-LJQANCHMSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 6-[(3-chloro-2-fluorophenyl)methyl]-1-[(2S)-1-hydroxy-3-methylbutan-2-yl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• IUPAC Traditional name: elvitegravir
• Synonyms: 6-[(3-Chloro-2-fluorophenyl)methyl]-1,4-dihydro-1-[(1S)-1-(hydroxymethyl)-2-methylpropyl]-7-methoxy-4-oxo-3-quinolinecarboxylic Acid; GS 9137; JTK 303; EVG; GS-9137; JTK-303; Elvitegravir

Database IDs

• CAS Number: 697761-98-1
• PubChem SID: 162037756
• PubChem CID: 5277135

CALCULATED PROPERTIES

• Acid pKa: 6.159547
• H Acceptors: 6
• H Donor: 2
• LogD (pH = 5.5): 4.5819654
• LogD (pH = 7.4): 3.4054427
• Log P: 4.667943
• Molar Refractivity: 116.2561 cm^3
• Polarizability: 43.77461 Å^3
• Polar Surface Area: 87.07 Å^2
• Rotatable Bonds: 7
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: DMSO; Methanol
• Apperance: Off-White to Pale Yellow Solid
• Melting Point: 93-96°C

Safety Information

• Storage Condition: -20°C; Refrigerator

Pharmacology Properties

• Target: Integrase

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S2001

Research Area

• Description: Immunology, Infection

Biological Activity

• Description: Elvitegravir (EVG, JTK-303/GS-9137) is a HIV integrase inhibitor for HIV-1 IIIB, HIV-2 EHO and HIV-2 ROD with IC50 of 0.7 nM, 2.8 nM and 1.4 nM, respectively.
• Targets:

  HIV-1 IIIB

  ;

  HIV-2 EHO

  ;

  HIV-2 ROD

• IC50:

  0.7 nM

  ;

  2.8 nM

  ;

  1.4 nM ^[1]

• In Vitro: Elvitegravir inhibits PBMC and PA with IC50 of 0.89 and 20 nM, respectively. Elvitegravir prevents the integration of HIV-1 cDNA through the inhibition of DNA strand transfer. Elvitegravir suppresses the replication of HIV-1, including various subtypes and multiple-drug-resistant clinical isolates, and HIV-2 strains with a 50% effective concentration in the subnanomolar to nanomolar range. Elvitegravir inhibits the replication of HIV-1 clinical isolates carrying NRTI, NNRTI, and PI resistance-associated genotypes. Elvitegravir inhibits the HIV replication at a step that occurs after reverse transcription but before proteolytic cleavage, consistent with the integration step. Elvitegravir inhibits the synthesis of strand transfer products with an IC50 of 54 nM. Elvitegravir blocks integration via the inhibition of IN-mediated strand transfer. ^[1] Elvitegravir inhibits the integration of the HIV-based vector used as a positive control for the luciferase assay with an EC50 of 0.8 nM, as observed in the MAGI assay with HIV-1IIIB. Elvitegravir suppresses the replication of MLV infection with IC50 of 5.8 nM as well as that of the primate retrovirus SIV (IC50 = 0.5 nM), revealing that IN inhibitors have antiviral activity against a broad range of retroviruses. EVG is active against HIV-1 and HIV-2 and has a serum-free antiviral IC50 of 0.3-0.9 nM in peripheral blood mononuclear cells. ^[2]
• Clinical Trials: Elvitegravir is currengly in a Phase III clinical trial in the treatment of HIV-1 Infection.

References

• References: [1] Shimura K, et al. J Virol. 2008, 82(2), 764-774.
• References: [2] Lampiris HW. Expert Rev Anti Infect Ther. 2012, 10(1), 13-20.

Toronto Research Chemicals - E509000

A novel inhibitor of human immunodeficiency virus type 1 integrase.

REFERENCES

• Shimura K, et al. J Virol. 2008, 82(2), 764-774.
• Lampiris HW. Expert Rev Anti Infect Ther. 2012, 10(1), 13-20.
• Baba, M., et al.: Antimicrob. Agents Chemother., 31, 1613 (1981)
• Craigie, R., et al.: J. Biol. Chem., 276, 23213 (1981)
• Chen, X., et al.: J. Mol. Biol., 380, 504 (1981)
• Chou, T., et al.: Eur. J. Biochem., 115, 207 (1981)