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编号: 72835
• 分子式: C23H23ClFNO5
• 平均质量: 447.8838232
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: 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传统名: elvitegravir
• 别名: 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

登记号

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

理论计算性质

• Acid pKa: 6.159547
• 质子受体: 6
• 质子供体: 2
• LogD (pH = 5.5): 4.5819654
• LogD (pH = 7.4): 3.4054427
• Log P: 4.667943
• 摩尔折射率: 116.2561 cm^3
• 极化性: 43.77461 Å^3
• 极化表面积: 87.07 Å^2
• 可自由旋转的化学键: 7
• 里宾斯基五规则: true

分子性质

理化性质

• 溶解度: DMSO; Methanol
• 外观: Off-White to Pale Yellow Solid
• 熔点: 93-96°C

安全信息

• 保存条件: -20°C; Refrigerator

药理学性质

• 作用靶点: Integrase

产品相关信息

• 成盐信息: Free Base

详细说明

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.

参考文献

• 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)