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N-[[P(S),2'R]-2'-Deoxy-2'-fluoro-2'-Methyl-6-O-Methyl-P-phenyl-5'-guanylyl]- L-alanine 1-Methylethyl ester

Names

[ CAS No. ]:
1231747-08-2

[ Name ]:
N-[[P(S),2'R]-2'-Deoxy-2'-fluoro-2'-Methyl-6-O-Methyl-P-phenyl-5'-guanylyl]- L-alanine 1-Methylethyl ester

[Synonym ]:
PSI-353661
(2S)-isopropyl-2-((((2R,3R,4R,5R)-5(2-amino-6-methoxy-9H-purin-9-yl)-4-fluoro- 3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propanoate
(S)-isopropyl 2-(((S)-((5-(2-amino-6-methoxy-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate

Biological Activity

[Description]:

PSI-353661 (GS-558093) is a purine nucleotide NS5B polymerase inhibitor against HCV infection (EC90: 8 nM). PSI-353661 can produce high concentrations of the active triphosphate in primary human hepatocytes[1][3].

[Related Catalog]:

Signaling Pathways >> Anti-infection >> HCV
Research Areas >> Infection

[Target]

NS5B polymerase[3]


[In Vitro]

PSI-353661 exhibits strong inhibition of HCV in the cell-based replicon assay, with EC90s of 8 nM and 11 nM for wild type and S282T resistant replicons[1]. PSI-353661 (24 h) produces high concentrations of (0.44 mM) triphosphate (TP) level in primary human hepatocytes[1]. PSI-353661 (4 days) inhibits viral replication with EC50 and EC90 value of 0.0030 μM and 0.0085 μM for genotype 1b replicon cells[2]. PSI-353661 (8 days) shows little cytotoxicity in Huh7, HepG2, BxPC3, and CEM cells, with IC50 more than 80 μM[2]. PSI-353661 (8-160 nM, 2 weeks) clears HCV replicon RNA and prevents viral rebound[2].

[In Vivo]

PSI-353661 (50 mg/kg, p.o., together with 400 mg/kg of Telaprevir (HY-10235), daily for 4 weeks) is effective against human hepatocyte chimeric mice infected with HCV[3]. Animal Model: Human hepatocyte chimeric mice infected with HCV Dosage: 50 mg/kg, together with 400 mg/kg of Telaprevir Administration: Oral administration (p.o.) Result: Achieved sustained eradication of the mutant virus or the end-of-treatment response. Reduced serum levels of HCV RNA.

Chemical & Physical Properties

[ Density]:
1.53

[ Molecular Formula ]:
C24H32FN6O8P

[ Molecular Weight ]:
582.51800

[ Exact Mass ]:
582.20000

[ PSA ]:
191.98000

[ LogP ]:
3.50910

Related Compounds