Phillip A Furman

Summary

Affiliation: Pharmasset Inc
Country: USA

Publications

  1. doi Nucleoside analog inhibitors of hepatitis C viral replication: recent advances, challenges and trends
    Phillip A Furman
    Pharmasset, Inc, Princeton, NJ 08540, USA
    Future Med Chem 1:1429-52. 2009
  2. doi Discovery of a β-d-2'-deoxy-2'-α-fluoro-2'-β-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus
    Michael J Sofia
    Pharmasset, Inc, 303A College Road East, Princeton, New Jersey 08540, USA
    J Med Chem 53:7202-18. 2010
  3. pmc Activity and the metabolic activation pathway of the potent and selective hepatitis C virus pronucleotide inhibitor PSI-353661
    Phillip A Furman
    Pharmasset, Inc, Princeton, NJ 08540, USA
    Antiviral Res 91:120-32. 2011
  4. ncbi β-D-2'-α-F-2'-β-C-Methyl-6-O-substituted 3',5'-cyclic phosphate nucleotide prodrugs as inhibitors of hepatitis C virus replication: a structure-activity relationship study
    Jinfa Du
    Pharmasset, Inc, Princeton 303A College Road East, Princeton, NJ 08540, USA
    Bioorg Med Chem Lett 22:5924-9. 2012
  5. pmc PSI-7851, a pronucleotide of beta-D-2'-deoxy-2'-fluoro-2'-C-methyluridine monophosphate, is a potent and pan-genotype inhibitor of hepatitis C virus replication
    Angela M Lam
    Pharmasset, Inc, 303A College Road East, Princeton, NJ 08540, USA
    Antimicrob Agents Chemother 54:3187-96. 2010
  6. ncbi Use of 2'-spirocyclic ethers in HCV nucleoside design
    Jinfa Du
    Pharmasset, Inc, 303A College Road East, Princeton, New Jersey 08540, United States
    J Med Chem 57:1826-35. 2014
  7. pmc Inhibition of hepatitis C virus replicon RNA synthesis by PSI-352938, a cyclic phosphate prodrug of β-D-2'-deoxy-2'-α-fluoro-2'-β-C-methylguanosine
    Angela M Lam
    Pharmasset, Inc, 303A College Road East, Princeton, NJ 08540, USA
    Antimicrob Agents Chemother 55:2566-75. 2011
  8. pmc Hepatitis C virus nucleotide inhibitors PSI-352938 and PSI-353661 exhibit a novel mechanism of resistance requiring multiple mutations within replicon RNA
    Angela M Lam
    Pharmasset, Inc, 303A College Road East, Princeton, NJ 08540, USA
    J Virol 85:12334-42. 2011
  9. pmc Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977
    Eisuke Murakami
    Pharmasset, Inc, Princeton, New Jersey 08540, USA
    J Biol Chem 285:34337-47. 2010
  10. pmc The mechanism of action of beta-D-2'-deoxy-2'-fluoro-2'-C-methylcytidine involves a second metabolic pathway leading to beta-D-2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-triphosphate, a potent inhibitor of the hepatitis C virus RNA-dependent RNA polymerase
    Eisuke Murakami
    Pharmasset, Inc, 303 A College Road East, Princeton, NJ 08540, USA
    Antimicrob Agents Chemother 52:458-64. 2008

Collaborators

Detail Information

Publications28

  1. doi Nucleoside analog inhibitors of hepatitis C viral replication: recent advances, challenges and trends
    Phillip A Furman
    Pharmasset, Inc, Princeton, NJ 08540, USA
    Future Med Chem 1:1429-52. 2009
    ..Herein, we discuss various classes of nucleoside inhibitors, with a focus on available structure-activity relationships, their mode of action and resistance profile...
  2. doi Discovery of a β-d-2'-deoxy-2'-α-fluoro-2'-β-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus
    Michael J Sofia
    Pharmasset, Inc, 303A College Road East, Princeton, New Jersey 08540, USA
    J Med Chem 53:7202-18. 2010
    ..51 (PSI-7977) was selected as a clinical development candidate...
  3. pmc Activity and the metabolic activation pathway of the potent and selective hepatitis C virus pronucleotide inhibitor PSI-353661
    Phillip A Furman
    Pharmasset, Inc, Princeton, NJ 08540, USA
    Antiviral Res 91:120-32. 2011
    ..PSI-352666 is equally active against wild-type NS5B and NS5B containing the S282T amino acid alteration...
  4. ncbi β-D-2'-α-F-2'-β-C-Methyl-6-O-substituted 3',5'-cyclic phosphate nucleotide prodrugs as inhibitors of hepatitis C virus replication: a structure-activity relationship study
    Jinfa Du
    Pharmasset, Inc, Princeton 303A College Road East, Princeton, NJ 08540, USA
    Bioorg Med Chem Lett 22:5924-9. 2012
    ..Compounds 12, 13 and 19 also demonstrated the ability to effectively deliver in vivo high levels of active nucleoside phosphates to rat liver...
  5. pmc PSI-7851, a pronucleotide of beta-D-2'-deoxy-2'-fluoro-2'-C-methyluridine monophosphate, is a potent and pan-genotype inhibitor of hepatitis C virus replication
    Angela M Lam
    Pharmasset, Inc, 303A College Road East, Princeton, NJ 08540, USA
    Antimicrob Agents Chemother 54:3187-96. 2010
    ..Clearance studies using replicon cells demonstrated that PSI-7851 was able to clear cells of HCV replicon RNA and prevent viral rebound...
  6. ncbi Use of 2'-spirocyclic ethers in HCV nucleoside design
    Jinfa Du
    Pharmasset, Inc, 303A College Road East, Princeton, New Jersey 08540, United States
    J Med Chem 57:1826-35. 2014
    ....
  7. pmc Inhibition of hepatitis C virus replicon RNA synthesis by PSI-352938, a cyclic phosphate prodrug of β-D-2'-deoxy-2'-α-fluoro-2'-β-C-methylguanosine
    Angela M Lam
    Pharmasset, Inc, 303A College Road East, Princeton, NJ 08540, USA
    Antimicrob Agents Chemother 55:2566-75. 2011
    ..PSI-352938 is currently being evaluated in a phase I clinical study in genotype 1-infected individuals...
  8. pmc Hepatitis C virus nucleotide inhibitors PSI-352938 and PSI-353661 exhibit a novel mechanism of resistance requiring multiple mutations within replicon RNA
    Angela M Lam
    Pharmasset, Inc, 303A College Road East, Princeton, NJ 08540, USA
    J Virol 85:12334-42. 2011
    ....
  9. pmc Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977
    Eisuke Murakami
    Pharmasset, Inc, Princeton, New Jersey 08540, USA
    J Biol Chem 285:34337-47. 2010
    ..PSI-7411 is then consecutively phosphorylated to the diphosphate, PSI-7410, and to the active triphosphate metabolite, PSI-7409, by UMP-CMP kinase and nucleoside diphosphate kinase, respectively...
  10. pmc The mechanism of action of beta-D-2'-deoxy-2'-fluoro-2'-C-methylcytidine involves a second metabolic pathway leading to beta-D-2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-triphosphate, a potent inhibitor of the hepatitis C virus RNA-dependent RNA polymerase
    Eisuke Murakami
    Pharmasset, Inc, 303 A College Road East, Princeton, NJ 08540, USA
    Antimicrob Agents Chemother 52:458-64. 2008
    ..RO2433-TP is a potent inhibitor of the HCV RdRp; however, both enzymatic and cell-based assays show that PSI-6130 triphosphate is a more potent inhibitor of the HCV RdRp than RO2433-TP...
  11. pmc Genotype and subtype profiling of PSI-7977 as a nucleotide inhibitor of hepatitis C virus
    Angela M Lam
    Pharmasset, Inc, Princeton, New Jersey, USA
    Antimicrob Agents Chemother 56:3359-68. 2012
    ....
  12. doi Phosphoramidate prodrugs of (-)-β-D-(2R,4R)-dioxolane-thymine (DOT) as potent anti-HIV agents
    Peiyuan Wang
    Pharmasset, Inc, Princeton, NJ, USA
    Antivir Chem Chemother 22:217-38. 2012
    ..D-(2R,4R)-dioxolane-thymine (DOT) is a thymidine analogue that is active against wild-type and NRTI-resistant HIV-1 mutants. It has been shown that the anti-HIV activity of DOT is limited due to poor monophosphorylation...
  13. doi Synthesis of stable isotope labeled analogs of the anti-hepatitis C virus nucleotide prodrugs PSI-7977 and PSI-352938
    Byoung Kwon Chun
    Pharmasset, Inc, 303A College Road East, Princeton, NJ 08540, USA
    Nucleosides Nucleotides Nucleic Acids 30:886-96. 2011
    ..As expected, these 2 '-C-(trideuterated-(13)C-methyl) nucleotide prodrugs showed similar anti-HCV activity to that of the corresponding unlabeled ones...
  14. doi A 2'-deoxy-2'-fluoro-2'-C-methyl uridine cyclopentyl carbocyclic analog and its phosphoramidate prodrug as inhibitors of HCV NS5B polymerase
    Jian Liu
    Pharmasset, Inc, Princeton, New Jersey 08540, USA
    Nucleosides Nucleotides Nucleic Acids 31:277-85. 2012
    ..This lack of activity might be attributed to the inability of the monophosphate to be converted to the corresponding diphosphate or triphosphate or the inactivity of triphosphate of 11 as an inhibitor of the polymerase...
  15. ncbi Evaluation of the in vitro anti-HBV activity of clevudine in combination with other nucleoside/nucleotide inhibitors
    Congrong Niu
    Pharmasset, Inc, Princeton, NJ, USA
    Antivir Ther 15:401-12. 2010
    ..We investigated the activity of clevudine (CLV) in combination with other nucleoside/nucleotide analogues to determine if these combinations were compatible in vitro...
  16. ncbi Discovery of a novel class of potent HCV NS4B inhibitors: SAR studies on piperazinone derivatives
    Ramesh Kakarla
    Pharmasset, Inc 303A College Road East, Princeton, New Jersey 08540, United States
    J Med Chem 57:2136-60. 2014
    ..However, the piperazonone class of compounds lacks GT-2 activity and, consequently, were not pursued further into development. ..
  17. pmc Metabolic activation of the anti-hepatitis C virus nucleotide prodrug PSI-352938
    Congrong Niu
    Pharmasset, Inc, Princeton, New Jersey, USA
    Antimicrob Agents Chemother 56:3767-75. 2012
    ..Since CYP3A4 is highly expressed in the liver, the CYP3A4-dependent metabolism of PSI-352938 makes it an effective liver-targeted prodrug, in part accounting for the potent antiviral activity observed clinically...
  18. pmc Mechanism of activation of beta-D-2'-deoxy-2'-fluoro-2'-c-methylcytidine and inhibition of hepatitis C virus NS5B RNA polymerase
    Eisuke Murakami
    Pharmasset, Inc, 303A College Road East, Princeton, NJ 08640, USA
    Antimicrob Agents Chemother 51:503-9. 2007
    ..Incorporation of PSI-6130-MP into RNA catalyzed by purified NS5B RNA polymerase resulted in chain termination...
  19. doi Synthesis and anti-HCV activity of 3',4'-oxetane nucleosides
    Wonsuk Chang
    Pharmasset, Inc, East, Princeton, NJ 08540, USA
    Bioorg Med Chem Lett 20:4539-43. 2010
    ..Lack of anti-HCV activity in the replicon assay may be due to the inability of the monophosphates to be converted to their corresponding diphosphates...
  20. doi Inhibition of hepatitis C virus NS5A by fluoro-olefin based γ-turn mimetics
    Wonsuk Chang
    Pharmasset, Inc, Princeton, NJ 08540, USA
    Bioorg Med Chem Lett 22:2938-42. 2012
    ....
  21. ncbi Inhibition of hepatitis C replicon RNA synthesis by beta-D-2'-deoxy-2'-fluoro-2'-C-methylcytidine: a specific inhibitor of hepatitis C virus replication
    Lieven J Stuyver
    Pharmasset Inc, Princeton, NJ, USA
    Antivir Chem Chemother 17:79-87. 2006
    ..Finally, the no-effect dose for mice treated intraperitoneally with PSI-6130 for six consecutive days was > or =100 mg/kg per day...
  22. ncbi Adenosine deaminase-like protein 1 (ADAL1): characterization and substrate specificity in the hydrolysis of N(6)- or O(6)-substituted purine or 2-aminopurine nucleoside monophosphates
    Eisuke Murakami
    Pharmasset, Inc, 303A College Road East, Princeton, New Jersey 08540, USA
    J Med Chem 54:5902-14. 2011
    ..Furthermore, amino acid sequence analysis in conjunction with crystallographic data and metal analysis suggested that ADAL1 contains a catalytic zinc ion. Finally, a potential physiological role of ADAL1 is discussed...
  23. doi Phenylpropenamide derivatives: anti-hepatitis B virus activity of the Z isomer, SAR and the search for novel analogs
    Peiyuan Wang
    Pharmasset, Inc, Princeton, NJ 08540, USA
    Bioorg Med Chem Lett 21:4642-7. 2011
    ..5 μM in vitro. Attempts to develop ring constrained analogs did not lead to active HBV inhibitors...
  24. ncbi Clevudine is efficiently phosphorylated to the active triphosphate form in primary human hepatocytes
    Congrong Niu
    Pharmasset, Inc, Princeton, NJ 08540, USA
    Antivir Ther 13:263-9. 2008
    ..Human hepatoma cell lines are the only liver-derived cells in which CLV metabolism has been investigated. Here, we examine CLV metabolism in primary human hepatocytes, which better represent CLV metabolism in the liver...
  25. doi 2'-deoxy-2'-α-fluoro-2'-β-C-methyl 3',5'-cyclic phosphate nucleotide prodrug analogs as inhibitors of HCV NS5B polymerase: discovery of PSI-352938
    P Ganapati Reddy
    Pharmasset, Inc, 303A College Road East, Princeton, NJ 08540, USA
    Bioorg Med Chem Lett 20:7376-80. 2010
    ..These studies ultimately led to the selection of the clinical development candidate 24a (PSI-352938)...
  26. ncbi Mechanism of action of (-)-(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl) thymine as an anti-HIV agent
    Eisuke Murakami
    Pharmasset Inc, Princeton, NJ, USA
    Antivir Chem Chemother 18:83-92. 2007
    ..Little or no resistance was observed with the enzymes harbouring mutations resistant to lamivudine (M184V) and non-nucleoside RT inhibitors (K103N)...
  27. ncbi Design, synthesis, and antiviral activity of 2'-deoxy-2'-fluoro-2'-C-methylcytidine, a potent inhibitor of hepatitis C virus replication
    Jeremy L Clark
    Pharmasset, Inc, 303 A College Road East, Princeton, New Jersey 08540, USA
    J Med Chem 48:5504-8. 2005
    ..Compound 1 shows increased inhibitory activity in the HCV replicon assay compared to 2'-C-methylcytidine and low cellular toxicity...
  28. ncbi Dioxolane guanosine 5'-triphosphate, an alternative substrate inhibitor of wild-type and mutant HIV-1 reverse transcriptase. Steady state and pre-steady state kinetic analyses
    Jerry L Jeffrey
    Triangle Pharmaceuticals, Inc, a subsidiary of Gilead Sciences, Durham, North Carolina 27717, USA
    J Biol Chem 278:18971-9. 2003
    ..Overall, the enzymatic data correlated well with the antiviral data obtained from cell culture experiments and further supported the use of amdoxovir for the treatment of nucleoside reverse transcriptase inhibitor-experienced patients...