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Literature DB >> 29670705

Amidate Prodrugs of Cyclic 9-(S)-[3-Hydroxy-2-(phosphonomethoxy)propyl]adenine with Potent Anti-Herpesvirus Activity.

Min Luo¹, Elisabetta Groaz¹, Steven De Jonghe², Robert Snoeck², Graciela Andrei², Piet Herdewijn¹.

Abstract

A series of amidate prodrugs of cyclic 9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine (cHPMPA) featuring different amino acid motifs were synthesized. All phosphonamidates derived from (S)-cHPMPA displayed a broad spectrum activity against herpesviruses with EC50 values in the low nanomolar range. A phosphonobisamidate prodrug of (S)-HPMPA also exhibited a remarkably potent antiviral activity. In addition, the leucine ester prodrug of (S)-cHPMPA and phosphonobisamidate valine ester prodrug of (S)-HPMPA proved stable in human plasma. These data warrant further development of cHPMPA prodrugs, especially against human cytomegalovirus (HCMV), for which there is a high need for treatment in transplant recipients.

Entities: Chemical Species

Year: 2018 PMID： 29670705 PMCID： PMC5900341 DOI： 10.1021/acsmedchemlett.8b00079

Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345

23 in total

1. Tyrosine-based 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine and -adenine ((S)-HPMPC and (S)-HPMPA) prodrugs: synthesis, stability, antiviral activity, and in vivo transport studies.

Authors: Valeria M Zakharova; Michaela Serpi; Ivan S Krylov; Larryn W Peterson; Julie M Breitenbach; Katherine Z Borysko; John C Drach; Mindy Collins; John M Hilfinger; Boris A Kashemirov; Charles E McKenna
Journal: J Med Chem Date: 2011-08-03 Impact factor: 7.446

Review 2. Herpesvirus DNA polymerases: Structures, functions and inhibitors.

Authors: Karima Zarrouk; Jocelyne Piret; Guy Boivin
Journal: Virus Res Date: 2017-01-30 Impact factor: 3.303

3. Antiviral activity of anti-cytomegalovirus agents (HPMPC, HPMPA) assessed by a flow cytometric method and DNA hybridization technique.

Authors: R Snoeck; D Schols; G Andrei; J Neyts; E De Clercq
Journal: Antiviral Res Date: 1991-07 Impact factor: 5.970

4. Amidate Prodrugs of Deoxythreosyl Nucleoside Phosphonates as Dual Inhibitors of HIV and HBV Replication.

Authors: Chao Liu; Shrinivas G Dumbre; Christophe Pannecouque; Chunsheng Huang; Roger G Ptak; Michael G Murray; Steven De Jonghe; Piet Herdewijn
Journal: J Med Chem Date: 2016-10-17 Impact factor: 7.446

5. A novel selective broad-spectrum anti-DNA virus agent.

Authors: E De Clercq; A Holý; I Rosenberg; T Sakuma; J Balzarini; P C Maudgal
Journal: Nature Date: 1986 Oct 2-8 Impact factor: 49.962

6. Conversion of 1-[((S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl]cytosine to cidofovir by an intracellular cyclic CMP phosphodiesterase.

Authors: D B Mendel; T Cihlar; K Moon; M S Chen
Journal: Antimicrob Agents Chemother Date: 1997-03 Impact factor: 5.191

7. Discovery of GS-9131: Design, synthesis and optimization of amidate prodrugs of the novel nucleoside phosphonate HIV reverse transcriptase (RT) inhibitor GS-9148.

Authors: Richard L Mackman; Adrian S Ray; Hon C Hui; Lijun Zhang; Gabriel Birkus; Constantine G Boojamra; Manoj C Desai; Janet L Douglas; Ying Gao; Deborah Grant; Genevieve Laflamme; Kuei-Ying Lin; David Y Markevitch; Ruchika Mishra; Martin McDermott; Rowchanak Pakdaman; Oleg V Petrakovsky; Jennifer E Vela; Tomas Cihlar
Journal: Bioorg Med Chem Date: 2010-03-27 Impact factor: 3.641

8. Expanding the Antiviral Spectrum of 3-Fluoro-2-(phosphonomethoxy)propyl Acyclic Nucleoside Phosphonates: Diamyl Aspartate Amidate Prodrugs.

Authors: Min Luo; Elisabetta Groaz; Graciela Andrei; Robert Snoeck; Raj Kalkeri; Roger G Ptak; Tracy Hartman; Robert W Buckheit; Dominique Schols; Steven De Jonghe; Piet Herdewijn
Journal: J Med Chem Date: 2017-07-06 Impact factor: 7.446

Amidate Prodrugs of Cyclic 9-(S)-[3-Hydroxy-2-(phosphonomethoxy)propyl]adenine with Potent Anti-Herpesvirus Activity.

1. Tyrosine-based 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine and -adenine ((S)-HPMPC and (S)-HPMPA) prodrugs: synthesis, stability, antiviral activity, and in vivo transport studies.

Review 2. Herpesvirus DNA polymerases: Structures, functions and inhibitors.

3. Antiviral activity of anti-cytomegalovirus agents (HPMPC, HPMPA) assessed by a flow cytometric method and DNA hybridization technique.

4. Amidate Prodrugs of Deoxythreosyl Nucleoside Phosphonates as Dual Inhibitors of HIV and HBV Replication.

5. A novel selective broad-spectrum anti-DNA virus agent.

6. Conversion of 1-[((S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl]cytosine to cidofovir by an intracellular cyclic CMP phosphodiesterase.

7. Discovery of GS-9131: Design, synthesis and optimization of amidate prodrugs of the novel nucleoside phosphonate HIV reverse transcriptase (RT) inhibitor GS-9148.

8. Expanding the Antiviral Spectrum of 3-Fluoro-2-(phosphonomethoxy)propyl Acyclic Nucleoside Phosphonates: Diamyl Aspartate Amidate Prodrugs.

Review 9. Antivirals for the treatment of herpesvirus infections.

10. Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines.

Review 1. Phosphonates and Phosphonate Prodrugs in Medicinal Chemistry: Past Successes and Future Prospects.

2. Amidate Prodrugs of O-2-Alkylated Pyrimidine Acyclic Nucleosides Display Potent Anti-Herpesvirus Activity.

Review 3. Overview of Biologically Active Nucleoside Phosphonates.

Review 4. Advances and Perspectives in the Management of Varicella-Zoster Virus Infections.