Synthesis and anti-HIV activity of cyclic pyrimidine phosphonomethoxy nucleosides and their prodrugs: A comparison of phosphonates and corresponding nucleosides

Richard L. Mackman; Lijun Zhang; Vidya Prasad; Constantine G. Boojamra; James Chen; Janet Douglas; Deborah Grant; Genevieve Laflamme; Hon Hui; Choung U. Kim; Jay Parrish; Antitsa D. Stoycheva; Swami Swaminathan; Ke Yu Wang; Tomas Cihlar

doi:10.1080/15257770701490126

Synthesis and anti-HIV activity of cyclic pyrimidine phosphonomethoxy nucleosides and their prodrugs: A comparison of phosphonates and corresponding nucleosides

Richard L. Mackman, Lijun Zhang, Vidya Prasad, Constantine G. Boojamra, James Chen, Janet Douglas, Deborah Grant, Genevieve Laflamme, Hon Hui, Choung U. Kim, Jay Parrish, Antitsa D. Stoycheva, Swami Swaminathan, Ke Yu Wang, Tomas Cihlar

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Cyclic phosphonomethoxy pyrimidine nucleosides that are bioisosteres of the monophosphate metabolites of HIV reverse transcriptase (RT) inhibitors AZT, d4T, and ddC have been synthesized. The RT inhibitory activities of the phosphonates were reduced for both dideoxy (dd) and dideoxydidehydro (d4) analogs compared to the nucleosides. Bis-isopropyloxymethylcarbonyl (BisPOC) prodrugs were prepared on selected compounds and provided > 150-fold improvements in antiviral activity.

Original language	English (US)
Pages (from-to)	573-577
Number of pages	5
Journal	Nucleosides, Nucleotides and Nucleic Acids
Volume	26
Issue number	6-7
DOIs	https://doi.org/10.1080/15257770701490126
State	Published - Jun 2007
Externally published	Yes

Keywords

Antiviral
HIV
Phosphonate
Prodrugs

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Genetics

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10.1080/15257770701490126

Cite this

Mackman, R. L., Zhang, L., Prasad, V., Boojamra, C. G., Chen, J., Douglas, J., Grant, D., Laflamme, G., Hui, H., Kim, C. U., Parrish, J., Stoycheva, A. D., Swaminathan, S., Wang, K. Y., & Cihlar, T. (2007). Synthesis and anti-HIV activity of cyclic pyrimidine phosphonomethoxy nucleosides and their prodrugs: A comparison of phosphonates and corresponding nucleosides. Nucleosides, Nucleotides and Nucleic Acids, 26(6-7), 573-577. https://doi.org/10.1080/15257770701490126

Synthesis and anti-HIV activity of cyclic pyrimidine phosphonomethoxy nucleosides and their prodrugs: A comparison of phosphonates and corresponding nucleosides. / Mackman, Richard L.; Zhang, Lijun; Prasad, Vidya et al.
In: Nucleosides, Nucleotides and Nucleic Acids, Vol. 26, No. 6-7, 06.2007, p. 573-577.

Research output: Contribution to journal › Article › peer-review

Mackman, RL, Zhang, L, Prasad, V, Boojamra, CG, Chen, J, Douglas, J, Grant, D, Laflamme, G, Hui, H, Kim, CU, Parrish, J, Stoycheva, AD, Swaminathan, S, Wang, KY & Cihlar, T 2007, 'Synthesis and anti-HIV activity of cyclic pyrimidine phosphonomethoxy nucleosides and their prodrugs: A comparison of phosphonates and corresponding nucleosides', Nucleosides, Nucleotides and Nucleic Acids, vol. 26, no. 6-7, pp. 573-577. https://doi.org/10.1080/15257770701490126

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AU - Prasad, Vidya

AU - Boojamra, Constantine G.

AU - Chen, James

AU - Douglas, Janet

AU - Grant, Deborah

AU - Laflamme, Genevieve

AU - Hui, Hon

AU - Kim, Choung U.

AU - Parrish, Jay

AU - Stoycheva, Antitsa D.

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AU - Cihlar, Tomas

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AB - Cyclic phosphonomethoxy pyrimidine nucleosides that are bioisosteres of the monophosphate metabolites of HIV reverse transcriptase (RT) inhibitors AZT, d4T, and ddC have been synthesized. The RT inhibitory activities of the phosphonates were reduced for both dideoxy (dd) and dideoxydidehydro (d4) analogs compared to the nucleosides. Bis-isopropyloxymethylcarbonyl (BisPOC) prodrugs were prepared on selected compounds and provided > 150-fold improvements in antiviral activity.

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Synthesis and anti-HIV activity of cyclic pyrimidine phosphonomethoxy nucleosides and their prodrugs: A comparison of phosphonates and corresponding nucleosides

Abstract

Keywords

ASJC Scopus subject areas

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