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Nucleoside Phosphonates (nucleoside + phosphonate)

Distribution by Scientific Domains
Chemistry100%

Selected Abstracts

Synthesis of acyclic nucleoside phosphonates as antiviral compounds

JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 5 2000
Frank Wormstädt
Reaction of 6-chloropyrimidines with diethyl [(2-aminoethoxy)methyl]phosphonate allows for a ready access to acyclic nucleoside phosphonates. A series of 5-substituted pyrimidines bearing a phosphonate side chain at position 6 were synthesized and tested against herpes simplex viruses (HSV-1 and HSV-2) and human immunodeficiency virus (HIV-1). Some compounds showed weak antiviral activity against HSV-1. [source]

Yet another ten stories on antiviral drug discovery (part D): Paradigms, paradoxes, and paraductions

MEDICINAL RESEARCH REVIEWS, Issue 4 2010
Erik De Clercq
Abstract This review article presents the fourth part (part D) in the series of stories on antiviral drug discovery. The stories told in part D focus on: (i) the cyclotriazadisulfonamide compounds; (ii) the {5-[(4-bromophenylmethyl]-2-phenyl-5H -imidazo[4,5- c]pyridine} compounds; (iii) (1H,3H -thiazolo[3,4- a]benzimidazole) derivatives; (iv) T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) and (v) its structurally closely related analogue pyrazine 2-carboxamide (pyrazinamide); (vi) new strategies for the treatment of hemorrhagic fever virus infections, including, as the most imminent, (vii) dengue fever, (viii) the veterinary use of acyclic nucleoside phosphonates; (ix) the potential (off-label) use of cidofovir in the treatment of papillomatosis, particularly RRP (recurrent respiratory papillomatosis); and (x) finally, the prophylactic use of tenofovir to prevent HIV infections. © 2009 Wiley Periodicals, Inc. Med Res Rev, 30, No. 4, 667,707, 2010 [source]

Novel multisubstrate inhibitors of mammalian purine nucleoside phosphorylase

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 11 2005
Angela V. Toms
In an effort to develop potent multisubstrate-analog inhibitors of purine nucleoside phosphorylase (PNP), three nucleoside phosphonates were designed utilizing structural information from the previously reported structures of complexes of bovine PNP with substrates and products. The nucleoside phosphonates contain an acetal linkage at the O2, and O3, positions and a two-C-atom spacer between the ribose and phosphate moieties. The linkage enables the compounds to simultaneously occupy the purine-, ribose- and phosphate-binding sites. The chemical syntheses, inhibition profiles and structural characterization of these novel multisubstrate analog inhibitors with bovine PNP are described. [source]

Aryloxy Phosphoramidate Triesters: a Technology for Delivering Monophosphorylated Nucleosides and Sugars into Cells

CHEMMEDCHEM, Issue 11 2009
Youcef Mehellou Dr.
Abstract Prodrug technologies aimed at delivering nucleoside monophosphates into cells (protides) have proved to be effective in improving the therapeutic potential of antiviral and anticancer nucleosides. In these cases, the nucleoside monophosphates are delivered into the cell, where they may then be further converted (phosphorylated) to their active species. Herein, we describe one of these technologies developed in our laboratories, known as the phosphoramidate protide method. In this approach, the charges of the phosphate group are fully masked to provide efficient passive cell-membrane penetration. Upon entering the cell, the masking groups are enzymatically cleaved to release the phosphorylated biomolecule. The application of this technology to various therapeutic nucleosides has resulted in improved antiviral and anticancer activities, and in some cases it has transformed inactive nucleosides to active ones. Additionally, the phosphoramidate technology has also been applied to numerous antiviral nucleoside phosphonates, and has resulted in at least three phosphoramidate-based nucleotides progressing to clinical investigations. Furthermore, the phosphoramidate technology has been recently applied to sugars (mainly glucosamine) in order to improve their therapeutic potential. The development of the phosphoramidate technology, mechanism of action and the application of the technology to various monophosphorylated nucleosides and sugars will be reviewed. [source]