From norbornane-based nucleotide analogs locked in South conformation to novel inhibitors of feline herpes virus

0428690 - ÚOCHB 2015 RIV GB eng J - Článek v odborném periodiku
Dejmek, Milan - Hřebabecký, Hubert - Šála, Michal - Dračínský, Martin - Procházková, Eliška - Leyssen, P. - Neyts, J. - Balzarini, J. - Nencka, Radim
From norbornane-based nucleotide analogs locked in South conformation to novel inhibitors of feline herpes virus.
Bioorganic & Medicinal Chemistry. Roč. 22, č. 11 (2014), s. 2974-2983. ISSN 0968-0896. E-ISSN 1464-3391
Grant CEP: GA MV VG20102015046
Institucionální podpora: RVO:61388963
Klíčová slova: carbocyclic nucleosides * nucleoside phosphonates * purine * norbornane * feline herpes virus
Kód oboru RIV: CC - Organická chemie
Impakt faktor: 2.793, rok: 2014

A synthetic route toward a series of unique cyclic nucleoside phosphonates locked in South conformation is described. The desired conformation is stabilized by a substitution of the sugar moiety by bicyclo[2.2.1] heptane (norbornane) bearing a purine or pyrimidine nucleobase in the bridgehead position. Although the final phosphonate derivatives are devoid of any significant antiviral activity probably due to the unfavorable conformational properties, several intermediates and their analogs exhibit surprising activity against feline herpes virus. Since these compounds do not possess an appropriate hydroxymethyl function allowing phosphorylation and subsequent incorporation into the polynucleotide chain, it seems to be likely that these compounds act by a novel unknown mechanism of action and may represent a new possible alternative for nucleoside and nucleotide therapeutics of this widely spread feline infection. A number of derivatives exerted also a significant antiviral activity against Coxsackievirus B3 and B4.
Trvalý link: http://hdl.handle.net/11104/0234000