Synthesis and biological evaluation of1',2'-seconucleo-5'- phosphonates.
A series of 1',2'-seconucleophosphonate analogues were prepared containing adenine, cytosine, thymine, and uracil as the nucleobase. The synthetic methodology is efficient and uses chloromethyl ethers derived from the chirons diethyl (3S)-(benzyloxy)-(2R)-hydroxybutane-phosphonate (1) and diethyl (3S),4-bis(benzyloxy)-(2R)-hydroxybutanephosphonate (2). Selected deblocked derivatives, i.e., two monoesters (13 and 14), four phosphonic acids (15-18), and one cyclic phosphonate (23), were screened for in vitro activity against certain RNA, adeno, and HIV viruses. All of them were found to be devoid of activity.
Racha
S
S
Department of Medicinal Chemistry, University of Rhode Island, Kingston, Rhode Island 02881, USA.
Vargeese
C
C
Vemishetti
P
P
El-Subbagh
H I
HI
Abushanab
E
E
Panzica
R P
RP
D000225:Adenine; D000260:Adenoviruses, Human / Q000187:drug effects; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D003553:Cystine; D006678:HIV / Q000187:drug effects; D015394:Molecular Structure; D009711:Nucleotides / Q000138:chemical synthesis* / Q000494:pharmacology; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D012328:RNA Viruses / Q000187:drug effects; D013941:Thymine; D014498:Uracil
D000998:Antiviral Agents; D009711:Nucleotides; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003553:Cystine; D014498:Uracil; D000225:Adenine; D013941:Thymine