Choo, Hyunah Beadle, James R. Kern, Earl R. Prichard, Mark N. Keith, Kathy A. Hartline, Caroll B. Trahan, Julissa Aldern, Kathy A. Korba, Brent E. Hostetler, Karl Y. 2024-01-21T01:34:12Z 2024-01-21T01:34:12Z 2021-08-31 2007-02 0066-4804 https://pubs.kist.re.kr/handle/201004/134716 Three acyclic nucleoside phosphonates are currently approved for clinical use against infections caused by cytomegallovirus (Vistide), hepatitis B virus (Hepsera), and human immunodeficiency virus type 1 (Viread). This important antiviral class inhibits viral polymerases after cellular uptake and conversion to their diphosphates, bypassing the first phosphorylation, which is required for conventional nucleoside antivirals. Small chemical alterations in the acyclic side chain lead to marked differences in antiviral activity and the spectrum of activity of acyclic nucleoside phosphonates against various classes of viral agents. We synthesized a new class of acyclic nucleoside phosphonates based on a 5-phosphono-pent-2-en-1-yl base motif in which the oxygen heteroatom usually present in acyclic nucleoside phosphonates has been replaced with a double bond. Since the intrinsic phosphonate moiety leads to low oral bioavailabillity and impaired cellular penetration, we also prepared the hexadecyloxypropyl esters of the 5-phosphono-pent-2-en-1-yl nucleosides. Our earlier work showed that this markedly increases antiviral activity and oral bioavailability. Although the 5-phosphonopent-2-en-1-yl nucleosides themselves were not active, the hexadecyloxypropyl esters were active against DNA viruses and hepatitis B virus, in vitro. Notably, the hexadecyloxypropyl ester of 9-(5-phosphono-pent-2-en-lyl)-adenine was active against hepatitis B virus mutants resistant to lamivudine, emtricitabine, and adefovir. English AMER SOC MICROBIOLOGY REPLICATION IN-VITRO HEPATITIS-B CYCLIC CIDOFOVIR HUMAN CYTOMEGALOVIRUS PHOSPHONATE ANALOGS NUCLEOTIDE ANALOGS VIRUS-INFECTION ALKYL ESTERS LIPID ESTERS RESISTANCE Antiviral activities of novel 5-phosphono-pent-2-en-1-yl nucleosides and their alkoxyalkyl phosphonoesters Article 10.1128/AAC.00444-06 1 ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, v.51, no.2, pp.611 - 615 ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 51 2 611 615 scie scopus 000243900600029 2-s2.0-33846624157 Microbiology Pharmacology & Pharmacy Microbiology Pharmacology & Pharmacy Article REPLICATION IN-VITRO HEPATITIS-B CYCLIC CIDOFOVIR HUMAN CYTOMEGALOVIRUS PHOSPHONATE ANALOGS NUCLEOTIDE ANALOGS VIRUS-INFECTION ALKYL ESTERS LIPID ESTERS RESISTANCE antiviral agent nucleoside phosphonoester