Substrate properties of C5-substituted pyrimidine 2'-deoxynucleoside 5'-triphosphates for thermostable DNA polymerases during PCR

In order to enhance a collection of modified deoxynucleoside triphosphates useful for in vitro selection or SELEX (systematic evolution of ligands by exponential enrichment) techniques, we designed and synthesized modified analogues of 2'-deoxyuridine triphosphate and 2'-deoxycytidine triphosphate bearing a flexible and hydrophilic 7-amino-2,5-dioxaheptyl linker at a C5 position. Both analogues were found to be substrates for thermostable DNA polymerases which belong to an evolutional family B during PCR.     

3-iodo-4-phenoxypyridinones (IOPY's), a new family of highly potent non-nucleoside inhibitors of HIV-1 reverse transcriptase

Building upon the potent anti-HIV-1 activities observed for the 3-dimethylamino-4-benzylpyridinone 2, and the corresponding 4-aryloxypyridinone analogue 3, a concise and efficient route to the 3-iodo-4-aryloxypyridinones 14a–c (IOPY's) was developed. This involved reaction of the 4-hydroxy substituted pyridinone 10 with the requisite dichloroiodobenzene reagent 11. IOPY compound 14c is active at IC₅₀=1–45 nM against wild type HIV-1 and a panel of six major simple/double HIV mutant strains.     

Discovery of triazolinone non-nucleoside inhibitors of HIV reverse transcriptase

Novel non-nucleoside inhibitors of HIV-RT that contain pyridazinone isosteres were prepared, and a series of triazolinones were found to be potent inhibitors of HIV replication. These compounds were active against several NNRTI-resistant virus strains. Pharmacokinetic studies indicated that inhibitor 7e has good bioavailability in rats. Several fragments of inhibitor 7c were prepared, and the binding of these compounds to HIV-RT was analyzed by surface plasmon resonance spectroscopy.