항 바이러스제로서 새로운 5′-데옥시뉴클레오사이드 포스폰산의 합성

Abstract

Novel Fluorinated phosphonic acid analogues were designed and synthesized to mimic naturally occurring purine monophosphate from commercially available 1,3-dihydroxyacetone. The discovery of threosyl phosphonate nucleoside (PMDTA, EC50 = 2.53 μM) as a potent anti-HIV agent has led to the synthesis and biological evaluation of 2',3'-modified 5'-deoxyversions of the threosyl phosphonate nucleosides. The synthesized 2´-fluoro-3´-hydroxymethyl 5´-deoxythreosyl phosphonic acid nucleoside analogues 14, 18, 23, and 27 were tested for anti-HIV activity as well as cytotoxicity. The adenine analogue 18 exhibits weak in vitro anti-HIV-1 activity (EC50 = 19.2 μM)