Design and Synthesis of Dually Branched 5′-Norcarbocyclic Adenosine Phosphonodiester Analogue as a New Anti-HIV Prodrug

Abstract

A novel 3',4'-dimethyl-5'-norcarbocyclic adenosine phosphonic acid was prepared using acyclic stereoselective route from 4-hydroxybutan-2-one (4). To improve the cellular permeability and enhance the anti-HIV activity of this phosphonic acid, a (bis)SATE phosphonodiester nucleoside prodrug (20) was prepared and its chemical stability was evaluated. The newly synthesized bis(SATE) analogue (20) and its parent nucleoside phosphonic acid (18) were assayed for anti-HIV activity using an in vitro assay system in a CEM cell line.

Prodrugs of Phosphonates and Phosphates: Crossing the Membrane Barrier

“…However, an advantage of this group is that it can be applied to both phosphonates (e.g. compound 24 , [63]) and phosphates (e.g. compound 25 , [64])…”

Blocking of Exchange Proteins Directly Activated by cAMP Leads to Reduced Replication of Middle East Respiratory Syndrome Coronavirus

“…In addition, it does so, not only without the need for treatment prior to infection, but also with an extended therapeutic window. Incidentally, adenosine and its analogs have been successfully investi- gated as potent inhibitors of the replication of hepatitis C virus, vaccinia virus, HIV-1, dengue virus, and other flaviviruses (29)(30)(31)(32). The dual role of CD26 as the MERS-CoV receptor and an adenosine deaminase (ADA)-anchoring protein (33)(34)(35)(36) provides a potential linkage between MERS-CoV infection and cAMP signaling.…”