1383381-63-2

Upstream product

• 13269-89-1 diethyl 2-(bis(2-hydroxyethyl)amino)ethylphosphonate 
• 76-83-5 trityl chloride 
• 682-30-4 Diethyl vinylphosphonate 

Downstream Products

• 1383381-71-2 diethyl 9-[(N-(2-(trityloxy)ethyl)-N-(2-phosphonoethyl))-2-aminoethyl]-6-chloropurine 
• 1383381-79-0 C₅₂H₅₃ClN₆O₄P₂ 

Relevant academic research and scientific papers

6-OXOPURINE PHOSPHORIBOSYLTRANSFERASE INHIBITORS

The invention relates to compounds which are useful as inhibitors of 6-oxopurine phosphoribosyltransferases such as hypoxanthine-guanine-(xanthine) phosphoribosyltransferase (HG(X)PRT).

Synthesis of novel N-branched acyclic nucleoside phosphonates as potent and selective inhibitors of human, plasmodium falciparum and plasmodium vivax 6-oxopurine phosphoribosyltransferases

Hypoxanthine-guanine-(xanthine) phosphoribosyltransferase (HG(X)PRT) is crucial for the survival of malarial parasites Plasmodium falciparum (Pf) and Plasmodium vivax (Pv). Acyclic nucleoside phosphonates (ANPs) are inhibitors of HG(X)PRT and arrest the growth of Pf in cell culture. Here, a novel class of ANPs containing trisubstituted nitrogen (aza-ANPs) has been synthesized. These compounds have a wide range of Ki values and selectivity for human HGPRT, PfHGXPRT, and PvHGPRT. The most selective and potent inhibitor of PfHGXPRT is 9-[N-(3-methoxy-3-oxopropyl)-N-(2-phosphonoethyl)-2-aminoethyl] hypoxanthine (Ki = 100 nM): no inhibition could be detected against the human enzyme. This compound exhibits the highest ever reported selectivity for PfHGXPRT compared to human HGPRT. For PvHGPRT, 9-[N-(2-carboxyethyl)-N-(2- phosphonoethyl)-2-aminoethyl]guanine has a Ki of 50 nM, the best inhibitor discovered for this enzyme to date. Docking of these compounds into the known structures of human HGPRT in complex with ANP-based inhibitors suggests reasons for the variations in affinity, providing insights for the design of antimalarial drug candidates.