Sulfide, sulfoxide and sulfone bridged acyclic nucleoside phosphonates as inhibitors of the Plasmodium falciparum and human 6-oxopurine phosphoribosyltransferases: Synthesis and evaluation

Abstract

sulfoxide and sulfone bridged acyclic nucleoside phosphonates as inhibitors of the Plasmodium falciparum and human 6-oxopurine phosphoribosyltransferases: Synthesis and evaluation,

Acyclic nucleoside phosphonates with adenine nucleobase inhibit Trypanosoma brucei adenine phosphoribosyltransferase in vitro

“…The thia-linked nucleotide analogs (thia-ANPs, Scheme 1 ) were prepared analogously to a known procedure 31 . Mitsunobu reaction of adenine with alcohols 1a and 1b in hot dioxane afforded compounds 2a and 2b , respectively.…”

“…The heteroatom increases the flexibility of the chain and modulates its position in the active site (compare activity of 3a and 3b ). While sulfur enables a change in the geometry via oxidation 31 , but results in the loss of the inhibitory activity (compare 3a and 4a ), nitrogen makes a facile attachment of the side chain possible. Moreover, these aza-ANPs are prochiral inhibitors ( 9a–9g and 17) , since nitrogen atom is protonated at physiological conditions.…”

“…Unless otherwise stated, the general remarks and methodology A, B, and C was adapted from Ref. 31 . Briefly, solvents were evaporated at 40 °C/2 kPa and prepared compounds were dried at 25–30 °C at 2 kPa.…”

“…Prepared by Method A from diisopropyl 5-hydroxy-2-thiapentanephosphonate 31 ( 1a ). Yield 0.68 g (35%).…”

1,2,3-Triazoles as leaving groups in SNAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

“…Compounds bearing a phosphonate moiety in their N9 side chain are well known as antiviral agents, such as adefovir, tenofovir, and cidofovir [7]. Lately, it was found that ANPs possess inhibitory activity against hypoxanthine-guanine-xanthine phosphoribosyltransferase of the parasite Plasmodium falciparum, and several research groups are focused on the development of this topic [8][9][10][11].…”