166318-75-8

Upstream product

• 104-87-0 4-methyl-benzaldehyde 
• 151029-28-6 5',5'-Di-O-(3'-azido-2',3'-dideoxythymidinyl) H-phosphonate diester 

Downstream Products

• 30516-87-1 3'-azido-2',3'-deoxythymidine 
• 124930-59-2 3'-azido-3'-deoxythymidin-5'-yl H-phosphonate monoester 

Relevant academic research and scientific papers

Homo dinucleoside-α-hydroxyphosphonate diesters as prodrugs of the antiviral nucleoside analogues 2',3'-dideoxythymidine and 3'-azido-2',3'- dideoxythymidine

The synthesis of a new prodrug system for antiviral nucleosides AZT (1) and ddT (2) based on α-hydroxyhenzylphosphonates 3 is described. 3 hydrolyze via different mechanisms yielding the H-phosphonate monoesters 4 or nucleoside monophosphates 5, respectively, 3 were more lipophilic than 1, 2 and showed marked activity against HIV-1/2.

Lipophilic &α-Hydroxybenzylphosphonates as Prodrugs of 3'-Azido-2',3'-dideoxythymidine (AZT)

The α-hydroxybenzylphosphonates 1a-1j of the antiviral drug 3'-azido-2',3'-dideoxythymidine 5 (AZT) as potential lipophilic prodrugs were readily accessible in 49percent to 87percent yield via a four-step synthetic pathway introducing the modifications in the aromatic ring system in the last step by making use of intermediate 6.All compounds 1a-1j exhibited higher partition coefficients in 1-octanol/water than AZT (5).In hydrolysis studies at pH 7.5 we observed that precursors to bioactive compounds were delivered by simple hydrolysis of the lipophilic precursors 1a-1j via two different mechanisms: the phosphonate-phosphate rearrangement leading to the benzylphosphotriesters 2 and/or the direct cleavage into the di-AZT phosphonate 6.Both compounds 2 and 6 were further degraded yielding the potentially antiviral active compounds 4 and 8, respectively.The hydrolysis pathway could be controlled by the substitution pattern in the benzylic moiety.Identical hydrolytic behavior of 1 was detected in "biological" hydrolysis kinetics by using a RPMI culture medium containing 10percent heat-inactivated fetal calf serum (FCS).The title compounds 1a-1j exhibited considerable HIV-1 and HIV-2 activity in wild-type CEM/O cells. - Keywords: AZT; Nucleoside α-hydroxybenzylphosphonates; Phosphonate-phosphate rearrangement; Prodrugs; HIV chemotherapy