147127-19-3Relevant articles and documents
Tenofovirpurification method
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Paragraph 0047-0049; 0064, (2020/01/25)
The invention provides a tenofovir purification method, which comprises: S1) dissolving a tenofovir crude product in an alkali liquid, and adjusting the pH value of the system to 6-12; and S2) adjusting the pH value of the system to 2.8-3.4 with an acid, and separating the solid to obtain a pure tenofovir product. According to the invention, tenofovir is dissolved in an alkaline environment to carry out a hydrolysis reaction on the main impuritycondensation impurity, and the product can be precipitated in an acid environment, so that various impurities in the tenofovir can be effectively reduced, the product quality is improved, the yield and the purity are greatly improved, the operation is easy and convenient, and the method is easy to apply to industrial production.
Inhibition of human purine nucleoside phosphorylase by tenofovir phosphate congeners
Votruba, Ivan,Tryznova, Jana,Brehova, Petra,Tloustova, Eva,Horska, Kvetoslava,Fanfrlik, Jindrich,Prenosil, Ondrej,Holy, Antonin
experimental part, p. 1249 - 1257 (2011/09/30)
The structure-activity study on the phosphates of phosphonomethoxypropyl derivatives of purine bases interacting with human purine nucleoside phosphorylase has shown that the most efficient inhibitors of the enzyme are (R)- and (S)-PMPGp with Ki ~ 1.9 × 10-8 and/or 2.2 × 10-8 mol/l. The kinetic experiments have proven, with the exception of both enantiomers of PMP-8-BrDAPp, strictly competitive character of inhibition for all ANP monophosphates tested. Bromine derivatives exhibited uncompetitive and mixed type of inhibition as well. These results were confirmed by docking studies. The substitution of purine moiety with the bromine at the position 8 lead to an allosteric binding of these compounds toward the enzyme.
SYNTHESIS OF ENANTIOMERIC N-(2-PHOSPHONOMETHOXYPROPYL)DERIVATIVES OF PURINE AND PYRIMIDINE BASES. II. THE SYNTHON APPROACH
Holy, Antonin,Dvorakova, Hana,Masojidkova, Milena
, p. 1390 - 1409 (2007/10/02)
Another approach to (R)- and (S)-N-(2-phosphonomethoxypropyl) derivatives of purine and pyrimidine bases (PMP derivatives) I and II is described, consisting in alkylation of the heterocyclic base with (R)- and (S)-2-propyl p-toluenesulfonates (X and XVIII) followed by transsilylation of the intermediary N- derivatives XI and XIX.The key intermediates X and XVIII were obtained from 1-benzyloxypropanols VI and XIV by two routes: (i) condensation with bis(2-propyl) p-toluenesulfonyloxymethylphosphonate (XIII), hydrogenolysis of the obtained 1-benzyloxy-2-bis(2-propyl)phosphonylmethoxypropanes VIII and XVI over Pd/C to 2-bis(2-propyl)phosphonylmethoxypropanols IX and XVII and tosylation of the latter or (ii) chloromethylation of compounds VI and XIV and subsequent reaction of the chloromethyl ethers VII and XV with tris(2-propyl) phosphite and further processing of the benzyl ethers VIII and XVI analogous to the enantiomeric propanols IX and XVII.This approach was used for the synthesis of derivatives of adenine (Ia, IIa), 2,6-diaminopurine (Ib, IIb) and 3-deazaadenine (Ic, IIc).Their guanine counterparts Ie and IIe were prepared by hydrolysis of 2-amino-6-chloropurine intermediates XId and XIXd. 6-Chloropurine was converted into diester XIi by reaction with tosylate X, which on reaction with thiourea and subsequent ester cleavage afforded the 6-thiopurine derivative Ij.Analogously, 2-amino-6-chloropurine derivative XId reacted with thiourea to give 9-(R)-(2-phosphonomethoxypropyl)-2-thioguanine (If), or with dimethylamine under formation of (2-phosphonomethoxypropyl)-2-amino-6-dimethylaminopurine (Ig).Hydrogenolysis of compound XId gave 9-(R)-(2-phosphonomethoxypropyl)-2-aminopurine (Ik).Hydrolytic deamination of adenine derivatives Ia and IIa led to enantiomeric (2-phoshonomethoxypropyl)hypoxanthines Ih and IIh.
