138247-60-6

Upstream product

• 1443683-73-5 C₁₃H₂₁ClN₅O₄P 
• 352211-52-0 C₈H₁₀ClN₅O 
• 10310-21-1 2-Amino-6-chloropurin 
• 160616-48-8 [(R)-2-(2-Benzoylamino-6-oxo-1,6-dihydro-purin-9-yl)-1-methyl-ethoxymethyl]-phosphonic acid diisopropyl ester 
• 160616-45-5 (R)-9-(2-hydroxypropyl)-N²-benzoylguanine 
• 160616-38-6 (R)-9-<2-(2-tetrahydropyranyloxy)propyl>2-amino-6-chloropurine 
• 160616-37-5 (R)-9-(2-hydroxypropyl)guanine 
• 138271-96-2 (S)-2-amino-6-chloro-9-<2-<(diisopropylphosphono)methoxy>propyl>purine 
• 170169-11-6 [(R)-2-(2-Amino-6-oxo-1,6-dihydro-purin-9-yl)-1-methyl-ethoxymethyl]-phosphonic acid diisopropyl ester 
• 170169-11-6 bis(2-propyl) (R)-9-(2-phosphonomethoxypropyl)guanine 

Relevant academic research and scientific papers

Inhibition of human purine nucleoside phosphorylase by tenofovir phosphate congeners

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.

GUANINE ANALOGS AS TELOMERASE SUBSTRATES AND TELOMERE LENGTH AFFECTORS

This invention relates to compounds useful for inhibiting telomere elongation. More specifically, the invention provides nucleotide analogs that are incorporated into telomeres by telomerase thereby inhibiting elongation of telomeres. The compounds are useful in treating cancer and other cell proliferative diseases.

SYNTHESIS OF ENANTIOMERIC N-(2-PHOSPHONOMETHOXYPROPYL) DERIVATIVES OF PURINE AND PYRIMIDINE BASES. I. THE STEPWISE APPROACH

The (R)- and (S)-N-(2-phosphonomethoxypropyl) derivatives of purine and pyrimidine bases (PMP derivatives) exhibit very high activity against retroviruses.This paper describes the synthesis of enantiomeric 9-(2-phosphonomethoxypropyl)adenines (I and XXVII), 9-(2-phosphonomethoxypropyl)-2,6-diaminopurines (II and XXXI), 9-(2-phosphonomethoxypropyl)guanines (III and XXIX) and 1-(R)-(2-phosphonomethoxypropyl)cytosine (XIX) by alkylation of N-protected N-(2-hydroxypropyl) derivatives of the corresponding bases with bis(2-propyl) p-toluenesulfonyloxymethylphosphonate (X), followed by stepwise N- and O-deprotection of the intermediates.The key intermediates, N-(2-hydropxypropyl) derivatives IX and XXV, were obtained by alkylation of the appropriate heterocyclic base with (R)- or (S)-2-(2-tetrahydropyranyloxy)propyl p-toluenesulfonate (VII or XXIII) ans acid hydrolysis of the resulting N- derivatives VIII and XXII.The chiral synthons were prepared by tosylation of (R)- or (S)-2-(2-tetrahydropyranyloxy)propanol (VI or XXI) available by reduction of enantiomeric alkyl 2-O-tetrahydropyranyllactates V and XXI with sodium bis(2-methoxyethyoxy)aluminum hydride.This approach was used for the synthsis of cytosine, adenine and 2,6-diaminopurine derivatives, while compounds derived from guanine were prepared by hydrolysis of 2-amino-6-chloropurine intermediates.Cytosine derivative IXe was also synthesized by alkylation of 4-methoxy-2-pyrimidone followed by ammonolysis of the intermediate IXf.

SYNTHESIS OF ENANTIOMERIC N-(2-PHOSPHONOMETHOXYPROPYL)DERIVATIVES OF PURINE AND PYRIMIDINE BASES. II. THE SYNTHON APPROACH

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.

Synthesis and antiviral activity of methyl derivatives of 9-[2- (phosphonomethoxy)ethyl]guanine

A number of methyl derivatives of 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG, 1) have been synthesized and tested in vitro for anti-herpes and anti- human immunodeficiency virus (HIV) activity. Among these analogues, (R)-2'- methyl-PMEG [(R)-3] and 2',2'-