144822-48-0

Usage

Chemical class

Pyrimidine nucleoside analogs

Application

Antiviral drug for HIV and hepatitis B treatment

Mechanism of action

Interferes with viral replication

Target enzyme

Reverse transcriptase

Potency

Potent inhibitor of reverse transcriptase

Structure

Allows effective binding to the active site of the enzyme

Function

Inhibits enzyme function and suppresses viral replication

Components

a. 5-O-[Bis(4-methoxyphenyl)phenylmethyl] group
b. 2-deoxy-2-fluoro-beta-D-arabinofuranosyl sugar moiety
c. 5-methyl-2,4(1H,3H)-pyrimidinedione base

Fluorination

Presence of a 2-fluoro group in the sugar moiety

Methylation

Presence of a 5-methyl group in the base

Phenyl groups

Bis(4-methoxyphenyl)phenylmethyl group attached to the sugar moiety

Methoxy groups

Two 4-methoxy groups on the phenyl rings of the bis(4-methoxyphenyl)phenylmethyl group

Stereochemistry

beta-D-arabinofuranosyl configuration in the sugar moiety

InChI:InChI=1/C31H31FN2O7/c1-19-17-34(30(37)33-28(19)36)29-26(32)27(35)25(41-29)18-40-31(20-7-5-4-6-8-20,21-9-13-23(38-2)14-10-21)22-11-15-24(39-3)16-12-22/h4-17,25-27,29,35H,18H2,1-3H3,(H,33,36,37)/t25-,26+,27-,29?/m1/s1

Upstream product

• 40615-36-9 4,4'-dimethoxytrityl chloride 
• 69256-17-3 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)thymine 
• 65-71-4 thymin 
• 97614-43-2 1,3,5-tri-O-benzoyl-2-deoxy-2-fluoro-α-D-arabinofuranose 
• 97614-47-6 1-(3',5'-di-O-benzoyl-2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)thymine 
• 7288-28-0 2,4-bis(trimethylsiloxy)-5-methylpyrimidine 
• 97614-44-3 2-deoxy-2-fluoro-3,5-di-O-benzoyl-α-D-arabinofuranosyl bromide 

Downstream Products

• 40615-39-2 5'-O-(4-4'-dimethoxytrityl)thymidine 

Relevant academic research and scientific papers

S-ANTIGEN TRANSPORT INHIBITING OLIGONUCLEOTIDE POLYMERS AND METHODS

Various embodiments provide STOPS? polymers that are S-antigen transport inhibiting oligonucleotide polymers, processes for making them and methods of using them to treat diseases and conditions. In some embodiments the STOPS? modified oligonucleotides include an at least partially phosphorothioated sequence of alternating A and C units having modifications as described herein. The sequence independent antiviral activity against hepatitis B of embodiments of STOPS? modified oligonucleotides, as determined by HBsAg Secretion Assay, is an EC50 that is less than 100 nM.

C2′-F Stereoconfiguration As a Puckering Switch for Base Stacking at the Dinucleotide Level

Fluorine configuration at C2′ of the bis(2′-fluorothymidine) dinucleotide is demonstrated to drive intramolecular base stacking. 2′-β F-Configuration drastically reduces stacking compared to the 2′-α series. Hence, base stacking emerges as being tunable by the C2′-F stereoconfiguration through dramatic puckering variations scrutinized by NMR and natural bond orbital analysis. Accordingly, 2′-β F-isomer photoreactivity is significantly reduced compared to that of the 2′-α F-isomer.

Synthesis and anti-HIV activity of 2′-deoxy-2′-fluoro-4′-C-ethynyl nucleoside analogs

Based on the favorable antiviral profiles of 4′-substituted nucleosides, novel 1-(2′-deoxy-2′-fluoro-4′-C-ethynyl-β-d-arabinofuranosyl)-uracil (1a), -thymine (1b), and -cytosine (2) analogs were synthesized. Compounds 1b and 2 exhibited potent anti-HIV-1 activity with IC50 values of 86 and 1.34 nM, respectively, without significant cytotoxicity. Compound 2 was 35-fold more potent than AZT against wild-type virus, and also retained nanomolar antiviral activity against resistant strains, NL4-3 (K101E) and RTMDR. Thus, 2 merits further development as a novel NRTI drug.