77421-68-2

Usage

Uses

Used in Pharmaceutical Synthesis:
[(2S,5R)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl]methyl acetate is used as an intermediate in the synthesis of nucleoside analogs for its potential applications in antiviral and anticancer drug development. Its unique structure allows for the creation of novel compounds with therapeutic properties.
Used in Chemical Research:
In the field of chemical research, [(2S,5R)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl]methyl acetate serves as a valuable compound for studying the properties and reactions of nucleoside derivatives. Its potential reactivity contributes to the advancement of knowledge in chemical synthesis and the development of new methodologies.
Used in Antiviral Applications:
[(2S,5R)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl]methyl acetate is used as a key component in the development of antiviral drugs, targeting the replication and life cycle of viruses. Its incorporation into nucleoside analogs can lead to the creation of effective antiviral agents.
Used in Anticancer Applications:
In the field of oncology, [(2S,5R)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl]methyl acetate is utilized in the synthesis of anticancer drugs. Its potential to be incorporated into nucleoside analogs allows for the development of compounds that can target and inhibit cancer cell growth.
Used in Drug Delivery Systems:
To enhance the bioavailability and therapeutic outcomes of nucleoside analogs derived from [(2S,5R)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl]methyl acetate, various drug delivery systems are being developed. These systems aim to improve the compound's delivery to target cells, increasing its efficacy in treating viral and cancerous conditions.

Upstream product

• 110483-43-7 1-(3,5-di-O-acetyl-2-bromo-2-deoxy-β-D-ribofuranosyl)thymine 
• 75-36-5 acetyl chloride 
• 3056-17-5 stavudin 
• 40635-67-4 acetoxyisobutyryl bromide 
• 1463-10-1 5-Methyluridine 
• 3180-76-5 2',3',5'-tri-O-benzoyluridine 
• 14215-97-5 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose 
• 143422-80-4 5'-acetyl-3'-selenophenylthymidine 
• 132747-40-1 (2R,3R)-3-(2,2-Dimethoxyethyl)oxiranemethanol 
• 143422-82-6 Acetic acid (2R,3S)-5-methoxy-3-phenylselanyl-tetrahydro-furan-2-ylmethyl ester 
• 3444-09-5 1,3-bis(trimethylsilyl)thymine 
• 143422-72-4 (2R,3S)-5,5-Dimethoxy-3-phenylselanyl-pentane-1,2-diol 
• 143422-74-6 ((2R,3S)-5-Methoxy-3-phenylselanyl-tetrahydro-furan-2-yl)-methanol 
• 108-24-7 acetic anhydride 

Downstream Products

• 134767-53-6 Octanoic acid (2S,5R)-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2,5-dihydro-furan-2-ylmethyl ester 
• 3056-17-5 1-(2,3-dideoxy-D-glycero-pent-2-enofuranosyl)thymine 
• 3056-17-5 stavudin 

Relevant academic research and scientific papers

Nasal absorption of 2',3'-didehydro-3'-deoxythymidine (D4T) and its esters in rats

Nasal absorption of 2',3'-didehydro-3'-deoxythymidine (D4T) and its esters (5'-acetyl D4T: C2-D4T and 5'-hemisuccinyl D4T: Suc-D4T) was investigated in rats. Bioavailability of D4T following intranasal (i.n.) administration was 98.0%, and the elimination from plasma was as rapid as that following intravenous administration of D4T. There seemed to be complete and rapid absorption of D4T from the nasal cavity. The plasma concentration- time profile of D4T following i.n. administration of C2-D4T was almost the same as that after administration of D4T itself. This suggests that C2-D4T was rapidly absorbed from the nasal cavity, and that some amount of dosing C2-D4T was hydrolyzed to D4T before entering the systemic circulation. In contrast, Suc-D4T showed slower absorption in the i.n. administration, and the plasma D4T level was maintained for a long period.

Synthesis and anti-HIV activity of [d4U]-[trovirdine analogue] and [d4T]-[trovirdine analogue] heterodimers as inhibitors of HIV-1 reverse transcriptase.

A series of eleven heterodimers containing both a nucleoside analogue (d4U, d4T) and a non-nucleoside type inhibitor (Trovirdine analogue) were synthesized and evaluated for their ability to inhibit HIV replication. Unfortunately, the (N-3)d4U-Trovirdine conjugates (9a-e) and (N-3)d4T-Trovirdine conjugates (10a-f) were found to be inactive suggesting that the two individual inhibitor compounds do not bind simultaneously in their respective sites.

Process for preparing 5′-acetylstavudine

The present invention relates to a process for preparing 5′-acetylstavudine, an intermediate which is useful in the preparation of 2′,3′-didehydro-3′-deoxythymidine, an active principle with antiviral action which is commonly known as stavudine (D4T).

Synthesis of 2',3'-dideoxy-2',3'-didehydro nucleosides via a serendipitous route.

This paper describes a "green" synthesis of 2',3'-unsaturated 2',3'-dideoxynucleosides via an electrochemical reaction. Using this approach d4T, d4U, ddA and ddI can be synthesized in high yields.

Direct Transport of 2',3'-Didehydro-3'-deoxythymidine (D4T) and Its Ester Derivatives to the Cerebrospinal Fluid via the Nasal Mucous Membrane in Rats

We investigated the absorption and transport of 2',3'-didehydro-3'-deoxythymidine (D4T) and its ester prodrugs from the nasal cavity in rats. The absorption of D4T and its acetate (C2-D4T) was rapid and almost complete, although the hemi-succinate (Suc-D4T) was absorbed rather slowly; the plasma concentrations of the prodrug, Suc-D4T, and regenerated D4T remained unchanged throughout the experimental period (180 min). Concentrations in the cerebrospinal fluid (CSF) following intravenous (i.v.) and intranasal (i.n.) administration were also measured. After i.n. administration, drug concentrations were higher in the fraction derived from the subarachnoid space located close to the nasal mucosa than those in the fractions located far from the nasal cavity. This difference was not found following the i.v. administration of the drugs. Following nasal administration, the intact Suc-D4T was found in the CSF at a concentration higher than that of D4T, although transport of the intact prodrug to the CSF was not observed following i.v. adinistration. These results suggest that direct transport of the drugs from the nasal cavity to the CSF significantly contributes to the higher concentrations in CSF of D4T and/or its ester prodrugs, and indicate the possible value of nasal administration for the treatment of patients with AIDS dementia.

Synthesis of 1-(2,3-dideoxy-β-D-glycero-pent-2-enofuranosyl(thymine (d4T; stavudine) from 5-methyluridine

A practical synthetic method of d4T (3) from 5-methyluridine (2a) was developed. The Marumoto-Mansuri method was modified using 2',3'-O-methoxyethylidene-5-methyluridine (10) as an intermediate to afford 1-(3,5-di-O-acetyl-2-bromo-2-deoxy-β-D-ribofuranosyl)thymine (6a) in high yield with less formation of byproducts. The reaction mechanism was also discussed.

Prodrugs of 2',3'-didehydro-3'-deoxythymidine (D4T): Synthesis, antiviral activity, and rapid pharmacokinetic evaluation

A series of 5'-derivatives and modified pyrimidine analogues of 2',3'- didehydro-3'-deoxythymidine (d4T, stavudine, 1) were synthesized to determine their potential as oral prodrugs of d4T. Utilizing a screen developed for the rapid evaluation of a variety of prodrugs in mice, it was determined that 5'- acetate 2 provided comparable plasma levels of d4T after oral administration of the prodrug to that when d4T was administered alone. The relative oral bioavailability of methoxy acetate 3 and cyclohexyl carbonate 5 was 79 and 41%, respectively. Dihydropyridine ester 6 did not provide detectable levels of d4T up to 1 h after oral administration of 6. Thiopyrimidines 8 and 9, as well as aminopyrimidine 10 also failed to provide measurable levels of d4T after oral administration. 5'-Derivatives 3, 5, and 6 showed similar activity to that of d4T against HIV and MuLV, as did 5'-benzoyl-4-thio derivative 8. However, the corresponding 4-thio 5'-alcohol 9 was inactive.

Prodrugs of 2',3'-didehydro-3'-deoxythymidine

Six ester prodrugs of 2',3'-didehydro-3'-deoxythymidine (D4T) were synthesized, and their physicochemical properties were evaluated. Marked differences were observed. All of the prodrugs were chemically stable within the pH range 2-7. Hydrolysis of these esters was observed in all cases for four rat enzyme systems (plasma, liver, duodenum, and kidney), with D4T being regenerated. D4T or the prodrug was administered orally to rats, and the plasma concentrations of D4T and a corresponding prodrug were measured. The half-life of D4T after intravenous administration was 35.9 min. The half- life calculated from the terminal phase and the maximum concentration in plasma following oral administration of D4T were 35.9 min and 48.4 μM, respectively. After oral prodrug administration (with water or olive oil as a solvent), though none of the prodrugs was detected in plasma except for 5'- hemisuccinyl D4T and 5'-hemiglutaryl D4T with olive oil as a solvent, retention time of plasma D4T concentration was extended and the elevated D4T concentration in plasma decreased.

Synthesis of antiviral nucleosides from crotonaldehyde. Part 3. Total synthesis of didehydrodideoxythymidine (d4T)

The total synthesis of the antiviral agent d4T 3 from the epoxyalcohol 2, itself derived from crotonaldehyde 1, in 6 steps and 18% overall yield is described.