Synthesis and antiviral activity of 6-benzyl analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents.

doi:10.1002/CHIN.199547187

Paper

Synthesis and antiviral activity of 6-benzyl analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents.

Published Aug 17, 2010 · H. Tanaka, H. Takashima, M. Ubasawa

Journal of medicinal chemistry

Q1 SJR score

38

Citations

3

Influential Citations

Full textSemantic Scholar

Abstract

Several 6-benzyl analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (1; HEPT) were synthesized and evaluated for their anti-HIV-1 activity. LDA (lithium diisopropylamide) lithiation of 5-ethyluracil derivatives 7 and 8 and subsequent reaction with an aryl aldehyde gave 6-(arylhydroxymethyl)-5-ethyluracil derivatives 9-12. 6-(Arylhydroxymethyl)-5-isopropyluracil derivatives 15-18 were prepared from the 5-isopropyl-2-thiouracil derivatives 13 and 14 by the above procedure following oxidative hydrolysis of the thione. Preparation of the target 5-alkyl-1-(alkoxymethyl)-6-benzyluracil derivatives 27-34 was carried out by acetylation of 9-14 followed by Pd-catalyzed hydrogenolysis. The 1-butyl- (37 and 39) and 1-(2-methoxyl)- (38 and 40) 5-alkyl-6-benzyluracils were synthesized by 1-alkylation of the 3-phenacyl derivatives 35 and 36 with alkyl halides followed by deprotection of the 3-phenacyl group. Compounds synthesized in this study inhibited HIV-1 replication in MT-4 cells in the submicromolar to namomolar concentration range. From this series of compounds, 6-benzyl-1-(ethoxymethyl)-5-isopropyluracil (33) was selected for clinical evaluation.

In Vitro Study

Study Snapshot

6-benzyl analogs of HEPT show potent and selective anti-HIV-1 activity, with 6-benzyl-1-(ethoxymethyl)-5-isopropyluracil (33) being selected for clinical evaluation.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

Synthesis and antiviral activity of 6-benzyl analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents.

Sign up to use Study Snapshot

References

Citations

Linker optimization of HEPT derivatives as potent non-nucleoside HIV-1 reverse transcriptase inhibitors: from S=O to CHOR

CHOR-HEPT non-nucleoside HIV-1 reverse transcriptase inhibitors show improved anti-HIV-1 activity and higher selectivity compared to lead compound 6.

Structure-Based design of [(2-Hydroxyethoxy)methyl]-6-(phenylthio)-thymine derivatives as nonnucleoside HIV-1 reverse transcriptase Inhibitors: From HEPTs to Sulfinyl-substituted HEPTs.

Sulfinyl-substituted HEPTs show improved anti-HIV-1 activity compared to HEPT and NVP, with compounds 11h, 11l, and 11ab showing the best anti-HIV-1 activity against wild-type and mutant strains.

In Vitro and In Vivo Antiviral Studies of New Heteroannulated 1,2,3-Triazole Glycosides Targeting the Neuraminidase of Influenza A Viruses

New 1,2,3-triazole glycosides show high antiviral activity against various influenza A viruses, including H5N1 and H1N1, and are suitable for further clinical studies as neuraminidase inhibitors.

Novel Thiazolidin-4-ones as Potential Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase

Novel thiazolidin-4-ones show potential as new HIV-1 reverse transcriptase inhibitors, with seven showing better activity than nevirapine and three showing IC50 values below 5 nM.

Eurotiumins A–E, Five New Alkaloids from the Marine-Derived Fungus Eurotium sp. SCSIO F452

Eurotiumins A-E, five new alkaloids from the marine-derived fungus Eurotium sp. SCSIO F452, show potential antioxidative properties and cytotoxic activities.

Novel HIV-1 non-nucleoside reverse transcriptase inhibitors: A combinatorial approach

A combinatorial approach using pyrimidine derivatives can create highly potent novel HIV-1 non-nucleoside reverse transcriptase inhibitors, potentially improving efficacy in combating HIV infection.