Synthesis and Anti-HIV-1 Activity of New Fluoro-HEPT Analogues: An Investigation on Fluoro versus Hydroxy Substituents

Yasser M Loksha, Erik Bjerregaard Pedersen, Roberta Loddo, Paolo La Colla

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Coupling of 6-benzyl-5-hydroxymethyluracil (1) with formaldehyde acetals followed by fluorination using (diethylamino)sulfur trifluoride (DAST) afforded 1-alkenyloxymethyl and 1-propargyloxymethyl 5-fluoromethyl-6-benzyluracils 3a-c. 6-(3,5-Dimethylbenzyl)-5-ethyl-1-[(2-fluoroethoxy)methyl]pyrimidine-2,4(1H,3H)-dione (6) was synthesized by fluorination of the corresponding hydroxy derivative 5. Sonogoshira reaction was performed on 6-(3,5-dimethylbenzyl)-5-ethyl-1-(4-iodobenzyl)uracil (7) with propargyl alcohol to afford 8 which was fluorinated to give the fluoro propargyl derivative 9. Compound 7 was synthesized by N1-alkylation of the corresponding uracil. Significant activity was found against HIV-1 except for compounds with 5-hydroxymethyl and 5-fluoromethyl substituents.
OriginalsprogEngelsk
TidsskriftArchiv der Pharmazie
Vol/bind344
Udgave nummer6
Sider (fra-til)366-71
Antal sider6
ISSN0365-6233
DOI
StatusUdgivet - 2011

Fingeraftryk

Uracil
HIV-1
Acetals
Formaldehyde
pyrimidine
5-hydroxymethyluracil
5-benzyluracil
propargyl alcohol

Citer dette

@article{7996c13f5eb645fe9166730ed701fe05,
title = "Synthesis and Anti-HIV-1 Activity of New Fluoro-HEPT Analogues: An Investigation on Fluoro versus Hydroxy Substituents",
abstract = "Coupling of 6-benzyl-5-hydroxymethyluracil (1) with formaldehyde acetals followed by fluorination using (diethylamino)sulfur trifluoride (DAST) afforded 1-alkenyloxymethyl and 1-propargyloxymethyl 5-fluoromethyl-6-benzyluracils 3a-c. 6-(3,5-Dimethylbenzyl)-5-ethyl-1-[(2-fluoroethoxy)methyl]pyrimidine-2,4(1H,3H)-dione (6) was synthesized by fluorination of the corresponding hydroxy derivative 5. Sonogoshira reaction was performed on 6-(3,5-dimethylbenzyl)-5-ethyl-1-(4-iodobenzyl)uracil (7) with propargyl alcohol to afford 8 which was fluorinated to give the fluoro propargyl derivative 9. Compound 7 was synthesized by N1-alkylation of the corresponding uracil. Significant activity was found against HIV-1 except for compounds with 5-hydroxymethyl and 5-fluoromethyl substituents.",
author = "Loksha, {Yasser M} and Pedersen, {Erik Bjerregaard} and Roberta Loddo and {La Colla}, Paolo",
note = "Copyright {\circledC} 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
year = "2011",
doi = "10.1002/ardp.201000187",
language = "English",
volume = "344",
pages = "366--71",
journal = "Archiv der Pharmazie",
issn = "0365-6233",
publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",
number = "6",

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Synthesis and Anti-HIV-1 Activity of New Fluoro-HEPT Analogues: An Investigation on Fluoro versus Hydroxy Substituents. / Loksha, Yasser M; Pedersen, Erik Bjerregaard; Loddo, Roberta; La Colla, Paolo.

I: Archiv der Pharmazie, Bind 344, Nr. 6, 2011, s. 366-71.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Synthesis and Anti-HIV-1 Activity of New Fluoro-HEPT Analogues: An Investigation on Fluoro versus Hydroxy Substituents

AU - Loksha, Yasser M

AU - Pedersen, Erik Bjerregaard

AU - Loddo, Roberta

AU - La Colla, Paolo

N1 - Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2011

Y1 - 2011

N2 - Coupling of 6-benzyl-5-hydroxymethyluracil (1) with formaldehyde acetals followed by fluorination using (diethylamino)sulfur trifluoride (DAST) afforded 1-alkenyloxymethyl and 1-propargyloxymethyl 5-fluoromethyl-6-benzyluracils 3a-c. 6-(3,5-Dimethylbenzyl)-5-ethyl-1-[(2-fluoroethoxy)methyl]pyrimidine-2,4(1H,3H)-dione (6) was synthesized by fluorination of the corresponding hydroxy derivative 5. Sonogoshira reaction was performed on 6-(3,5-dimethylbenzyl)-5-ethyl-1-(4-iodobenzyl)uracil (7) with propargyl alcohol to afford 8 which was fluorinated to give the fluoro propargyl derivative 9. Compound 7 was synthesized by N1-alkylation of the corresponding uracil. Significant activity was found against HIV-1 except for compounds with 5-hydroxymethyl and 5-fluoromethyl substituents.

AB - Coupling of 6-benzyl-5-hydroxymethyluracil (1) with formaldehyde acetals followed by fluorination using (diethylamino)sulfur trifluoride (DAST) afforded 1-alkenyloxymethyl and 1-propargyloxymethyl 5-fluoromethyl-6-benzyluracils 3a-c. 6-(3,5-Dimethylbenzyl)-5-ethyl-1-[(2-fluoroethoxy)methyl]pyrimidine-2,4(1H,3H)-dione (6) was synthesized by fluorination of the corresponding hydroxy derivative 5. Sonogoshira reaction was performed on 6-(3,5-dimethylbenzyl)-5-ethyl-1-(4-iodobenzyl)uracil (7) with propargyl alcohol to afford 8 which was fluorinated to give the fluoro propargyl derivative 9. Compound 7 was synthesized by N1-alkylation of the corresponding uracil. Significant activity was found against HIV-1 except for compounds with 5-hydroxymethyl and 5-fluoromethyl substituents.

U2 - 10.1002/ardp.201000187

DO - 10.1002/ardp.201000187

M3 - Journal article

VL - 344

SP - 366

EP - 371

JO - Archiv der Pharmazie

JF - Archiv der Pharmazie

SN - 0365-6233

IS - 6

ER -