Bicyclic anti-VZV nucleosides: Thieno analogues retain full antiviral activity

Brancale, Andrea; McGuigan, Christopher; Algain, Berthe; Savy, Pascal; Benhida, Rachid; Fourrey, Jean‐Louis; Andrei, Gracíela; Snoeck, Robert; Clercq, Erik De; Balzarini, Jan

doi:10.1016/s0960-894x(01)00471-1

Cited by 25 publications

(12 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6 Yet, terminal halogen substitution of the 6-alkyl side chain afforded activity and selectivity comparable to those of the parent compounds (Table V). 7 Changing the heteroatom in the bicyclic pyrimidine ring of the 6-alkyl-substituted derivatives from oxygen to sulfur (thus converting the furo into a thieno moiety) resulted in equipotent anti-VZV activity, 8 whereas replacement of furo by pyrrolo resulted in a markedly decreased antiviral activity 9 (Table VI).…”

Section: S T R U C T U R E -A C T I V I T Y R E L a T I O N S H I Pmentioning

confidence: 99%

Highly potent and selective inhibition of varicella‐zoster virus replication by bicyclic furo[2,3‐d]pyrimidine nucleoside analogues

Clercq

2003

Medicinal Research Reviews

View full text Add to dashboard Cite

The bicyclic furo[2,3-d]pyrimidine nucleoside analogues represent an entirely new class of fused furopyrimidine derivatives with unprecedented selectivity for varicella-zoster virus (VZV). From extensive structure-activity relationship (SAR) studies, the 6-(p-alkylphenyl)substituted furopyrimidine derivatives Cf 1742 and Cf 1743 emerged as the most potent inhibitors of VZV replication: they were found to inhibit both laboratory VZV strains and clinical VZV isolates at subnanomolar concentrations, while not being toxic to the host cells at 100,000-fold higher concentrations. Although the precise mechanism of action of these compounds remains to be elucidated, it is clear that for their antiviral activity they depend on phosphorylation by the VZV-encoded thymidine kinase. The furo[2,3-d]pyrimidine nucleoside analogues are not susceptible to degradation by human or bacterial thymidine phosphorylase, which may otherwise release the free aglycone. Also, the latter is not inhibitory to dihydropyrimidine dehydrogenase, an enzyme involved in the degradation of thymine, uracil, and the anticancer agent 5-fluorouracil. Further development of the furo[2,3-d]pyrimidine nucleoside analogues as new therapeutic modalities for the treatment of VZV infections (i.e., varicella and herpes zoster) seems highly justified.

show abstract

Section: S T R U C T U R E -A C T I V I T Y R E L a T I O N S H I Pmentioning

confidence: 99%

Highly potent and selective inhibition of varicella‐zoster virus replication by bicyclic furo[2,3‐d]pyrimidine nucleoside analogues

Clercq

2003

Medicinal Research Reviews

View full text Add to dashboard Cite

show abstract

“…These facts stimulated intensive search of new agents capable of inhibiting influenza viruses of different origins . On the other hand, thienopyrimidines are known to possess anticancer , antiviral , antimicrobial , analgesic and anti‐inflammatory , anti‐HIV as well as antihistaminic activities. Therefore, the main target of the present work is building a new series of thienopyrimidines and evaluation of their activities against influenza A virus (H3N2).…”

Section: Introductionmentioning

confidence: 99%

New Potent SARS‐CoV 3C‐Like Protease Inhibitors Derived from Thieno[2,3‐d]‐pyrimidine Derivatives

El-All

Atta

Roaiah

et al. 2016

Archiv der Pharmazie

View full text Add to dashboard Cite

2-Amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (1) condensed with carbaldehydes 2a,b to give the respective thienopyrimidines (3a,b), which reacted with phosphoryl chloride and hydrazine hydrate to afford the respective pyrimidinohydrazines (4a,b). Compound 4a condensed with acetophenone under Vilsmeier conditions to afford the formylated pyrazolopyrimidine 6. Condensation of 4a with active methylenes produced the respective pyrazolopyrimidines (7-11). Besides, 4a condensed with succinic anhydride and with phthalic anhydride, yielding the pyrrolidine-2,5-dione 12 and the isoindoline-1,3-dione 13, respectively. Moreover, 4a reacted with isatin to afford the hydrazono-indolin-2-one 14. Structural elucidations for the new thienopyrimidines were based upon compatible analytical and spectroscopic results. Eleven of the new compounds were tested and found active against influenza A neuraminidase virus (H3N2). Compounds 12 and 13 were the most potent.

show abstract

“…Thienopyrimidines occupy a special position among these compounds. Thienopyrimidine derivatives are characterized by a very broad spectrum of biological activities, such as anticancer [1][2][3][4], antiviral [5,6], antimicrobial [7][8][9], analgesic and anti-inflammatory [10][11][12][13][14] anticonvulsant [15,16], thymidine phosphorylase inhibitors [17], anti-HIV [18], and antihistaminic [19]. The present work is an extension of our ongoing efforts towards the synthesis and evaluation of some new substituted thieno [2,3-d]pyrimidine derivatives as analgesic and anti-inflammatory agents.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Pharmacological Evaluation of New Nonsteroidal Anti-Inflammatory Derived from 3-Aminobenzothieno[2,3-<i>d</i>]pyrimidines

Hafez¹,

Al-Duaij²,

El‐Gazzar³

2013

IJOC

View full text Add to dashboard Cite

During the last few years, condensed thienopyrimidine derivatives have received considerable attention. The therapeutic importance of thienopyrimidines prompted us to synthesize some of spiro(benzothieno[2,3-d]pyrimidine-4-one) derivatives. Some of the novel benzothino-pyrimidine derivatives 3a, 9b, 10b, 11a, 11b, and 11c showed considerable potent anti-inflammatory and analgesic activity of superior G.I.T. safety profile in experimental rats in comparing to indomethacin and tramadol as reference drugs.

show abstract

Bicyclic anti-VZV nucleosides: Thieno analogues retain full antiviral activity

Cited by 25 publications

References 7 publications

Highly potent and selective inhibition of varicella‐zoster virus replication by bicyclic furo[2,3‐d]pyrimidine nucleoside analogues

Highly potent and selective inhibition of varicella‐zoster virus replication by bicyclic furo[2,3‐d]pyrimidine nucleoside analogues

New Potent SARS‐CoV 3C‐Like Protease Inhibitors Derived from Thieno[2,3‐d]‐pyrimidine Derivatives

Design, Synthesis and Pharmacological Evaluation of New Nonsteroidal Anti-Inflammatory Derived from 3-Aminobenzothieno[2,3-<i>d</i>]pyrimidines

Contact Info

Product

Resources

About

Bicyclic anti-VZV nucleosides: Thieno analogues retain full antiviral activity

Cited by 25 publications

References 7 publications

Highly potent and selective inhibition of varicella‐zoster virus replication by bicyclic furo[2,3‐d]pyrimidine nucleoside analogues

Highly potent and selective inhibition of varicella‐zoster virus replication by bicyclic furo[2,3‐d]pyrimidine nucleoside analogues

New Potent SARS‐CoV 3C‐Like Protease Inhibitors Derived from Thieno[2,3‐d]‐pyrimidine Derivatives

Design, Synthesis and Pharmacological Evaluation of New Nonsteroidal Anti-Inflammatory Derived from 3-Aminobenzothieno[2,3-&lt;i&gt;d&lt;/i&gt;]pyrimidines

Contact Info

Product

Resources

About

Design, Synthesis and Pharmacological Evaluation of New Nonsteroidal Anti-Inflammatory Derived from 3-Aminobenzothieno[2,3-<i>d</i>]pyrimidines