Novel Potential Agents for Human Cytomegalovirus Infection:  Synthesis and Antiviral Activity Evaluation of Benzothiadiazine Dioxide Acyclonucleosides

Martı́nez, Ana; Esteban, Ana; Castro, Ana; Gil, Carmen; Conde, Santiago; Andrei, Gracíela; Snoeck, Robert; Balzarini, Jan; Clercq, Erik De

doi:10.1021/jm980327z

Cited by 26 publications

(29 citation statements)

References 22 publications

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“…1) showed a marked activity against HCMV and varicellazoster virus (VZV) [11].The structure of these compounds is unique with regard to the nature of the heterocyclic base but also for the absence of the 5 -OH mimetic group present in ganciclovir and other current anti-HCMV drugs, which points to a different mechanism of action [12]. In particular, compound 4 possess activity against HCMV at concentrations slightly higher than that found for ganciclovir [50% inhibitory concentration (IC 50 ) = 3.5-3.7 μg/mL, 50% cytotoxic concentrations (CC 50 ) 40μg /mL].…”

Section: Benzothiadiazine Dioxides Acyclonucleosidesmentioning

confidence: 99%

Recent Advances in Antiviral Activity of Benzo/Heterothiadiazine Dioxide Derivatives

Zhan¹,

Liu²,

Clercq

2008

CMC

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Benzo/heterothiadiazine dioxides have been identified as important fused heterocyclic systems possessing a broad spectrum of biological activities and potential pharmacological applications. Recently, a large number of structurally novel compounds derived from these heterocycle scaffolds were identified as antiviral agents. Especially, substituted benzo/heterothiadiazine dioxide derivatives have been shown to inhibit the replication of HCMV, VZV, HCV and HIV. Of particular interest, some potent HCV polymerase inhibitors possess a benzothiadiazine dioxide scaffold, which is critical for the anti-HCV potency through strong hydrogen bond formation of the SO(2)NH group with the active site of the enzyme, as shown by X-ray crystallography. Also, some compounds belonging to the benzothiadiazine dioxide class have been found to be potent antiviral agents against HCMV and VZV. Moreover, some novel heterothiadiazine dioxide derivatives have been synthesized and evaluated as potential HIV inhibitors with lower toxicity and/or increased activity against drug-resistant virus strains. No systematic review is available in the literature on these thiadiazine derivatives in the design of potent antiviral inhibitors. In this article, we review the recent advances in the antiviral profile of this kind of compounds, as well as the impact of structural modifications and the structure-activity relationship (SAR).

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Section: Benzothiadiazine Dioxides Acyclonucleosidesmentioning

confidence: 99%

Recent Advances in Antiviral Activity of Benzo/Heterothiadiazine Dioxide Derivatives

Zhan¹,

Liu²,

Clercq

2008

CMC

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“…The assay procedures for human cytomegalovirus (HCMV) and varicella-zoster virus (VSV) have been described previously (Martinez et al, 1999, De Clercq et al, 1986. Two reference strains of VZV expressing viral thymidine kinase (TK + ) (YS and OKA) and two reference strains of VZV lacking the thymidine kinase (TK -) (O7/1 and YS-R) and the Davis and AD-169 strains of HCMV were included in the present study.…”

Section: Biological Assaysmentioning

confidence: 99%

Synthesis and Antiviral Activities of 3-Aralkyl-Thiomethylimidazo[1,2-b]Pyridazine Derivatives

Galtier

Mavel

Snoeck

et al. 2003

Antivir Chem Chemother

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“…81 The structure of this compound is quite unique, not only with respect of the nature of the heterocyclic base, but also because of the lack of the 5 H -OH mimetic group present in GCV and other current anti-CMV drugs, which points to a different mechanism of action. 82 Initial structure±activity data showed the necessity of a double substitution in the heterocycle, while monosubstituted compounds were completely devoid of antiviral activity. 83 Simultaneously, lipophilicity in the acyclic side chain is essential to preserve the anti-HCMV activity.…”

Section: Nonnucleoside Hcmv Inhibitorsmentioning

confidence: 99%

Recent strategies in the development of new human cytomegalovirus inhibitors

Martı́nez¹,

Castro²,

Gil³

et al. 2001

Medicinal Research Reviews

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Human cytomegalovirus (HCMV) is one of the most common opportunistic infections in immunucompromised individuals, such as AIDS patients and organ transplant recipients, and is the most frequent congenital viral infection in humans. Despite a reduction of the incidence of AIDS‐related opportunistic infections in patients under highly active antiretroviral treatment, attention should be paid to the HCMV risk factor in these individuals. Furthermore, HCMV may have an important role in atherosclerosis. Existing antiviral treatments for the HCMV infection suffer from poor bioavailability, toxicity, and limited effectiveness, mainly due to the development of drug resistance. Fortunately there are novel and potentially very effective new compounds undergoing pre‐clinical and clinical evaluation. This review provides an overview in the last five years of new HCMV inhibitors (chemical structures, SAR, and new mechanisms of action) with the aim to provide new clues for the development of future drugs against this opportunistic virus. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 3, 227–244, 2001

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Novel Potential Agents for Human Cytomegalovirus Infection: Synthesis and Antiviral Activity Evaluation of Benzothiadiazine Dioxide Acyclonucleosides

Cited by 26 publications

References 22 publications

Recent Advances in Antiviral Activity of Benzo/Heterothiadiazine Dioxide Derivatives

Recent Advances in Antiviral Activity of Benzo/Heterothiadiazine Dioxide Derivatives

Synthesis and Antiviral Activities of 3-Aralkyl-Thiomethylimidazo[1,2-b]Pyridazine Derivatives

Recent strategies in the development of new human cytomegalovirus inhibitors

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