3866-81-7

Upstream product

• 56379-96-5 benzylaminosulfonyl chloride 
• 134-20-3 2-carbomethoxyaniline 
• 1030-88-2 Benzylammonium-benzylsulfamidat 
• 98-88-4 benzoyl chloride 
• 100-39-0 benzyl bromide 
• 2225-37-8 1H-2,1,3-benzothiadiazin-4(3H)-one-2,2-dioxide 

Downstream Products

• 221632-92-4 Acetic acid 2-(3-benzyl-2,2,4-trioxo-3,4-dihydro-2H-2λ⁶-benzo[1,2,6]thiadiazin-1-ylmethoxy)-ethyl ester 
• 190835-48-4 3-Benzyl-2,2-dioxo-1-prop-2-ynyloxymethyl-2,3-dihydro-1H-2λ⁶-benzo[1,2,6]thiadiazin-4-one 
• 190835-45-1 3-Benzyl-1-benzyloxymethyl-2,2-dioxo-2,3-dihydro-1H-2λ⁶-benzo[1,2,6]thiadiazin-4-one 
• 221632-96-8 3-Benzyl-1-(2-hydroxy-ethoxymethyl)-2,2-dioxo-2,3-dihydro-1H-2λ⁶-benzo[1,2,6]thiadiazin-4-one 

Relevant academic research and scientific papers

Benzothiadiazine dioxide dibenzyl derivatives as potent human cytomegalovirus inhibitors: Synthesis and comparative molecular field analysis

The benzothiadiazine dioxide (BTD) derivatives are potent nonnucleoside human cytomegalovirus (HCMV) inhibitors. As part of our comprehensive structure-activity relationship study of these compounds, we have now synthesized N,N- and N, O-dibenzyl derivatives with different para-substituents (alkyl, phenyl, electron-donating, electron-withdrawing) in the phenyl ring of the benzyl moieties. The antiviral activity against HCMV (AD-169 strain) was also experimentally measured showing IC50 values between 2.5 and 50 μM. Comparative molecular field analysis (CoMFA) was employed to generate a model, based upon 32 diverse BTD derivatives, to delineate structural and electrostatic features important for enhanced activity against HCMV. The steric (van der Waals) interactions with the receptor majoritary describes the variation in antiviral activity among the inhibitors. Finally, the CoMFA model was used to design two sets of novel BTD derivatives. Synthesis and subsequent anti-HCMV evaluation of these compounds enabled us to maintain the activity of this new kind of HCMV inhibitors.

2,1,3-Benzothiadiazine derivatives: Synthesis and screening versus PDE4 enzyme

A series of N-1,3 disubstituted 2,1,3-benzothiadiazine derivatives (BTDs) were synthesized and evaluated for their inhibitory activity versus enzymatic isoform PDE4 extracted from U937 cell line. Some of the tested compounds showed a high PDE4 inhibitory activity at 100:μM and the IC50 value of the most interesting terms were evaluated. The structure-activity relationships of these compounds showed that the 3,5-di-tert-butyl-4-hydroxybenzyl moiety at N-1 position is important to obtain activity at micromolar level as previously reported. For the same compounds the antioxidant activity were evaluated highlighting 14 as the most significative one. The introduction of other bulky substituents in N-1 position is detrimental.

Synthesis and antiviral activity of new benzothiadiazine dioxide derivatives

A series of 2,1,3- and 1,2,4-benzothiadiazine derivatives were synthesized by alkylation via Mitsunobu reaction and evaluated for their antiviral activity against ADV, HHV-6, Cox-B5 and H-CMV. Most of them were active at micromolar level against one or more viral strains. All the molecules studied are poorly cytotoxic (maximum non toxic concentrations were >25μM), except one compound that presents a higher cytotoxicity (maximum non toxic concentration was 6 μM).

Novel potential agents for human cytomegalovirus infection: Synthesis and antiviral activity evaluation of benzothiadiazine dioxide acyclonucleosides

The first acyclonucleosides based on the benzothiadiazine dioxide system were synthesized following the silylation procedure. Several acyclic moieties, including acetoxyethoxymethyl, benzyloxymethyl, and propargyloxymethyl groups, were introduced. Two synthetic strategies were designed to selectively obtain the N-1 or N-3 derivatives. Lipase-mediated deacylation was used for the deprotection of the acyclonucleosides. Some of the benzothiadiazine dioxide acyclonucleosides, in particular 16, proved active against human cytomegalovirus (CMV) at concentrations slightly higher than that found for ganciclovir [50% inhibitory concentration (IC50) = 3.5- 3.7 μg/mL, cytotoxicity (CC50) ≥ 40 μg/mL, MCC = 20 μg/mL]. Additionally, compound 16 inhibited the replication of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in CEM cells at concentrations that were 5- fold lower than its cytotoxic concentration.

Benzothiadiazine dioxide acyclonucleosides as lead compounds for the development of new agents against human cytomegalovirus and varicella-zoster virus infections

The first acyclonucleosides derived from 2,1,3-benzothiazine dioxides were synthesized. From their antiviral activity evaluation results these compounds might be considered as new leads in the search for inhibitors of human cytomegalovirus (CMV) and varicella-zoster virus (VZV) infections.