13338-00-6

Usage

Synthesis Reference(s)

Journal of Heterocyclic Chemistry, 27, p. 1909, 1990 DOI: 10.1002/jhet.5570270712

Upstream product

• 112974-35-3 2-ethoxycarbonylamino-benzenesulfonic acid amide 
• 75-44-5 phosgene 
• 3306-62-5 2-AMINOBENZENESULFONAMIDE 
• 57-13-6 urea 
• 20926-33-4 3-methylsulfanyl-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide 
• 20926-33-4 3-(methylthio)-4H-benzo[e][1,2,4]thiadiazine 1,1-dioxide 
• 1189-71-5 isocyanate de chlorosulfonyle 
• 62-53-3 aniline 
• 4826-13-5 3-methylsulfanyl-2H-benzo[e][1,2,4]thiadiazine 1-oxide 
• 132975-13-4 [(methylaminocarbonyl)amino]benzenesulfonamide 
• 50881-48-6 N-chlorosulfonyl-N'-phenyl-urea 
• 201230-82-2 carbon monoxide 
• 1694-92-4 2-Nitrobenzenesulfonyl chloride 
• 808766-62-3 2-sulfamoyl-benzoyl azide 

Downstream Products

• 13514-00-6 2-Methyl-3-oxo-2,3-dihydro-4H-1.2.4-benzothiadiazin-1.1-dioxid 
• 13338-03-9 2,4-Dimethyl-3-oxo-2,3-dihydro-4H-1.2.4-benzothiadiazin-1.1-dioxid 
• 102308-74-7 4-ethyl-2H-1,2,4-benzothiadiazine-3 (4H)-one 1,1-dioxide 
• 103565-19-1 2,4-diethyl-1,1-dioxo-4H-1λ⁶-benzo[e][1,2,4]thiadiazin-3-one 
• 112974-35-3 2-ethoxycarbonylamino-benzenesulfonic acid amide 
• 360-81-6 3‐methyl‐2H‐benzo[e][1,2,4]thiadiazine 1,1‐dioxide 
• 3306-62-5 2-AMINOBENZENESULFONAMIDE 
• 13338-02-8 3,4-Dihydro-4-methyl-2H-1,2,4-benzothiadiazin-3-on-1,1-dioxid 
• 59943-35-0 3-(3-nitro-benzenesulfonyloxy)-2⁽⁴⁾H-benzo[1,2,4]thiadiazine 1,1-dioxide 
• 14141-71-0 7-bromo-3-oxo-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide 
• 691361-76-9 2-amino-5-(methanesulfonylamino)benzenesulfonamide 
• 20896-44-0 2,5-diaminobenzenesulfonamide 
• 59794-92-2 ethyl 2-oxo-2-((2-sulfamoylphenyl)amino)acetate 
• 72357-88-1 2-benzyl-2H-1,2,4-benzothiadiazin-3(4H)-one 1,1-dioxide 

Relevant academic research and scientific papers

Coumarins and other fused bicyclic heterocycles with selective tumor-associated carbonic anhydrase isoforms inhibitory activity

Herein we report for the first time a series of 2-benzamido-N-(2-oxo-4-(methyl/trifluoromethyl)-2H-chromen-7-yl) benzamide 3a–f and substituted quinazolin-4(3H)-ones and 2H-benzo[e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxides (5, 6, 8 and 10a–c) as selective inhibitors of the tumor associated hCA IX and XII isoforms. Among the compounds reported the trifluoromethyl derivative 3d resulted the most potent against these CA isoforms with KIs of 10.9 and 6.7?nM.

Easy preparation of novel 3,3-dimethyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide: Molecular structure, Hirshfeld surface, NCI analyses and molecular docking on AMPA receptors

We present in this study the synthesis and characterization of a new 3,3-dimethyl-substituted 1,2,4-benzothiadiazine 1,1-dioxide. 3,3-dimethyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide 10, was obtained by reacting 2-aminobenzenesulfonamide with acetone. The molecular structures of the starting sulfonamide and the new benzothiadiazine were obtained by X-ray diffraction analysis and the interactions like hydrogen bonds stabilizing the crystal packing were discussed. The contacts are confirmed by non-covalent interaction analysis. Analyses of Hirshfeld surface mapped over di, de, dnorm and shape-index were further used to identify the intermolecular interactions. The fingerprint histogram allow to show that H···H (45.7%) and O···H (30.1%) contacts are the dominant interactions in the crystal packing of 10. The effects of the molecular environment were accessed by analyzing the electron density isosurface and the 3D-topology of energy frameworks. The prediction of physicochemical properties suggested that 10 could be considered as a lead-like drug. Therefore, molecular docking study was performed on the α-amino-3?hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and suggested that 10 could interact with the allosteric site located on the ligand binding domain of AMPAR and could be a positive allosteric modulator. Docking results show that 10 can bind in a symmetrical way in the GluA2 ligand binding domain with two molecules at the dimer interface. The results also demonstrated that the presence of two methyl groups at the 3-position of the thiadiazine ring induced rotation of 10 in the binding site leading to close contacts with Pro494, Ser497, Ser729 and Ser754.

Discovery of Halogenated Benzothiadiazine Derivatives with Anticancer Activity**

Mitochondrial respiratory complex II (CII), also known as succinate dehydrogenase, plays a critical role in mitochondrial metabolism. Known but low potency CII inhibitors are selectively cytotoxic to cancer cells including the benzothiadiazine-based anti-hypoglycemic diazoxide. Herein, we study the structure-activity relationship of benzothiadiazine derivatives for CII inhibition and their effect on cancer cells for the first time. A 15-fold increase in CII inhibition was achieved over diazoxide, albeit with micromolar IC50 values. Cytotoxicity evaluation of the novel derivatives resulted in the identification of compounds with much greater antineoplastic effect than diazoxide, the most potent of which possesses an IC50 of 2.93±0.07 μM in a cellular model of triple-negative breast cancer, with high selectivity over nonmalignant cells and more than double the potency of the clinical agent 5-fluorouracil. No correlation between cytotoxicity and CII inhibition was found, thus indicating an as-yet-undefined mechanism of action of this scaffold. The derivatives described herein represent valuable hit compounds for therapeutic discovery in triple-negative breast cancer.

HALOGENATED BENZOTHIADIAZINES FOR THE TREATMENT OF CANCER

Provided herein are compounds and methods for modulating the mitochondrial respiratory complex II (CII) and vascular endothelial growth factor (VEGF) pathways. More particularly, provided are inhibitors of the mitochondrial respiratory complex II (CII) an

"a Sweet Combination": Developing Saccharin and Acesulfame K Structures for Selectively Targeting the Tumor-Associated Carbonic Anhydrases IX and XII

The sweeteners saccharin (SAC) and acesulfame K (ACE) recently entered the topic of anticancer human carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, as they showed to selectively inhibit the tumor-associated CAs IX/XII over ubiquitous CAs. A drug design s

Benzothiadiazine derivatives as well as preparation method and application thereof

The invention discloses benzothiadiazine derivatives as well as preparation methods and application thereof. The compounds have the structures of formula I or II. The invention also relates to preparation methods of the compounds containing the structures of formula I or II, pharmaceutical compositions and the application of the compounds in the preparation of anti-HBV drugs. The formula I or II are shown in the description.

Design of Benzoxathiazin-3-one 1,1-Dioxides as a New Class of Irreversible Serine Hydrolase Inhibitors: Discovery of a Uniquely Selective PNPLA4 Inhibitor

The design and examination of 4,1,2-benzoxathiazin-3-one 1,1-dioxides as candidate serine hydrolase inhibitors are disclosed, and represent the synthesis and study of a previously unexplored heterocycle. This new class of activated cyclic carbamates provi

Integrated structure-based activity prediction model of benzothiadiazines on various genotypes of HCV NS5b polymerase (1a, 1b and 4) and its application in the discovery of new derivatives

This work presents the first structure-based activity prediction model for benzothiadiazines against various genotypes of HCV NS5b polymerase (1a, 1b and 4).The model is a comprehensive workflow of structure-based field template followed by guided docking. The field template was used as a pre-filter and a tool to provide hits in good orientation and position. It was created based on detailed molecular interaction field analysis which includes Topomer CoMFA, grid independent analysis and Superstar. On the other hand, Guided docking was used as a refinement and assessment tool. It was actively directed by two scores: Moldock score as an interaction descriptor (r2 = 0.65) and a template similarity score as a measure for accurate binding-mode compliance. The docking template was based on energy-based pharmacophore analysis. The whole procedure was formulated and tweaked for both screening (ROC of AUC = 0.91) and activity prediction (r2 of 0.8) for the genotype 1a. In order to widen the model scope, linear interaction energy was used as a tool for predicting activities of other genotypes based on the docked ligand poses while mutation binding energy was used to investigate the effect of each amino acid mutation in genotype 4. The model was applied for structure-based fragment hopping by screening a library designed by reaction enumeration. A top scoring hit was used to generate a focused library such that it has lower TPSA than the original class ligands and thus better pharmacokinetic properties. After that, experimental validation was carried out by the synthesis of this library and its biological evaluation which yielded compounds that exhibit EC50 ranging from 1.86 to 23 μM.

Synthesis and pharmacological activity of N-(2,2-dimethyl-3,4-dihydro-2H-1- benzopyran-4-yl)-4H-1,2,4-benzothiadiazine-3-carboxamides 1,1-dioxides on rat uterus, rat aorta and rat pancreatic β-cells

N-(2,2-Dimethyl-3,4-dihydro-2H-1-benzopyran-4-yl)-4H-1,2, 4-benzothiadiazine-3-carboxamides 1,1-dioxides were prepared and evaluated on rat uterus, rat aortic rings and rat pancreatic β-cells. Pharmacological studies conducted on rat uterus indicated that several of these original hybrid compounds displayed a strong myorelaxant activity. The most active compounds hold a bromine atom at the 6-position of the dihydrobenzopyran ring. Moreover, the compounds failed to display a marked inhibitory effect on insulin secretion and vascular myogenic activity. These features suggest that the 6-bromo compounds could be relatively selective towards the uterine smooth muscle.