- 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.
- Etsè, Koffi Sénam,Zaragoza, Guillermo,Etsè, Kodjo Djidjolé
-
-
- INHIBITORS OF PHOSPHOLIPID SYNTHESIS AND METHODS OF USE
-
Inhibitors of Glycerol 3-Phosphate Acyltransferase (GPAT) are provided; and methods of use in the treatment of cancer; and treatment of conditions relating to metabolic syndrome, hyperlipidemia, infection and inflammation.
- -
-
Page/Page column 92
(2021/02/26)
-
- Benzothiadiazine methoxy acrylate derivatives and preparation method and application thereof
-
The invention provides benzothiadiazine methoxy acrylate derivatives and a preparation method and application thereof, and the benzothiadiazine methoxy acrylate derivatives have the following chemicalstructural general formula VII as shown in the description, wherein R1 is hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, methoxy or nitro; and R2 is hydrogen, methyl or benzyl. According to the invention, an active group 3, 4-dihydro-2H-1, 2, 4-benzothiadiazine-1, 1-dioxo substitutes the side chain part of the methoxy acrylate bactericide and then is reasonably spliced with the pharmacophore of the methoxy acrylate bactericide, so that the bactericide with novel structure, broad spectrum, high efficiency and low toxicity is synthesized, the bactericide can be alternately used with the existing bactericide, the generation of resistance is avoided or delayed, the preparation conditions are conventional, the subsequent treatment is simple and convenient, and the industrialization is easy to realize.
- -
-
Paragraph 0023-0025
(2020/07/24)
-
- FUSED [1,2,4]THIADIAZINE DERIVATIVES WHICH ACT AS KAT INHIBITORS OF THE MYST FAMILY
-
A compound of formula (I): which inhibits the activity of one or more KATs of the MYST family, i.e., TIP60, KAT6B, MOZ, HBO1 and MOF.
- -
-
Page/Page column 51
(2019/03/17)
-
- MYELINATION STIMULATOR COMPOUNDS, AND METHODS OF TREATMENT
-
The invention is directed towards compounds, methods of stimulating myelination, stimulating proliferation of oligodendrocytes (OLs) or stimulating oligodendrocyte precursor cells and methods of treating diseases, disorders or symptoms thereof.
- -
-
Page/Page column 27
(2019/11/28)
-
- Iridium-Catalyzed ortho-C?H Amidation of Benzenesulfonamides with Sulfonyl Azides
-
We developed herein an iridium-catalyzed direct C?H activation/ C?N bond formation reaction of benzenesulfonamides with sulfonyl azides. The amidation reaction provides a protocol for the synthesis of 2-aminobenzesulfonamides in good to excellent yields. This strategy features a wide substrate scope, tolerates a broad range of functional groups under external oxidant-free conditions and only releases molecular nitrogen as the sole by-product. Moreover, the preliminary mechanism was investigated and the proposed reaction pathway was provided. (Figure presented.).
- Hou, Hongcen,Zhao, Yongli,Sheng, Shouri,Chen, Junmin
-
p. 4393 - 4398
(2019/08/28)
-
- Cobalt-based nanoparticles prepared from MOF-carbon templates as efficient hydrogenation catalysts
-
The development of efficient and selective nanostructured catalysts for industrially relevant hydrogenation reactions continues to be an actual goal of chemical research. In particular, the hydrogenation of nitriles and nitroarenes is of importance for the production of primary amines, which constitute essential feedstocks and key intermediates for advanced chemicals, life science molecules and materials. Herein, we report the preparation of graphene shell encapsulated Co3O4- and Co-nanoparticles supported on carbon by the template synthesis of cobalt-terephthalic acid MOF on carbon and subsequent pyrolysis. The resulting nanoparticles create stable and reusable catalysts for selective hydrogenation of functionalized and structurally diverse aromatic, heterocyclic and aliphatic nitriles, and as well as nitro compounds to primary amines (>65 examples). The synthetic and practical utility of this novel non-noble metal-based hydrogenation protocol is demonstrated by upscaling several reactions to multigram-scale and recycling of the catalyst.
- Murugesan, Kathiravan,Senthamarai, Thirusangumurugan,Sohail, Manzar,Alshammari, Ahmad S.,Pohl, Marga-Martina,Beller, Matthias,Jagadeesh, Rajenahally V.
-
p. 8553 - 8560
(2018/11/30)
-
- 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.
- -
-
-
- Highly chemoselective reduction of nitroarenes over non-noble metal nickel-molybdenum oxide catalysts
-
The chemoselective reduction of nitroarenes is an important transformation for the production of arylamines, which are the primary intermediates in the synthesis of pharmaceuticals, agrochemicals and dyes. Heterogeneous non-noble metal nickel-molybdenum oxide catalysts supported on ordered mesoporous silica SBA-15 (Ni-MoO3/CN@SBA-15) were prepared for the first time by treating SBA-15-supported nickel-molybdenum oxide materials with 1,10-phenanthroline, and exhibited unprecedented catalytic activity and chemoselectivity for the reduction of various substituted nitroarenes to the corresponding aromatic amines in ethanol with hydrazine hydrate as a hydrogen donor under mild conditions owing to the synergistic effect of metal Ni and MoO3 species, affording excellent yields of >99% within very short reaction periods (≤60 min). The Ni-MoO3/CN@SBA-15 catalysts were highly stable and could easily be recovered by simple filtration or by an external magnetic field for at least ten recycling reactions without any observable loss of catalytic performance or leaching of metal components.
- Huang, Haigen,Wang, Xueguang,Li, Xu,Chen, Chenju,Zou, Xiujing,Ding, Weizhong,Lu, Xionggang
-
p. 809 - 815
(2017/08/15)
-
- 1. 1 - dioxo - 4H - benzo [1, 2, 4] - thiadiazine hydrochloric acid salt compound and its preparation method
-
The invention discloses a 1,1-dioxo-4H-benzo[1,2,4]-thiadiazine hydrochloride compound and a preparation method thereof, belonging to the technical field of organic synthesis. The technical scheme has the key point as follows: the 1,1-dioxo-4H-benzo[1,2,4]- thiadiazine hydrochloride compound has the structure as shown in the specification, wherein R is H, -CH3 or -C2H5. The invention also discloses the preparation method of the 1,1-dioxo-4H-benzo[1,2,4]-thiadiazine hydrochloride compound. The preparation method is simple, convenient and easy to operate, relatively high in reaction efficiency and relatively good in repeatability, and raw materials are cheap and available.
- -
-
Paragraph 0028-0030
(2017/03/08)
-
- Selective synthesis of Rh5 carbonyl clusters within a polyamine dendrimer for chemoselective reduction of nitro aromatics
-
The selective synthesis of the [Rh5(CO)15] - cluster within the PPI dendrimer was successfully demonstrated. The dendrimer-encapsulated [Rh5(CO)15]- was resistant to decomposition under the catalytic reaction conditions and exhibited extremely high selectivity for the chemoselective reduction of nitro groups of various nitro aromatics with other reducible groups using CO/H2O as a reductant. This journal is the Partner Organisations 2014.
- Maeno, Zen,Mitsudome, Takato,Mizugaki, Tomoo,Jitsukawa, Koichiro,Kaneda, Kiyotomi
-
supporting information
p. 6526 - 6529
(2014/06/09)
-
- 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.
- Khelili, Smail,Kihal, Nadjib,Yekhlef, Mohamed,De Tullio, Pascal,Lebrun, Philippe,Pirotte, Bernard
-
scheme or table
p. 873 - 878
(2012/09/10)
-
- 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.
- Ismail, Mohamed A.H.,Abou El Ella, Dalal A.,Abouzid, Khaled A.M.,Mahmoud, Amr H.
-
supporting information; experimental part
p. 2455 - 2478
(2012/05/05)
-
- Acetic acid derivatives of 3,4-dihydro-2 H-1,2,4-benzothiadiazine 1,1-dioxide as a novel class of potent aldose reductase inhibitors
-
A series of novel benzothiadiazine 1,1-dioxide derivatives were synthesized and tested for their inhibitory activity against aldose reductase. Of these derivatives, 17 compounds, having a substituted N2-benzyl group and a N4-acetic acid group on the benzothiadiazine, were found to be potent and selective aldose reductase inhibitors in vitro with IC50 values ranging from 0.032 to 0.975 μM. 9m proved to be the most active in vitro. The eight top-scoring compounds coming from the in vitro test for ALR2 inhibition activity were then tested in vivo, whereby three derivatives, 9i, 9j, and 9m, demonstrated a significantly preventive effect on sorbitol accumulation in the sciatic nerve in the 5-day streptozotocin-induced diabetic rats in vivo. Structure-activity relationship and molecular docking studies highlighted the importance of substitution features of N4-acetic acid group and halogen-substituted N2-benzyl group in the benzothiadiazine scaffold and indicated that substitution with hallogen at C-7 had a remarkably strong effect on ALR2 inhibition potency.
- Chen, Xin,Zhu, Changjin,Guo, Fan,Qiu, Xiaowei,Yang, Yanchun,Zhang, Shuzhen,He, Minlan,Parveen, Shagufta,Jing, Chaojun,Li, Yan,Ma, Bing
-
experimental part
p. 8330 - 8344
(2011/02/23)
-
- Hepatitis C NS5B polymerase inhibitors: 4,4-Dialkyl-1-hydroxy-3-oxo-3,4-dihydronaphthalene-3-yl benzothiadiazine derivatives
-
4,4-Dialkyl-1-hydroxy-3-oxo-3.4-dihydronaphthalene-3-yl benzothiadiazine derivatives were synthesized and evaluated as inhibitors of genotypes 1a and 1b HCV NS5B polymerase. A number of these compounds exhibited potent activity against genotypes 1a and 1b HCV polymerase in both enzymatic and cell culture activities. A representative compound also showed favorable pharmacokinetics in the rat.
- Hutchinson, Douglas K.,Rosenberg, Teresa,Klein, Larry L.,Bosse, Todd D.,Larson, Daniel P.,He, Wenping,Jiang, Wen W.,Kati, Warren M.,Kohlbrenner, William E.,Liu, Yaya,Masse, Sherie V.,Middleton, Tim,Molla, Akhteruzzaman,Montgomery, Debra A.,Beno, David W.A.,Stewart, Kent D.,Stoll, Vincent S.,Kempf, Dale J.
-
scheme or table
p. 3887 - 3890
(2009/04/07)
-
- Inhibitors of HCV NS5B polymerase: Synthesis and structure-activity relationships of N-1-benzyl and N-1-[3-methylbutyl]-4-hydroxy-1,8-naphthyridon-3-yl benzothiadiazine analogs containing substituents on the aromatic ring
-
A series of non-nucleoside HCV NS5B polymerase inhibitors based on the N-1-benzyl or N-1-[3-methylbutyl]-4-hydroxy-1,8-naphthyridon-3-yl benzothiadiazine core substituted in the D-ring aromatic moiety have been prepared and evaluated. Aromatic substituents extending from position 7 of the D-ring exhibited excellent potency against both genotypes 1a and 1b.
- Rockway, Todd W.,Zhang, Rong,Liu, Dachun,Betebenner, David A.,McDaniel, Keith F.,Pratt, John K.,Beno, David,Montgomery, Debra,Jiang, Wen W.,Masse, Sherie,Kati, Warren M.,Middleton, Tim,Molla, Akhteruzzaman,Maring, Clarence J.,Kempf, Dale J.
-
p. 3833 - 3838
(2007/10/03)
-
- Simple and chemoselective reduction of aromatic nitro compounds to aromatic amines: Reduction with hydriodic acid revisited
-
Reduction of aromatic nitro compounds to amines with hydriodic acid was reinvestigated. Under a milder non-refluxing condition (at 90°C for 2-4 h), the reduction proceeded efficiently with excellent chemoselectivity without affecting other functional groups including nitrile, ester, halide, carbonyl, amide, sulfonamide, imidazole and methylthio groups.
- Kumar, J.S.Dileep,Ho, ManKit M.,Toyokuni, Tatsushi
-
p. 5601 - 5603
(2007/10/03)
-
- Herbicidally active phenoxyalkanecarboxylic acid derivatives
-
A compound of the formula: STR1 wherein Q1 is CH or N; R is H or C1 -C5 alkyl; X is H, halogen, CF3, or NO2 ; Y is H or halogen; Z is --O-- or --NH--; A is STR2 wherein Q2, and Q3 are each CH or N; R1 and R2 are each H, C1 -C5 alkyl, C1 -C5 alkoxy, or C2 -C6 alkxoycarobnyl; R3, R4, and R5 are each H or C1 -C5 alkyl; R6 is H, halogen, or C1 -C5 alkyl; R7, R8, R9, and R10 are each H or C1 -C5 alkyl; R11 is H, C1 -C5 alkyl, C1 -C5 alkoxy, C2 -C6 alkenyl, C6 -C10 aryl, C7 -C15 aryloxyalkyl, or C7 -C15 aralkyl; R12 and R13 are each H or C1 -C5 alkyl; R14 is C1 -C5 alkyl, C2 -C6 alkenyl, C5 -C10 aryl, or C7 -C15 aralkyl; or R13 and R14 taken together form C3 -C4 alkylene, V1 and V2 are each H, halogen, NO2, CN, or CF3 ; V3 is halogen or CF3 ; W1 is --O-- or --NH--; W2 is --(CH2)n -- wherein n is 0 or 1, or CO; X1 is halogen, or a salt thereof, which is effective as a herbicidal agent.
- -
-
-
- Triphendioxazine reactive dyestuffs
-
Dyestuffs of the formula STR1 having the substituent meanings mentioned in the description, are suitable for dyeing and printing hydroxyl- or carbamoyl-containing materials, on which they produce light- and wet-fast dyeings and prints respectively.
- -
-
-