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Tin reduction of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine afforded perchloro-9-thia-1,5,8,10-tetraazaspiro[5.5]undeca-1,4,7,10-tetraene (10%) and 3,5-dichloro-4H-1,2,6-thiadiazine-4-thione (27%), the structures of which were supported by single crystal X-ray crystallography. Treating the tetrachlorothiadiazine with Ph3P (1 equiv.) afforded the corresponding spirocycle in a useful 66% yield, the degradation of which with BnEt3NCl (0.5 equiv.) afforded densely functionalized 4,5,6-trichloropyrimidine-2-carbonitrile in 81% yield. Rational mechanisms for the formation of products are proposed. © 2017 Elsevier Ltd 58 26 2618 2621

A near-quantitative acid and/or thermal mediated ring contraction of 3′,5′-diarylspiro(benzo[d][1,3]dioxole-2,4′-[1,2,6]thiadiazines) affords 3-aryl-4-(2-arylbenzo[d][1,3]dioxol-2-yl)-1,2,5-thiadiazoles. The reaction scope was studied providing 11 examples of this ring contraction. A double Wagner-Meerwein reaction mechanism is proposed. © 2016 American Chemical Society. 18 16 4056 4059 Cited By :1

The reactivity of 3,5-dichloro-4H-1,2,6-thiadiazine 4,4-ketals towards nucleophilic substitution or palladium-catalyzed C–C coupling at the C-3/5 positions led to seven new 3,5-disubstituted 4H-1,2,6-thiadiazine ethylene glycol 4,4-ketals and seven 3,5-disubstituted 4H-1,2,6-thiadiazine catechol 4,4-ketals in 83–98% yields. Furthermore, 3,5-diphenyl-4H-1,2,6-thiadiazine ethylene glycol and catechol 4,4-ketals were successfully hydrolysed in conc. H2SO4at 20 °C to afford 3,5-diphenyl-4H-1,2,6-thiadiazin-4-one in 74% and 89% yields. © 2016 Elsevier Ltd 57 30 3307 3310 Cited By :2

Tetraphenylhexaazaanthracene (TPHA), a fluorescent zwitterionic biscyanine with a closed-shell singlet ground state, on treatment with manganese dioxide or phenyliodine bis(trifluoroacetate) (PIFA), undergoes oxidative dimerization to give a near-zero dipole scissor 5,5′-dimer DI-TPHA. Both acene components of the new dimer DI-TPHA maintain their biscyanine closed-shell singlet ground state motifs, as judged by analysis of both single crystal X-ray crystallographic and density functional theory computational studies however, unlike TPHA, DI-TPHA is only very weakly fluorescent. © 2016 American Chemical Society. 18 5 1116 1119

2-Amino-N′-phenylbenzamidine (1a) reacts with tetracyanoethene (TCNE) to give 2-[2-(2-aminophenyl)-5-imino-1-phenyl-1H-imidazol-4(5H)-ylidene]malononitrile (11a), 4-(phenylamino)quinazoline-2-carbonitrile (5a) and 4-imino-3-phenyl-3,4-dihydroquinazoline-2-carbonitrile (9a). By optimizing the reaction conditions each of the compounds can be isolated as the main product and seven examples of these reactions are described. The [1H-imidazol-4(5H)-ylidene]malononitrile 11a was also independently synthesized in three steps from 2-amino-N′-(2-nitrophenyl)benzamidine (25) and TCNE in an overall yield of 56%. Dimroth rearrangement of either 2-aminophenyl- or 2-nitrophenyl-substituted [1H-imidazol-4(5H)-ylidene]malononitriles 11a or 27 with DBU in hot DCM gave the 2-[2-(2-aminophenyl)- and 2-[2-(2-nitrophenyl)-5-(phenylimino)-3H-imidazol-4(5H)-ylidene]malononitriles 28 (71%) and 34 (59%), respectively. Treatment of the [3H-imidazol-4(5H)-ylidene]malononitrile 28 with ethyl orthoformate in DMA at 165°C gave (Z)-2-[3-(phenylimino)imidazo[1,2-c]quinazolin-2(3H)-ylidene]malononitrile (36) (70%), thermolysis of which gave quinolino[3′,2′:4,5]imidazo[1,2-c]quinazoline-13-carbonitrile (30) (97%). © 2015 Elsevier Ltd. 71 46 8766 8780

Tetraphenylhexaazaanthracene, TPHA-1, is a fluorescent zwitterionic biscyanine with a closed-shell singlet ground state. TPHA-1 overcomes its weak 16π antiaromaticity by partitioning its π system into 6π positive and 10π negative cyanines. The synthesis of TPHA-1 is low yielding and accompanied by two analogous TPHA isomers: the deep red, non-charge-separated, quinoidal TPHA-2, and the deep green TPHA-3 that partitions into two equal but oppositely charged 8π cyanines. The three TPHA isomers are compared. © 2015 American Chemical Society. 17 16 4026 4029 Cited By :5

A chemical genomic screen of an in-house library of small molecule heterocycles was carried out using Xenopus laevis embryos. This led to the identification of N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-4-methoxyaniline (1c), which elicits loss of pigmentation in melanophores and the retinal pigment epithelium (RPE) of developing embryos, independent of the developmental stage of initial exposure. The phenotype was reversible, since pigmentation returned upon compound removal while analysis of neural crest cell markers (Pax7) and melanophore markers (Dct/Xtrp2) revealed that both neural crest precursors and fully differentiated melanophores were present in the dithiazole 1c treated embryos. A subsequent focused structure-activity relationship (SAR) study identified the more active dithiazole 4-benzyloxy-N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-aniline (1l) and the need for a chlorine substituent at the dithiazole C-4 position. Both the initial chemical genomic screen and the focused SAR study highlighted the toxicity of (dithiazolylidene)aminoazines, and also of methoxyaniline (anisidine) analogues that hosted strong electron-withdrawing or electronegative substituents or acidic hydroxyl groups on the anisidine moiety. This study suggests that 1,2,3-dithiazoles can act as reversible melanin synthesis inhibitors, revealing a new biological activity for this class of compounds. The inhibition of melanin synthesis is medically relevant as a potential treatment for pigmentation disorders such as melasma. © The Royal Society of Chemistry 2015. 6 935 946 Cited By :2

The optical, electrochemical, morphological and transport properties of a series of thiadiazinone (acceptor) and (thienyl)carbazoles (donor) containing π-extended donor-acceptor-donors (D-A-D) are presented. Systematic variations in the number of the thienyl units, the choice of branched or straight alkyl side chains and the use of a processing additive demonstrate their use as electron donors in bulk heterojunction solar cells blended with fullerene acceptors. The best power conversion efficiency (PCE) of 2.7% is achieved by adding to the D-A-D 3:fullerene blend a polydimethylsiloxane (PDMS) additive, that improves the morphology and doubles the hole mobility within the D-A-D:fullerene blend. © The Royal Society of Chemistry. 3 10 2358 2365 Cited By :7

Three 3,5-dichloro-4H-1,2,6-thiadiazines, which differ according to the electron withdrawing nature of their substituent at C-4: (a) 3,5-dichloro-4-methylene-4H-1,2,6-thiadiazine (5a), (b) 3,5-dichloro-4H-1,2,6-thiadiazin-4-one (5b) and (c) 2-(3,5-dichloro-4H-1,2,6-thiadiazin-4-ylidene)malononitrile (5c), are characterized using resonance Raman (RR), absorption (UV/vis) and photoluminescence (PL) spectroscopies. These weakly aromatic and electron-deficient heterocycles are potential components as acceptors in donor-acceptor systems for organic electronics. Experimental results, which include the synthesis, characterization and single crystal X-ray structure of 3,5-dichloro-4-methylene-4H-1,2,6-thiadiazine (5a), combined with theoretical calculations of their orbitals and vibrational frequencies, provide an understanding of the optical properties, on the basis of molecular geometry and electron distribution. © The Royal Society of Chemistry 2015. 5 24 18471 18481 Cited By :3

A Pd(0)-catalyzed double C-N coupling of 5,5′-dibromo-2,2′-bithiazoles with (het)arylamines and subsequent in situ Ag2O-mediated oxidation provides access to cross-conjugated quinoidal 5,5′-diarylimino-2,2′-bithiazoles in moderate to high yield. The highly colored quinoidal 2,2′-bithiazoles were studied by UV/vis spectroscopy, cyclic voltammetry and computational methods. © 2016 American Chemical Society. 19 1 174 177

Reacting N-aryliminophosphoranes with 1-(het)aroyl-2-aryldiazenes in preheated diphenyl ether at ca. 150-250 °C for 5-25 min affords in most cases the 1,3-diaryl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yls (aka Blatter radicals) in moderate to good yields. All new compounds are fully characterized, including EPR and CV studies for the radicals. Single-crystal X-ray structures of 1-benzoyl-2-(perfluorophenyl)diazene and 1-(perfluorophenyl)-3-phenyl-1,4-dihydrobenzo[e][1,2,4]triazinyl are also presented. © 2017 American Chemical Society. 82 14 7564 7575

1,3-Diaryl-1,4-dihydro-1,2,4-benzotriazin-4-yls are air stable organic radicals which have been exploited for their interesting magnetic properties. Herein, we present the optical properties of the "parent" radical namely 1,3-diphenyl-1,4-dihydro-1,2,4-benzotriazin-4-yl (aka "the Blatter radical"), which possesses absorption bands that span the UV and visible spectrum that lead to broadband emission across the same spectral region. As shown in our experiments, the emission originates from excited electronic states of the radical, with, however, low quantum yield. Emission across the visible is also observed from thin films of the radical when inserted into PMMA matrices. As radical concentration within the polymer matrix is increased, systematic modifications in the spectral and temporal characteristics of the fluorescence indicate the formation of radical ground state aggregates. © 2017 The Royal Society of Chemistry and the Centre National de la Recherche Scientifique. 41 16 8604 8613

3-Deazacanthin-4-one and nine analogues, including the 8-aza analogue, were prepared rapidly and in high yields from 8-iodoquinolones and 2-chloro(het)arylboronic acids. The strategy involves construction of the central B ring via concomitant Pd-catalyzed Suzuki-Miyaura C[sbnd]C and Cu-catalyzed Buchwald-Hartwig C[sbnd]N coupling reactions. © 2017 Elsevier Ltd 58 27 2661 2664

The LAT1 transporter is acknowledged as a pharmacological target of tumours since it is strongly overexpressed in many human cancers. The purpose of this work was to find novel compounds exhibiting potent and prolonged inhibition of the transporter. To this aim, compounds based on dithiazole and dithiazine scaffold have been screened in the proteoliposome experimental model. Inhibition was tested on the antiport catalysed by hLAT1 as transport of extraliposomal [3H]histidine in exchange with intraliposomal histidine. Out of 59 compounds tested, 8 compounds, showing an inhibition higher than 90% at 100 µM concentration, were subjected to dose-response analysis. Two of them exhibited IC50 lower than 1 µM. Inhibition kinetics, performed on the two best inhibitors, indicated a mixed type of inhibition with respect to the substrate. Furthermore, inhibition of the transporter was still present after removal of the compounds from the reaction mixture, but was reversed on addition of dithioerythritol, a S-S reducing agent, indicating the formation of disulfide(s) between the compounds and the protein. Molecular docking of the two best inhibitors on the hLAT1 homology structural model, highlighted interaction with the substrate binding site and formation of a covalent bond with the residue C407. Indeed, the inhibition was impaired in the hLAT1 mutant C407A confirming the involvement of that Cys residue. Treatment of SiHa cells expressing hLAT1 at relatively high level, with the two most potent inhibitors led to cell death which was not observed after treatment with a compound exhibiting very poor inhibitory effect. © 2017 Elsevier Inc. 143 39 52

Reacting ( Z)-N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-1H-pyrazol-5-amines 5 with Et2NH and then with concd H2SO4 gives 5H-pyrazolo[3,4-e ][1,2,4]dithiazine-3-carbonitriles 7 in good yields (74-85%) and 6H-pyrazolo-[3,4-f][1,2,3,5]trithiazepine-4-carbonitriles 9 as minor products (0-6%). Furthermore, the 1,3-dimethylpyrazole analogue 5a was transformed into the dithiazine 7a in two discrete steps, allowing the isolation of a disulfide intermediate (Z)-2-[(diethylamino)disulfan-yl]-2-[(1H-pyrazol-5-yl)imino]-acetonitrile (8a). The one-pot, two-step reaction also worked with electron-rich hydroxy- and methoxy-substituted anilines. Thermolysis of the pyrazolo[3,4-e][1,2,4]dithiazines 7 gave the ring-contracted 1H-pyrazolo[3,4-d]thiazole-5-carbonitriles 6 (94-100%). With active sulfur, 1,3-dimethyl-5H-pyrazolo[3,4-e ][1,2,4]dithiazine-3-carbonitrile (7a) gave 1,3-dimethyl-6Hpyrazolo[3,4-f][1,2,3,5]trithiazepine-4-carbonitrile (9a), but on prolonged reaction times, it gave 5,7-dimethyl-5H-[1,2,3]-dithiazolo[4,5-b]pyrazolo[3,4-e][1,4]thiazine (13). Finally, in the absence of acid, heating a solution of (Z)-2-[(diethylamino)-disulfanyl]-2-[(1,3-dimethyl-1H-pyrazol-5-yl)imino]acetonitrile (8a) gave 4,6,10,12-tetramethyl-6H-pyrazolo[3,4-f]pyrazolo-[3′,4′:4,5]pyrimido[6,1-d][1,2,3,5]trithiazepine-8,12 b(10H)-dicarbonitrile (19) (67%). (Chemical Equation Presented). © 2014 American Chemical Society. 79 20 9717 9727 Cited By :7

Palladium catalyzed direct C-H arylation of 3-bromoisothiazole-5-carbonitrile with aryl/hetaryl iodides in the presence of AgF gave 13 4-aryl/hetaryl-3-bromoisothiazole-5-carbonitriles. The scope of this arylation was investigated and explanations for the limitations proposed. 3-Bromoisothiazole-5-carboxamide was isolated as a side-product, and its formation was attributed to Ag+-catalyzed hydration of the C-5 nitrile. The analogous phenylation of 3-chloroisothiazole-5-carbonitrile and 3-bromoisothiazole-4-carboxamide gave 3-chloro-4-phenylisothiazole-5-carbonitrile and 3-bromo-5-phenylisothiazole-4-carboxamide in 83 and 64% yields, respectively. © 2014 Elsevier B.V. All rights reserved. 38 6796 6802 Cited By :1

Ring transformation of readily prepared (4-chloro-5H-1,2,3-dithiazol-5- ylidene)acetonitriles afford 3-haloisothiazole-5-carbonitriles in good to excellent yields. The transformation can be mediated using HBr (g), HCl (g) or BnEt3NCl. Mechanisms for the transformations are discussed, together with rationalizations for the formation of side products. Furthermore, single crystal X-ray structures are provided for (Z)-2-(4-chloro-5H-1,2,3-dithiazol-5- ylidene)acetonitrile and (E)-2-bromo-2-(4-chloro-5H-1,2,3-dithiazol-5-ylidene) acetonitrile confirming the stereochemistry of the exocyclic ethene bond. © 2014 The Royal Society of Chemistry. 4 15 7735 7748 Cited By :6

Electrospun nanocomposite fibers consisting of crosslinked polyvinylpyrrolidone (PVP) chains and gold nanoparticles (Au NPs) were fabricated, starting from highly stable PVP/Au NP colloidal solutions with different NP loadings, followed by thermal treatment. Information on the morphological characteristics of the fibers and of the embedded Au NPs was obtained by electron microscopy. Cylindrical, bead-free fibers were visualized by Scanning Electron Microscopy (SEM) while Transmission Electron Microscopy (TEM) and Energy Diffraction X-ray (EDX) analysis supported the presence of Au NPs within the fibers and gave information on their morphologies and average diameters. These materials were briefly evaluated as heterogeneous catalytic supports for the gold-catalyzed intramolecular cyclisation of 2-(phenylethynyl)aniline to form 2-phenyl-1H-indole. The performance of the gold catalyst was strongly dependent on the Au NP size, with the system containing the smallest Au NPs being the more effective. Moreover, a slight drop of their catalytic efficiency was observed after three consecutive reaction runs, which was attributed to morphological changes as a consequence of fiber merging. © 2016 by the authors licensee MDPI, Basel, Switzerland. 21 9

The thioredoxin (Trx)-thioredoxin reductase (TrxR) system plays a key role in maintaining the cellular redox balance with Trx being over-expressed in a number of cancers. Inhibition of TrxR is an important strategy for anti-cancer drug discovery. The natural product pleurotin is a well-known irreversible inhibitor of TrxR. The cytotoxicity data for benzo[1,2,4]triazin-7-ones showed very strong correlation (Pearson correlation coefficients ~0.8) to pleurotin using National Cancer Institute COMPARE analysis. A new 3-CF3 substituted benzo[1,2,4]triazin-7-one gave submicromolar inhibition of TrxR, although the parent compound 1,3-diphenylbenzo[1,2,4]triazin-7-one was more cytotoxic against cancer cell lines. Benzo[1,2,4]triazin-7-ones exhibited different types of reversible inhibition of TrxR, and cyclic voltammetry showed characteristic quasi-reversible redox processes. Cell viability studies indicated strong dependence of cytotoxicity on substitution at the 6-position of the 1,3-diphenylbenzo[1,2,4]triazin-7-one ring. F.A. thanks the Irish Research Council (IRC) for a Government of Ireland Postgraduate Scholarship for Martin Sweeney and College of Science, National University of Ireland Galway (NUI Galway) for a postgraduate scholarship for Robert Coyle. We thank the National Cancer Institute (USA), Development Therapeutic Program for providing us with a small quantity of pleurotin. P.A.K. thanks the Cyprus Research Promotion Foundation [Grants: NEAYPODOMH/NEKYP/0308/02 and YGEIA/BIOS/0308(BIE)/13], the University of Cyprus (Medium Sized Grant), and the following organizations in Cyprus for generous donations of chemicals and glassware: the State General Laboratory, the Agricultural Research Institute, the Ministry of Agriculture, Medochemie Ltd and Biotronics Ltd. Furthermore, P.A.K. thanks the A. G. Leventis Foundation for helping to establish the NMR facility in the University of Cyprus. peer-reviewed 2018-05-30

ID: 1149 In: ChemInform, Vol. 47, no. 9 ( 2016), p.no-no. Summary: AbstractThe reaction of 2‐amino‐N‐arylbenzamidines with tetracyanoethene is investigated under different reaction conditions to provide either imidazoline of type (III), quinazolines (IV) or (V) as sole or main products.

ID: 1070 In: ChemInform, Vol. 47, no. 4 ( 2016), p.no-no. Summary: AbstractThe required pharmaceutically important ring system can be prepared via 3 routes as is demonstrated for derivative (IIa).

N-(4-Chloro-5H-1,2,3-dithiazol-5-ylidene)anilines react with DABCO in hot PhCl to give N-{4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazol-5-ylidene}anilines in high yields (70-92%). The reaction also works with 4-chloro-5H-1,2,3-dithiazol-5-one and -thione, giving the corresponding products in 85% and 76% yields, respectively. While the reaction of several (4-chloro-5H-1,2,3-dithiazol-5-ylidene)methanes with DABCO failed to give {4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazol-5-ylidene}methanes, these can be prepared in moderate yields via classical cycloaddition-retrocycloaddition strategies from 4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazole-5-thione. The 2-chloroethyl moiety on selected dithiazoles was also modified without cleavage of the 1,2,3-dithiazole by reaction with various nucleophiles, giving access to 4-[N-(2-substituted)piperazin-1-yl]-5H-1,2,3-dithiazoles in moderate to high yields. © 2015 American Chemical Society. 81 2 615 631 Cited By :3

ID: 1081 In: ChemistrySelect, Vol. 1, no. 11 ( 2016), p.2635-2641. Summary: AbstractColloidal polyvinylpyrrolidone‐stabilized Pd nanoparticles were embedded within 1,2‐bis(2‐iodoethoxy)ethane (BIEE)‐crosslinked poly(2‐dimethylamino)ethyl methacrylate homopolymer networks with defined structural characteristics. In the presented synthetic approach, the crosslinking step is realised in ambient conditions, thus avoiding nanoparticle agglomeration phenomena. These 3D polymer‐based nanocomposite networks were evaluated as heterogeneous catalysts for Heck, Suzuki‐Miyaura and Sonogashira coupling reactions. High catalytic activity and reusability was demonstrated in Heck reactions, substrate‐specific outcomes were observed in Sonogashira couplings, while poor reactivity was observed in Suzuki‐Miyaura couplings. The existing diversity in material structure and composition allows for further improvements leading to highly stable and robust 3D polymer‐based nanocomposite heterogeneous catalysts that could find use in a wide range of transition metal‐catalysed organic reactions.AbstractStructure‐defined 3D catalytic nanocomposite polymer networks were synthesized based on monodisperse polyvinylpyrrolidone (PVP)‐stabilized Pd colloidal nanohybrids encapsulated within 1,2‐bis‐(2‐iodoethoxy)ethane (BIEE)‐crosslinked poly(2‐dimethylamino)ethyl methacrylate homopolymer networks. These materials were evaluated as heterogeneous catalytic supports in Heck, Suzuki‐Miyaura and Sonogashira coupling reactions.

ID: 1080 In: ChemInform, Vol. 47, no. 19 ( 2016), p.no-no. Summary: AbstractTreatment of title compound (I) with selected alcohols, phenols, and thiols leads to the regiospecific substitution of both geminal C‐4 chlorines to afford the corresponding ketal, or thioketal derivatives, respectively.

18 4

ID: 1078 In: ChemInform, Vol. 47, no. 22 ( 2016), p.no-no.

ID: 1066 In: Tetrahedron letters, Vol. 57, no. 2 ( 2016), p.203-205. Summary: Graphical abstractAbstractTreatment of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine (2) with selected alkanols, arenols and thiols led to regiospecific substitution of both geminal C-4 chlorines resulting in the formation of ketal or thioketal 3,5-dichloro-4H-1,2,6-thiadiazines8a–hin 31–97% yields.

Over the last few decades the number of stable heterocyclic neutral radicals has dramatically increased. There have been significant efforts to use these unusual open-shell compounds in a broad array of applications that include use as reagents in synthesis, spin active probes in analysis, polymerization initiators, redox active ligands, and in the material sciences for their potential use in electronic devices. In this brief review, which covers the period since 2000, we survey advances in heterocyclic neutral organic radicals that contain either an endocyclic hydrazyl or thiazyl unit. Emphasis is on new synthetic methods, physical properties, and applications. © 2016 Elsevier Inc. 119 173 207 Sponsors: Conference code: 130618 Cited By :6

ID: 1082 In: Tetrahedron letters, Vol. 57, no. 30 ( 2016), p.3307-3310. Summary: Graphical abstractHighlights•3,5-Dichloro-4H-1,2,6-thiadiazine 4,4-ketals undergo Pd-catalyzed C–C coupling at the C-3/5 positions.•Nucleophilic substitution at C-3/5 can occur with methoxide, phenoxide and pyrrolidine.•3,5-Diphenyl derivatives can be hydrolysed to 3,5-diphenyl-4H-1,2,6-thiadiazin-4-one.AbstractThe reactivity of 3,5-dichloro-4H-1,2,6-thiadiazine 4,4-ketals towards nucleophilic substitution or palladium-catalyzed C–C coupling at the C-3/5 positions led to seven new 3,5-disubstituted 4H-1,2,6-thiadiazine ethylene glycol 4,4-ketals and seven 3,5-disubstituted 4H-1,2,6-thiadiazine catechol 4,4-ketals in 83–98% yields. Furthermore, 3,5-diphenyl-4H-1,2,6-thiadiazine ethylene glycol and catechol 4,4-ketals were successfully hydrolysed in conc. H2SO4at 20 °C to afford 3,5-diphenyl-4H-1,2,6-thiadiazin-4-one in 74% and 89% yields.

The ASCT2 transport system catalyses a sodium-dependent antiport of glutamine and other neutral amino acids which is involved in amino acid metabolism. A library of 1,2,3-dithiazoles was designed, synthesized and evaluated as inhibitors of the glutamine/amino acid ASCT2 transporter in the model system of proteoliposomes reconstituted with the rat liver transporter. Fifteen of the tested compounds at concentration of 20μM or below, inhibited more than 50% the glutamine/glutamine antiport catalysed by the reconstituted transporter. These good inhibitors bear a phenyl ring with electron withdrawing substituents. The inhibition was reversed by 1,4-dithioerythritol indicating that the effect was likely owed to the formation of mixed sulfides with the protein's Cys residue(s). A dose-response analysis of the most active compounds gave IC50 values in the range of 3-30μM. Kinetic inhibition studies indicated a non-competitive inhibition, presumably because of a potential covalent interaction of the dithiazoles with cysteine thiol groups that are not located at the substrate binding site. Indeed, computational studies using a homology structural model of ASCT2 transporter, suggested as possible binding targets, Cys-207 or Cys-210, that belong to the CXXC motif of the protein. © 2012 Elsevier Inc. 265 1 93 102 Cited By :23

Asymmetric 3,5-diaryl substituted 4H-1,2,6-thiadiazin-4-ones can be prepared from 3,5-dichloro-4H-1,2,6-thiadiazin-4-one (1) via a multi-step protocol: selective nucleophilic mono-chloro substitution gives either the mono-methoxy or benzyloxy substituted mono-chlorothiadiazinones that can be phenylated via Suzuki-Miyaura coupling. Subsequent BBr 3 mediated dealkylation gives 3-hydroxy-5-phenyl-4H-1,2,6-thiadiazin-4-one (9) that can be activated by a modified Finkelstein halodehydroxylation via the triflate, enabling further arylation reactions using Suzuki-Miyaura or Stille coupling chemistry. © 2012 Elsevier Ltd. All rights reserved. 68 36 7380 7385 Cited By :5

The reactions of 2-, 3- and 4-aminopyridines with 4,5-dichloro-1,2,3- dithiazolium chloride (Appel salt) 4 to give N-(4-chloro-5H-1,2,3-dithiazol-5- ylidene)pyridin-Xamines 1a (X = 2), 1g (X = 3) and 1k (X = 4) were optimized with respect to base, temperature and reaction time. Based on these conditions a total of thirteen [(dithiazolylidene) amino]azines 1a-m were prepared and fully characterized. © 2011 by the authors licensee MDPI, Basel, Switzerland. 16 11 8992 9002 Cited By :10

Silver(I) fluoride (AgF)-mediated intramolecular nonoxidative and oxidative palladium-catalyzed cyclizations of 1,3-diphenyl- and 8-iodo-1,3- diphenylbenzo[e][1,2,4]triazin-7(1H)-ones 6a (R = H) and 7a (R = I) afford a new 'alkaloid like' ring system 2-phenyl-6H-[1,2,4]triazino[5,6,1-jk]carbazol-6-one 8a (triazafluoranthenone) in 86 and 100% yields, respectively. Furthermore, these cyclization protocols were used to prepare triazafluoranthenone analogues 8b - e bearing dialkylamino, methoxy, and phenylsulfanyl substituents at C-5, which were also independently synthesized from triazafluoranthenone 8a by regioselective nucleophilic addition. Similar AgF-mediated intramolecular nonoxidative and oxidative palladium-catalyzed cyclizations of 8,10-dihydro-1-iodo-10-phenylphenazin-2(7H)-ones 13 gave the new 'alkaloid like' ring system 8H-indolo[1,2,3-mn]phenazin-8-one 14 in 80 and 18% yields, respectively. © 2011 American Chemical Society. 76 14 5793 5802 Cited By :16

Ethyl canthin-6-one-1-carboxylate (1b) and nine analogues 1c-k were prepared from readily prepared ethyl 4-bromo-6-methoxy-1,5-naphthyridine-3- carboxylate (2b) via a three-step non-classical approach that focused on construction of the central pyrrole (ring B) using Pd-catalyzed Suzuki-Miyaura coupling followed by Cu-catalyzed C-N coupling. Furthermore, treatment of the ethyl canthinone-1-carboxylate 1b with NaOH in DCM/MeOH (9:1) gave the canthin-6-one-1-carboxylic acid (6) in high yield. All compounds are fully characterized. © 2011 American Chemical Society. 76 12 5113 5122 Cited By :20

In this work we have developed an in silico model to predict the inhibition of β-amyloid aggregation by small organic molecules. In particular we have explored the inhibitory activity of a series of 62 N-phenylanthranilic acids using Kohonen maps and Counterpropagation Artificial Neural Networks. The effects of various structural modifications on biological activity are investigated and novel structures are designed using the developed in silico model. More specifically a search for optimized pharmacophore patterns by insertions, substitutions, and ring fusions of pharmacophoric substituents of the main building block scaffolds is described. The detection of the domain of applicability defines compounds whose estimations can be accepted with confidence. © 2010 Elsevier Masson SAS. All rights reserved. 46 2 497 508 Cited By :63

Attempted detosylation of the 3-amino-1-(p-tosylamino)indole-2-carbonitriles 4a-c using either K2CO3 in EtOH or DBU in PhH at reflux gives unexpectedly the 3-(N-p-tosylamino)indole-2-carbonitriles 5a-c, respectively in high yields. Nevertheless, treatment of 1-(p-tosylamino)indoles 4a-c with thiophenol and DBU in PhH at reflux gives the detosylated 3-aminoindole-2-carbonitriles 5a-c. Reaction mechanisms supporting the tosyl migration (4→5) and the reductive detosylation (4→2) are proposed. All new compounds are fully characterised. © 2010 Elsevier Ltd. All rights reserved. 66 16 3016 3023 Cited By :7

[3,5-Bis(dialkylamino)-4H-1,2,6-thiadiazin-4-ylidene]propanedinitriles 6a-c, react with sodium methoxide or ethoxide to give the corresponding 6-alkoxy-4-dialkylamino substituted pyrrolo[2,3-c][1,2,6]thiadiazine-5-carbonitriles 7a-f in variable yields. These new compounds are fully characterised and two rational mechanisms are proposed for their formation. © 2010 Elsevier Ltd. All rights reserved. 66 10 1817 1820 Cited By :9

Treatment of 1,2-bis(4-chloro-5H-1,2,3-dithiazol-5-ylidene)hydrazine 4 with benzyltriethylammonium iodide (1 equiv) affords dicyano-1,3,4-thiadiazole 3 and 5-cyano-1,3,4-thiadiazole-2-carboxamide 5 in 79 and 21% yields, respectively. By using polymer bound triphenylphosphine instead of benzyltriethylammonium iodide the dicyano-1,3,4-thiadiazole 3 can be isolated in 70% yield without chromatography. The reaction of DAMN with Appel salt 8 gave 2-(4-chloro-5H-1,2,3-dithiazol-5-ylideneamino)-2-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)acetonitrile 7 (14%), 2,3-bis-(4-chloro-5H-1,2,3-dithiazol-5-ylideneamino)fumaronitrile 10 (14%), and 2,3-bis(4-chloro-5H-1,2,3-dithiazol-5-ylideneamino)maleonitrile 11 (24%) together with other products. The maleonitrile 11 isomerizes into the fumaronitrile 10 on irradiation at 365 nm. Reaction of aminoacetonitrile with Appel salt 8 gives the (dithiazolylidene)acetonitrile 7 in 33% yield. Treatment of (dithiazolylidene)acetonitrile 7 with polymer bound triphenylphosphine gives tricyanothiazole 6 in 76% yield. A rational general mechanism for the transformation of bisdithiazoles to percyanoheteroles is proposed. © 2009 Elsevier Ltd. All rights reserved. 65 48 9967 9972 Cited By :18

4,5-Dichloro-1,2,3-dithiazolium chloride 1 (Appel salt) reacts in wet DCM, THF or MeCN to give elemental sulfur, dithiazole-5-thione 4, dithiazol-5-one 5 and thiazol-5-one 6. Furthermore the reaction of 2-phenylthiazol-5(4H)-one 12 with Appel salt 1 at ca. 20 °C gives 4-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-2-phenylthiazol-5(4H)-one 13 (26%) while at ca. 82 °C a new product 2,2′-diphenyl-4,4′-bithiazol-ylidene-5,5′-dione 14 (36%) is additionally isolated. Finally, 4,4′-bithiazolylidene-5,5′-dione 14 is prepared directly by treating 2-phenylthiazol-5(4H)-one 12 with N-chlorosuccinimide. All new compounds are fully characterised and rational mechanisms are proposed for the formation of all key compounds. © 2009 Elsevier Ltd. All rights reserved. 65 34 6859 6862 Cited By :3

A linear Quantitative Structure-Activity Relationship (QSAR) is developed in this work for modeling and predicting HDAC inhibition by 5-pyridin-2-yl- thiophene-2-hydroxamic acids. In particular, a five-variable model is produced by using the Multiple Linear Regression (MLR) technique and the Elimination Selection-Stepwise Regression Method (ES-SWR) on a database that consists of 58 recently discovered 5-pyridin-2-yl-thiophene-2-hydroxamic acids and 69 descriptors. The physical meaning of the selected descriptors is discussed in detail. The validity of the proposed MLR model is established using the following techniques: cross validation, validation through an external test set and Y-randomization. Furthermore, the domain of applicability which indicates the area of reliable predictions is defined. Based on the produced model, an in silico-screening study explores novel structural patterns and suggests new potent lead compounds. © 2009 Springer Science+Business Media B.V. 13 3 301 311 Cited By :35

A series of d-block metal complexes of the recently reported coordinating neutral radical ligand 1-phenyl-3-(pyrid-2-yl)-1,4-dihydro-1,2,4-benzotriazin-4-yl (1) was synthesized. The investigated systems contain the benzotriazinyl radical 1 coordinated to a divalent metal cation, MnII, FeII, CoII, or NiII, with 1,1,1,5,5,5-hexafluoroacetylacetonato (hfac) as the auxiliary ligand of choice. The synthesized complexes were fully characterized by single-crystal X-ray diffraction, magnetic susceptibility measurements, and electronic structure calculations. The complexes [Mn(1)(hfac)2] and [Fe(1)(hfac)2] displayed antiferromagnetic coupling between the unpaired electrons of the ligand and the metal cation, whereas the interaction was found to be ferromagnetic in the analogous NiII complex [Ni(1)(hfac)2]. The magnetic properties of the complex [Co(1)(hfac)2] were difficult to interpret owing to significant spin-orbit coupling inherent to octahedral high-spin CoII metal ion. As a whole, the reported data clearly demonstrated the favorable coordinating properties of the radical 1, which, together with its stability and structural tunability, make it an excellent new building block for establishing more complex metal-radical architectures with interesting magnetic properties. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. 21 44 15843 15853 Cited By :9

ID: 1067 In: ChemInform, Vol. 47, no. 1 ( 2016), p.no-no.

The cyclisation reactions of 2-(4-chloro-5H-1,2,3-dithiazol-5-ylidene-amino)phenol (5a), 3-(4-chloro-5H-1,2,3-dithiazol-5-ylideneamino)pyridin-2-ol (5b) and 2-(4-chloro-5H-1,2,3-dithiazol-5-ylideneamino)pyridin-3-ol (5c) are investigated. Thermolysis in hot PhCl (132 °C) or under solvent free conditions at ca. 200 °C gave benzo[d]oxazole-2-carbonitrile (4a), oxazolo[5,4-b]pyridine-2-carbonitrile (4b) and oxazolo[4,5-b]pyridine-2-carbonitrile (4c) in high yields, while treatment with either NaH in dry THF at 66 °C or with i-Pr2NEt in DCM at 20 °C gave benzo[b][1,2,3]dithiazolo[5,4-e][1,4]oxazine (6a), [1,2,3]dithiazolo[5,4-e]pyrido[2,3-b][1,4]oxazine (6b) and oxazolo[4,5-b]pyridine (4c), respectively. The transformation of benzoxazine 6a and the pyridoxazine 6b into the corresponding oxazoles 4a and 4b was also investigated, and tentative mechanistic pathways for these transformations are proposed. © 2014 Elsevier Ltd. 71 39 7181 7190 Cited By :1

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The high yielding transformations of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine into 3,5-dichloro-4H-1,2,6-thiadiazin-4-one (up to 85%) and 2-(3,5-dichloro-4H-1,2,6- thiadiazin-4-ylidene)malononitrile (up to 83%) have been investigated and compared to the analogous transformations of the closely-related 4,5-dichloro-1,2,3-dithiazolium chloride (Appel's salt) into 4-chloro-5H-1,2,3-dithiazol-5-one and 2-(4-chloro-5H-1,2,3-dithiazol-5- ylidene)malononitrile. Furthermore, cyclocondensation of 3,4,4,5-tetrachloro-4H-1,2,6- thiadiazine with 2-aminophenol and 1,2-benzenediamines gave fused 4H-1,2,6-thiadiazines in 68%-85% yields. © 2015 by the authors. 20 8 14576 14594 Cited By :4

Benzo[4,5]imidazo[1,2-c]quinazoline-6-carbonitriles are prepared in high yields via three new routes: (1) a Cu(OTf)2 (0-5 mol %) catalyzed hypervalent iodine [PhI(OTf)2] mediated oxidative coupling of 4-anilinoquinazoline-2-carbonitriles in neat trifluoroacetic acid (TFA) (2) a Pd(OAc)2 (10 mol %) or CuI (10 mol %) mediated nonoxidative coupling of 4-(2-bromoanilino)quinazoline-2-carbonitrile and (3) a nonoxidative Pd(Ar3P)3 [Ar = 3,5-(F3C)2C6H3] [aka Superstable Pd(0) Catalyst] (10 mol %) mediated intramolecular C-N cyclization of 3-(2-bromophenyl)-4-imino-3,4-dihydroquinazoline-2-carbonitriles. All new compounds are fully characterized. © 2015 American Chemical Society. 80 16 8329 8340 Cited By :6

ID: 1068 In: ChemInform, Vol. 47, no. 1 ( 2016), p.no-no. Summary: AbstractThe thermolysis of pyridinol (I) leads to oxazolo[5,4‐b]pyridine‐2‐carbonitrile (II), whilst the treatment with a base gives oxazine (III).

ID: 1142 In: RSC advances, Vol. 5, no. 24 ( 2015), p.18471-18481. Summary: AbstractThe effect of C-4 substitution with electron withdrawing groups on the structure and electronic properties of three 3,5-dichloro-4H-1,2,6-thiadiazines is characterized using resonance Raman, absorption and photoluminescence spectroscopies.

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80 17 8943 8944 Cited By :2