Search

In this paper, we not only give the parity check matrix of the [1, 0]-twisted generalized Reed-Solomon (in short, TGRS) code, but also determine the weight distribution. Especially, we show that the [1, 0]-TGRS code is not GRS or EGRS. Furthermore, we present a sufficient and necessary condition for any punctured code of the [1, 0]-TGRS code to be self-orthogonal, and then construct several classes of self-dual or almost self-dual [1, 0]-TGRS codes. Finally, on the basis of these self-dual or almost self-dual [1, 0]-TGRS codes, we obtain some LCD [1, 0]-TGRS codes. [ABSTRACT FROM AUTHOR]

Strategies commonly used for the synthesis of functionalised bicyclo[1.1.1]pentanes (BCP) rely on the reaction of [1.1.1]propellane with anionic or radical intermediates. In contrast, electrophilic activation has remained a considerable challenge due to the facile decomposition of BCP cations, which has severely limited the applications of this strategy. Herein, we report the electrophilic activation of [1.1.1]propellane in a halogen bond complex, which enables its reaction with electron-neutral nucleophiles such as anilines and azoles to give nitrogen-substituted BCPs that are prominent motifs in drug discovery. A detailed computational analysis indicates that the key halogen bonding interaction promotes nucleophilic attack without sacrificing cage stabilisation. Overall, our work rehabilitates electrophilic activation of [1.1.1]propellane as a valuable strategy for accessing functionalised BCPs.

This article reports [1, 2, 4, 5-tetra(4'-carboxyphenyl)-benzene] (1) and its tetraethyl ammonium and tetrabutylammonium inclusion compounds (C34H21O8−·N+(C2H5)4·H2O (2) C34H21O8−·N+(n-C3H7)4·H2O (3). Compound one eventually forms a "molecular column" along the direction of [110], and the solvent molecules are filled by two adjacent columns to form a stable crystal structure. In compound 2, the tetravalent host anion forms rectangular three-dimensional pores with water molecules by O-H... O hydrogen bonds, two tetraethyl ammonium ions are neatly arranged in the pores to form a tighter structure, In structure 3, the formation of the main skeleton mainly relies on O...H...O hydrogen bond formed by the contact between the proton H shared between the two host anions and the O-H...O generated by the water molecule and one of the two anions. In the three crystal structures, [1, 2, 4, 5-tetra(4'-carboxyphenyl)-benzene], as an "X" polycyclic polycarboxylate aromatic molecule, constructs a large 3 D hole by using its configuration feature. Corresponding solvent molecules and different guest molecules are contained in the 3 D pores, forming various stable crystal structures. [ABSTRACT FROM AUTHOR]

Introducing new and green methods and finding environmentally friendly solvents in the synthesis of organic compounds is very important. In this study, the synthesis of [1,3] dithiine derivatives using the glycerol: potassium carbonate as deep eutectic solvent was investigated, in addition, the antibacterial effects of the synthesized compounds against two bacterial strains named Edwardsiella tarda and Lactococcus garvieae according to the CLSI standard using microdilution broth base on inhibition zone diameter (IZD), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were tested. The results showed that glycerol: potassium carbonate could be used as a green solvent in the synthesis of [1,3] dithiine derivatives and the results of antibacterial activities against study also showed that these compounds, especially f5, were capable of inhibiting Edwardsiella tarda and Lactococcus garvieae at concentrations of 64 and 8 μg / ml, respectively. In addition, it was demonstrated that there was a clear relationship between the structure of the derivatives and the antibacterial activity, with the highest effect being on the chlorine-containing compounds, followed by chlorine, bromine, and nitrogen.

For a graph $G=(V,E)$, a set $S \subseteq V$ is a $[1,2]$-set if it is a dominating set for $G$ and each vertex $v \in V \setminus S$ is dominated by at most two vertices of $S$, i.e. $1 \leq \vert N(v) \cap S \vert \leq 2$. Moreover a set $S \subseteq V$ is a total $[1,2]$-set if for each vertex of $V$, it is the case that $1 \leq \vert N(v) \cap S \vert \leq 2$. The $[1,2]$-domination number of $G$, denoted $\gamma_{[1,2]}(G)$, is the minimum number of vertices in a $[1,2]$-set. Every $[1,2]$-set with cardinality of $\gamma_{[1,2]}(G)$ is called a $\gamma_{[1,2]}$-set. Total $[1,2]$-domination number and $\gamma_{t[1,2]}$-sets of $G$ are defined in a similar way. This paper presents a linear time algorithm to find a $\gamma_{[1,2]}$-set and a $\gamma_{t[1,2]}$-set in generalized series-parallel graphs.

Reaction of methyl 2-aryl-5-(chlorosulfonyl)-1,3-oxazole-4-carboxylates with 1H-pyrazol-5-amines and 1H-1,2,4-triazol-5-amines proceeds with the participation of endocyclic aminoazole nitrogen atoms to yield products containing a primary amino group. Being treated by sodium hydride these products undergo a further transformation into the tricyclic compounds. It has been shown that the cyclocondensation pathway includes the Smiles rearrangement with extrusion of SO2 followed by the elimination of MeOH. This reaction sequence is a convenient approach to the synthesis of new annulated [1,3]oxazolo[5,4-d]pyrimidine derivatives.

Interaction of 8-lithio-3-tert-butyl-4-oxopyrazolo[5,1-c][1,2,4]triazin-1-ide with elemental sulfur or selenium in THF with further in situ alkylation at –97 °C followed by warming to room temperature furnished a series of 3-tert-butyl-8-X-pyrazolo[5,1-c][1,2,4]triazin-4(6H)-ones (X = n-BuS, n-BuSe, MeSe, PhCH2S) in good yields. 8,8'-Diselanediylbis(3-tert-butylpyrazolo[5,1-c][1,2,4]triazin-4(1H)-one) was also isolated as a by-product in these reactions. One-pot interaction of the n-BuSe substituted derivative with diborane/boron trifluoride led to reduction of the 1,2,4-triazine core and partial elimination of the alkylselanyl moiety. The structures of the synthesized products were established on the basis of IR, 1H, 13C, 2D HMBC 1H–77Se NMR and high resolution mass spectra, as well as X-ray single crystal diffraction analyses. Two of the prepared compounds were also tested for antimicrobial and antifungal activities. [ABSTRACT FROM AUTHOR]

A subset S Ç V in a graph G = (V, E) is called a [1, k]-set, if for every vertex v 6 V\S, 1 < |NG(v) nS| < k. The [1, k]-domination number of G, denoted by Y[i,k](G) is the size of the smallest [1,k]-sets of G. A set S' Ç V (G) is called a total [1,k]-set, if for every vertex v e v, 1 < |.ezG(v) ns| $\ k. If a {graph G has at least one total [1, k]-set then the cardinality of the smallest such setz is denoted by Yt[1,k](G). In this paper, we investigate the existence of [1,k]-sets in lexicographic products Go Ti. Furthermore, we completely characterize graphs whose lexicographic product lias £it leaet one total [1,k]-set. Finally, we show that finding smallest total [1, k]-set is an NP-complete problem. [ABSTRACT FROM AUTHOR]

The energetics, structures, reaction paths and mechanisms for the conversion XCN ⟷ XNC, with X = H, Li, CH3 and H2B have been investigated through the use of improved virtual orbitals (IVO) in a second-order multireference perturbation theory (MRPT) treatment within the framework of state-specific (SS) parametrisation of the wave function for the target state (IVO-SSMRPT). Due to its flexibility, IVO-SSMRPT formulation allows us to take into account the major part of the coupling between the dynamic and nondynamic correlation effects in an accurate manner. The results obtained by our calculations agree well with the state-of-the-art electronic structure methods and reference values which illustrates that IVO-SSMRPT, when applied judiciously, can be very accurate for reaction surfaces of XCN ⟷ XNC isomerisation, barrier and bond-parameters. [ABSTRACT FROM AUTHOR]

This article included the photostabilization study for poly(vinyl chloride)) by using newly stabilizers derived from [1,1 -Bis (4-aminophenyl)-4-Phenyl Cyclohexane] as additives against photodegradation. For that purpose, many samples (films) has been prepared by adding additives to the poly(vinyl chloride) with different weight percentages from additives and by different thickness. The photostabilization activities of these compounds were determined by detecting the carbonyl group (The position off carbonyl absorption is specified at 1724-1770 cm-1) with irradiation time. The absorption spectra of poly vinyl chloride films were followed using Shimadzu Spectrophotometer Also, change the viscosity of the averagee molecular weight and the degree of deterioration (α) and the average number of chain scission (s) was studied .We found through results that the rate of photostabilization in the presences of additives follows the following trend:- C4 > C3 > C2 > C1 > PVC UV absorption peroxide decomposer, for mechanisms haven been suggested according to experimental results obtained. [ABSTRACT FROM AUTHOR]

Seven mild, efficient and novel inhibitors were obtained in good to excellent yield by addition of Thiadiazole derivatives with an acids-molecular sieve system at moderate temperature (5°C). The structures of the prepared compounds are characterized by IR and 1HNMR Spectroscopy, and the catalyst can be recovered by filtration and reused several times. The resulted showed that the process was then applied to [1, 3, 4] thiadiazde derivatives using 0.75 g of Catalyst for acids and performing the reactions at 50 °C for 1 hour with sulfuric acid as solvent ( 15mL, 70% ). We have shown for the first time that a heterogeneous catalyst, namely commercially available AlPO4-5 and kSBA-15 molecular sieve, can be successfully and efficiently utilized for the highly selective synthesis of 3. Moreover, the use of sulfuric acid as solvent, the high atom economy, and the possibility of recycling the catalyst for several runs, make this approach practical and environmentally acceptable. [ABSTRACT FROM AUTHOR]

The dual chromogenic and fluorogenic chemodosimetric behaviour of substituted 5-amino-1,2-dihydro-2-methyl-1,6-naphthyridine-8-carbonitriles was investigated. The reaction-based indicators operate by an unusual rearrangement followed by ring contraction to generate a pyrrolopyridine, with a "naked-eye" response and chromofluorogenic selective sensing for Cu2+ ions. The structure of the pyrrolopyridine was confirmed by single-crystal X-ray analysis. [ABSTRACT FROM AUTHOR]

In this paper, we propose a theoretical model for characterization and upper bounds of [1,2]-domination set of network which has tree structure. In detail, we propose a theoretic model for upper bounds on [1,2]-domination set of a tree network which has some typical constrains. To that purpose, we introduce a graph theory to model and analyze the characteristics of tree structure networks. We assume a node subset D of a graph G=(V,E). We define that D is a [1,2]-dominant set if for any node v in set V which is not an element of a set D is adjacent to a node or two nodes of an element in a set D (that is, 1≤ ∩D ≤ 2 for every node v ∈ V-D ). The minimum cardinality of a [1,2]-dominating set of G, which is denoted by γ[1,2] , is called the [1,2]-domination number of G. In this paper, we show new upper bounds and characteristics about the [1,2]-domination number of tree. [ABSTRACT FROM AUTHOR]

A series of novel [1,2,4]triazolo[1,5-a]pyrimidine derivatives has been designed and synthesized in order to find novel anti-tumor compounds. The structures of all the compounds were confirmed by IR, 1H-NMR, MS and elemental analysis. Their anti-tumor activities against cancer cell lines (HT-1080 and Bel-7402) were tested by the MTT method in vitro. Among them, compound 19 displayed the best anti-tumor activity with IC50 values of 12.3 μM and 6.1 μM against Bel-7402 and HT-1080 cell lines respectively.

A variety of novel [1,2,4]triazolo[1,5-c]pyrimidine-13-ones (4a-f) and (5b-d) could be obtained via reaction of 9-amino-7-(4’-chlorophenyl)-8,9-dihydro-8-imino-6H,7H-[1]benzopyrano[3`,4`:5,6]pyrano[2,3-d]pyrimidine-6-one (3) with a variety of reagents. Pyrano[2,3-d]pyrimidine-6-ones 5a, 8a-c and pyrimido[1,6-b][1,2,4]-triazine-3,14-dione (6) were also prepared. The antimicrobial activity of some of the synthesized compounds was tested.

Copper-catalyzed tandem reactions between 2-iodobenzamides with a propargyl group on the nitrogen atom moiety and sodium azide are presented, providing an efficient method for the synthesis of 3-substituted [1,2,3]triazolo[1,5-a][1,4]benzodiazepin-6(5H)-ones under mild conditions in moderate yields. [ABSTRACT FROM AUTHOR]

Triazole derivatives constitute an important group of heterocyclic compounds have have been the subject of extensive study in the recent past. These compounds have shown a wide range of biological and pharmacological activities. In this work, new fused tricyclic 1-(3-nitrophenyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]-benzodiazepines have been synthesized by the thermal cyclization of N'-(2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-3- nitrobenzohydrazides. After screening ethanol, toluene and 1-butanol as solvents, butanol-1 was found to be the best choice for the cyclization reaction in order to obtain the highest yields of tricyclic derivatives. The chemical structures of the synthesized compounds were elucidated by the analysis of their IR, 1H- and 13C-NMR spectral data. For tentative rationalization of the reaction processes, the global and local reactivity indices of certain compounds, taking part in the reaction pathway, were assessed by means of quantum mechanical calculations using the conceptual density functional theory (DFT) approach. This work could be useful for the synthesis of new heterocyclic compounds bearing a fused triazole ring. [ABSTRACT FROM AUTHOR]

A concise route to 3-aryl-1-trifluoromethyltetrahydroisoquinolines by a benzylic [1,5]-hydride shift-mediated C--H bond functionalization was developed. The [1,5]-hydride shift of the benzylic C(sp3)-H bond to the trifluoromethylketimine derived from para-anisidine occurred smoothly to produce cis-1-trifluoromethyl-3-aryltetrahydroisoquinolines in good to excellent chemical yields with good diastereoselectivities. In contrast, use of the N--H ketimine furnished N-unprotected tetrahydroisoquinolines in good yields in favor of the trans-isomer. [ABSTRACT FROM AUTHOR]

n/a

The series of novel N-R-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)thio]acetamides with thiazole and thiadiazole fragments in a molecule were obtained by alkylation of potassium salts 1.1-1.4 by N-hetaryl-2-chloro-acetamides and by aminolysis of activated acids 2.1-2.4 with N,N'-carbonyl-diimidazole (CDI). The structures of compounds were determined by IR, 1H NMR, MS, and EI-MS analysis. The results of cytotoxicity evaluated by the bio-luminescence inhibition of bacterium Photobacterium leiognathi, Sh1 showed that the compounds have considerable cytotoxicity. The synthesized compounds were tested for anticancer activity in NCI against 60 cell lines. Among the highly active compounds 3.1, 3.2, and 6.5, 2-[(3-methyl-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)thio]-N-(1,3-thiazol-2-yl)acetamide (3.1) was found to be the most active anticancer agent against the cell lines of colon cancer (GI50 at 0.41-0.69 μM), melanoma (GI50 0.48-13.50 μM), and ovarian cancer (GI50 0.25-5.01 μM). The structure-activity relationship (SAR-analysis) was discussed. [ABSTRACT FROM AUTHOR]

A simple strategy for the synthesis of the hitherto unreported 3-arylazo-4- phenyl- [1,2,4]triazepino[2,3-a]quinazoline-2,7(1H)-diones is described. Spectral data indicated that the studied compounds exist predominantly in the hydrazone tautomeric form. The antimicrobial activity of the newly synthesized compounds was also evaluated. The results indicated that some of these compounds have moderate activity towards bacteria. [ABSTRACT FROM AUTHOR]

Microwave-assisted synthesis of some novel compounds, namely, 3-(2-methyl-1H-indol-3-yl)-6-aryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 5a,b was accomplished via bromination of 2-methyl-3-[4-(arylideneamino)-5-mercapto-4H-[1,2,4]triazol-3-yl]-1Hindoles 3a,b. Also, new [1,3,4]thiadiazoles 12a,b, [1,2,4]triazoles 15a,b and [1,3,4]oxadiazoles 19a,b, with indole moieties, were prepared by cyclization of 1-[(2-methyl-1H-indole)-3-carbonyl]thiosemicarbazides 8a,b under microwave irradiation using different reaction conditions. Moreover, reaction of acid hydrazide 7 with ethyl 2-(N-phenylhydrazono)-3-oxobutanoate (20) gave the respective phenylhydrazonopyrazole derivative 21 under the reaction conditions employed. The structures of the synthesized compounds were assigned based on elemental analyses and spectral data (IR, ¹H-NMR, 13C-NMR, MS). The antifungal and antibacterial activities of the new products were also evaluated. [ABSTRACT FROM AUTHOR]

A series of new 8-aryl-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-ones were synthesized via a three-component reaction of 3,4-methylenedioxyphenol, aromatic aldehydes and Meldrum's acid in the presence of CeCl3·7H2O under solvent-free conditions. The method provided several advantages such as easy work-up, high yields and environmentally benign procedure. [ABSTRACT FROM AUTHOR]

In an attempt to search for more potent positive inotropic agents, a series of N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3- a]quinolin-7-yl)-2-(substitutedbenzyl-[1,4]diazepan-1-yl)acetamides were synthesized and evaluated for positive inotropic activity by measuring left atrium stroke volume in isolated rabbit heart preparations. Some of these derivatives exhibited favorable activity compared with the standard drug, milrinone, among which 2-(4-(4-methylbenzyl)-[1,4]-diazepan-1-yl)- N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3- a]quinolin-7-yl)acetamide () was the most potent, increasing stroke volume by 8.38 ± 0.16% (milrinone 2.45 ± 0.06%) at 3 × 10 . The chronotropic effects of those compounds having inotropic effects were also evaluated in this work. [ABSTRACT FROM AUTHOR]

Arylhydrazonomalononitriles 1a,b react with phenylhydrazine to yield amidrazones 2a,b that cyclize to give 2-aryl-5-phenylhydrazono-2,5-dihydro-[1,2,4]-triazine-6-carbonitriles 5a,b upon reaction with dimethylformamide dimethylacetal (DMFDMA). Refluxing 5a,b in glacial acetic acid resulted in the formation of the pyrazolo-1,2,4-triazines 6a,b. Compounds 6a,b were also formed upon treatment of 3-amino-4-phenylhydrazono-1-phenyl-2-pyrazolin-5-ones 7a,b with DMFDMA. Reacting these triazinyl arylhydrazononitriles 5a,b with hydroxylamine hydrochloride in ethanolic sodium acetate afforded amidrazones 8a,b that are readily cyclized in refluxing dimethylformamide into [1,2,4]triazino[1,2,3]triazines 10a,b. [ABSTRACT FROM AUTHOR]

Mesomorphic properties of three-ring systems such as 2,5-dibenzoyloxytropones, 5-benzoylamino-2-benzoyloxytropones and 2,5-dibenzoylaminotropones with 4-alkoxy, 3,4-dialkoxy, and 3,4,5-trialkoxy groups on the benzoyl groups were investigated together with those of the corresponding benzenoids. Derivatives with two monoalkoxybenzoyl groups showed nematic and smectic A and C phases. Troponoid tetracatenars with two dialkoxybenzoyl groups had hexagonal columnar phases except for troponoids with two ester-connecting groups, whereas the corresponding benzenoids with two dialkoxybenzoyl groups were non-mesomorphic. All troponoid hexacatenars with two trialkoxybenzoyl groups formed hexagonal columnar phases. With the exception of benzenoid hexacatenars with two ester-connecting groups, the benzenoid hexacatenars showed hexagonal and tetragonal columnar phases. These mesomorphic properties were discussed from the standpoint of the difference of the core structure and the connecting group, where the amide-connecting group played a role to induce and enhance mesomorphic properties through hydrogen bonding. [ABSTRACT FROM AUTHOR]

The synthesis of a series of 10-substituted 5,5-dioxo-5,10-dihydro[1,2,4]triazolo[4,3- b][1,2,4]benzothiadiazine coupled with sulfanylacetamido benzothiazole pharmacophores ( 5a– g) is described. All the synthesized compounds have been evaluated for their anticancer activity. Most of the compounds showed significant growth inhibitory activity against selected human tumor cell lines. Interestinlgy, one of the synthesized compounds 5d, exhibited GI50 values of 1.4 and 2.1 μm against RPMI-8226 (leukemia) and HOP-62 (lungs) cell lines, respectively. [ABSTRACT FROM AUTHOR]

Focal ischemia leads to functional deafferentation of regions connected to the ischemic area via fiber tracts. Using i.v. administration of 13C-labeled glucose and acetate combined with ex vivo13C MR spectroscopy and HPLC of brain extracts we identify the effect of middle cerebral artery occlusion (MCAO) on neurotransmitter synthesis and turnover, and on neuro-astrocytic interactions in the non-ischemic cerebellum and in contralesional lateral caudoputamen plus lower parietal cortex (LPC), and upper frontoparietal cortex (UFPCx) in the rat after 30, 60, 120 and 240 min of ischemia. In all regions, there was a significant persisting loss of glutamate, and in LCP and UFPCx also of glutamine, but only in LCP was GABA reduced at all times. Metabolism and blood flow were uncoupled in all regions. In cerebellum, glucose metabolism as well as utilization of intermediates derived from astrocytic tricarboxylic acid cycle activity were significantly decreased at all times in both glutamatergic and GABAergic neurons. In LCP and UFPCx, there were normal or increased enrichment in glutamate and GABA from glucose. Glutamate derived from astrocytic acetate metabolism was increased, but GABA synthesis from acetate was initially impaired. The results showed that both the type of afferent connection, i.e., glutamatergic and/or GABAergic, and local cytoarchitecture, determined the effect MCAO had on metabolic activity in the non-ischemic regions. In conclusion, it was primarily excitatory input into non-ischemic regions that was affected by MCAO, perhaps enabling resetting of the excitatory/inhibitory balance, aiding reshaping of the receptive fields and thus facilitating recovery. [ABSTRACT FROM AUTHOR]

[1,3]Dioxane-4,6-diones with (azulen-1-yl)methylene attached to position 5 were obtained by condensation of azulene-1-carbaldehydes with Meldrum's acid. The reaction was performed either neat or in absolute ethanol using a base as a catalyst. The involvement of the generated C=C bond either in electrophilic or radical reactions appears to be restricted. The advanced molecular polarization of the obtained products can account for the low reactivity of this bond. With the electrophilic reagents only the 3-position of azulenyl moiety was substituted. The azulene acylation with acetylsalicyloyl chloride occurred with rearrangement of the acyl chloride and, the formed products are 4H-1,3-benzodioxin-4-ones where azulen-1-yl moiety occupies the position 2 of the heterocyclic system. [ABSTRACT FROM AUTHOR]

The title compounds were easily synthesized by reacting the 4-aminopyrazole hydrochloride 2 and the substituted 2-nitrobenzoyl chlorides 3a-d. The obtained 2-nitrobenzamides 4a-d were methylated and then reduced to give the corresponding amines 6a-d. These were hydrolyzed then directly converted into 4,10-dihydro-1H-pyrazolo[3,4-c][1,5]benzodiazocine-5,11-diones 1a-d by the action of SOCl2 in benzene. These were tested for their COX inhibitory activity, showing an inhibitory profile against both COX-1 and COX-2, being slightly more selective against COX-2 with a percentage of inhibition, at the concentration of 10 μM, in the range 42.0 - 55.0. [ABSTRACT FROM AUTHOR]

New 5-hydroxymethyl-8-methyl-3-(3-aryl-[1,2,4]oxadiazol-5-yl)-2H-pyrano-[2,3-c]pyridin-2-ones and their esters were synthesized. The structure of obtained compounds was determined through a complete 1H NMR analysis. [ABSTRACT FROM AUTHOR]

Abstract: Systemic administration of selective 5-HT1A agonists, such as 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OHDPAT), stimulates the electrical activity of ventral tegmental area (VTA) dopamine neurons by a mechanism which remains unknown. We have examined if this activation is dependent on glutamatergic, serotonergic and GABAergic neurotransmission and if 5-HT1A receptors located within the VTA or within the prefrontal cortex (PFC) could contribute. In vivo electrophysiological recordings were obtained from VTA dopamine neurons from anesthetized rats. The i.v. administration of the 5-HT1A agonist 8-OHDPAT induced a strong stimulation of burst and firing activity of dopamine neurons. This activation remained unchanged in rats pre-treated with the 5-HT depleting agent parachlorophenylalanine. However, pre-administration of the GABAB receptor antagonist phaclophen, but not of the GABAA antagonist picrotoxin, significantly reduced the 8-OHDPAT-induced activation. The N-methyl-d-aspartate (NMDA) antagonist MK 801 (dizocilpine), but not the AMPA/kainate antagonist [1,2,3,4-tetrahydro-7-morpholinyl-2,3-dioxo-6-(fluoromethyl)quinoxalin-1-yl] methyl-phosphonate (ZK 200775), partially prevented or reversed the effects of 8-OHDPAT. However, only the combined pre-administration of the two glutamate antagonists did completely prevent the activatory response to 8-OHDPAT and even converted the effect of 8-OHDPAT into an inhibition, in half of the dopamine neurons tested. Inactivation of the local 5-HT1A receptors by the microinfusion within the VTA of the selective 5-HT1A antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate (WAY 100,635), or of pertussis toxin, reduced the ability of 8-OHDPAT to stimulate the firing of dopamine neurons but not their burst activity. On the other hand, burst activation elicited by 8-OHDPAT was strongly reduced following the inactivation of prefrontal 5-HT1A receptors achieved by the microinfusion of WAY 100,635 within the PFC. These results show that activation of midbrain dopamine neurons by the systemic administration of 5-HT1A agonists does involve the inactivation of a tonic GABAergic tone, involving mainly the GABAB receptors, probably leading to the stimulation of a glutamatergic excitatory drive from the PFC to the VTA and an increase in glutamate release. This will excite dopamine neurons, preferentially through NMDA receptors. Furthermore, our results suggest that some 5-HT1A receptors located within the VTA may also participate in this activation. [Copyright &y& Elsevier]

Abstract: A series of N-(4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(piperazin-1-yl)acetamide derivatives were synthesized and their positive inotropic activity was evaluated by measuring left atrium stroke volume on isolated rabbit heart preparations. Several compounds showed favorable activity compared with the standard drug, milrinone, among which N-(1-benzyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(4-benzylpiperazin-1-yl)acetamide 6j was found to be the most potent with the 13.2% increased stroke volume (milrinone 4.7%) at concentration of 3×10−5 M in our in vitro study. The chronotropic effects of those compounds having inotropic effects were also evaluated in this work. [Copyright &y& Elsevier]

Abstract: Uracil-annulated pyrano heterocycles are regioselectively synthesized in excellent yields (92–100%) via a palladium-catalyzed unusual [1,3] aryloxy shift followed by 6-endo dig cyclization and [1,3] prototropic shift. [Copyright &y& Elsevier]

The acetic acid derivatives of [1,2,4]triazino[4,3-a]benzimidazole as aldose reductase inhibitors were subjected for QSAR (quantitative structure activity relationship) modeling studies. A total 25 compounds were modelled in MOE. The QSAR model was generated using training set of 17 compounds employing sequential multiple linear regression analysis method. The internal consistency of the training set was confirmed by using leave-one-out (LOO) crossvalidation method to ensure the robustness of the model. The model gave conventional and cross-validated r2 values of 0.920 and 0.723, respectively. The predictive ability of model was further confirmed by a test set of eight compounds, which were not included in the model generation. The predicted activities of the test set were in good agreement with experimentally determined values. The model can be used to improve the activity of [1,2,4]triazino[4,3- a]benzimidazole acetic acid derivatives. [ABSTRACT FROM AUTHOR]

Abstract: Terminalia arjuna has been marked as a potential cardioprotective agent since vedic period. The present study was aimed to investigate the effects of butanolic fraction of Terminalia arjuna bark (TA-05) on Doxorubicin (Dox)-induced cardiotoxicity. Male wistar rats were used as in vivo model for the study. TA-05 was administered orally to Wistar rats at different doses (0.42mg/kg, 0.85mg/kg, 1.7mg/kg, 3.4mg/kg and 6.8mg/kg) for 6days/week for 4 weeks. Thereafter, all the animals except saline and TA-05-treated controls were administered 20mg/kg Dox intraperitonially. There was a significant decrease in myocardial superoxide dismutase (38.94%) and reduced glutathione (23.84%) in animals treated with Dox. Concurrently marked increase in serum creatine kinase-MB (CKMB) activity (48.11%) as well as increase in extent of lipid peroxidation (2.55-fold) was reported. Co-treatment of TA-05 and Dox resulted in an increase in the cardiac antioxidant enzymes, decrease in serum CKMB levels and reduction in lipid peroxidation as compared to Dox-treated animals. Electron microscopic studies in Dox-treated animals revealed mitochondrial swelling, Z-band disarray, focal dilatation of smooth endoplasmic reticulum (SER) and lipid inclusions, whereas the concurrent administration of TA-05 led to a lesser degree of Dox-induced histological alterations. These findings suggest that butanolic fraction of Terminalia arjuna bark has protective effects against Dox-induced cardiotoxicity and may have potential as a cardioprotective agent. [Copyright &y& Elsevier]

Cyclocondensation of N-prop-2-ynyl-o-phenylenediamine with phenyl isothiocyanate leads to the formation of 1-(3-arylprop-2-ynyl)-2,3-dihydro-1H-benzimidazole-2-thiones. In the reactions of diacetylene derivatives — N-penta-2,4-diynyl-o-phenylenediamine — with phenyl isothiocyanate the formation of two heterocyclic nuclei occurs simultaneously to form [1,3]thiazolidino[3,2-a]benzimidazoles. [ABSTRACT FROM AUTHOR]

Abstract: Necroptosis is a regulated caspase-independent cell death mechanism that results in morphological features resembling non-regulated necrosis. This form of cell death can be induced in an array of cell types in apoptotic deficient conditions with death receptor family ligands. A series of [1,2,3]thiadiazole benzylamides was found to be potent necroptosis inhibitors (called necrostatins). A structure–activity relationship study revealed that small cyclic alkyl groups (i.e. cyclopropyl) and 2,6-dihalobenzylamides at the 4- and 5-positions of the [1,2,3]thiadiazole, respectively, were optimal. In addition, when a small alkyl group (i.e. methyl) was present on the benzylic position all the necroptosis inhibitory activity resided with the (S)-enantiomer. Finally, replacement of the [1,2,3]thiadiazole with a variety of thiophene derivatives was tolerated, although some erosion of potency was observed. [Copyright &y& Elsevier]

Abstract: The synthesis, single crystal structure, luminescent and electrochemistry properties of a Cu(I) compound based on in situ formation ligand, namely [1,2,3]triazolo[1,5-α]quinoline(L1), are reported. Complex [] (1) is the first example of Cu(I) species with [1,2,3]triazole-ligand and provides the direct evidence for Cu(II) role to the ring-closure of hydrazone. [Copyright &y& Elsevier]

Abstract: We have previously reported the discovery and initial SAR of the [1,7]naphthyridine-3-carbonitriles and quinoline-3-carbonitriles as Tumor Progression Loci-2 (Tpl2) kinase inhibitors. In this paper, we report new SAR efforts which have led to the identification of 4-alkylamino-[1,7]naphthyridine-3-carbonitriles. These compounds show good in vitro and in vivo activity against Tpl2 and improved pharmacokinetic properties. In addition they are highly selective for Tpl2 kinase over other kinases, for example, EGFR, MEK, MK2, and p38. Lead compound 4-cycloheptylamino-6-[(pyridin-3-ylmethyl)-amino]-[1,7]naphthyridine-3-carbonitrile (30) was efficacious in a rat model of LPS-induced TNF-α production. [Copyright &y& Elsevier]

Abstract: The synthesis of some novel 3′-spirocyclic-oxindole compounds, based on the spiro[indole-3,5′-isoxazolidin]-2(1H)-one, the 2′H-spiro[indole-3,6′-[1,3]oxazinane]-2,2′(1H)-dione and the 2′H-spiro[indoline-3,3′-pyrrolo[1,2-c][1,3′]oxazine]-1′,2(1H)-dione heterocyclic structures, is described. These compounds were prepared from methyl α-(2-nitrophenyl)acrylate via [1,3]-dipolar cycloaddition reactions with two acyclic nitrones and one cyclic nitrone followed by reduction of the cycloadducts and then treatment with triphosgene. Two of these compounds showed significant cytostatic activity on three cancer cell lines with GI50 values of 2.6–4.1μM on the human breast cancer cell line, MCF-7. [Copyright &y& Elsevier]

Abstract: Intramolecular Michael reaction of methyl (R)-6-(tert-butoxycarbonylamino)oxy-4-hydroxy-2-hexenoate, in turn obtained from tert-butyl (R)-3-hydroxy-4-pentenoate, paved the way to the synthesis of both enantiomers of 2-oxa-6-azabicyclo[3.3.0]octan-3-one (the Geissman–Waiss lactone), a precursor for necine bases. Key intermediates in this approach were represented by enantiomeric bicyclic lactones incorporating a [1,2]-oxazinane nucleus, which has been conveniently used to install the pyrrolidine framework of the target compounds through a synthetic scheme featuring the reduction of the nitrogen–oxygen bond and an intramolecular SN2 reaction. [Copyright &y& Elsevier]

Abstract: Triazolopyridines are an important class of biologically active heterocyclic compounds. In this letter, we describe a new method for the synthesis of [1,2,4]triazolo[4,3-a]pyridines starting from 2-hydrazinopyridine and carboxylic acids. The resulting acetohydrazides are cyclized in a key step using the Lawesson’s reagent. The reaction conditions were explored, as well as the scope of this reaction concerning the substituent in position 3 of the triazolopyridine ring. We also demonstrated that this heterocyclization is racemization free in the presence of a chiral carbon in position α to the heterocycle. [Copyright &y& Elsevier]