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The stereoselective synthesis of the imidazolidinedione (+)-2, an inhibitor of aldose reductase, has been achieved via heterocyclic bislactim ether substitution, acidic cleavage and cyclization with urea.

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The present invention relates to novel terpene alkaloids and their use as antiparasitic agents. The present invention also relates to an antiparasitic agent which comprises a terpene alkaloid compound of this invention as an effective ingredient in an antiparasitic formulation. More particularly, the present invention relates to derivatives of the terpene alkaloid (1S,2R,4aS,5R,8R,8aR)-2-(acetyloxy)-8a-hydroxy-3,8-dimethyl-5-(1-methylethenyl)-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl (2S,3aR,9bR)-6-chloro-9b-hydroxy-5-methyl-1,2,3,3a,5,9b-hexahydropyrrolo[2,3-c][2,1]benzoxazine-2-carboxylate. Pharmaceutical compositions comprising the same are also disclosed.

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In this paper, we introduce a novel and convenient method for the transformation of heterocyclic amides into heteocyclic thioamides. A two-step approach was applied for this transformation: Firstly, we applied a chlorination of the heterocyclic amides to afford the corresponding chloroheterocycles. Secondly, the chloroherocycles and N-cyclohexyl dithiocarbamate cyclohexylammonium salt were heated in chloroform for 12 h at 61C to afford heteocyclic thioamides in excellent yields.

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Triselenium dicynide (TSD) has been reported for the first time to be a novel cyanation reagent for the microwave-assisted one-pot synthesis of a series of various types of cyano N-heterocycles such as pterin, deazapterin, quinoxaline, naphthyridine, and pyridine in good yields. Copyright Taylor & Francis Group, LLC.

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A new efficient procedure for the chlorination of hydroxyquinoxaline derivatives into the corresponding chlorides is described. It has been found that the use of 1-chlorobutane produces the highest yield, reduces the time of reaction and facilitates direct formation of crystals without any purification.

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The present invention is directed to triazolopyrazine compounds of Formula (I). Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds as therapeutic agents treating neurological and psychiatric disorders

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Chloropyrimidines 2, 3 and Chlorquinazolines 9, 10, after conversion into trimethylammonio derivatives 4, 5, 11, 12, react with tetraethylammonium cyanide 1a under very mild conditions to give pyrimidine carbonitriles 6, 7 and quinazoline carbonitriles 13, 14.Direct synthesis of quinoxaline carbonitriles 19 is possible by reaction of chloroquinoxalines 15, 18 with 1a.

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The present invention provides a tri-substituted pyrimidine compound having an excellent PDE10 inhibitory activity. The present invention relates to a tri-substituted pyrimidine compound represented by the following formula [I0] or a pharmaceutically acceptable salt thereof, a method for preparing the same, and use of said compound for PDE10 inhibitor, and a pharmaceutical composition comprising said compounds as an active ingredient: wherein: either one of X1 and X2 is N, and the other of X1 and X2 is CH; A is *-CH?CH?, *-C(Alk)=CH?, *-CH2?CH2? or *-O?CH2? (* is a bond with R1); Alk is a lower alkyl group; Ring B is an optionally substituted nitrogen-containing aliphatic heterocyclic group; R1 is an optionally substituted quinoxalinyl or an optionally substituted quinolyl; Y0 is mono- or di-substituted amino group, or a pharmaceutically acceptable salt thereof.

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2-Chloro-3-methylquinoxaline reacts with aromatic amines in basic medium forming 2-arylamino-3-methylquinoxalines, also it reacts with mercaptoacetic acid.The 3-methyl-2(1H)-quinoxalinone condenses with aromatic aldehydes forming the corresponding 3-(substituted styryl)-2(1H)-quinoxalinones which add bromine in acetic acid to yield the corresponding dibromo derivatives which react with morpholine, sodium methoxide, and piperidine to give the corresponding compounds. 3-Methyl-2(1H)-quinoxalinone undergoes side-chain bromination to yield 3-bromomethyl-2(1H)-quinoxalinone, which reacts with aromatic amines, sodium salt of saccharine, potassium phthalimide… 3-Methyl-2(1H)-quinoxalinone with P2S5 gave 3-methyl-2(1H)-quinoxalinethione which reacts with 2-aminoethanol, dimethyl sulfate, and halo acids.

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Design, synthesis, biological evaluation and molecular docking study on peptidomimetic analogues of XK469

XK469 is identified as a potent quinoxaline antineoplastic agent based on its significant clinical efficacy. It probably exerts its activity via DNA topoisomerase II (topo II) inhibition. To obtain more effective antineoplastic agents, a spectrum of peptidomimetic-type quinoxaline analogues of XK469 was herein designed, synthesized, and evaluated. Few compounds (e.g. 13a and 13b) exhibited obvious cytotoxicity indicated by in vitro anti-proliferative assay. SAR investigation revealed that introducing of hydrophobic tert-butylamine or dodecylamine moiety at the 3-position of quinoxaline core is favorable for achieving a better anti-proliferative potency, while peptidomimetic derivatives only yielded moderate cytotoxicity. Compounds with improved anti-proliferative activities also demonstrated decent anti-metastatic potencies comparable with that of doxorubicin (Doxo) based on in vivo mouse model study. The topo II-mediated kinetoplast DNA (kDNA) decatenation assay as well as molecular docking studies implicated that these compounds tend to be potent topo II inhibitors. Overall, compounds 13a and 13b, 13b in particular, standed out from various assessments and might be promising candidates for further chemical optimization.

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