- Synthesis and domino reactions of polymethylene-3-cyanopyridine-2(1Н)-thiones
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A new and facile three-component method was developed for the synthesis of polymethylene-3-cyanopyridine-2(1Н)-thiones by the domino Knoevenagel → Michael → heterocyclization → dehydrogenation reaction from cycloalkanones, cyanothioacetamide, and polymethoxy-substituted benzaldehydes. The final dehydrogenation step was found to involve arylidenecyanothioacetamide. The resulting pyridinethiones and 4-chloroacetoacetic ester were introduced into the domino SN2 → Thorpe-Ziegler → Guareschi-Thorpe reaction to synthesize tetracyclic dipyridothiophenes. Starting from these compounds, 8,9-polymethylenepyranothienodipyridines were also synthesized by the domino Knoevenagel → Michael → hetero-Thorpe-Ziegler reaction. Furthermore, a method for the synthesis of thienodipyridine annulated to the steroid skeleton is proposed.
- Shestopalov, Anatoliy M.,Rodinovskaya, Lyudmila A.,Zubarev, Andrey A.,Nesterov, Vladimir N.,Ugrak, Bogdan I.,Dutova, Tatyana Ya.
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p. 913 - 922
(2019/12/27)
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- 4-Arylthieno[2,3-b]pyridine-2-carboxamides Are a New Class of Antiplasmodial Agents
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Malaria causes hundreds of thousands of deaths every year, making it one of the most dangerous infectious diseases worldwide. Because the pathogens have developed resistance against most of the established anti-malarial drugs, new antiplasmodial agents are urgently needed. In analogy to similar antiplasmodial ketones, 4-arylthieno[2,3-b]pyridine-2-carboxamides were synthesized by Thorpe-Ziegler reactions. In contrast to the related ketones, these carboxamides are only weak inhibitors of the plasmodial enzyme PfGSK-3 but the compounds nevertheless show strong antiparasitic activity. The most potent representatives inhibit the pathogens with IC50values in the two-digit nanomolar range and exhibit high selectivity indices (>100).
- Alder, Arne,Gilberger, Tim,Kunick, Conrad,Schwed, Sandra I.
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- 3-Amino-thieno[2,3-b]pyridines as microtubule-destabilising agents: Molecular modelling and biological evaluation in the sea urchin embryo and human cancer cells
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A series of 3-amino-thieno[2,3-b]pyridines was prepared and tested in a phenotypic sea urchin embryo assay to identify potent and specific molecules that affect tubulin dynamics. The most active compounds featured a tricyclic core ring system with a fused cycloheptyl or cyclohexyl substituent and unsubstituted or alkyl-substituted phenyl moiety tethered via a carboxamide. Low nano-molar potency was observed in the sea urchin embryos for the most active compounds (1–5) suggestive of a microtubule-destabilising effect. The molecular modelling studies indicated that the tubulin colchicine site is inhibited, which often leads to microtubule-destabilisation in line with the sea urchin embryo results. Finally, the identified hits displayed a robust growth inhibition (GI50of 50–250?nM) of multidrug-resistant melanoma MDA-MB-435 and breast MDA-MB-468 human cancer cell lines. This work demonstrates that for the thieno[2,3-b]pyridines the most effective mechanism of action is microtubule-destabilisation initiated by binding to the colchicine pocket.
- Eurtivong, Chatchakorn,Semenov, Victor,Semenova, Marina,Konyushkin, Leonid,Atamanenko, Olga,Reynisson, Jóhannes,Kiselyov, Alex
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p. 658 - 664
(2016/12/27)
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- ACETYL-COA CARBOXYLASE MODULATORS
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Provided herein are compounds that exhibit activity as acetyl-CoA carboxylase modulators (e.g., inhibitors) and are useful, for example, in methods for the control of fungal pathogens in plants.
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- Synthesis of 4-alkyl(aryl, hetaryl)-2-thioxo-5,6,7,8-tetrahydroquinoline-3- carbonitriles and their derivatives by cross-recyclization of 4-alkyl(aryl, hetaryl)-2,6-diamino-4H-thiopyran-3,5-dicarbonitriles with 4-(cyclohex-1-en-1- yl)-morpholine, alkyl halides, and cyclohexanone
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Cross recyclization of 4-substituted 2,6-diamino-4H-thiopyran-3,5- dicarbonitriles with 4-(cyclohex-1-en-1-yl)morpholine, alkyl halides, and cyclohexanone gave the corresponding substituted 2-thioxo-1,2,5,6,7,8- hexahydroquinoline-3-carbonitriles, 2-alkylsulfanyl-5,6,7,8-tetrahydroquinoline- 3-carbonitriles, 3-amino-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2- carboxamides, and 4-oxo-2,2-pentamethylene-1,2,3,4,7,8,9,10- octahydropyrimido[4′,5′:4,5]thieno[2,3-b]quinolines. The structure of 3-(4-bromophenyl)-2,2-pentamethylene-11-(2-thienyl)-1,2,3,4,7,8,9,10- octahydropyrimido[4′,5′:4,5]thieno[2,3-b]quinoline was proved by X-ray analysis.
- Dyachenko,Dyachenko
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p. 412 - 420
(2008/12/22)
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- CYCLIZATION OF NITRILES. XXXV. ANNELLATION OF 2-ARYLIDENE-3-OXOQUINUCLIDINES TO 4-ARYL-3-CYANO-5,8-ETHANO-5,6,7,8-TETRAHYDRO-1,5-NAPHTHIRIDINE-2(1H)-THIONES
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The reaction of 2-arylidene-3-oxoquinuclidines with cyanothioacetamide in the presence of piperidine leads to the formation of piperidinio-4-aryl-3-cyano-5,8-ethano-1,4,5,6,7,8-hexahydro-1,5-naphthiridine-thiolates.The latter are dehydrogenated in an acidic medium to 4-aryl-3-cyano-5,8-ethano-5,6,7,8-tetrahydro-1,5-naphthiridine-2(1H)-thiones.In contrast, the analogous reaction of 2-arylidenecyclohexanones (ketones which do not contain the amino bridging fragment) takes place with dehydrogenation and leads to the formation of 4-aryl-3-cyano-2(1H)-quinolinethiones.Methods based on the obtained compounds were developed for the synthesis of the new annellated heterocycles thieno1,5-naphthiridine and thiazolo1,5-naphthiridine.
- Shestopalov, A. M.,Mortikov, V. Yu.,Sharanin, Yu. A.,Turov, A. V.,Litvinov, V. P.
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p. 1789 - 1793
(2007/10/02)
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- CYCLIZATION OF NITRILES. X. ENAMINO NITRILES OF THE 1,3-DITHIA-4-CYCLOHEXENE SERIES AND THEIR RECYCLIZATION TO DERIVATIVES OF PYRIDINE AND THIAZOLE
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The recyclization of 4-amino-6-aryl-5-cyano-2-cyclopentane(cyclohexane)spiro-1,3-dithia-4-cyclohexenes, obtained from gem-dithiols and arylidenemalononitriles, leads to the formation of 4-aryl-5,6-polymethylene-3-cyano-2-(1H)-pyridinethiones.The latter are used in the synthesis of various 3-aminothienopyridines, 4-aryl-3-amino-5,6,7,8-tetrahydrothienoquinolines, and other heterocyclic compounds condensed with quinoline. 1-Cyano-1-(4-aryl-2-thiazolyl)-2-arylethylenes were obtained by the reaction of the 1,3-dithia-4-cyclohexenes with phenacyl bromides.
- Sharanin, Yu. K.,Shestopalov, A. M.,Promonenkov, V. K.,Rodinovskaya, L. A.
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p. 1402 - 1415
(2007/10/02)
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