Convenient synthesis and anticancer evaluation of novel pyrazolyl-thiophene,thieno[3,2-b]pyridine,pyrazolo[3,4-d]thieno[3,2-b]pyridine and pyrano[2,3-d]thieno[3,2-b]pyridine derivatives

The newly synthesized 3-(3-amino-5-(phenylamino)-4-(phenylcarbamoyl)thiophen-2-yl)-3-oxopropanoate was utilized as a precursor for the synthesis of pyrazolyl-thiophene derivative, which undergoes cyclization upon treatment with benzaldehyde derivatives to provide pyrazolo[3,4-d]thieno[3,2-b]pyridines. Basic treatment of pyrazolyl-thiophene derivative with phenyl isothiocyanate followed by subsequent addition of chloroacetone and/or ethyl bromoacetate yielded the thiazolylidene-pyrazolyl thiophenes. In addition, the building block 3-(3-amino-5-(phenylamino)-4-(phenylcarbamoyl)thiophen-2-yl)-3-oxopropanoate was converted into the corresponding thieno[3,2-b]pyridine compounds through its reactions with (DMF-DMA) and/or heating in sodium ethoxide. Moreover, the reaction of 7-hydroxy-5-oxo-N-phenyl-2-(phenylamino)-4,5-dihydrothieno[3,2-b]pyridine-3-carboxamide with 2-arylidenemalononitrile produced the new annulated pyrano[2,3-d]thieno[3,2-b]pyridines. The prepared thiophene-based compounds were evaluated against HepG2, PC3, and MCF-7 cancer cells, and normal fibroblast cell (WI38). The pyrazolo[3,4-d]thieno[3,2-b]pyridine and pyrano[2,3-d]thieno[3,2-b]pyridine compounds substituted with chlorophenyl group presented promising cytotoxic activities against HepG2 cancer cell line without any human toxicity. Docking study for the synthesized thiophene compounds delivered valuable insights about the binding interactions with the crystal structure of NS5B enzyme with PDB ID (4TLR).     

Novel 5-(4-alkoxyphenyl)thieno[3,2-b]thiophene-2-carboxylate esters: Highly efficient synthesis and mesogenic evaluation of a new class of materials exhibiting the smectic C phase

A series of alkyl 5-(4-alkoxyphenyl)thieno[3,2-b]thiophene-2-carboxylates were prepared via a direct, efficient Pd(0)-catalysed Suzuki–Miyaura coupling approach. A series of long-chain alkyl thieno[3,2-b]thiophene-2-carboxylate esters, synthesised from newly reported alkyl mercaptoacetates, were elaborated into the target compounds via regioselective (C-5) halogenation followed by cross-coupling with 4-alkoxyphenyltrifluoroborate salts. As expected, these target alkyl 5-(4-alkoxyphenyl)thieno[3,2-b]thiophene-2-carboxylate ester mesogens exhibited the orthogonal smectic A phase; notably, they are the first materials built on the thieno[3,2-b]thiophene motif to also exhibit the smectic C mesophase.     

Convenient Synthesis and Antimicrobial Evaluation of Multicyclic Thienopyridines

Thieno[2,3-b]pyridines 7, 8, and 10 could be obtained via the S-alkylation of 3-cyano-4,6-di-2-furyl-2(1H)pyridinethione (3) with a variety of alkylating agents. These compounds were conveniently converted into novel pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidines 12–15 and 17–20 and thieno[2,3-b;4,5-b′]dipyridine 11 derivatives. Structures of the products have been determined by elemental analyses and spectral data studies. All the tested compounds were found to exhibit moderate antimicrobial activity.     

Novel ferroelectric liquid crystals based on fused thieno[3,2‐b]furan and thieno[3,2‐b]thiophene cores

Several series of new benzofused thieno[3,2‐b]furan‐ and thieno[3,2‐b]thiophene‐based derivatives have been synthesized and their mesomorphic properties investigated. All the studied compounds exhibit a SmC* phase with very wide temperature interval. Additionally, some types of the compounds show the cholesteric, SmA or blue phase. In the ferroelectric SmC* phase we evaluated physical properties of relevance for possible applications.     

Synthesis and antimicrobial activity of new derivatives of pyrano[4',3':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidine and new heterocyclic systems

Taking into account previously obtained biological results on some polyheterocyclic compounds (containing different heteroatoms) and in particular on several 8-amino-5-isopropyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano[4’’,3’’:4’,5’]pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidines Ia-v we have carried out the synthesis of twentyone 8-amino-5-isobutyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano[4’’,3’’:4’,5’]pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidines 6. Therefore we have slightly modified the structure of the previously studied I introducing at C-5 an isobutyl group instead of the previously examined isopropyl ones in order to see if this variation (changing a little the lipophilicity) will affect the biological activity. Furthermore thieno[3,2-d]pyrimidine-8-thione 7 and their S-alkylated 8 were synthesized. Finally by alkylation of 5-isobutyl-2,2-dimethyl-10-thioxo-1,4,10,11-tetrahydro-2H-pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidin-8(9H)-one 3 with alkyl dichlorides (bifunctional reagents) we realized the cyclization of a thiazole or thiazine ring on the [b] side of the pyrimidine ring with formation of the new condensed pentaheterocyclic systems: pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d][1,3]thiazolo[3,2-a]pyrimidin-8-one 11 and pyrano[4''',3''':4'',5'']pyrido[3'',2'':4',5']thieno[3',2':4,5]pyrimido[2,1-b][1,3]thiazin-8-one 12. It was found that some of the synthesized compounds showed interesting antimicrobial activity (by agar diffusion method) against some gram-positive and gram-negative bacilli strains.     

Synthesis of New Fused Pirano[4,3-b]pyridine Derivatives

A method was developed for the synthesis of pyrano[4,3-b]thieno[3,2-e]pyridine derivatives based on the reaction of 3-amino-7-ethyl-7-methyl-7,8-dihydro-5H-pyrano[4,3-b]thieno[3,2-e]pyridine-2-carboxylic acid ethyl ester with chloroacetic acid chloride, triethyl orthoformate, hydrazine hydrate, and also phenyl chloroformate. The synthesis of various new representatives of pyrano[2″,3″:5′,6′]pyrido[3′,2′:4,5]thieno[3,2-dl-pyrimidine series was carried out.

     

Synthesis and S-methylation of 2-thioxopyrido[3′,2′:4,5]thieno[3,2-d]-pyrimidin-4(3H)-ones with and without a phase transfer catalyst

A number of 2-thioxopyrido[3′,2′:4,5]thieno[3,2-H]pyrimdin-4(3H-ones (5) have been synthesized by cyclocondensation of 2-carbethoxy-3-amino-4-phenyl-6-substituted-thieno[2,3-b]pyridines (3) with various isothiocyanates. Compounds 5 were S-methylated routinely and the reactions compared under solid-liquid phase transfer conditions to obtain 2-methylthiopyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-^ones (6). The new triheterocyclic pyridothienopyrimidines were prepared with the objective to study their pharmacological properties.     

Synthesis,Reactions, and Antimicrobial Evaluation of Some Polycondensed Thienopyrimidine Derivatives

Some novel indeno[2,1-b]thiophenes, indeno[1′,2′:4,5]thieno[2,3-d][1,2,3]triazines, indeno[1′,2′:4,5]thieno[2,3-d]pyrimidines, indeno[1′,2′:4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidines, and indeno[1′,2′:4,5]thieno[2,3-d][1,2,4]triazolo[4,3-a]pyrimidines 2–16 were prepared starting with 2-aminoindeno[2,1-b]thiophene-3-carboxylic acid amide ( 1 ). Furthermore, the antimicrobial evaluation of the prepared products showed that many of them revealed promising antimicrobial activity.     

Construction of new heteroacenes based on benzo[b]thieno[2,3-d]thiophene / quinoline or 1,8-naphthyridine systems using the Friedländer reaction

Two new classes of heteroacenes, namely benzo[4′,5′]thieno[2′,3′:4,5]thieno[3,2-b]quinolines and benzo[4′,5′]thieno[2′,3′:4,5]thieno[3,2-b][1,8]naphthyridines, have been formed using the Friedländer reaction to annulate the benzo[b]thieno[2,3-d]thiophene scaffold to quinoline or 1,8-naphthyridine fragments. In accordance with this synthetic strategy, benzo[b]thieno[2,3-d]thiophen-3(2H)-ones were treated with 2-aminobenzaldehydes or 2-aminonicotinaldehyde in the presence of pyrrolidine in glacial acetic acid at reflux to give the desired quinoline- or 1,8-naphthyridine-fused compounds, respectively. The optical and electrochemical properties of selected heteroacenes were determined.     

New method for the synthesis of substituted thieno[3,2-b]pyridines and 5H-pyrano[2,3-d]thieno[3,2-b]pyridines derived from them

A new highly selective method was developed for the synthesis of substituted thieno[3,2-b]-pyridines based on the domino reaction of monopotassium salt (rather than dipotassium one) of carbamoylcyanodithioacetic acid with ethyl 4-chloroacetoacetate. Substituted 5H-pyrano[2,3-d]-thieno[3,2-b]pyridines were synthesized based on these thieno[3,2-b]pyridines.     

Syntheses with heterocyclic β-enaminonitriles: A facile preparation of polyfunctionally substituted thiophene,thieno[3,2-b]pyridine and thieno[3,2-d]pyrimidine derivatives

Summary A convenientGewald synthesis of 3,5-diaminothiophene-2-carbonitrile derivatives (2) is reported. The synthetic potential of the -enaminonitrile moiety in2 has been explored; it proved to be a promising candidate for the synthesis of polyfunctionally substituted thieno[3,2-b]pyridines and thieno[3,2-d]pyrimidines.

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Synthesen mit heterocyclischen -Enaminonitrilen: Eine einfache Methode zur Herstellung polyfunktionell substituierter Thiophen-, Thieno[3,2-b]pyridin- und Thieno[3,2-d]pyrimidinderivate

Zusammenfassung Eine bequeme Methode zur Herstellung von 3,5-Diaminothiophen-2-carbonitril-Derivaten (2) nachGewald wird vorgestellt. Das synthetische Potential der -Enaminonitrilfunktion von2 wurde untersucht.2 ist ein geeignetes Ausgangsmaterial für die Synthese polyfunktionell substituierter Thieno[3,2-b]pyridine und Thieno[3,2-d]pyrimidine.

     

Intramolecular 4+2 cycloaddition of thieno[2,3-e][1,2,4]triazines: routes towards condensed thieno[2,3-b]pyridines

Synthetic approaches towards new condensed thienopyridine ring systems including furo[2,3-b]thieno[3,2-e]pyridines, bisthieno[2,3-b:3′,2′-e]pyridines, 5H-chromeno[2,3-b]thieno[3,2-e]pyridines, 5H-benzo(f)chromeno[2,3-b]thieno[3,2-e]pyridines have been achieved by application of intramolecular 4+2 cycloaddition reactions of suitably designed thieno[2,3-e][1,2,4]triazines tethered with alkene or alkyne terminals.     

Recyclization of 1,3-dimethylbenzo[b]furo[2,3-c]- and 1,3-dimethylbenzo[b]thieno[2,3-c]pyrylium when treated with secondary amines. Synthesis of 3-dialkylamino derivatives of dibenzofuran and dibenzothiophene

We have established that 2,4-dimethylbenzo[b]furo[3,2-c]pyrylium and 2,4-dimethylbenzo[b]thieno[3,2-c]pyrylium salts can undergo recyclization to 3-dialkylamino derivatives of dibenzofuran and dibenzothiophene when treated with secondary amines. We compare the physicochemical and spectral characteristics of the compounds obtained with the recyclization products of 1,3-dimethylbenzo[b]furo[2,3-c]- and 1,3-dimethylbenzo[b]thieno[2,3-c]pyrylium salts. L. M. Litvinenko Institute of Physical Organic Chemistry and Coal Chemistry, National Academy of Sciences of Ukraine, Donetsk 340114. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 182–185, February, 1998.     

Chemistry of thienopyridines. XII. Selective formation of N-oxides,sulfoxides, and sulfones in some tricyclic systems

Direct conversion of [1]benzothieno[3,2-b]pyridine (IVa), thieno[3,2-b:4,5-b']dipyridine (Va), and thieno[2,3-b:4,5-b']dipyridine (VIa) into their sulfoxides was effected by means of an equimolar quantity of iodobenzene dichloride in aqueous acetonitrile. Treatment of IVa-VIa with excess chlorine gas in carbon tetrachloride and then with water gave the corresponding sulfones, IVc-VIc. Hydrogen peroxide in glacial acetic acid converted Va and VIa into di-N-oxides, thieno[3,2-b]pyridine into its N-oxide, and sulfone VIc into an N-oxide sulfone (X). Spectral and chemical means of distinguishing amongst the oxide functions are noted, and rationalizations for selectivity in the oxidations are discussed.     

On the synthesis and reactivity of 4,10-dihydrobenzo-[b]thieno[2,3-e]thiepin-10-acetic acid and 5,10-dihydrobenzo[e]thieno[3,2-b]thiepin-10-acetic acid

A simple method to synthesize 4,10-dihydrobenzo[b]thieno[2,3-e]thiepin-10-acetic acid (8a) and 5,10-dihydrobenzo[e]thieno[3,2-b]thiepin-10-acetic acid (8b) starting from ketones la,b is described. The reactivity of the acid 8a has been investigated and some derivatives are reported.     

Palladium-catalyzed reductive N-heterocyclization of alkenyl-substituted nitroarenes as a viable method for the preparation of bicyclic pyrrolo-fused heteroaromatic compounds

Palladium-catalyzed, carbon monoxide-mediated reductive N-heterocyclization of nitro-heteroaromatic compounds having an alkene adjacent to the nitro-group affords bicyclic pyrrolo-fused heteroaromatic molecules. This type of reaction was used to prepare the fused bicyclo[3.3.0] ring-system: thieno[3,2-b]pyrrole, thieno[2,3-b]pyrrole, furo[2,3-b]pyrrole, pyrrolo[3,2-d]thiazole, and pyrrolo[2,3-d]imidazole and the bicyclo[4.3.0] ring-systems: pyrrolo[3,2-b]pyridine, pyrrolo[2,3-b]pyridine, pyrrolo[3,2-c]pyridine, pyrrolo[2,3-c]pyridine, pyrrolo[3,2-c]pyridazine, and pyrrolo[3,2-d]pyrimidine in 32-94% yield.     

Angular polycyclic thiophenes containing two thiophene rings. I

We describe the synthesis of thieno[2,3-c]dibenzothiophene ( 6 ), thieno[3,2-c]dibenzothiophene ( 10 ), thieno-[3,2-a]dibenzothiophene ( 14 ), thieno[2,3-a]dibenzothiophene ( 16 ), benzo[1,2-b:4,3-b]bisbenzo[b]thiophene ( 18 ), benzo[1,2--6:3,4-b]bisbenzo[b]thiophene ( 20 ), benzo[2,1--6:3,4-b]bisbenzo[b]thiophene ( 22 ), benzo[1,2-b:3,4-g]bisbenzo[b]thiophene ( 27 ), benzo[1,2-b:4,3-e]bisbenzo[b]thiophene ( 29 ), benzo[2,1--6:3,4-g]bisbenzo[b]thiophene ( 36 ), benzo[2,1--6:4,3-e]bisbenzo[b]thiophene ( 38 ), benzo[1,2--6:4,3-g]bisbenzo[b]thiophene ( 41 ), benzo[1,2-b:4,5-g]bisbenzo[b]thiophene ( 42 ), benzo[1,2-b:3,4-e]bisbenzo[b]thiophene ( 44 ) and benzo-[1,2-b:5,4-e]bisbenzo[b]thiophene ( 45 ).     

Chemistry of thienopyridines. XXXVI. Further studies on nitration in the thieno[2,3-b]- and thieno[3,2-b]pyridine systems

Three compounds, thieno[3,2-b]pyridine 4-oxide, 7-nitrothieno[3,2-b]pyridine 4-oxide ( 1 c), and 6-cyano-thieno[2,3-b]pyridine, undergo nitration by means of a mixture of nitric and sulfuric acids to yield 3,7-dinitro-thieno[3,2-b]pyridine (3%), 3,7-dinitrothieno[3,2-b]pyridine 4-oxide ( 1d ) (26%), and 6-carbamoyl-5-nitrothieno[2,3-b]pyridine ( 6b ) (11%), respectively. Structures of the products were ascertained by spectral means, notably infrared, ¹H nmr, and ¹³C nmr. It is proposed that 1d exists (at least in part) as a tricyclic structure and that 6b may result from an intramolecular mechanism of nitration. An attempt to de-N-oxygenate 1c with excess triphenylphosphine removes more than one oxygen atom per molecule (as triphenylphosphine oxide) without producing an identified thienopyridine product.     

Synthesis of Substituted 1,3-Cyclohexadienes,Pyridine-2(1H)-thiones,and Thieno[2,3-d]pyrimidine- 4(3H)-thiones by the Michael Reaction

Cyclopentylidene- and cyclohexylidene(cyano)acetamides reacted with malononitrile and cyano-(thioacetamide) according to the Michael pattern with exchange of the methylene components to give substituted 1-amino-2,6,6-tricyano-1,3-cyclohexadienes and thieno[2,3-d]pyrimidine-4(3H)-thiones. Condensation of cyclopentylidene- and cyclohexylidene(cyano)acetamide with 1,3-dicarbonyl compounds afforded 4,6-di-methyl-3-cyanopyridine-2(1H)-thione and morpholinium 4-methyl-6-oxo-3-cyano-1,6-dihydropyridine-2-thiolate which were converted into substituted 2-alkylsulfanylpyridines, thieno[2,3-b]pyridines, thiazolo[3,2-a]pyridine, and 2H-[1,3]thiazino[3,2-a]pyridine.     

Synthesis in the thienobenzoxazepine series. First synthesis of a diethienoxazepine

In an investigation of novel tricyclic systems, synthesis of several thieno[2,3-b][1,4]benzoxazepines and thieno[3,2-b][1,5]benzoxazepines were effected by ring closure of appropriately amino aldehyde compounds. A new oxazepine fused with two heterocyclic rings, the dithieno[3,2-b:2,3-f][1,4]oxazepine, is described.