Synthesis and antitumor evaluation of some new derivatives and fused heterocyclic compounds derived from thieno[2,3‐b]pyridine

On the basis of the proven activity of thieno[2,3‐b]pyridines as anticancer, we have designed to synthesize a novel several heterocyclic compounds utilizing thieno[2,3‐b]pyridine as a skeleton through various chemical reactions. The synthesized compounds bear rings that are either directly attached to the thieno[2,3‐b]pyridine as in compounds 4 to 6 and 9 or connected through an amide bridge as compounds 2 , 3a ‐ b , 7 , and 8 . As well as, compounds 10 , 12 to 28 , 30 , 31 , and 33 to 36 bear fused rings to the thieno[2,3‐b]pyridine backbone. The newly synthesized compounds were screened for their antiproliferative activity in vitro against hepatocellular carcinoma (HepG‐2) and breast cancer (MCF‐7) compared with the standard drug (doxorubicin). Compounds 3b , 4 , 6 , 22 , and 28 exhibited promising growth inhibitory effect toward both HepG‐2 and MCF‐7 cell lines with IC₅₀ values ranging from 5.88 to 11.70 μg/mL and 9.64 to 15.10 μg/mL, respectively.     

Nitriles in heterocyclic synthesis: A novel synthesis of some thieno[2,3-d]pyrimidine and thieno[2,3-b]pyridine derivatives

A simple route to the synthesis of the pharmaceutically important thieno[2,3-d]pyrimidine derivatives and of thieno[2,3-b]pyridine derivatives via the use of 5-amino-3-phenylthiophene-2,4-dicarbonitrile (2) as a starting material is described. © 1996 John Wiley & Sons, Inc.     

A simple synthesis of thieno[2,3-b]pyrazine and thieno[2,3-b] pyridine

A facile synthesis of thieno[2,3-b]pyrazine (1) and thieno[2,3-b]pyridine (9) is reported. Furthermore, convenient preparations of a variety of synthetically useful compounds derived from these ring systems is also presented.     

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).     

1H-pyrazolo[3,4-d]thieno[2,3-b]pyridine and its derivatives

The synthesis of the parent ring system and some of the derivatives of 1H-pyrazolo[3,4-d]thieno[2,3-b]pyridine are described.     

Synthesis of new derivatives of thieno[2,3‐b]pyridine fused with octyl ring

Derivatives of thiophene, thieno[2,3‐b]pyridine, thieno[5′,4′:4,5]pyrimido[3,2‐a]pyridine and thiepine fused with octyl ring have been synthesized and tested for antimicrobial and antifungal activities. The structure of the newly synthesized compounds have been established on the basis of their analytical and spectral data.     

Synthesis of condensed tricyclic pyrazolo[3,4-b]thieno[2,3-d]pyridine and related isostere derivatives

In this paper we report the synthesis of an isosteric series of new heterotricyclic derivatives, corresponding to pyrazolo[3,4-b]thieno[2,3-d]pyridine ( 1 ), pyrazolo[3,4-b]furano[2,3-d]pyridine ( 2 ) and pyrazolo[3,4-b]pyrrolo[2,3-d]pyridine ( 3 ). These functionalized compounds were obtained, in high overall yield, by an ‘one-pot’ reaction of the chloroester intermediate 4 , possessing the pyrazolo[3,4-b]pyridine system, with an adequate α-hetero-acetyl ester derivative, in SNAr/Dieckman cyclization type consecutive reactions.     

Synthesis and reactivity of thieno[2,3-b]quinoline derivatives (Part II)

As a continuation of our previous review entitled “Vilsmeier-Haack cyclisation as a facile synthetic route to thieno[2,3-b]quinolines (Part I).” This review describes the methods of preparation and the chemical reactivity of thieno[2,3-b]quinolines, which might show interesting biological activities.     

Phenyl isothiocyanate in heterocyclic synthesis: Novel synthesis of thiazoles,thieno[2,3-b]pyridine,thiophene and thieno[3,2-c]pyridazine derivatives

Summary The enamino nitriles1 and2 react with phenyl isothiocyanate followed by cyclization with -haloketones3 and10 to afford in each case the thiazole5, thiophene11 and the thieno[2,3-b]pyridine derivatives19 and21. Chemical and spectroscopic evidences for the structures of the new compounds are described.

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Phenylisothiocyanate in der Heterocyclensynthese: Neue Synthesen für Thiazol-, Thieno [2,3-b]pyridin-, Thiophen- und Thieno[3,2-c]pyridazin-Derivate

Zusammenfassung Die Enamin-nitrile1 und2 ergaben nach Reaktion mit Phenylisothiocyanaten und nachfolgender Cyclisierung mit -Halogenketonen3 und10 die entsprechenden Thiazole5, die Thiophene11 und die Thieno[2,3-b]pyridine19 und21. Chemische und spektroskopische Untersuchungen wurden als Strukturbeweise für die neuen Verbindungen herangezogen.

     

Polymethine dyes — Benzofuro[2,3-b]pyridine and selenonaphtheno[2,3-b]pyridine derivatives

Polymethine dyes — benzofuro[2,3-b]pyridine and selenonaphtheno[2,3-b]pyridine derivatives — were synthesized, and their spectral properties are discussed. Replacement of a vinylene group by an oxygen or selenium atom in one benzene ring of the 2-benzo[h]quinoline residue in the cyanines causes a large bathochromic shift of the absorption maxima of the dyes as compared with replacement by a sulfur atom. The dyes derived from benzofuro[2,3-b]pyridine derivatives are more deeply colored than the derivatives of both thionaphtheno[2,3-b]-pyridine and selenonaphtheno[2,3-b]pyridine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp.1611–1614, December, 1972.     

Preparation of reissert compounds derived from the thieno[3,2-c]pyridine,thieno[2,3-d]pyridazine and the thieno[2,3-d]pyrimidine ring systems

The use of tributyltin cyanide, trimethylsilyl cyanide and potassium cyanide in the Reissert reaction is contrasted in the furo[3,2-c]pyridine, thieno[3,2-c]pyridine, thieno[2,3-dpyridazine, and thieno[2,3-d]pyrimidine ring systems.     

Fluorine-containing heterocycles: Part III. Synthesis of some new furo[2,3-b]-, pyrazolo[3,4-b]- and thieno[2,3-b]pyridines with anticipated biological activities

3-Cyano-6-(2-thienyl)-4-trifluoromethylpyridine-2(1H)-one (1) and its thiono analog 2 were prepared by the reaction of (2-thenoyl)-ω,ω,ω-trifluoroacetone with cyanoacetamide or cyanothioacetamide, respectively. Interaction of compound 1 with ethyl chloroacetate or chloroacetamide led to the regioselective formation of O-alkylated pyridines 3 and 10. The latter compounds underwent some successive reactions to furnish the promising furopyridines (4 and 7–9) and pyrazolopyridines (12–15). The reaction of 2 with chloroacetamides or chloroacetonitrile furnished 2-functionalized 3-amino-6-(2-thienyl)-4-trifluoromethyl-thieno[2,3-b]pyridines (16a, b) which were used as key intermediates in the synthesis of the title thienopyridines. Structures of the newly synthesized compounds were established on the basis of their elemental and spectral (IR, ¹H NMR and mass) analyses.     

DIPEA catalyzed step-by-step synthesis and photophysical properties of thieno[2,3-b]pyridine derivatives

A series of novel 5,6-disubstituted ethyl 3-amino-4-cyanothieno[2,3-b]pyridine-2-carboxylates was synthesized. The reaction conditions were thoroughly studied and intermediate ethyl 2-((3,4-dicyanopyridin-2-yl)thio)acetates were successfully isolated in good yields. For all synthesized compounds, spectral-fluorescent properties were carefully investigated and correlation thereof with chemical structure was found.     

Synthesis of 2-substituted-2,3- dihydro-1,4-dioxino[2,3-b]pyridine derivatives

[reaction--see text] A variety of 2-substituted-2,3-dihydro-1,4-dioxino[2,3-b]pyridines B have been synthesized from the readily available 2-nitro-3-oxiranylmethoxypyridine 1 via a Smiles rearrangement. We demonstrate how variations of reaction conditions affect the product distribution of A and B.     

Synthesis of certain 5-substituted thieno[2,3-b]thiophene-2-sulfonamides and thieno[2,3-b]thiophene-2-sulfonamide 6,6-dioxides

A series of the title compounds were prepared for evaluation as inhibitors of carbonic anhydrase II. Oxidation of 5-substituted thieno[2,3-b]thiophene-2-sulfonamides provided the first examples of thiophene[2,3-b]thiophene-2-sulfonarnide 6,6-dioxides. These cyclic vinyl sulfones readily underwent addi tion to give predominately that 4,5-cis addition product.     

Facile and convenient synthesis of new thieno[2,3-b]-thiophene derivatives

A facile and convenient synthesis of bis(2-(1H-benzo[d]imidazol-2(3H)-ylidene)-3-oxopropanenitrile), bis((3-amino-5-(methylthio)-1H-pyrazol-4-yl)methanone) and bis(2-thioxo-1,2-dihydropyrimidine-5-carbonitrile) derivatives incorporating a thieno- [2,3-b]thiophene moiety via versatile, readily accessible diethyl 3,4-dimethylthieno-[2,3-b]thiophene-2,5-dicarboxylate is described.     

Synthesis and characterizations of some new selenolo[2,3-b]quinoxaline derivatives

In this paper, we present the synthesis of new selenoloquinoxaline derivatives starting from 2-chloroquinoxaline-3-carbonitrile 1 . The compound 1 was subjected to a reaction with selenium metal in the presence of NaBH₄ as a reducing agent in ethanol, under a nitrogen atmosphere. This reaction resulted in the formation of the sodium salt of 3-cyanoquinoxaline-2-selenolate, which was subsequently reacted with α-halogenated carbonyl compounds in situ. This reaction produced a series of newly synthesized 3-aminoselenolo[2,3-b]quinoxaline-2-substituents. Ethyl 3-aminoselenolo[2,3-b]quinoxaline-2-carboxylate 3a was hydrolyzed by sodium hydroxide to give the corresponding sodium salt 9 . This salt was then refluxed with acetic anhydride to produce oxazinone compound 10 . The reaction of compound 10 with ammonium acetate afforded pyrimidoselenolo[2,3-b]quinoxaline derivative 11 . Compound 11 was then chlorinated using phosphorous oxychloride to give the corresponding chlorocompound.