Utility of 2‐Acetyl Benzofuran for the Synthesis of New Heterocycles as Potential Anticancer Agents

A novel series of benzofuran derivatives containing thiazole, thiadiazine, and pyridotriazolopyrimidine were synthesized starting from 1‐(benzofuran‐2‐yl)‐3‐(1H –indol‐3‐yl)prop‐2‐en‐1‐one. Also, triazolopyrimidine derivatives were prepared from the reaction of 2‐acetylbenzofuran and pyrazole‐4‐carbaldehyde with 2‐thiobarbutyric acid and reaction of the product with hydrazonoyl halides. The structures of the newly synthesized compounds were elucidated on the basis of elemental analyses, spectral data, and alternative synthetic routes whenever possible. Anticancer activity against 60 different human tumor cell lines representing leukemia, melanoma, and cancers of the lung, colon, brain, ovary, breast, prostate, and kidney was validated by the U.S. National Cancer Institute using a two‐stage process. The results revealed that pyrazoline‐1‐thiocarbohydrazide 4b , triazolopyrimidine 20d , and pyrimidine thione 25 have promising antitumor activity against most cell lines.     

A Facial Synthesis and Anticancer Activity of (Z)‐2‐((5‐(4‐nitrobenzylidene)‐4‐oxo‐4,5‐dihydrothiazol‐2‐yl)amino)‐substituted Acid

In order to explore the anticancer and antimicrobial activity associated with the thiazole framework, we synthesized the new series (Z )‐2‐((5‐(4‐nitrobenzylidene)‐4‐oxo‐4,5‐dihydrothiazol‐2‐yl)amino)‐substituted acid derivatives 6a – l . All the synthesized compounds were evaluated for anticancer and antimicrobial activity in vitro. Among these, the compounds 6a , 6b, 6c , 6e , 6f , 6g , 6h , 6i , 6j , and 6k showed highest antibacterial and antifungal activity. The compound 6a exhibited significant antibacterial activity against Bacillus subtilis , whereas compound 6j displays significant antifungal activity against fungal strains, that is, A. oryzae . The in vitro anticancer studies revealed that 6e , 6g , 6h , 6k , and 6l are the most active compounds against MCF‐7 and BT‐474 human breast cancer cell lines, which can be regarded as the promising drug candidate for development of anticancer drugs.     

Synthesis of Novel 1,2,4‐oxadiazoline Derivatives Containing Quinoline Moiety by 1,3‐Dipolar Cycloaddition

A series of novel 1,2,4‐oxadiazoline derivatives containing 2‐(1,2,4‐triazol‐1‐yl)quinoline were synthesized by the reaction of imines with benzohydroximinoyl chlorides in the presence of Et₃N via 1,3‐diplolar cycloaddition reaction. The structures of the target compounds were confirmed by IR, ¹H NMR, MS, elemental, and X‐ray crystallographic analysis.     

Synthesis of indazol‐4,7‐dione derivatives as potential trypanocidal agents

The synthesis of new indazol‐4,7‐dione derivatives via 1,3‐dipolar cycloaddition of diazomethane with 2,3‐dimethyl‐1,4‐benzoquinone ( 2 ) and 1,4‐naphthoquinone ( 7 ) followed by N‐alkylation of the pyrazol nitrogen atom of the corresponding quinones ( 3 ) and ( 8 ) with methyl chloroacetate is described. A series of amides from esters ( 5 ) and ( 10 ) were also obtained. These compounds were tested in vitro as potential anti‐trypanosomal agents. Compounds ( 4 ) and ( 8 ) were found to have significant activity.     

Microwave‐Assisted Synthesis of Novel Spiro Phosphonyl Thiazolo Pyrazole Glycosides as Potential Nematicidal Agents

A series of novel dimethyl 7‐((3aR,5S,6S,6aR)‐6‐((1‐(4‐chlorophenyl)‐1H‐1,2,3‐triazol‐4‐yl)methoxy)‐2,2‐dimethyltetrahydrofuro[2,3‐d][1,3]dioxol‐5‐yl)‐4‐(4‐fluorophenyl)‐9‐oxo‐8‐phenyl‐6‐thia‐1,2,8‐triazaspiro[4.4]non‐2‐en‐3‐ylphosphonate 2a – g were synthesized by the reaction of chalcone derivatives of 2‐((3aR,5S,6S,6aR)‐6‐((1‐(4‐chlorophenyl)‐1H‐1,2,3‐triazol‐4‐yl)methoxy)‐2,2‐dimethyltetrahydrofuro[2,3‐d][1,3]dioxol‐5‐yl)‐3‐phenylthiazolidin‐4‐one 1 with Bestmann–Ohira reagent. The chemical structures of newly synthesized compounds were elucidated by IR, NMR, MS, and elemental analysis. The compounds 2a – g were evaluated for their nematicidal activity against Dietylenchus myceliophagus and Caenorhabditis elegans; compounds 2b , 2c , 2g , and 2f showed appreciable nematicidal activity.     

Novel Pyrano[2,3‐d]thiazole and Thiazolo[4,5‐b]pyridine Derivatives: One‐pot Three‐component Synthesis and Biological Evaluation as Anticancer Agents,c‐Met,and Pim‐1 Kinase Inhibitors

Preparation of pyrano[2,3‐d]thiazole and thiazolo[4,5‐b]pyridine derivatives through multicomponent reactions (MCRs) was achieved by the reaction of 2‐(2‐amino‐4,5,6,7‐tetrahydrobenzo[b]thiophen‐3‐yl)thiazol‐4(5H)‐one with various active methylene reagents such as ethyl cyanoacetate or malononitrile in basic conditions containing diverse aromatic aldehyde. Furthermore, this study aims to evaluate the in vitro cytotoxic activity of the synthetic compounds against six cancer cell lines, and all the prepared compounds revealed valuable activity compared with the CHS‐828, which is the 2‐[6‐(4‐chlorophenoxy)hexyl]‐1‐cyano‐3‐pyridin‐4‐ylguanidine as the standard drug. Some of the pyrano[2,3‐d]thiazole and thiazolo[4,5‐b]pyridine derivatives showed the highest antitumor activity towards the six cancer cell lines. Moreover, (c‐Met) enzymatic activity of the most potent compounds showed that compounds 3b 2‐(2‐amino‐4,5,6,7 tetrahydrobenzo[b]thiophen‐3‐yl)‐5‐hydroxy‐7‐(2‐hydroxy‐phenyl)‐7H‐pyrano[2,3‐d]thiazole‐6 carbonitrile and 5e 2‐(2‐amino‐4,5,6,7‐tetrahydrobenzo[b]thiophen‐3‐yl)‐5‐hydroxy‐7‐phenyl‐4,7‐dihydrothiazolo[4,5‐b]pyridine‐6‐carbonitrile were with higher activities than foretinib. Three compounds were selected to examine their Pim‐1 kinase where compounds 3b and 7b showed the highest inhibitions.     

Synthesis and Antimicrobial Activity of 2‐(Pyridine‐3‐yl)‐4H‐chromen‐4‐one Derivatives

An efficiently synthesis of chromones via cyclodehydration of corresponding 1‐(2‐hydroxyphenyl)‐3‐(pyridine‐3‐yl)propane‐1,3‐dione is described under ultrasound irradiation. A series of novel 2‐(pyridine‐3‐yl)‐4H‐chromen‐4‐one derivatives was confirmed on the basis of ¹H‐NMR, mass, IR spectral data, and elemental analysis. The synthesized compounds were evaluated for their antibacterial and antifungal activities. Most of the compounds were found to be comparable potent than the reference standard drugs. Utilization of ultrasound irradiation, simple reaction conditions, isolation, and purification makes this manipulation very interesting from an economic and environmental perspective.     

Synthesis,antimicrobial, and antioxidant activities of new pyridyl‐ and thiazolyl‐bearing carbohydrazides

A series of novel substituted (E)‐N′‐benzylidene‐4‐methyl‐2‐(2‐propylpyridin‐4‐yl)thiazole‐5‐carbohydrazide derivatives ( 6a‐l ) have been synthesized by following the multistep synthetic route starting from prothionamide. The resulting compounds were characterized via ¹H, ¹³C NMR, and HRMS spectral data. The synthesized carbohydrazides were evaluated for their in vitro antimicrobial and antioxidant activities. Tested molecules have displayed moderate to good growth inhibition activity. Among the screened compounds, 6b , 6e , 6j, and 6k are found to be the more promising antimicrobial agents. A 2,2‐diphenyl‐1‐picrylhydrazyl assay was used to test the antioxidant activity of the carbohydrazides. The carbohydrazide derivatives 6b and 6i have shown better free‐radical scavenging ability than the other investigated compounds.     

Synthesis of New 3‐(Furan‐2‐yl)‐Substituted Dibenzo‐Diazepin‐1‐one Derivatives

A new series of 3‐(furan‐2‐yl) dibenzo‐diazepin‐1‐one derivatives were synthesized by condensation of 5‐(furan‐2‐yl)‐1,3‐cyclohexanedione, o‐phenylenediamine, and aromatic aldehydes, in which in some of them existed two very close isomer compounds. All the compounds were characterized by IR, MS, ¹H NMR, and elemental analysis. Also presented were the crystal structures of 3a , 3b and 3e , which were obtained and determined by X‐ray single‐crystal diffraction.     

Synthesis and Reactivity of 3‐oxoprop‐1‐en‐1‐olate Derivative as a Building Block for the Synthesis of Azole and Azine Derivatives

Several new heterocyclic compounds such as 7‐substituted pyrazolo[1,5‐a ]pyrimidine ( 5a–e ) derivatives have been synthesized by the reactions of the versatile unreported sodium 3‐(4‐methyl‐2‐(4‐methylphenylsulfonamido)thiazol‐5‐yl)‐3‐oxoprop‐1‐en‐1‐olate (2) with amino heterocyclic ( 3a–e ) derivatives. Reaction of (2) with hydrazonyl halide ( 7a–d ) and hydroximoyl chloride ( 11a,b ) derivatives followed by reaction with hydrazine hydrate afforded pyrazolo[3,4‐d ]pyridazine and isoxazolo[3,4‐d ]pyridazine derivatives, respectively incorporating a thiazole moiety have been described. All newly synthesized compounds were elucidated by considering the data of both elemental and spectral analysis.     

Three New Phthalides from Gnaphalium adnatum

Three new phthalides, gnaphalides A–C ( 1 – 3 , resp.), together with three known phthalides, were isolated from the aerial part of Gnaphalium adnatum. The structures of the new compounds were elucidated as 6‐(1,1‐dimethylprop‐2‐en‐1‐yl)‐5,7‐dihydroxy‐2‐benzofuran‐1(3H)‐one ( 1 ), 5‐hydroxy‐7‐[(2‐hydroxy‐3‐methylbut‐3‐en‐1‐yl)oxy]‐2‐benzofuran‐1(3H)‐one ( 2 ), and 1,3‐dihydro‐7‐[(3‐methylbut‐2‐en‐1‐yl)oxy]‐1‐oxo‐2‐benzofuran‐5‐yl β‐D ‐glucopyranoside ( 3 ) on the basis of spectral analyses. The structure of 1 was also confirmed by X‐ray crystallographic analysis. The three known phthalides, identified as 5,7‐dihydroxyisobenzofuran‐1(3H)‐one ( 4 ), anaphatol ( 5 ), and 7‐O‐(β‐glucopyranosyl)‐5‐hydroxyisobenzofuran‐1(3H)‐one ( 6 ), were isolated from the genus Gnaphalium for the first time.     

Structural Elucidation and Antimicrobial Evaluation of Novel [1,2,4]Triazolo[4,3‐a]pyrimidines and Pyrido[2,3‐d][1,2,4]triazolo[4,3‐a]pyrimidinones

1,3‐Di(thiophen‐2‐yl)prop‐2‐en‐1‐one ( 1 ) was utilized in the synthesis of 4,6‐di(thiophen‐2‐yl)‐3,4‐dihydropyrimidine‐2(1H)‐thione ( 2 ) and 5,7‐di(thiophen‐2‐yl)‐2‐thioxo‐2,3‐dihydropyrido[2,3‐d]pyrimidin‐4(1H)‐one ( 4 ). The latter thiones were used in the synthesis of two new series of [1,2,4]triazolo[4,3‐a]pyrimidines 10a – i and pyrido[2,3‐d][1,2,4]triazolo[4,3‐a]pyrimidinones 5a – i via reaction with the appropriate hydrazonoyl halides using triethylamine as a basic catalyst in dioxane. The mechanism of formation of the synthesized compounds was discussed, and the assigned structure was established via microanalysis, spectral data (infrared, ¹H NMR, and Mass), and density functional calculations. Moreover, the newly synthesized products were evaluated for their antimicrobial activities, and the results show that some derivatives have been well with mild activities. Finally, quantum chemistry calculations confirmed the mechanism and structure of the products.     

Synthesis and Anticancer Evaluation of Some Novel Thiophene,Thieno[3,2‐d]pyrimidine,Thieno[3,2‐b]pyridine,and Thieno[3,2‐e][1,4]oxazepine Derivatives Containing Benzothiazole Moiety

In an attempt to establish novel candidate with promising anticancer activity, two derivatives of (benzo[d]thiazol‐2‐yl)thiophene backbone 1 and 14 were synthesized, and they further reacted with various chemical reagents to afford the corresponding substituted thiophene derivatives 6 , 8 , 10 , 15 , 17 , and 20 , thieno[3,2‐d]pyrimidine derivatives 2 – 5 , 7 , 9 , 16 , 21 , 23 , and 24 , thieno[3,2‐b]pyridine derivatives 11 – 13 , and thieno[3,2‐e][1,4]oxazepine derivative 18 . Structures of prepared compounds were affirmed via spectral and elemental data. Among the obtained compounds, seven derivatives 2 , 3 , 4 , 5 , 11 , 12 , and 13 were chosen by National Cancer Institute, USA. Such compounds were screened for their antitumor activity versus 60 cancer cell lines in one‐dose (10 μmol) screening assay. The outcomes showed that all selected compounds exhibited moderate to high anticancer activity towards many cancer cell lines among which compounds 5 and 11 exerted potent antitumor activity against numerous malignant growth cell lines particularly Ovarian Cancer IGROV1.     

Synthesis of novel isoindolone‐based medium‐sized macromolecules and triazole containing heterocyclic compounds

A series of novel isoindolone‐based macromolecules of medium‐sized heterocyclic rings, such as 7,8‐dihydro‐6H‐benzo[4,5][1,6,3]dioxazonino[2,3‐a]isoindol‐14(9aH)‐one derivatives ( 5a‐l ), were synthesized and its frame work incorporating with a triazole moiety on phenol, ie, 2‐(4‐((1‐(2‐methoxyphenyl)‐1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)isoindoline‐1,3‐dione ( 9a‐f ) and also a triazole moiety on carboxylic acid, ie, (1‐(2‐methoxyphenyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl 4‐(1,3‐dioxoisoindolin‐2‐yl)benzoate derivatives ( 13a‐e ) with various substitutions on aryl ring system have synthesized. All the synthesized compounds were characterized and confirmed with IR, ¹H NMR_, ¹³C NMR, and ESI mass spectral analysis.     

Synthesis,Characterization, and Molecular Docking of Novel bis‐thiazolyl Thienothiophene Derivatives as Promising Cytotoxic Antitumor Drug

A novel, facile reaction for the synthesis of series of bis‐thiazole derivatives has been developed from the reaction of the appropriate thiosemicarbazone derivatives and bis‐2‐bromoacetylthieno[2,3‐b ]thiophene derivatives in ethanol under reflux. The structures of the newly synthesized products were established on the basis of spectral data (mass, IR, and ¹H and ¹³C NMR) and elemental analyses. Fifteen compounds of the synthesized compounds were evaluated for their anticancer activity against human liver hepatocellular carcinoma cell line (HepG2). All compounds showed anticancer activity but differs in potency comparable with the reference drug Cisplatin. Moreover, molecular docking study using MOE software predicted the best binding mode between the most active compound 5o into the active site of human heat‐shock protein 90. The computational studies are confirming the results in biological activity.     

Design,Synthesis, and Fungicidal Activity of Novel Imidazo[4,5‐b]pyridine Derivatives

A series of novel imidazo[4,5‐b]pyridine derivatives were designed and synthesized. The structures of all the newly synthesized compounds were identified by spectroscopic data NMR, MS, and elemental analysis. Bioassay showed that the compounds exhibited potent fungicidal activities against Erysiphe graminis, Puccinia polysora, and so forth. Particularly, 2‐chloro‐5‐((5‐methoxy‐2‐(2‐(trifluoromethyl)phenyl)‐3H‐imidazo[4,5‐b]pyridin‐3‐yl)methyl)thiazole ( 9b ) displayed fungicidal potency against P. polysora. Its EC₅₀ value: 4.00 mg/L is comparable with that of tebuconazole. The structure–activity relationship for the target compounds is discussed.     

Synthesis and characterization of bromo‐, arylazo‐, and heterocyclic‐fused troponoids containing a 1,3‐benzodioxole system

A facile synthesis of a series of novel bromo‐, arylazo‐, and heterocyclic fused troponoid compounds containing 1,3‐benzodioxole system is described. The 7‐bromo‐, 5,7‐dibromo‐, and 5‐arylazo‐substituted 3‐[(2E)‐3‐(1,3‐benzodioxol‐5‐yl)prop‐2‐enoyl]tropolones ( 2 , 3 , and 5 , 6 , 7 ) were obtained by direct bromination or azo‐coupling reactions of 3‐[(2E)‐3‐(1,3‐benzodioxol‐5‐yl)prop‐ 2‐enoyl]tropolone ( 1 ) with bromine, and diazonium salts of aniline derivatives, respectively. 3‐[(2E)‐3‐(1,3‐Benzodioxol‐5‐yl)prop‐2‐enoyl]‐5‐bromotropolone ( 4 ) was obtained from 3‐acetyl‐5‐bromotropolone via one‐pot aldol dehydration reaction with piperonal. Tropolones 2, 3 , and 4 were subjected to nucleophilic cyclization with bifunctional hydroxylamine hydrochloride and phenylhydrazine hydrochloride to give the corresponding isoxazolo‐ and pyrazolo‐fused tropones ( 8 , 9 , 10 , 11 , 12 , 13 ), respectively. J. Heterocyclic Chem., (2012).     

Synthesis and biological evaluation of some novel thiadiazole-benzofuran hybrids as potential antitumor agents

Two series of novel 1,3,4-thiadiazole-benzofuran and 1,3,4-thiadiazole-furochromene derivatives were synthesized through heterocyclization of alkyl 2-(1-(6-hydroxy-4,7-dimethoxybenzofuran-5-yl)ethylidene)hydrazine-1-carbodithioate 3a–f and 2-(1-(5-methoxy-8-methyl-2,6-dioxo-2,6-dihydropyrano[3,2-g]chromen-3-yl)ethylidene)hydrazinecarbothioamide 9a,b with various hydrazonoyl halides, respectively. The structure of the newly synthesized products was elucidated through elemental analysis, spectral data and alternative routes whenever possible. Ten new compounds were evaluated for their anticancer activity against the human breast carcinoma (MCF-7) cell lines in comparison with reference doxorubicin using MTT assay. The results showed that some new compounds have promising anticancer activity.     

New Lignan,Benzofuran, and Sesquiterpene Derivatives from the Roots of Leontopodium alpinum and L. leontopodioides

Three new compounds, including a benzofuran, 1‐{(2R*,3S*)‐3‐(β‐D ‐glucopyranosyloxy)‐2,3‐dihydro‐2‐[1‐(hydroxymethyl)vinyl]‐1‐benzofuran‐5‐yl}ethanone ( 1 ), a lignan, [(2S,3R,4R)‐4‐(3,4‐dimethoxybenzyl)‐2‐(3,4‐dimethoxyphenyl)tetrahydrofuran‐3‐yl]methyl (2E)‐2‐methylbut‐2‐enoate ( 2 ), and a silphiperfolene‐type sesquiterpene, [(1S,2Z,3aS,5aS,6R,8aR)‐1,3a,4,5,5a,6,7,8‐octahydro‐1,3a,6‐trimethylcyclopenta[c]pentalen‐2‐yl]methyl acetate ( 3 ), together with the known coumarins obliquin ( 4 ) and its 5‐methoxy derivative 5 were isolated from the roots of Leontopodium alpinum. Another known coumarin derivative, 5‐hydroxyobliquin ( 6 ), was isolated from the roots of L. leontopodioides. The structures of these compounds were established by spectroscopic studies.     

A Convenient Synthesis and Pharmacological Activity of Novel Annelated Pyrimidine Derivatives

Simple and convenient synthesis for a series of 2,3‐diglycosylpyrimidine 4 , pyrazolo[3,4‐d]pyrimidine 8 , ditetrazolo[1,5‐a;1′,5′‐c]pyrimidine 9 , 2,9a,10‐triazaanthracene 12 , thieno[2,3‐d]pyrimidine 14 , 1,3,5,7‐tetraazafluorene‐8‐one 15 , 1,3,5‐triazafluorene‐8‐one 16 , 1,3‐diazafluorene 21a,b derivatives have been synthesized via a sequence of heterocyclization reactions of suitably functionalized 6‐[5‐(4‐bromophenyl)ox‐azol‐4‐yl]‐4‐oxo‐2‐thioxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carbonitrile ( 2 ) with different electrophiles and nucleophiles. The new compounds were prepared with the objective to study their pharmacological properties.