Novel Aryl‐Modified Benzoylamino‐N‐(5,6‐dimethoxy‐1H‐benzoimidazol‐2‐yl)‐heteroamides as Potent Inhibitors of Vascular Endothelial Growth Factor Receptors 1 and 2

Tumor angiogenesis has become an important target for antitumor therapy, with most current therapies aimed at blocking the vascular endothelial growth factor (VEGF) pathway. The VEGF and its receptors have been implicated as key factors in tumor angiogenesis and are major targets in cancer therapy. A series of aryl‐modified benzoylamino‐N‐(5,6‐dimethoxy‐1H‐benzoimidazol‐2‐yl)‐heteroamides were synthesized from 2‐amino‐5,6‐dimethoxy benzimidazole and aryl‐substituted benzoylamino hetero acids. The new compounds were tested for inhibition of VEGF receptors I and II (VEGFR‐1 and VEGFR‐2). Compound 6e displayed VEGFR‐2 inhibitory activity with a 50% inhibition concentration value as low as 0.020 μM in a homogeneous time‐resolved fluorescence enzymatic assay. VEGFR‐2 active compounds display good activity against VEGFR‐1 as well.     

Synthesis and In Vitro Urease Inhibition of Some Novel Benzimidazole‐based Hydrazones

A novel series of N′‐(substituted benzylidene)‐2‐(5,6‐dichloro‐2‐methyl‐1H‐benzimidazol‐1‐yl)acetohydrazides and N′‐(1‐(substituted phenyl)ethylidene)‐2‐(5,6‐dichloro‐2‐methyl‐1H‐benzimidazol‐1‐yl)acetohydrazides were synthesized and then studied for their urease inhibitory activities using thiourea as a standard drug. All newly synthesized compounds were found to exhibit potent inhibitory properties against urease enzyme in the range of IC₅₀ = 0.0155 ± 0.0039–0.0602 ± 0.0071 μM, when compared with the thiourea as standard (IC₅₀ = 0.5115 ± 0.0233 μM). All target molecules were characterized by ¹H‐NMR, ¹³C‐NMR, IR, and electrospray ionization mass spectrometry.     

The Synthesis and Biological Evaluation of N‐Substituted 1H‐Benzimidazol‐2‐yl‐1H‐pyrazole‐3,5‐diamines

The synthesis of 1H‐benzimidazol‐2‐yl‐1H‐pyrazole‐3,5‐diamines has been developed. Synthesized bisheteroaryls contain two privileged medicinal scaffolds, aminopyrazole and benzimidazole, with two diversity positions at N1 of benzimidazole and C3 of pyrazole, respectively. The three‐step synthesis includes the Mitsunobu N‐alkylation of benzimidazole and subsequent one‐pot formation of aminopyrazole involving substitution of methylthio groups with amine and hydrazine followed with final ring closure. Inhibitory activity toward cyclin‐dependent kinase 2/cyclin E and cytotoxicity against two cancer cell lines were evaluated for all novel pyrazoles. Two compounds showed modest cyclin‐dependent kinase inhibition activity and cytotoxicity against cancer cell lines K562 and MCF7.     

An Efficient Synthesis of Novel 2‐(5‐indolyl)‐1H‐benzimidazole Derivatives and Evaluation of Their Antimicrobial Activities

In this paper, we report the synthesis of novel 2‐(5‐indolyl)‐1H‐benzimidazole derivatives. The methodology involves the Sonogashira reaction of 4‐(1H‐benzimidazol‐2‐yl)‐2‐bromo‐N,N‐dimethylaniline ( 3 ) with variety of terminal alkynes to get corresponding novel 4‐(1H‐benzimidazol‐2‐yl)‐2‐alkynyl‐N,N‐dimethylaniline derivatives ( 4 ). These compounds on iodocyclization afforded novel iodoindolylbenzimidazole derivatives ( 5 ). The resulting compounds were functionalized further via palladium‐mediated carbon–carbon bond formation for generating novel structurally diversified heterocyclic compounds. All these newly synthesized compounds were evaluated for antimicrobial activity.     

Microwave‐mediated synthesis and antibacterial activity of some novel 2‐(substituted biphenyl) benzimidazoles via Suzuki‐Miyaura cross coupling reaction and their N‐substituted derivatives

A series of some novel 2‐(substituted biphenyl) benzimidazoles and their N‐substituted derivatives were synthesized via microwave‐mediated Suzuki‐Miyaura coupling of 2‐(4‐iodophenyl)‐1H‐benzimidazole or 2‐(4‐iodophenyl)‐6‐amino‐1H‐benzimidazole and arylboronic acids. The method reported herein offers advantageous shorter reaction times, higher yields and is applicable to a large set of substrates. All the synthesized compounds were screened for their antibacterial activity against Staphylococcus aureus and Salmonella typhimurium bacterial species. J. Heterocyclic Chem., (2011).     

Synthesis and Cytotoxicity in Vitro of N‐Aryl‐4‐(tert‐butyl)‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazol‐2‐amine

A series of novel N‐aryl‐4‐(tert‐butyl)‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazol‐2‐amines synthesized in a green way. H₂O₂‐NaBr Brominating circulatory system was used in the synthesis of the key intermediate in a mild condition. All of the target compounds were confirmed by ¹H NMR and elemental analysis and tested for their cytotoxicity against two different human cancer cell lines. The cytotoxicity assay revealed that some of the title compounds showed moderate to strong cytotoxic activities. Compound 2i was the most potent compound with the IC₅₀ values of 9 μM against Hela cells and 15 μM against Bel–7402 cells, respectively.     

Complexation du 2‐[(5‐méthyl­pyrazolyl)méthyle]benzimidazole par les chlorures de cuivre et de cadmium

The structures of dichloro{2‐[(5‐methyl‐1H‐pyrazol‐3‐yl‐κN²)methyl]‐1H‐1,3‐benzimidazole‐κN³}copper(II), [CuCl₂(C₁₂H₁₂N₄)], and di‐μ‐chloro‐bis(chloro{2‐[(5‐methyl‐1H‐pyrazol‐3‐yl‐κN²)methyl]‐1H‐1,3‐benzimidazole‐κN³}­cadmium(II)), [Cd₂Cl₄(C₁₂H₁₂N₄)₂], show that these compounds have the structural formula [ML(Cl)₂]_n, where L is 2‐[(5‐methylpyra­zolyl)methyl]benzimidazole. When M is copper, the complex is a monomer (n = 1), with a tetrahedral coordination for the Cu atom. When M is cadmium (n = 2), the complex lies about an inversion centre giving rise to a centrosymmetric dimer in which the Cd atoms are bridged by two chloride ions and are pentacoordinated.     

Synthesis of six new 2‐Aryl‐N‐biphenyl benzimidazoles and crystal structure of methyl 4′ [(2‐p‐Chlorophenyl‐1H‐benzimidazole‐1‐yl)‐methyl]biphenyl‐2‐carboxylate

Six new 2‐aryl‐N‐biphenyl benzimidazoles were designed and synthesized, starting with O‐phenylenediamine and carboxylic acids via cyclization, followed by N‐alkylation. All new compounds were identified by H NMR, IR, MS spectra and elemental analysis. The crystal structure of methyl 4′‐[(2‐p‐chlorophenyl‐1H benzimidazole‐1‐yl)methyl]biphenyl‐2‐carboxylate ( 4f ) was determined by single crystal X‐raydiffraction.     

Synthesis,cytotoxicity and antibacterial studies of symmetrically and non‐symmetrically benzyl‐ or p‐cyanobenzyl‐substituted N‐Heterocyclic carbene–silver complexes

From the reaction of 1H‐imidazole ( 1a ), 4,5‐dichloro‐1H‐imidazole ( 1b ) and 1H‐benzimidazole ( 1c ) with p‐cyanobenzyl bromide ( 2 ), symmetrically substituted N‐heterocyclic carbene (NHC) [( 3a–c )] precursors, 1‐methylimidazole ( 5a ), 4,5‐dichloro‐1‐methylimidazole ( 5b ) and 1‐methylbenzimidazole ( 5c ) with benzyl bromide ( 6 ), non‐symmetrically substituted N‐heterocyclic carbene (NHC) [( 7a–c )] precursors were synthesized. These NHC? precursors were then reacted with silver(I) acetate to yield the NHC‐silver complexes [1,3‐bis(4‐cyanobenzyl)imidazole‐2‐ylidene] silver(I) acetate ( 4a ), [4,5‐dichloro‐1,3‐bis(4‐cyanobenzyl)imidazole‐2‐ylidene] silver(I) acetate ( 4b ), [1,3‐bis(4‐cyanobenzyl)benzimidazole‐2‐ylidene] silver(I) acetate ( 4c ), (1‐methyl‐3‐benzylimidazole‐2‐ylidene) silver(I) acetate ( 8a ), (4,5‐dichloro‐1‐methyl‐3‐benzylimidazole‐2‐ylidene) silver(I) acetate ( 8b ) and (1‐methyl‐3‐benzylbenzimidazole‐2‐ylidene) silver(I) acetate ( 8c ) respectively. The four NHC‐precursors 3a–c, 7c and four NHC–silver complexes 4a–c and 8c were characterized by single crystal X‐ray diffraction. The preliminary antibacterial activity of all the compounds was studied against Gram‐negative bacteria Escherichia coli, and Gram‐positive bacteria Staphylococcus aureus using the qualitative Kirby‐Bauer disc‐diffusion method. All NHC–silver complexes exhibited medium to high antibacterial activity with areas of clearance ranging from 4 to 12 mm at the highest amount used, while the NHC‐precursors showed significantly lower activity. In addition, all NHC–silver complexes underwent preliminary cytotoxicity tests on the human renal‐cancer cell line Caki‐1 and showed medium to high cytotoxicity with IC₅₀ values ranging from 53 ( ± 8) to 3.2 ( ± 0.6) µM. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis and Biological Screening of 2‐Substituted 5,6‐Dihydro‐5‐oxo‐ 4H‐1,3,4‐oxadiazine‐4‐propanenitriles and of Their Intermediates

To evaluate the effect of substituents on biological activities of electron‐rich N‐containing heterocycles, the variably 2‐substituted 5,6‐dihydro‐5‐oxo‐4H‐1,3,4‐oxadiazine‐4‐propanenitriles 26 – 33 were synthesized and evaluated for antibacterial, antifungal, and enzyme‐inhibition activities. The target compounds were obtained from alkyl 4‐ or 3‐hydroxy benzoates 1 and 2 , respectively, and from methyl indoleacetate 3 . The phenolic OH group of benzoates 1 and 2 were substituted with p‐toluenesulfonyl (→ 4 and 5 ), benzoyl (→ 6 and 7 ), and benzyl groups (→ 8 and 9 ) and then converted to 5,6‐dihydro‐5‐oxo‐4H‐1,3,4‐oxadiazine‐4‐propanenitriles. To establish structure‐activity relationships (SAR), a pharmacological screening of the intervening intermediates was also conducted, which revealed that the intermediate hydrazide 11 possesses significant antimicrobial and MAO‐A inhibiting properties and intermediates 12, 24, 28 , and 29 appreciable antifungal activities. Compound 7 inhibits α‐chymotrypsin.     

Synthesis and Characterization of New Heterocyclic Compounds Containing Thienylbenzo[h]Quinoline Moiety

In this paper the reaction of 2‐(2′‐thienylmethylene)‐3,4‐dihydronaphthalen‐2(1H)‐one ( 1 ) with cyanothioacetamide gave a mixture of 3‐cyano‐5,6‐dihydro‐4‐(2′‐thienyl)‐benzo[h]quinolin‐2(1H)‐thione ( 2 ) and the related disulfide 3 . Compound 2 was reacted with some halo compounds namely; ethyl chloroacetate, chloroacetamide, chloro(N‐(p‐chlorophenyl))acetamide, N¹‐chloroacetylsulfanilamide, and 2‐chloromethyl‐1H‐benzimidazole to produce a series of 2‐(substituted)methylthio‐3‐cyano‐5,6‐dihydro‐4‐(2′‐thienyl)benzo[h]quinolines 4a , 4b , 4c , 4d , 4e and 11 . Upon heating the latter compounds with sodium ethoxide, they underwent intramolecular Thorpe–Zeigler cyclization to furnish the corresponding 2‐(substituted)‐3‐amino‐5,6‐dihydro‐4‐(2′‐thienyl)‐benzo[h]thieno[2,3‐b]quinolines 5a , 5b , 5c , 5d , 5e and 12 . (3‐Cyano‐5,6‐dihydro‐4‐(2′‐thienyl)‐benzo[h]quinolin‐2‐ylthio)acethydrazide ( 8 ) and the related isomer, 3‐amino‐5,6‐dihydro‐4‐(2′‐thienyl)thieno[2,3‐b]benzo[h]quinoline‐2‐carbohydrazide ( 9 ), were also synthesized. Most of the aforementioned compounds were used as key intermediates for synthesizing other benzo[h]quinolines, benzo[h]thieno[2,3‐b]quinolines as well as benzo[h]pyrimido[4′,5′:4,5] thieno[2,3‐b]quinolines. The structure of all synthesized compounds was confirmed by spectroscopic measurements and analytical analyses.     

Synthesis,Cytotoxicity and Antibacterial Studies of Novel Symmetrically and Nonsymmetrically 4‐(Methoxycarbonyl)benzyl‐Substituted N‐Heterocyclic Carbene–Silver Acetate Complexes

From the reaction of 1H‐imidazole ( 1a ), 4,5‐dichloro‐1H‐imidazole ( 1b ), 1H‐benzimidazole ( 1c ), 1‐methyl‐1H‐imidazole ( 1d ), and 1‐methyl‐1H‐benzimidazole ( 1f ) with methyl 4‐(bromomethyl)benzoate ( 2 ), symmetrically and nonsymmetrically 4‐(methoxycarbonyl)benzyl‐substituted N‐heterocyclic carbene (NHC) precursors, 3a – 3f , were synthesized. These NHC precursors were then reacted with silver(I) acetate (AgOAc) to yield the NHC–silver acetate complexes (acetato‐κO){1,3‐bis[4‐(methoxycarbonyl)benzyl]imidazol‐2‐ylidene}silver ( 4a ), (acetato‐κO){4,5‐dichloro‐1,3‐bis[4‐(methoxycarbonyl)benzyl]‐2,3‐dihydro‐1H‐imidazol‐2‐yl}silver ( 4b ), (acetato‐κO){1,3‐bis[4‐(methoxycarbonyl)benzyl]‐2,3‐dihydro‐1H‐benzimidazol‐2‐yl}silver ( 4c ), (acetato‐κO){1‐[4‐(methoxycarbonyl)benzyl]‐3‐methyl‐2,3‐dihydro‐1H‐imidazol‐2‐yl}silver ( 4d ), (acetato‐κO){4,5‐dichloro‐1‐[4‐(methoxycarbonyl)benzyl]‐3‐methyl‐2,3‐dihydro‐1H‐imidazol‐2‐yl}silver ( 4e ), and (acetato‐κO){1‐[4‐(methoxycarbonyl)benzyl]‐3‐methyl‐2,3‐dihydro‐1H‐benzimidazol‐2‐yl}silver ( 4f ), respectively. The three NHC–AgOAc complexes 4a, 4c , and 4d were characterized by single‐crystal X‐ray diffraction. All compounds studied in this work were preliminarily screened for their antimicrobial activities in vitro against Gram‐positive bacteria Staphylococcus aureus, and Gram‐negative bacteria Escherichia coli using the qualitative disk‐diffusion method. All NHC–AgOAc complexes exhibited weak‐to‐medium antibacterial activity with areas of clearance ranging from 4 to 7 mm at the highest amount used, while the NHC precursors showed significantly lower activity. In addition, NHC–AgOAc complexes 4a and 4b , and 4d – 4f exhibited in preliminary cytotoxicity tests on the human renal‐cancer cell line Caki‐1 medium‐to‐high cytotoxicities with IC₅₀ values ranging from 3.3±0.4 to 68.3±1 μM .     

Two mononuclear octahedral complexes with benzimidazole‐2‐carboxylate: supramolecular networks constructed by hydrogen bonds

The title compounds, trans‐bis(1H‐benzimidazole‐2‐carboxylato‐κ²N³,O)bis(ethanol‐κO)cadmium(II), [Cd(C₈H₅N₂O₂)₂(C₂H₆O)₂], (I), and trans‐bis(1H‐benzimidazole‐κN³)bis(1H‐benzimidazole‐2‐carboxylato‐κ²N³,O)nickel(II), [Ni(C₈H₅N₂O₂)₂(C₇H₆N₂)₂], (II), are hydrogen‐bonded supramolecular complexes. In (I), the Cd^II ion is six‐coordinated by two O atoms from two ethanol molecules, and by two O and two N atoms from two bidentate benzimidazole‐2‐carboxylate (HBIC) ligands, giving a distorted octahedral geometry. The combination of O—H...O and N—H...O hydrogen bonds results in two‐dimensional layers parallel to the ab plane. In (II), the six‐coordinated Ni^II atom, which lies on an inversion centre, shows a similar distorted octahedral geometry to the Cd^II ion in (I); two benzimidazole molecules occupy the axial sites and the equatorial plane contains two chelating HBIC ligands. Pairs of N—H...O hydrogen bonds between pairs of HBIC anions connect adjacent Ni^II coordination units to form a one‐dimensional chain parallel to the a axis. Moreover, these one‐dimensional chains are further linked via N—H...O hydrogen bonds between HBIC anions and benzimidazole molecules to generate a three‐dimensional supramolecular framework. The two compounds show quite different supramolecular networks, which may be explained by the fact that different co‐ligands occupy the axial sites in the coordination units.     

From Homoconjugated Push–Pull Chromophores to Donor–Acceptor‐Substituted Spiro Systems by Thermal Rearrangement

Series of homoconjugated push–pull chromophores and donor–acceptor (D–A)‐functionalized spiro compounds were synthesized, in which the electron‐donating strength of the anilino donor groups was systematically varied. The structural and optoelectronic properties of the compounds were investigated by X‐ray analysis, UV/Vis spectroscopy, electrochemistry, and computational analysis. The homoconjugated push–pull chromophores with a central bicyclo[4.2.0]octane scaffold were obtained in high yield by [2+2] cycloaddition of 2,3‐dichloro‐5,6‐dicyano‐p‐benzoquinone (DDQ) to N,N‐dialkylanilino‐ or N,N‐diarylanilino‐substituted activated alkynes. The spirocyclic compounds were formed by thermal rearrangement of the homoconjugated adducts. They also can be prepared in a one‐pot reaction starting from DDQ and anilino‐substituted alkynes. Spiro products with N,N‐diphenylanilino and N,N‐diisopropylanilino groups were isolated in high yields whereas compounds with pyrrolidino, didodecylamino, and dimethylamino substituents gave poor yields, with formation of insoluble side products. It was shown by in situ trapping experiments with TCNE that cycloreversion is possible during the thermal rearrangement, thereby liberating DDQ. In the low‐yielding transformations, DDQ oxidizes the anilino species present, presumably via an intermediate iminium ion pathway. Such a pathway is not available for the N,N‐diphenylanilino derivative and, in the case of the N,N‐diisopropylanilino derivative, would generate a strained iminium ion (A1,3 strain). The mechanism of the thermal rearrangement was investigated by EPR spectroscopy, which provides good evidence for a proposed biradical pathway starting with the homolytic cleavage of the most strained (CN)C?C(CN) bond between the fused four‐ and six‐membered rings in the homoconjugated adducts.     

1,3‐Bis(ethylamino)‐2‐nitrobenzene, 1,3‐bis(n‐octylamino)‐2‐nitrobenzene and 4‐ethylamino‐2‐methyl‐1H‐benzimidazole

1,3‐Bis(ethylamino)‐2‐nitrobenzene, C₁₀H₁₅N₃O₂, (I), and 1,3‐bis(n‐octylamino)‐2‐nitrobenzene, C₂₂H₃₉N₃O₂, (II), are the first structurally characterized 1,3‐bis(n‐alkylamino)‐2‐nitrobenzenes. Both molecules are bisected though the nitro N atom and the 2‐C and 5‐C atoms of the ring by twofold rotation axes. Both display intramolecular N—H...O hydrogen bonds between the amine and nitro groups, but no intermolecular hydrogen bonding. The nearly planar molecules pack into flat layers ca 3.4 Å apart that interact by hydrophobic interactions involving the n‐alkyl groups rather than by π–π interactions between the rings. The intra‐ and intermolecular interactions in these molecules are of interest in understanding the physical properties of polymers made from them. Upon heating in the presence of anhydrous potassium carbonate in dimethylacetamide, (I) and (II) cyclize with formal loss of hydrogen peroxide to form substituted benzimidazoles. Thus, 4‐ethylamino‐2‐methyl‐1H‐benzimidazole, C₁₀H₁₃N₃, (III), was obtained from (I) under these reaction conditions. Compound (III) contains two independent molecules with no imposed internal symmetry. The molecules are linked into chains via N—H...N hydrogen bonds involving the imidazole rings, while the ethylamino groups do not participate in any hydrogen bonding. This is the first reported structure of a benzimidazole derivative with 4‐amino and 2‐alkyl substituents.     

Metallorganische 5d6‐Übergangsmetallkomplexe von zwei 1‐Methyl‐(2‐alkylthiomethyl)‐1H‐benzimidazol‐Liganden: Strukturen und elektrochemische Oxidation

Organometallic 5d⁶ Transition Metal Complexes of 1‐Methyl‐(2‐alkylthiomethyl)‐1H‐benzimidazole Ligands: Structures and Electrochemical Oxidation The complexes [(mmb)Re(CO)₃Cl], [(mtb)Re(CO)₃Cl], [(mmb)OsCl(Cym)](PF₆) and [(Cym)OsCl(mtb)](PF₆) where Cym = p‐cymene, mmb = 1‐methyl‐(2‐methylthiomethyl)‐1H‐benzimidazole and mtb = 1‐methyl‐(2‐tert‐butylthiomethyl)‐1H‐benzimidazole were synthesized and, except for the latter, structurally characterized. In comparison with other late transition metal compounds of these N‐S chelate ligands the rhenium(I) systems exhibit a balanced coordination to both N and S donor atoms. Anodic one‐electron oxidation produces EPR‐silent rhenium(II) states whereas the osmium(III) species [(mmb)OsCl(Cym)]²⁺ could be identified via EPR and UV/VIS spectroelectrochemistry.     

A facile synthesis and antimicrobial activity of 2,10‐dichloro‐6‐(aryloxy/thiophenoxy)‐4,8‐dinitrodibenzol[d,g][1,3,6,2]‐dioxathiaphosphocin‐ 6‐oxides

Novel 6‐substituted 2,10‐dichloro‐4,8‐dinitrodibenzo[d,g][1,3,6,2]dioxathiaphosphocin‐6‐oxides 4 were synthesized by reacting 5,5′‐dichloro‐3,3′‐dinitro‐2,2′‐dihydroxydiphenyl sulfide ( 2 ) with different aryl phosphorodichloridates, trichloromethylphosphonic dichloride and O‐2‐chloroethyl phosphoryldichloride (3) in the presence of triethylamine at 55–60°. Some of these compounds are prepared by reacting the monochloride, 2,6,10‐trichloro‐4,8‐dinitrodibenzo[d,g][1,3,6,2]dioxathiaphosphoein‐6‐oxide ( 5 ) in situ with substituted phenols and thiols. 5 is prepared by condensing 2 with phosphorus oxychloride. The ¹H nmr chemical shifts of the dibenzodioxathiaphosphocin moiety indicates the presence of more than one conformer in solution. However the presence of more than one conformer in each example cannot be entirely eliminated. Interestingly 4d on oxidation to 12‐sulphone by H₂O₂ in acetic acid medium yielded only 12‐sulphoxide 6a . The ir, ¹H, ¹³C, ³¹P nmr and mass spectral data are discussed. Some of these compounds were screened for antifungal activity against Curvularia lunata and Aspergillus niger and antibacterial activity on Bacillus subtilis and Klebsiella pneumoniae. A few of them possess significant activity.     

First synthesis of novel pentaheterocyclic ring system of 1,2,4‐triazolo[2″,3″:6′,1′]pyrimido[4′,5′:2,3]pyrido[1,2‐a]benzimidazole

Reaction of 1‐amino‐3‐arylpyrido[1,2‐a]benzimidazole‐2,4‐dicarbonitrile (1) with dimethylformamide‐dimethylacetal (DMF‐DMA) gave 1 ‐[N,N‐(dimethylaminomethylene)amino]‐3‐arylpyrido[1,2‐a]benzimidazole‐2,4‐dicarbonitrile (2). Compounds (1) reacted with triethylorthoformate yielding 1‐[N‐(ethoxymethylene)amino]‐3‐arylpyrido[1,2‐a]benzimidazole‐2,4‐dicarbonitrile (3). 3‐Amino‐4‐imino‐5‐aryl‐6‐cyanopyrimido[5′,4′:5,6]pyrido[1,2‐α] benzimidazole (4) was synthesized via condensation of either (2) or (3) with hydrazine hydrate. Reactions of (4) with acetic anhydride, ethyl chloroformate or aryl isothiocyanate yielded the respective derivative of the new ring system namely 1,2,4‐triazolo[2″,3″:6′,1′]pyrimido[4′,5′:2,3]pyrido[1,2‐a]benzimidazole (5–7).     

Synthesis of some new Pyridine‐based Heterocyclic Compounds with Anticipated Antitumor Activity

A novel class of 5‐amino‐N′‐(1‐(pyridin‐4‐yl)ethylidene)‐1H‐pyrazole‐4‐carbohydrazides and 8‐(pyridin‐4‐yl)pyrido[2,3‐d][1,2,4]triazolo[4,3‐a]pyrimidin‐5(1H)‐ones was synthesized from reaction of 2‐cyano‐N′‐(1‐(pyridin‐4‐yl)ethylidene)‐acetohydrazide and 7‐(pyridin‐4‐yl)‐2‐thioxo‐2,3‐dihydropyrido[2,3‐d]pyrimidin‐4(1H)‐one with the appropriate hydrazonoyl halides. Moreover, 2‐cyano‐N′‐(1‐(pyridin‐4‐yl)‐ethylidene)‐acetohydrazide was used for the synthesis of 2‐cyano‐N′‐(1‐(pyridin‐4‐yl)ethylidene)‐acrylohydrazides and 2‐oxo‐2‐(2‐(1‐(pyridin‐4‐yl)ethylidene)‐hydrazinyl)‐acetohydrazonoyl cyanides. The structures of the newly prepared compounds were confirmed by both elemental and spectral analyses as well as by alternate synthesis. The anticancer activities of the prepared compounds were screened against the hepatocellular carcinoma (HepG2) cell line, and the results showed that most of the compounds exhibit considerable activities.     

Syntheses of N‐[3‐(1‐methyl‐1H‐2‐imidazolyl)propyl]benzamides and N‐[3‐(1‐methyl‐1H‐2‐imidazolyl)propyl]benzenesulfonamides

A series of substituted N‐(4‐substituted‐benzoyl)‐N‐[3‐(1‐methyl‐1H‐imidazol‐2‐yl)propyl]amines ( 13 ) and N‐arylsulfonyl‐N‐[3‐(1‐methyl‐1H‐imidazol‐2‐yl)propyl]amines ( 14 ) were prepared from the reaction of 3‐(1‐methyl‐1H‐imidazol‐2‐yl)propan‐1‐amine ( 7 ) with substituted benzoyl chloride or substituted‐benzene sulfonyl chloride respectively. Compound 7 was prepared by two independent methods.