Synthesis of Some New Benzimidazole–Thiazole Derivatives as Anticancer Agents

4‐(1H‐benzo[d]imidazol‐2‐yl)thiazol‐2‐amine and its 1‐methyl derivative ( 1 ) were reacted with different reagents such as acid anhydrides, malononitrile, chloroacetyl chloride, and aromatic aldehydes to produce the corresponding benzimidazole products 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , respectively. Also, 2‐chloro‐N‐(4‐(1‐methyl‐1H‐benzo[d]imidazol‐2‐yl)thiazol‐2‐yl) acetamide ( 6 ) was reacted with diaminoethane, ortho‐substituted aniline, thioglycolic acid, thiosemicarbazide derivatives, secondary amines, and potassium isothiocyanate to afford the corresponding derivatives 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , respectively. The cytotoxic activity of some newly synthesized derivatives was studied against two different cell lines HepG2 and PC12. Compounds 9 and 15b showed promising anticancer activity against both types of the tested cancerous cell lines.     

Synthesis and Antimicrobial Screening of 2‐Aryl‐5‐((2‐arylthiazol‐4‐yl)methyl)‐1,3,4‐oxadiazole Derivatives

A new series of 2‐aryl‐5‐((2‐arylthiazol‐4‐yl)methyl)‐1,3,4‐oxadiazole derivatives was synthesized by condensation of 2‐(2‐substituted thiazol‐4‐yl)acetohydrazide with aryl aldehydes followed by oxidative cyclocondensation using iodobenzene diacetate. The structure of synthesized compounds was characterized by IR, NMR, and mass analysis. All the newly synthesized compounds were evaluated for their in vitro antimicrobial activity. Some of the compounds showed moderate antimicrobial activity.     

Antimicrobial Properties of Some New Synthesized Benzothiazole Linked Carboxamide,Acetohydrazide, and Sulfonamide Systems

We report herein the interaction of diethylethoxymethylene malonate ( 1 ) with 2‐cyanomethylbenzothiazole ( 7 ) to give diethyl 2‐(2‐benzothiazole‐2‐(3H)‐ylidiene)‐2‐(cyano ethyl) malonate ( 8a ) in excellent yield. Ethyl 4‐cyano‐1‐oxo‐1H‐benzo[4,5]thiazolo[3,2‐a]pyridine‐2‐carboxylate (9) was synthesized from 8a and subjected to react with hydrazine hydrate to give its corresponding acid hydrazide 10 . Condensation of 10 with different acid anhydrides afforded the corresponding benzothiazolo pyridine carboxamide derivatives 11 – 15 . In addition, we report a simple synthesis of N′‐(benzo[d]thiazol‐2‐yl)‐2‐((4‐ayl)amino)acetohydrazide derivative ( 17 ), which then reacted with different amines to give the corresponding acetohydrazide derivatives 19a – c . Moreover, compound 17 reacted with some sulfonamide derivatives to give the corresponding sulfonamide derivatives 20 and 22a , b .The newly synthesized compounds were established their structures on the bases of their correct analytical and spectral data and evaluated their antimicrobial activity. It was found that compounds 22a , b displayed the highest antimicrobial activity against the tested organisms.     

Synthesis and Antimicrobial Activities of Novel Series of 3‐(4‐(2‐substituted thiazol‐4‐yl)phenyl)‐2‐(4‐methyl‐2‐substituted thiazol‐5‐yl)thiazolidin‐4‐one Derivatives

In the present investigation, a novel series of 3‐(4‐(2‐substituted thiazol‐4‐yl)phenyl)‐2‐(4‐methyl‐2‐substituted thiazol‐5‐yl)thiazolidin‐4‐one derivatives were synthesized by condensation of 2‐substituted‐4‐methylthiazole‐5‐carbaldehyde with 4‐(2‐substituted thiazol‐4‐yl)benzenamine followed by cyclo‐condensation with thioglycolic acid in toluene. All the newly synthesized compounds were characterized by spectral (IR, ¹H NMR, ¹³C NMR, and Mass) methods. The title compounds were screened for quantitative antibacterial activity (minimal inhibitory concentration). All compounds 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h and 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h show moderate to good antimicrobial activity, whereas compounds ( 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h ) also show moderate antifungal activity.     

Microwave‐Assisted Synthesis of Some Novel Benzimidazole Derivatives Containing Imine Function and Evaluation of Their Antimicrobial Activity

4‐Bromo‐o‐phenylenediamine and ethylimido‐p‐bromophenylacetate, 1 , were subjected to microwave irradiation to synthesize benzimidazole derivative, compound 2 . Ester derivative, 3 , and hydrazide derivative, 4 , of compound 2 were also synthesized, respectively. Finally, compound 4 was treated with 11 different aromatic aldehydes to obtain benzimidazole derivatives containing imine function. All reactions were carried out with microwave irradiation and conventional heating, and results were compared. Some of the newly synthesized compounds showed moderate antimicrobial activity against some tested organisms.     

Synthesis and Antimicrobial Activity of Novel Thiazole Substituted Pyrazole Derivatives

A series of new 1‐[4‐(2,3,4‐substituted‐phenyl) thiazol‐2‐yl]‐3‐(2,3,4‐substituted‐phenyl)‐1H‐pyrazole‐4‐carbaldehyde ( 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j , 4k , 4l , 4m ), 4‐[4‐(4‐substituted‐phenyl) thiazol‐2‐yl]‐3‐(4‐substituted‐phenyl)‐1‐phenyl‐1H‐pyrazole ( 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h , 7i ), 4‐[4‐(4‐substituted phenyl)thiazol‐2‐yl]‐1‐phenyl‐1H‐pyrazol‐3‐amine ( 10a , 10b , 10c , 10d , 10e , 10f , 10g ) have been synthesized by using Vilsmeier Haack formylation and Hantzsch reaction in high yield. All the synthesized compounds were tested qualitative (Zone of inhibition) and quantitative antimicrobial activities (MIC). Most of the synthesized compounds showed potent antimicrobial activity against gram positive and gram negative bacteria as well as fungi species.     

Synthesis and cytotoxic activity of certain new arylazothiazole containing compounds

2‐Amino‐5‐arylazo‐4‐(2‐chlorophenyl)thiazoles ( 2a‐e ) were prepared by the coupling of aryldiazonium chlorides with 2‐amino‐4‐(2‐chlorophenyl) thiazole ( 1 ). The thioureas 3a‐e were obtained by condensing the arylazothiazoles 2a‐c with the appropriate isothiocyanates. Reaction of 2d with aromatic aldehydes afforded the chalcone analogues 4a‐c . The pyridone derivatives 5a,b were synthesized by reacting the ketone 2d with different aromatic aldehydes, ethyl cyanoacetate and ammonium acetate. On the other hand, 5b was also prepared by cyclizing 4c with ethyl cyanoacetate and ammonium acetate. Furthermore, 6‐chloroimidazo[2,l‐b]‐thiazole 7 was obtained from the acid derivative 6b by treatment with POC1₃. While, the imidazo[2,l‐b]‐thiazolones 9a‐d were produced by the cyclization of the chloroacetyl derivatives 8a‐d with DMAP/pyri‐dine. Representative examples of the prepared compounds were tested for in vitro antitumor activity against two human tumor cell lines. Some compounds showed activity against brain tumor cell lines.     

Synthesis,Characterization, and Screening for Analgesic and Anti‐Inflammatory Activities of Schiff Bases of 1,3,4‐Oxadiazoles Linked With Quinazolin‐4‐One

Sixteen Schiff bases of quinazolin‐4‐one‐linked 1,3,4‐oxadiazoles were synthesized by reaction with different aromatic aldehydes. Purity of newly synthesized derivatives was confirmed through thin‐layer chromatography, combustion analysis, and melting point. The structure of the derivatives was confirmed by determining infrared spectroscopy, nuclear magnetic resonance, and mass spectroscopy. All the synthesized derivatives were evaluated for their analgesic and anti‐inflammatory activities in mice and rats, respectively. In animal studies, the derivative (E )‐3‐(5‐(4‐(4‐methoxybenzylideneamino)phenyl)‐1,3,4‐oxadiazol‐2‐yl)‐2‐phenylquinazolin‐4(3H )‐one showed more potent analgesic activity and the derivative (Z )‐3‐(5‐(2‐(2‐hydroxybenzylideneamino)phenyl)‐1,3,4‐oxadiazol‐2‐yl)‐2‐phenylquinazolin‐4(3H )‐one showed more potent anti‐inflammatory activity as compared with other derivatives. The results of the present study indicate that reactions of 3‐(5‐(4‐aminophenyl)‐1,3,4‐oxadiazol‐2‐yl)‐2‐phenylquinazolin‐4(3H )‐one and 3‐(5‐(2‐aminophenyl)‐1,3,4‐oxadiazol‐2‐yl)‐2‐phenylquinazolin‐4(3H )‐one with different aromatic aldehydes produce Schiff bases of quinazolin‐4‐one‐linked 1,3,4‐oxadiazoles with potent analgesic and anti‐inflammatory activities.     

Synthesis and Antimicrobial Activity of Some Novel Substituted Bis‐Pyridone,Pyrazole, and Thiazole Derivatives

A variety of novel bis‐heterocyclic derivatives were synthesized via the reaction of bis‐cyanoacetanilide derivative 3 with various aromatic aldehydes (1:2 molar ratio), to give the corresponding bis‐arylidene derivatives 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j , 5k , 5l , 5m . On the other hand, reacting compound 3 with substituted 2‐hydroxybenzaldehydes 6a , 6b , 6c afforded 2‐iminochromene‐3‐carboxamides 7a , 7b , 7c . The reaction of compound 5 with malononitrile afforded the novel bis‐pyridones 9a , 9b , 9c , 9f , 9g , 9h . The reaction of 5 with hydrazine derivatives afforded pyrazoles 11a , 11b , 11c , 11d , 11e , 11f , respectively. Compound 3 reacts with phenyl isothiocyanate in the presence of potassium hydroxide at room temperature followed by addition of some different halo‐carbonyl compounds to afford bis‐poly‐functionalized thiazole derivatives 13a , 13b , 13c . The bis‐enamine derivative 15 reacts also with hydrazine hydrate, guanidine, and hydroxylamine to give bis‐pyrazole 17 , pyrimidine 19 , and isoxazole 21 derivatives, respectively. Some of the newly synthesized compounds show moderate to high antimicrobial activity.     

Synthesis and Antimicrobial Evaluation of Some New Thiophene Derivatives

2-(2-Cyano-acetylamino)-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carboxamide(3) was used as starting material for synthesis of 4-thiazolidinone, thiazolidine, and thiophene derivatives 6, 7a, b, and 8a, b, respectively. Thiocarbomyl derivative 5, 4-thizolidinone 9, and thioxothiazolidine 10 were obtained from reaction of 3 with thioglycolic acid and phenyl isothiocyanate/sulfur, respectively. Condensation of 3 with selected cyclic ketones and aromatic aldehydes yielded the arylidine derivatives 11a, b and 13, respectively. Refluxing of 11a, b with sulfur and morpholine yielded the thiophene derivatives 12a, b, respectively. Diazocoupling of compound 3 withp-tolyl diazonium chloride yielded the hydrazone derivative 14. The newly synthesized compounds were characterized by infrared, ¹H NMR, and mass spectral studies. Representative compounds of the synthesized product were tested and evaluated as antimicrobial agents. Compound 12b gives very high antimicrobial activity against Ampicillin.     

Synthesis and Antimicrobial Activity of N‐[(2Z)‐3‐(4,6‐Substitutedpyrimidin‐2‐yl)‐4‐phenyl‐1,3‐thiazol‐2(3H)‐ylidene]‐3, 5‐dinitrobenzamide Analogues

In this study, we have synthesized 1‐(4,6‐disubstitutedpyrimidin‐2‐yl)‐3‐(3,5‐dinitrobenzoyl)‐thiourea derivatives ( 1a , 1b , 1c , 1d , 1e , 1f , 1g , 1h ) and N‐[(2Z)‐3‐(4,6‐disubstitutedpyrimidin‐2‐yl)‐4‐phenyl‐1,3‐thiazol‐2(3H)‐ylidene]‐3, 5‐dinitrobenzamide ( 2a‐2h ) analogues and characterized by IR spectroscopy, NMR spectroscopy, elemental analysis, and single crystal X‐ray diffraction data. The compounds ( 2a‐2h ) were screened for antimicrobial activity against Gram positive, Gram negative, and fungal species. The results of antimicrobial study indicated that compounds showed most potential and appreciable antibacterial and antifungal activities.     

Synthesis and antitumor activity evaluation of some schiff bases derived from 2‐aminothiazole derivatives

A novel series of thiazolyl Schiff bases have been designed and synthesized. These new compounds were obtained by the reactions of 4‐phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl) thiazol‐2‐amine and substituted aromatic aldehydes and were characterized on the basis of ¹H NMR and elemental analysis. The newly synthesized compounds were screened for their antitumor activity against human cancer cell lines, namely HL‐60 (leukemia), BGC‐823 (stomach), and HEP‐2 (larynx cancer). © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:55–59, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20256     

Synthesis of Biologically Active[4-(4-Bromophenyl)-2-thiazolyl]hydrazones and their D-Galactose Derivatives

Benzaldehyde [4‐(4‐bromophenyl)thiazol‐2‐yl]hydrazones 5a – 5d were prepared by reacting the thiosemicarbazones 2a – 2d with 2,4′‐dibromoacetophenone ( 1 ) in absolute ethanol. Acetylation of 5a and 5b with Ac₂O/Py at room temperature gave the N‐acetyl derivatives 6a and 6b . 4‐Methyl‐2‐pentanone/cyclopentanone [4‐(4‐bromo‐phenyl)thiazol‐2‐yl]hydrazones ( 8a ) and ( 8b ) were similarly obtained from the reaction of 1 with the thiosemicarbazones 7a and 7b , respectively. Cyclization of D‐galactose thiosemicarbazone ( 9 ) and its tautomers 10 and 11 with 1 afforded an equilibrium mixture of the acyclic 2‐thiazolylhydrazone 12 , together with its respective cyclic galactosyl derivatives 13 and 14 , whose structures were studied by using ¹H and ¹³C NMR spectra. The antimicrobial activity of the synthesized thiazole derivatives was evaluated in vitro by using an agar diffusion technique, and some of these compounds showed potential activity against Candida albicans.     

Pyridinium Ylide Assisted Highly Stereoselective One‐Pot Synthesis of trans‐2‐(4‐Chlorobenzoyl)‐3‐aryl‐spiro[cyclopropane‐1,2′‐inden]‐1′,3′‐diones and Their Antimicrobial and Nematicidal Activities

A series of highly stereoselective polysubstituted cyclopropane derivatives were synthesized via one‐pot two‐step tandem reaction starting from pyridine, 4‐chloro phenacyl bromide, 1,3‐indandione and aromatic aldehydes in acetonitrile using triethylamine as catalyst. Pyridinium ylide generated from 4‐chloro phenacyl bromide undergo cyclopropanation with 2‐arylidene‐2H‐indene‐1,3‐dione in situ afford the title compounds. Structures of all the compounds were confirmed by their analytical and spectral studies. Single crystal X‐ray analysis was also performed on compound 4c in order to determine the crystal structure. All the compounds were screened for antimicrobial and nematicidal activities. Significant antimicrobial activity was shown by the compounds derived from 2‐hydroxybenzaldehyde ( 4i ) and 4‐(dimethylamino)benzaldehyde ( 4m ) against all the tested bacterial and fungal strains. Compound 4i has shown good activity (48% mortality) against Meloidogyne incognita after 48 h of exposure at 250 µg/mL concentration.     

Synthesis of Certain Fused Thienopyrimidines of Biological Interest

4‐(4‐Acetylphenylamino)cycloocteno[4,5]thieno[2,3‐d]pyrimidine ( 4 ) was prepared and condensed with certain aldehydes, phenylhydrazine, malononitrile to obtain 5a‐d , 6 and 7 , respectively. 4‐Hydrazino & 4‐substituted amino derivatives of 2‐arylcycloocteno[4,5]thienopyrimidines 10a‐c & 11a‐i were synthesized. Cyclization of the hydrazino compounds 10a‐c with orthoalkanoate esters or the arylidene derivatives 12a‐c with bromine in acetic acid afforded the fused triazolo system 13a‐i . Reaction of the hydrazino compound 10c with acetic anhydride gave 15 while the reaction of 10b,c with acid chlorides gave 16a‐d . Furthermore, the tetrazolothienopyrimidines 17a‐c were synthesized. Some of the newly synthesized compounds were tested for their antimicrobial activity.     

Synthesis,characterization, and biological activity of some aza‐uracil derivatives

Thiation of 1 by LR gave the corresponding 3,5‐dithioxo derivative 2 and the trimer 3 . Methylation of 1 afforded the S‐methyl derivative 4 . Compound 1 was fused with 6‐bromo‐2‐phenyl‐benzo[1,3‐d]oxazin‐4‐one ( 5 ) and gave 6 . Condensation of 1 with some acid derivatives 7a , 7b , 7c , 7d and/or 8a , 8b , 8c yielded thiadiazolo‐triazine derivatives 9a , 9b , 9c , 9d and 10a , 10b , 10c . Compounds 9a , 9c and 10c were hydrolyzed to furnish 11a , 11b , 11c Acetylation of 14 afforded mono‐ and diacetyl‐derivatives 15 and 16 . Benzoylation of 14 afforded mono‐ and dibezoyl‐derivatives 17 and 18 . 14 with some aromatic aldehydes yielded 9a , 9b , 9c . Reacting 14 with phenyl (iso‐ and/or isothio‐) cyanate gave the urea derivatives 20a , 20b . Thiation of 14 with P₄S₁₀ furnished 21 . The newly synthesized compounds were tested as antimicrobial agents. J. Heterocyclic Chem., (2011)     

Design,Synthesis, and Characterization of Quinoxaline Derivatives as a Potent Antimicrobial Agent

A series of quinoxalinone derivatives were synthesized by the reaction of o‐phenylenediamine with oxalic acid to yield 1, 4‐dihydro quinoxaline‐2, 3‐dione ( 1 ) and then treated with thionyl chloride to yield 2, 3 dichloro quinoxaline ( 2 ). This was further reacted with hydrazine hydrate to produce 2, 3‐dihydrazinyl quinoxaline ( 3 ). This was finally reacted with substituted aromatic aldehydes to produce 2,3‐bis[2‐(sustituted benzylidine) hydrazinyl] quinoxalines ( 4 ). These quinoxalinone derivatives were characterized by infrared spectroscopy and nuclear magnetic resonance spectroscopy and MASS spectral data. All the synthesized compounds were evaluated for their antimicrobial activity. The results of the antimicrobial study revealed that compounds 4c , 4d , and 4i were active and exhibited better inhibitory activities as compared to standard drug ciprofloxacin. The results were further checked with protein legend interaction by using docking studies, and all the compounds exhibited good docking scores between ?8.72 and ?11.29 kcal/mol against dihydrofolate reductase protein fragment from Staphylococcus aureus (PDB ID‐4XE6). Among all compound, 4c has shown maximum docking score and found in agreement to in vitro studies.     

Facile Synthesis of N‐(Benzyl‐1H‐1,2,3‐Triazol‐5‐yl) Methyl)‐4‐(6‐Methoxybenzo [d] Thiazol‐2‐yl)‐2‐Nitrobenzamides via Click Chemistry

A series of novel N‐((l‐benzyl‐lH‐l,2,3‐triazol‐5‐yl) methyl)‐4‐(6‐methoxy benzo[d ]thiazol‐2‐yl)‐2‐nitrobenzamide derivatives were prepared from 4‐(6‐methoxybenzo[d ]thiazol‐2‐yl)‐2‐nitro‐N‐(prop‐2‐ynyl) benzamide with benzyl azides by using click reaction (copper‐catalyzed Huisgen 1,3‐dipolar cycloaddition reaction) in the presence of CuSO₄.5H₂O and sodium ascaorbate. All the newly synthesized compounds were evaluated further in vitro antimicrobial activity against Gram‐positive bacteria (Staphylococcus aureus and Bacillus subtillis ), Gram‐negative bacteria (Echerichia coli and Pseudomonas aeuroginosa ), and fungi (Aspergillus niger and Aspergillusfumigatus ) strains. The new compounds were characterized based on spectroscopic evidence. Among them compounds 10a , 10h , and 10i were showed promising activity when compared with standard drugs Ciprofloxacin and Miconazole.     

Exploration of quinoxaline derivatives as antimicrobial and anticancer agents

Novel 2 and 3‐substituted quinoxaline derivatives were synthesized through various synthetic pathways, among which cyanoacetamide and cyanoacetohydrazide quinoxaline derivatives 4a‐c and 11a‐c , respectively, were synthesized. Furthermore, methoxy quinoxaline derivatives 3c and quinoxaline derivatives bearing substituted pyridines 6a,b , 12a,b , and 13a,b were designed to be synthesized. However, we have synthesized acrylohydrazide 5a,b and 7 /acrylamide derivatives, Schiff base analogues 14a‐f , pyrazole derivatives 15a‐e, amide derivatives 16a‐f , guanidine derivatives 16 g,h as well as, quinoxalin‐2‐methylallyl propionate derivative 14g . All the synthesized compounds were confirmed via spectral data and elemental analyses. Moreover, the newly synthesized compounds were evaluated for their antimicrobial activity (Gm +ve, Gm ?ve in comparison to Gentamycin a standard) and fungi (in comparison to Ketoconazole as a standard). Thus, compound 16b showed promising antimicrobial activity against B. subtilis, P. vulgaris, and S. mutants with values ranging from 20 to 27‐mm zone of inhibition. While compounds 5a , 14e,f, and 16a,c,d,g,h showed potent antimicrobial activity. Moreover, the National Cancer Institute (NCI) selected 20 compounds that were submitted for anticancer screening against 60 types of cancer cell lines. The most active compounds are 5b and 12a where compound 5b containing 2,4‐dichlorophenyl moiety at cyanoacetamide linkage of hydrazine quinoxaline backbone exerted significant growth inhibition activity against Leukemia MOLT‐4, Renal cancer UO‐31, and Breast cancer MCF‐7. In addition, compound 12a having 4,6‐diaminopyridinone side chain at position‐3 of quinoxaline nucleus exhibited remarkable anticancer activity against renal cancer UO‐31.     

Synthesis of Some Thienotetrahydroquinoline Derivatives

2‐Thioxo‐1,2,5,6,7,8‐hexahydroquinoline‐3‐carbonitrile ( 2 ) was easily S‐alkylated to produce alkyl mercapto derivatives 3a‐g . The latter compounds were cyclized to afford thienotetrahydroquinolines 4a‐g . Several pyrimidothienotetrahydroquinolines 5a‐d , and 6a‐d were obtained from the condensation of compounds 4c‐f with different reagents. o‐Aminocarbohydrazide derivative 11 was reacted with aromatic aldehydes, acetylacetone, nitrous acid and CS₂ to afford compounds 12–15 . Compound 24 was coupled with aryldiazonium chloride to afford arylazo derivatives 25 . Also it condensed with aromatic aldehydes to give arylidene derivatives 26 . The latter compounds were reacted with malononitrile to give pyrano derivative 27 .