Novel Synthesis of 3‐Amino‐4‐oxo‐(2H)‐pyrazolo[3′,4′:4,5]pyrimido‐[2,1‐b]benzothiazole and its 2‐ and 3‐Substituted Derivatives

Reaction of 4H‐pyrimido[2,1‐b]benzothiazole‐2‐thiomethyl‐3‐cyano‐4‐one (1) with hydrazine hydrate/aryl hydrazine/heteryl hydrazine in the presence of anhydrous potassium carbonate and dimethyl formamide afforded 3‐amino‐4‐oxo‐(2H)/aryl/heteryl pyrazolo[3′,4′:4,5]pyrimido[2,1‐b]benzothiazoles in good yield. These pyrazole derivatives on diazotization followed by replacement with hydroxy, chloro, bromo, iodo and on reduction gave the corresponding 3‐substituted derivatives.     

Synthesis and biological activities of a novel series of 3,6‐disubstituted‐1,2,4‐triazolo‐[3,4‐b]‐1,3,4‐thiadiazoles containing gem‐dimethylbenzyl moiety

A novel series of 3,6‐disubstituted‐1,2,4‐triazolo‐[3,4‐b]‐1,3,4‐thiadiazoles (6a–r) containing gem‐dimethyl benzyl moiety were prepared by the condensation of 4‐amino‐3‐aryl/aralkyl substituted‐5‐mercapto‐1,2,4‐triazoles ( 5a , 5b , 5c ) with various fluoro substituted aromatic acids in the presence of POCl₃. IR, ¹H NMR, ¹³C NMR, 2D NMR (COSY), and mass spectral data confirmed the structures of all the synthesized compounds. All the compounds were also screened for their antibacterial, antifungal and analgesic activities. Compounds 6b , 6d , 6f , 6g , 6h , 6i , 6m , 6n , 6o , 6p , and 6r exhibited promising antibacterial and compounds 6a , 6d , 6f , 6g , 6h , 6k , 6m , 6o , 6p , and 6q showed significant analgesic activities. J. Heterocyclic Chem., (2011)     

Synthesis of Polysubstituted Pyrazolo[3,4‐b]pyridine‐3‐Carbohydrazide and Pyrazolo[3,4‐d]pyridazine Derivatives

5‐Amino‐4‐formyl pyrazole carboxylate gave facile reactions with malononitrile, hydrazine, and ketones in the presence of piperidine furnished substituted pyrazolo[3,4‐b]pyridines and pyrazolo[3,4‐b]quinolones. The pyridazine sulfonamides were obtained by the reaction of 5‐chloro 4‐formyl pyrazole carboxylate with sulfonamide derivatives.     

Synthesis,Characterization, and In Vitro Antimicrobial Activity of a New Class of 7‐Substituted Amino‐2‐phenyl‐3H‐pyrimido[4,5‐d]pyrimidin‐4‐one

A new class of pyrimido pyrimidine derivatives that exhibits in vitro antimicrobial activity was synthesized. The protection of amino group in the compound 1 with acetic anhydride, followed by the reaction with POCl₃, gave 3 . The reaction of 3 with different substituted phenyl methanediamine in dry TEA under inert atmosphere led to the formation of 4 . Deprotection of 4 followed by refluxion with different acid chlorides yielded title compounds 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j , 6k , 6l , 6m in good yields. The identities of these compounds were confirmed following elemental analysis, IR, ¹H, ¹³C NMR, and mass spectral studies. All the title compounds exhibited pronounced in vitro antibacterial and antifungal activities.     

Synthesis,antimicrobial activity,and molecular docking study of formylnaphthalenyloxymethyl‐triazolyl‐N‐phenylacetamides

In the present study, substituted formylnaphthalenyloxymethyl‐triazolyl‐N‐phenylacetamide derivatives ( 6a – k ) have been designed and synthesized employing click chemistry approach and evaluated for their in vitro antifungal and antibacterial activities. All the newly synthesized compounds were thoroughly characterized by ¹H NMR, ¹³C NMR, and HRMS spectral techniques. Among the screened compounds, 6d , 6e , 6j , and 6k have shown good antifungal and antibacterial activities. Compound 6k has shown very effective antimicrobial activity. We further performed exploratory docking studies on microbial DNA gyrase to rationalize the in vitro biological data and to demonstrate the mechanism of antimicrobial activity. This is the first report to demonstrate the formylnaphthalenyloxymethyl, triazole, and N‐phenylacetamide hybrids as potential antimicrobial agents.     

1,3‐Benzothiazoles as Antimicrobial Agents

Starting from 2‐amino‐1,3‐mercaptobenzothiazoles recently reported ( 1a , 1b , 1c , 1d , 1e , 1f , 1g , 1h ), a series of the corresponding 2‐mercapto‐1,3‐benzothiazole isosters ( 2a , 2b , 2c , 2d , 2e , 2f , 2g , 2h ) were screened for their in vitro antibacterial and antifungal activities. Results underline that the presence of the mercapto moiety at the 2‐position of the heterocyclic nucleus is crucial for activity against bacteria. The biological screening against Candida spp. identified commercial 2f as the most promising compound as antifungal against Candida albicans and tropicalis. Molecular modeling studies supported these results. Then, to enlarge structure‐activity relationship (SAR) studies on series 1 , newly synthesized compounds ( 1k , 1l , 1m , 1n , 1o , 1p ) were reported. All the compounds belonging to this series and bearing a bulky substituent at the 6‐position of the aryl moiety showed high antifungal activity.     

Synthesis and antimicrobial activity of 2‐(acyl or carboxyalkyl)‐3‐(H or alkyl or aryl)‐5 (or ‐6 or ‐8)‐monochloro, 7‐fluoro‐substituted‐4H‐1,4‐benzothiazines

A series of 2‐(acyl or carboxyalkyl)‐3‐(H or alkyl or aryl)‐5 (or ‐6 or ‐8)‐monochloro, 7‐fluoro‐substituted‐4H‐1,4‐benzothiazines 3a‐x were prepared to investigate their potential biological activity. In this work the 3a‐w structures are supported with physical and analytical data and the results of their in vitro antimicrobial activity against some strains Gram positive, Gram negative, and Fungi are reported. It was found that compounds 3a, 3d displayed interesting antibacterial activity, whereas compound 3f displayed interesting antifungal activity.     

Synthesis of Novel 1‐(5‐(Benzylsulfinyl)‐3‐methyl‐1,3,4‐thiadiazol‐2(3H)‐ylidene)‐thiourea/urea Derivatives and Evaluation of Their Antimicrobial Activities

A new series of 1‐(5‐(benzylsulfinyl)‐3‐methyl‐1,3,4‐thiadiazol‐2(3H)‐ylidene)‐thiourea/urea derivatives ( 1a – j ) were designed and synthesized. For the first time, (i) a new process was developed for N‐methylation of 1,3,4‐thiadiazole moiety using dimethyl carbonate an environmentally benign reagent in presence of N,N,N′,N′‐tetramethylethylenediamine and (ii) the sulfide was selectively oxidized to sulfoxide in higher yield by using chlorine (g) in aqueous acetic acid media under mild reaction condition. The synthesized compounds ( 1a – j ) were investigated for their antimicrobial activities. The tested compounds ( 1a – j ) were exhibited moderate to excellent antibacterial activities against both Gram‐positive and Gram‐negative bacterial strains. The same compounds exhibited good antifungal activities against selected fungal strains. Particularly, the compounds 1b , 1d , 1h , and 1i were proved to be promising leads exhibiting both antibacterial and antifungal activities compared with standard drugs, ciprofloxacin, and fluconazole. The presence of 1,3,4‐thiadiazole moiety has a significant role in the display of antimicrobial activity. In addition, the presence of both sulfinyl and thiourea or urea functionalities has enhanced the activity as per obtained antimicrobial activity data.     

Synthesis and Antimicrobial Activity of Novel Heterocycles Utilizing 3‐(1,4‐Dioxo‐3,4‐dihydrophthalazin‐2(1H)‐yl)‐3‐oxopropanenitrile as Precursors

The reaction of 3‐(1,4‐dioxo‐3,4‐dihydrophthalazin‐2(1H)‐yl)‐3‐oxopropanenitrile 1 and salicyladehyde furnished coumarin derivatives 4 and 5 . Coupling reaction of 1 with aryl diazonium chlorides and benzene‐1,4‐bis (diazonium) chloride gave the corresponding hydrazones 6a , b and bishydrazone 9 , respectively. Hydrazones 6 underwent intramolecular cyclization upon treating with hydrazine hydrate to give 3‐aminopyrazoles 7 . Pyranyl phthalazine 13 was prepared from the reaction of 1 with ethyl 2‐cyano‐3‐ethoxyacrylate 10 . Enaminonitrile 14 was reacted with hydrazine hydrate/phenylhydrazine and hydroxylamine to afford the corresponding pyrazoles 16 and oxime 17 . The antimicrobial evaluation revealed pyrazole derivatives 7a , b and 16a , b displayed a broad spectrum activity against most strains. 3‐Aminopyrazole derivative 7b showed potent antibacterial activity against all tested microorganisms.     

Microwave Induced Synthesis of 3‐Aryl‐6‐(6‐/8‐substituted 4‐chloroquinoline‐3‐yl) ‐ s ‐triazolo [3,4‐b] −1,3,4‐thiadiazoles

The condensation of 4‐amino‐3‐aryl‐5‐mercapto‐1, 2, 4‐triazoles (1a‐f) with 6‐/8‐substituted 1,4‐dihydro‐4‐oxo‐quinoline‐3‐carboxylic adds (2a‐d) in the presence of phosphorus oxychloride on refluxng or under microwave irradiation gave twenty four novel 3‐aryl‐6‐ (6‐/8‐substituted 4‐chloroquinoline‐3‐yl)‐s‐triazolo[3,4‐b]‐1, 3,4‐thiadiazoles (4a‐x), Considerable increase in the reaction rate has been observed with improved yields under microwave irradiation. The structures of the compounds synthesized were determined by elemental analyses, IR, ¹H NMR and MS spectra. Their spectral properties and the reaction mechanism were also discussed. The preliminary biological test showed that some of compounds bad moderate antibacterial activities.     

Design and Synthesis of Antimicrobial Active (E)‐(3‐(Substituted‐styryl)‐7H‐furo[2,3‐f]chromen‐2‐yl)(phenyl)methanone Derivatives and Their In Silico Molecular Docking Studies

Nine new (E)‐(3‐(substituted‐styryl)‐7H‐furo[2,3‐f]chromen‐2‐yl)(phenyl)methanone derivatives, 7 ( a – i ), with an efficient microwave‐assisted synthetic method was achieved by reacting with (E)‐3‐(aryl)‐1‐(5‐hydroxy‐2H‐chromen‐6‐yl)prop‐2‐en‐1‐ones and 2‐bromo‐1‐(4‐bromophenyl)ethanone. The microwave irradiation method was found to be best with high yields and with shorter reaction times compared with the conventional method. All the new products structural assignments were confirmed by spectral data like FTIR, ¹H NMR, ¹³C NMR, ESI MS, and analytical data. Moreover, these newly synthesized compounds were tested in vitro for their antimicrobial activity against various bacterial and fungal strains. Some of these new chromen derivatives like 7b , 7c , and 7d exhibits good antibacterial and antifungal activities. Furthermore, these biological evolution results were a good correlation with molecular docking studies performed based on their computational DFT minimized structures exhibited high binding energies.     

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,Dissociation Constants,and Antimicrobial Activity of Novel 2,3‐Disubstituted‐1,3‐thiazolidin‐4‐one Derivatives

In this article, a new series of 2,3‐disubstituted‐1,3‐thiazolidin‐4‐one derivatives have been designed, synthesized, and evaluated as antimicrobial agents. New compounds were prepared by the cyclization reaction of N‐substituted carboxylic acid hydrazide derivatives with mercaptoacetic acid. The structures of the obtained compounds were confirmed by means of IR, ¹H NMR, and ¹³C NMR spectra. The dissociation constants were determined using spectrophotometric method. All synthesized compounds were tested for their in vitro antibacterial and antifungal activities using the broth microdilution method.     

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 3‐(substituted)‐2,4,8,15‐tetroxa‐3‐phosphadispiro[5.2.5]hexadecane‐3‐oxides

Novel 3‐(substituted)‐2,4,8,15‐tetroxa‐3‐phosphadispiro[5.2.5]hexadecane‐3‐oxides (3‐12) have been synthesized by cyclization of 1,5‐dioxaspiro[5.5]undecande‐3,3‐dimethanol (1) with various substituted aryl phosphorus dichloridates (2) in dry toluene‐THF in the presence of triethylamine at 40‐60 ^oC. Their molecular structures were determined by ir, nmr and mass spectral studies and were screened for antifungal activity against Curvularia lunata and Aspergillus niger, and antibacterial activity on Staphylococcus aureus and Escherichia coli. Most of them possess significant activity.     

Design,Synthesis, and Biological Evaluation of Thieno[2,3‐c]pyrazole Hydrazide Derivatives as Potential Antimicrobial Agents

In search of new antimicrobial agents with enhanced potency, we have designed and synthesized three series of hydrazones with 3‐methyl‐1‐phenyl‐1H‐thieno[2,3‐c ]pyrazole‐5‐carbohydrazide. All the synthesized compounds have been screened for their in vitro antibacterial and antifungal activities by employing broth microdilution method. It is observed that compounds are more susceptible to Vibrio cholerae than other tested strains. In particular, compounds ( 3a ), ( 3c ), ( 5g ), and ( 5 h ) are highly potent against bacterial strain V. cholerae . The results suggest that hydrazones bearing two core pyrazole scaffolds would be potent antimicrobial agents.     

Synthesis and in vitro Biological Evaluation of Some Novel Triazole‐Based Heterocycles as Potential Antimicrobial Agents

A series of novel 6‐{5‐aryl‐4H‐1,2,4‐triazol‐3‐ylthio}methyl‐3‐substituted‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazoles and 2‐{(5‐aryl‐4H‐1,2,4‐triazol‐3‐ylthio)‐N‐4‐aryl}acetamides containing 1,2,4‐triazole moiety were synthesized and characterized by ¹H, ¹³C, DEPT, and D₂O. The synthesized compounds were evaluated for their antibacterial activity against three strains of bacteria along with antifungal activity against five fungal species. It has been found that tested compounds showed moderate activity.     

Synthesis of novel dipodal-benzimidazole,benzoxazole and benzothiazole from cyanuric chloride: Structural,photophysical and antimicrobial studies

In the present study, new benzimidazole, benzoxazole and benzothiazole derivatives were prepared and screened for antimicrobial activity. The structure of 4,4′-((6-(4-(diethylamino)phenyl)-1,3,5-triazine-2,4-diyl)bis(oxy))dibenzaldehyde (DIPOD) 5 was established from p-hydroxy benzaldehyde 4 and 4-(4,6-dichloro-1,3,5-triazin-2-yl)-N,N-diethylaniline 3. The reaction of DIPOD 5 with different o-phenylenediamine or o-amino phenol or o-amino thiophenol in ethanol gave benzimidazole, benzoxazole and benzothiazole 7. Novel heterocycles showed excellent broad-spectrum antimicrobial activity against bacterial strain (Escherichia coli, Staphylococcus aureus) and fungal strain (Candida albicans, Aspergillus niger) cultures. Activity data was compared with standard Streptomycin and Fluconazole drug. Photophysical and thermal properties of synthesized compounds were also studied.     

Facile access to 6‐substituted 1,4,5,7‐tetrahydropyrrolo[3,4‐b]‐pyridines via hantzsch type dimethyl 4‐aryl‐2‐formyl‐6‐methyl‐1,4‐dihydropyridine‐3,5‐dicarboxylates

Efficient assembly of 6‐substituted 4‐aryl‐5‐oxo‐1,4,5,7‐tetrahydropyrrolo[3,4‐b]pyridines (7a‐f) is described according to a Hantzsch type reaction from formyl‐ester 4 by imination, borohydride reduction and intramolecular thermal amino‐ester cyclization. The starting compound 4 was prepared in three steps from the readily available formyl derivative 1, methyl 4,4‐dimethoxy‐3‐oxobutanoate and methyl 3‐aminocrotonate.