• Bulletin of the Korean Chemical Society
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• v.34 no.8
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• pp.2297-2304
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• 2013

A series of novel benzimidazole derivatives bearing a heterocyclic ring as oxadiazole (21-32), thiadiazole (33-34), triazole (35-36) were synthesized and evaluated for their activities against Coxsackie virus B3 and B6 in Vero cells. Compounds 21-26, 31-36 with moieties of 2'-pyridyl, 3'-pyridyl and 4'-pyridyl at the 2-position and oxadiazoles, thiadiazole, or triazole substituent at the 4- or 5-position generally displayed activities against CVB3 and CVB6. Especially compound 24 ($IC_{50}=1.08{\mu}g/mL$, SI = 61.7 against CVB3) was the promising candidate as lead compound for anti-enteroviral drug. It was observed in the incorporation of heterocyclic rings in benzimidazole at the 5-position could enhance their biological activities.

• Journal of the Korean Chemical Society
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• v.64 no.1
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• pp.7-18
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• 2020

An efficient and facile procedure has been developed for the synthesis of novel bichalcone derivatives (4a, 4b). The key step contains the solvent-free aldol synthesis of bichalcones based on quinones. Bichalcones (4a, 4b) were used as precursors for the synthesis of some interesting heterocyclic compounds like, diazepines (5a, 5b), pyrazolo-pyrimidines (7a, 7b), and pyrazoline derivatives (8a, 8b). Moreover, new thioxopyrimidine derivatives (9a, 9b) were furnished and used as a functionalizing agent to produce the triazole-pyrimidines (11, 12) and the carbonitrile derivative (14). All the synthesized compounds were fully characterized using physical and spectral data like, FT-IR, ¹H NMR, ¹³C NMR, and MS. Bichalcones (4a, 4b) and diazepines (5a, 5b) were screened for their anticonvulsant activity, where compounds (4a, 5a, and 5b) revealed potent anticonvulsant activity compared to diazepam. On the other hand, some of the prepared compounds were screened for their antiproliferative activity and they showed significant cytotoxic effects on most of the cancer cell lines with regard to broad spectrum antitumor activity.

• Journal of the Korean Chemical Society
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• v.54 no.4
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• pp.414-418
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• 2010

Ethyl 1-aminotetrazole-5-carboxylate (1) reacted with hydrazine hydrate to give the corresponding aminohydrazide 2. Cyclization of 2 by carbon disulfide yielded 1,3,4-oxadiazole-5-thiol structure 3. Reaction of 3 with either chloroacetone or ethyl chloroacetate furnished S-acyl 1,3,4-oxadiazole derivatives 4 and 5, respectively. Also compound 3 reacted with hydrazine hydrate afforded 4-amino-1,2,4-triazole-5-thiol derivative 6. 6-Methyl-1,3,4-triazolo[3,4-b]-1,3,4-thiadiazole structure 7 was synthesized by reaction of aminothiol 6 with glacial acetic acid. Diazotization of 1 with sodium nitrite in presence of hydrochloric acid yielding the diazonium salt which on treating with hippuric acid, oxazolone derivative 8 was obtained. Furthermore, tetrazolo[5,1-f]-1,2,4-triazine 9 was constructed via cyclization of aminoester 1 with formamide. Compound 9 reacted with carbon disulfide to furnish 8-thione derivative 10 which reacting with chloroacetone, ethyl chloroacetate, and hydrazine hydrate, the corresponding chemical structures 11, 12, and 13 were synthesized. 1,2,4-Triazolo[4,3-d]tetrazolo[5,1-f]-1,2,4-triazines 14 and 15 were resulted by treating of compound 13 with triethyl orthoformate, and glacial acetic acid, respectively. The structures of the newly synthesized products were elucidated according to elemental analyses and spectroscopic evidences. Some of the representative members of the prepared compounds were screened for antimicrobial activity.

• Bulletin of the Korean Chemical Society
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• v.33 no.9
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• pp.2985-2990
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• 2012

New thiazoline derivatives 7a-c, and thiophenes 9a-c linked to indole moiety were easily prepared via the reaction of the acrylamide derivative 3 with phenacyl bromides 4a-c, depending on the reaction conditions. In addition, the reaction of compound 3 with hydrazonoyl chlorides 11a-f afforded a series of 1,3,4-thiadiazole derivatives 13a-f. Moreover, coupling of 3-(3-methyl-1H-indol-2-yl)-3-oxopropanenitrile (2) with the diazonium salts of 3-phenyl-5-aminopyrazole 16 or 3-amino-1,2,4-triazole 17 gave the corresponding hydrazones 18 and 19, respectively. Cyclization of the latter hydrazones yielded the corresponding pyrazolo[5,1-c]-1,2,4-triazine and 1,2,4-triazolo[5,1-c]-1,2,4-triazine derivatives 20 and 21, respectively. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, $^1H$ NMR and mass spectral data. All the synthesized compounds were tested for in vitro activities against certain strains of fungi such as Aspergillus niger, Aspergillus nodulans, Alternaria alternate. Compounds showed marked inhibition of fungal growth nearly equal to the standards.

• Bulletin of the Korean Chemical Society
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• v.32 no.1
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• pp.229-238
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• 2011

A series of novel glucose derived benzyl and alkyl 1,2,3-triazoles and their hydrochlorides have been synthesized via Cu(I)-catalyzed 1,3-dipolar cycloaddition. All the new compounds were characterized by MS, IR and NMR spectra. The DEPT, APT, $^1H$-$^1H$ and $^1H-^{13}C$ 2D NMR spectra for some compounds were also recorded. These compounds were evaluated for their in vitro antibacterial activities against Staphylococcus aureus ATCC 29213, Bacillus subtilis, Bacillus proteus, Pseudomonas aeruginosa, Escherichia coli ATCC 25922, and antifungal activities against Candida albicans and Aspergillus fumigatus. The bioactive data revealed that (3R,4S,5S,6S)-2-(hydroxymethyl)-6-methoxy-4,5-bis((1-octyl-1H-1,2,3-triazol-4-yl)methoxy)-tetrahydro-2H-pyran-3-ol 8a exhibited excellent antifungal activity against A. fumigatus with an MIC value of 0.055 mM compared to Fluconazole. It also showed broad inhibitory efficacy against tested bacterial strains with MIC values ranging from 0.049 mM to 0.39 mM.

• Bulletin of the Korean Chemical Society
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• v.33 no.12
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• pp.4180-4184
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• 2012

The target compounds 6-11a-e were synthesized by condensing 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones 5a-f with various aromatic carboxylic acids in the presence of phosphorous oxychloride. The structures of newly synthesized compounds were characterized by IR, $^1H$ NMR, $^{13}C$ NMR, elemental analysis and mass spectrometric studies. All the synthesized compounds were screened for their antibacterial activity. Almost all the tested compounds were potent against four different strains of bacteria when compared with that of reference drug ciprofloxacin. Compounds 6c, 6e, 8d, 9b, 9e, 11a and 11b showed nearly equal or lower MIC values than standard drug, against all four tested bacterial strains but rest of the compounds showed excellent antibacterial activities.

• Bulletin of the Korean Chemical Society
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• v.33 no.12
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• pp.3943-3949
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• 2012

A series of aromatic hydrazides 3a-j were prepared by refluxing esters 2a-j with hydrazine hydrate in methanol, which were prepared by the esterification of 1a-j. Acetohydrazides 3a-j upon treatment with carbon disulfide and methanolic potassium hydroxide yielded potassium dithiocarbazate salts 4a-j, which on refluxing with hydrazine hydrate yielded substituted 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones 5a-j. The target compounds 6a-j were synthesized by condensing furan-3-carboxylic acid in the presence of polyphosphoric acid under reflux. The structures of newly synthesized compounds were characterized by IR, $^1H$ NMR, $^{13}C$ NMR, elemental analysis and mass spectrometric studies. All the synthesized compounds were screened for their urease, acetylcholine esterase inhibition, antioxidant and alkaline phosphatase inhibition activity. Almost all of the compounds 6a-j showed good to excellent activities against urease and acetylcholine esterase more than the reference drugs. Compounds 6f and 6g were more potent scavenger of free radicals than the reference n-propyl gallate. Compound 6b and 6h showed excellent activities of alkaline phosphatase as compare to the reference $KH_2PO_4$.

• Bulletin of the Korean Chemical Society
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• v.33 no.12
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• pp.4074-4078
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• 2012

The first step in the common pathway for the biosynthesis of branched chain amino acids is catalyzed by acetohydroxyacid synthase (AHAS). The AHAS is found in plants, fungi and bacteria. With an aim to identify new anti-tuberculosis drugs that inhibit branched chain amino acid biosynthesis, we screened a chemical library against Mycobacterium tuberculosis AHAS. The screening identified four compounds, AVS 2087, AVS 2093, AVS 2236, and AVS 2387 with $IC_{50}$ values of 0.28, 0.21, 3.88, and $0.25{\mu}M$, respectively. Moreover, these four compounds also showed strong inhibition against reconstituted AHAS with $IC_{50}$ values of 0.37, 0.26, 1.0, and $1.18{\mu}M$, respectively. The basic scaffold of the AVS group consists of 1-pyrimidin-2-yl-1H-[1,2,4]-triazole-3-sulfonamide. The most active compound, AVS 2387, showed the lowest total interaction energy -8.75 Kcal/mol and illustrates its binding mode by hydrogen bonding with $H_{\varepsilon}$ of Gln517 with the distance of $2.24{\AA}$.

• Bulletin of the Korean Chemical Society
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• v.31 no.12
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• pp.3684-3692
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• 2010

A series of azole-containing piperazine derivatives have been designed and synthesized. The obtained compounds were investigated in vitro for their antibacterial, antifungal and cytotoxic activities. The preliminary results showed that most compounds exhibited moderate to significant antibacterial and antifungal activities in vitro. 1-(4-((4-chlorophenyl) (phenyl)methyl)piperazin-1-yl)-2-(1H-imidazol-1-yl)ethanone and 1-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1-yl)-2-(2-phenyl-1H-imidazol-1-yl)ethanone gave remarkable and broad-spectrum antimicrobial efficacy against all tested strains with MIC values ranging from 3.1 to $25\;{\mu}g/mL$, and exhibited comparable activities to the standard drugs chloramphenicol and fluconazole in clinic. Moreover, 2-((4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)methyl)-1H-benzo[d]imidazole was found to be the most effective in vitro against the PC-3 cell line, reaching growth inhibition values (36.4, 60.1 and 76.5%) for each tested concentration: $25\;{\mu}g/mL$, $50\;{\mu}g/mL$ and $100\;{\mu}g/mL$ in dose-dependent manner. The results also showed that the azole ring had noticeable effect on their antimicrobial and cytotoxic activities, and imidazole and benzimidazole moiety were much more favourable to biological activity than 1,2,4-triazole.

• Bulletin of the Korean Chemical Society
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• v.26 no.5
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• pp.719-728
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• 2005

A novel 2-amino-4-(8-quinolinol-5-yl)-1- (p-tolyl)-pyrrole-3-cabonitrile (2) was obtained by the reaction of 2-[2-bromo-1-(8-hydroxyquinolin-5-yl)-ethylidene]-malononitrile (1) with p-toluidene. The new synthon compound (2) could be annelated to the corresponding pyrrolo[2,3-d]pyrimidines (4, 6, 7, 26-28), triazolo[1,5-c]pyrrolo[3,2-e]pyrimidines (10, 29, 30), pyrrolo[2,3-c]pyrazoles (11-15), pyrrolo[1,2-a]pyrrolo[3,2-e] pyrimidine (17) and imidazo[1,2-c]pyrrolo[3,2-e]pyrimidines (18-25) via the reaction with some reagents such as acetic anhydride, formamide, triethyl orthoformate, hydrazine hydrate, hydroxylamine, ethylenediamine, carbon disulfide and phosphorus oxychloride. Chemical and spectroscopic evidences for the structures of these compounds are presented. The antifungal and antibacterial activity of the newly synthesized comounds were evaluated.