Anti-Helicobacter pylori activity and structure-activity relationship study of 2-alkylthio-5-[nitroaryl]-1,3,4-thiadiazole derivatives

Nitro-containing heteroaromatic derivatives structurally related to nitroimidazole [Metronidazole] are being extensively evaluated against Helicobacter pylori isolates. On the other hand, 1,3,4-thiadiazole derivatives have also demonstrated promising antibacterial potential. In present study, we evaluated anti-H. pylori activity of novel hybrid molecules bearing nitroaryl and 1,3,4-thiadiazole moieties. Anti-H. pylori activity of novel 5-[5-nitroaryl]-1,3,4-thiadiazole derivatives bearing different bulky alkylthio side chains at C-2 position of thiadiazole ring, were assessed against three different metronidazole resistant H. pylori isolates by paper disk diffusion method. Most of the compounds demonstrated moderate to strong inhibitory response especially at 25 micro g/disk. The structure-activity relationship study of the compounds demonstrated that introduction of different alkylthio moieties at C-2 position of thiadiazole ring alter the inhibitory activity which is mainly dependent on the type of C-5 attached nitrohetercyclic ring. The promising compound of this scaffold, bearing 1-methyl-5-nitroimidazole moiety at C-5 and alpha -methylbenzylthio side chain at C-2 position of thiadiazole ring, showed strong inhibitory response against metronidazole resistant H. pyloriisolates at 12.5 micro g/disk [the inhibition zone diameter at all evaluated concentrations [12.5-100 micro g/disk] is > 50 mm]. Novel 5-[5-nitroaryl]-1,3,4-thiadiazole scaffold bearing different C-2 attached thio-pendant moieties with promising anti-H. pylori potential were identified. Among different nitroheterocycles, 5-nitrofuran and 5-nitroimidazole moieties were preferable for the substitution at C-5 position of 1,3,4-thiadiazole ring. Introduction of different alkylthio side chains at C-2 position of central ring alter the inhibitory activity which is mainly dependent on the type of C-5 attached nitrohetercyclic ring

Microwave mediated facile synthesis of some novel pyridine, pyrimidine, pyrazole, pyrazolo [1,5-a] pyrimidine and triazolo[1,5-a]pyrimidine pendant to pyrrole

The synthetic potency of E-3-[dimethylamino]-1-[1H-pyrrol-2-yl]prop-2-en-1-one towards some nitrogen nucleophiles was investigated under microwave irradiations as a convenient route for the synthesis of some novel pyridine, pyrimidine, pyrazole, pyrazolo [1,5-a] pyrimidine and Triazolo[1,5-a] pyrimidine derivatives

Heterocycles from 2-Amino-4-[3,4,5-trimethoxy-phenyl]-Naphtho[2,1-b]-4H-pyran-3-carbonitrile

The TITLE compound 1 was prepared and subjected to react with different electrophilic reagents such as phenyl isothiocyanate, benzoyl chloride, 2-cyanocinnamonitrile, ethoxymethylenediethyl- malonate, formamide and carbon disulphide to give the naphtha-pyranopyrimidine derivative 3, naphtha [2,1-b]-4H-pyran derivative 7-9, naphtha [2,1-b]-4H-pyranopyrimidine 10 and naphtha [2,1-b]-4H-pyrano-1,3-thiazine derivative 11, respectively. Treatment of 3 with ethyl bromoacetate and hydrazine hydrate afforded 4 and 5. The hydrazine derivative 5 reacted with benzoylacetone and yielded the pyrazole derivative 6. The IR, [1]H-NMR and Mass spectra of the synthesized compounds were discussed

Synthesis of thiaphosphetane, thiadiphosphetane and thiazadiphosphetidine derivatives from the reaction of phosphacumulenes, phosphallene and phosphinimine with Lawesson's reagent

The active phosphacumulene ylides namely, N-phenylimino-[2], 2-oxo- [4] or 2-thioxo-vinylidenetriphenylphosphorane [6] are nucleophilic reagents which can be considered as versatile synthons for the synthesis of new heterocycles. They react with Lawesson's reagent [1] to give the corresponding thiaphosphetane derivatives 3, 5 and 7 respectively, which constitute an important class of heterocyclic compounds with medicinal and biological importance. On the other hand, Lawesson's reagent [1] can be converted by reaction with the active heteroallylic phosphonium ylide, hexaphenylcarbodiphosphorane [8], into the thiadiphosphetane 9. When the phosphinimine 10 reacts with Lawesson's reagent [1], the thiazadiphosphetidine 11 was obtained

reaction of substituted pyrazolin-5-ones with het-arylidene-malononitriles

3-Methyl-L-phenylpyrazolin-5-one 1a reacts with the heterocyclic arylidenes 2a,b to afford the pyrano[2,3-c] pyrazole derivatives 3a,b and/or the acyclic adducts 4a,b depending on the reaction conditions. l,3-Diphenylpyrazolin-5-one 1b reacts with 2a,b to afford the oxinobispyrazole derivatives 5a,b along with pyrano[2,3-c] pyrazole derivatives 6a,b when the reaction was catalyzed by piperidine, while the pyrano[2,3-c]pyrazole derivatives 6a,b were only obtained when the reaction was catalyzed by sodium ethoxide. 3-Methyl and 3-phenylpyrazolin-5-ones 1c,d react with 2a,b to afford solely the pyrano [2,3-c] pyrazole derivatives 9a-d. A plausible mechanism is presented to account for these results

6- [2-furylvinyl] -1,2,4- triazinone derivatives as a source of polyfunctional mono- and biheterocycles

Reaction of 6-[2-furylvinyl]-3-thioxo- 2,3,4,5- tetrahydro-1,2,4-triazin-5-one [1] with chloroacetone gave acetonylthiotriazinone derivative [2] and thiazolotriazinone [3]. 2,4-Bis- [2-furoyl]-6-[2-furyl-vinyl] triazinone [4], 3-amino-thiazolotriazinone [5] were prepared by reaction of 1 with furoyl chloride, dibromoacetonitrile, separately. Also, compound 1 was reacted with formaldehyde to give 6 and 7. Methylthiotriazinone [8] was prepared, thereafter transferred into the hydrazinotriazinone [9]. Compound 9 was reacted with aromatic aldehydes and formic acid to give dihydrotriazolotriazinones [10a,b] and triazolo -triazineone [11], respectively. Moreover, when compound 9 was refluxed with acetic anhydride, tetrabromophthalic anhydride, the products were N, N-diacetyl triazinyl acetate [12] and triazinyltetrabromo phthalazindione [13], respectively

Heterocyclic synthesis with biologically active S-[6-aryl pyridazin 3-yl] thioglycollic acid hydrazides

A number of S-[6-ary1pyridazin-3-yl] thioglycollic acid hydrazides [Ia-c] and thiosemicarbazide derivatives IIa-c have been prepared. 6-Arylpyridazin-3-mercaptomethenyl[4-phenyl--l,2,4-triazolo-5-thiones] [IIIa-c]; 6-arylpyridazin-3-mercaptometheny]-[4-phenyl-l,2,4-triazolo-5-mercaptomethyl ether [IVa]; 6-aryl pyridazin-3-mercaptomethyl-[4-phenyl-I,2,4-triazolo-5-mercaptocyanoethyl] [IVb] and the Mannich bases Va-c have been synthesized from III. The 6-arylpyridazin-3-mercaptomethenyl [5-aminophenyl-l,3-4-thiadiazolines] [VIa-c] and the corresponding 1,3-4-oxadiazoline derivative VII have been synthesized from the phenyl-thiosemicarbazide derivatives IIa-c. The antibacterial activity of the prepared compounds has been screened

Reaction of cyanoacetamide with benzoyl isothiocyanate: synthesis of pyridine, pyrido [2,1-a] 1,2,3-triazine, pyrazolo[3,4-d] 1,2,3-triazine and thiazole derivatives

The reaction of cyanocetamide [1] with benzoyl isothiocyanate [2] gave the thiourea derivative 3. The reactivity both of the methylene group as well as the thiourea moiety in the latter product was studied to afford pyridine, pyrido[2,1-a] 1, 2, 3-triazine, pyrazolo [3,4-d] 1, 2, 3-triazine and thiazole derivatives.

Estudos visando a síntese da macrosfelida (+)-A e síntese de anéis diidropirrólicos / Macrosfelide (+)-A and dihydropyrrol rings synthesis study

A primeira etapa deste trabalho refere-se à síntese da macrosfelida (+)-A, produto natural isolado da cultura de fungos Microsphaeropsis sp. FO5050, pertencente a uma classe de compostos que apresentam atividade antineoplásica. Para isso, foram utilizados sulfóxidos quirais, como indutores diastereosseletivos na síntese dos dois fragmentos propostos, A e B. A segunda parte deste trabalho refere-se a reações de ciclofuncionalização, utilizando iodo como eletrófilo. Na primeira etapa foram sintetizados compostos...

Activated nitriles in heterocyclic synthesis: synthesis of substituted pyrazolopyridine, pyridine, 4H-pyran and naphthodiapyran derivatives

Several new pyrazolopyridines VIa-c were synthesized by reacting 4-nitrosoantipyrine [IIa] with arylidenemalononitriles Ia-c or ethyl arylidenecyanoacetates If-h. Reaction of Ia-c with 4-[azidomethylcarbonyl] antipyrine [IIb] afforded the pyridine derivatives XVI. The 4H-pyrans and naphthodipyran derivatives XVIII- XXI were prepared by reacting I with polyhydric phenols

Synthesis of some new coumarin derivatives incorporated to heterocyclie aromatic rings

3-bromo-4-methyl-7-coumarinyloxy acetic acid hydrazide was condensed with some aromatic aldehydes to give Schiff's bases 5 a-e which cyclized to thiazolidine derivatives 6a-e. Also, 7-O-[N-[succinimido] acetamido]-and 7-O-[[2-oxy-3-indolinylidene] acetic acid hydrazido]-3-bromo-4-methyl coumarins [3] and [4] were prepared. 7-O-[N-[sulfa drug] carbonyl methoxy]-3-bromo-4-methylcoumarin derivatives 10a-f were prepared via the formation of the acid chloride 9. Some of the new coumarin derivatives showed satisfactory results as molluscicidal activity against Biomphalaria alexandrina snails

Heterocyclic synthesis with nitriles: synthesis of some novel furo [2,3-b] nicotinic acid derivatives of anticipated biological activity

2-Amino-5-phenylfuran-3-carbonitrile 2 reacts with malonic acid derivatives 3a-d and 6 to afford the furo [2, 3-b] pyridine derivatives 5a-c. Compounds 2 reacts with urea and thiourea to afford the pyrrole derivative 10 which was also obtained from 2 and ammonium acetate. The reaction of 2 with the arylidene derivatives 11a-f yield the furo [2, 3-b] nicotinonitrile derivatives 13a, c, e; which were hydrolyzed to the nicotinic acid derivatives 14a, c, e, respectively. Compound 2 reacts also with the acrylic acid derivatively 15a-c to afford the furo [2, 3-b] nicotinic acid derivatives 17a-c, which were hydrolyzed to give the furo [2, 3-b] nicotinic acid 18. Compounds 5b, c undergo S-or N-alkylation on reaction with phenacyl bromide 19a and ethyl bromoacetate 19b to yield compounds 20a-d, respectively. Compound 5b reacts with hydrazine hydrate to afford the hydrazino derivative 22 which could be cyclized into the furopyridopyrazole derivative 23. Compound 5b reacts also with I2/Kl in DMF to afford the disulphide 24

Metal chelates of 3-amino-2-substituted crotononitrile

Synthetic heterocyclic organic chemistry involves specially designed reagents which are readily generated and then used to provide molecules built-in functional moieties usually utilized several applications. Important examples of such reagents are Beta-amino crotononitrile which have been proven to be valuable in the synthesis of a wide variety of unique heterocyclic systems such as pharmaceuticals, fungicides and solvatochromatic dyes [1-4]. It is known that metal complexes have greater activity than the coordinating agents themselves [5]. Synthesis and characterization of solid complexes of several transition metal cations were the primary concern of our earlier work [6-15]. However, it seems that no studies have been made on the complexes of compound [I] in the solution phase or in the solid state, which will be investigated in the present study. Conductometric, spectrophotometric measurements are used for characterization of some of these complexes as well as elemental analysis, magnetic measurements and spectral [electronic, IR] studies. The mechanism of the chelation process will also be investigated for each of the different ions used

On the rearrangement of dehydro-l-ascorbic acid 2-p-mitcphenyl hydmzene to nitrogen heteiocyeles

The 3-hydroxyiminomethylpyrazole derivative II existed in keto-enol as evidenced by production of two acetyl derivatives IV and V, respectively. The enol form III gave the benzoyl derivative VI. Similarly, the 3-formylhydranone derivative VII gave the acetyl derivative IX. Condensation of VII with o- and m-nitrobenzaldehyde gave the benzylidene derivatives X and XI, respectively. The thiosemicarbazone XII also existed in the keto-enol forms. Both gave the acetyl bicyclic derivatives XIV and XV upon acetylation, and the enol form XIII gave the benzoyl derivative XVI. The 2-p- nitrophenylhydrazone 3-oxime XVII gave the triazole derivative XVIII upon oxidation with cupric chloride. The 2-p-nitrophenylhydrazone 3- oxime XVII gave the triazole derivative XVIII, which yielded the acetyl derivative XIX. Mild acetylation of XVII with AcOH gave the monoacetyl derivative XX which upon acetylation with Ac2O gave the triacetyl derivative XXI

Benzylidenation of l-threo and d-erythro-trihydroxybutylquinoxalinones and a dehydrative heterocyclization of the glycerolyl residue during the reaction

The regioselective formation of alpha-terminal 1,3-dioxolanes via the benzylidenation of 3-[1-[arylhydrazono]-L-threo and D-erythro-2,3,4- trihydroxy-1-oxobutyl] quinoxalin-2-ones has been studied. The role of configuration of the glycerolyl part in the formation and location of dioxolane rings was discussed. A competing dehydrative cyclization process was found to occur during the benzylidenation to give 3-[5-[hydroxymethyl]-1-[aryl] pyrazol-3-yl] quinoxalin-2-ones