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Microwave-assisted synthesis and spectral analysis of certain novel derivatives of 3,4-diaminothieno[2,3

The current study aims to investigate the therapeutic potential of bone marrow-derived mesenchymal stem cells (MSCs) as a solo therapy in ameliorating both skin lesions and liver injury induced by cutaneous severe burn injury (SBI) in rats.In anesthetized male adult Wistar albino rats, 30 % total burn surface area and established hepatic injury was achieved via direct contact of each experimental animal's dorsum with heated metal rod (100 °C) for 10 s. On the next day following burn, human MSCs or mouse MSCs was administered locally around the burn site and intraperitonially (0.5 × 10Both types of MSCs significantly improved skin and liver histology, decreased liver enzymes, and ameliorated oxidative stress in hepatocytes of SBI-rats. Further, SBI-induced rises in hepatic apoptotic marker (caspase-3, Bax) and serum inflammatory markers (TNF-α, IL-1β, and IL-6) were reduced following either human or mouse MSC administration. In addition, MSCs augmented insulin receptor substrate-1, phosphorylated protein kinase-B (phospho-Akt), while alleviating serum glucose levels in SBI-rats. These previous effects persisted even at the 14-day time point.Following single administration, bone marrow-derived MSCs is capable of counteracting SBI-induced skin lesions as well as related hepatic complications, specifically via mitigating postburn hyperglycemia and hyperinflammation.

Comparison of the absorption spectra of the ethanolic solution (3 ppm) of some diethyl 3,4-diaminothieno[2,3-b]thiophene-2,5-dicarboxylate (TT amino ester) derivatives has revealed that the azo dye derivative compound 4 manifests smaller band gap and higher absorption maximum close to solar maximum wavelength. Very good adhesive thin films to glass substrates of the azo dye compound 4 have been successfully prepared by thermal evaporation technique. The optical spectral analysis of such compound film revealed three absorption transitions corresponding to the optical gap, the electron transition between impurity levels in band gap and the fundamental band gap (HOMO to LUMO π→π* transitions). Absorption, dielectric and dispersion parameters have been determined for as- deposited and gas treated films and discussed. This film manifested a fast response and high sensitivity toward iodine vapor with a reasonable recovery time indicating a reversibility of iodine adsorption process. In contrast, the film illustrated slow response and weak sensitivity toward HCl gas with irreversible adsorption process. Besides, the azo dye compound 4 solution manifests strong emissive properties that recommend it as promising candidate for fluorescence sensors.

The study aimed to investigate the potential nephroprotective effects of vitamin D3 in metabolic syndrome (MetS) and the molecular basis of the underlying mechanisms of its action.MetS was induced in adult male Wistar rat‏s by adding fructose (10%) to every day drinking water and salt (3%) to the diet. Six weeks after fructose/salt consumption, fasting serum lipid profile and uric acid levels were determined, an oral glucose tolerance test (OGTT) was performed and kidney function was checked. MetS rats were then treated orally with vitamin D3 (10 µg/kg/day) for 6 weeks. At the end of the study period (12 weeks), the OGTT test was reperformed, anthropometrical parameters were measured, urine, blood and tissue samples were collected and the animals were euthanised.The incidence of MetS was confirmed 6 weeks after fructose/salt consumption, when the rats exhibited significant weight gain, dyslipidemia, hyperuricemia, insulin resistance, hyperinsulinemia and impaired glucose tolerance. After 12 weeks, MetS rats displayed markedly declined renal function alongside with extravagant renal histopathological damages and interstitial fibrosis. Furthermore, significantly enhanced renal oxidative stress and inflammation were manifested. Vitamin D3 supplementation in MetS rats significantly reversed all the above-mentioned deleterious effects.The study has indeed provided mounting evidence of the promising therapeutic potential of vitamin D3 against development and progression of MetS-induced nephropathy. A new insight has been introduced into the crucial role of dipeptidyl peptidase-4 inhibition and sirtuin-1/5'adenosine monophosphate-activated protein kinase activation in the renoprotective effects of vitamin D3.

Under phase transfer catalysis conditions, 6-amino-4-phenyl-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitrile (1) was allowed to react with halo compounds, acrylonitrile, chloroacetyl chloride, ethyl cyanoacetate, formamide, triethylorthoformate, or formic acid to give new derivatives of fused pyridines 2–22, respectively. Acetylation of compound 1 using acetic anhydride afforded product 23, which in turn underwent intramolecular cyclization in pyridine to give the corresponding pyrido[2,3-d]pyrimidine 24.

Reaction of dicyandiamide with series of amino acids afforded guanidinyl pyrazolones , respectively. Although reaction of dicyandiamide with urea, acetamide, bezamide, allantion, p-aminobenzoic acid, sulphanilic acid, and adenine gave biguanides , respectively. All compounds have been characterized on the basis of IR and 1H-NMR.

5-Amino-3-anilino-1H-pyrazole-4-carbonitrile 1 was alkylated with various halo reagents under phase transfer conditions to give the corresponding imidazopyrazole derivatives 2a, 2b, 2c, 3, 4, 5, 6. Pyrazolo[1,5-a] pyrimidine derivatives 11, 12, 13, 14 were prepared by treating compound 1 with different dicarbonyl reagents, namely, diethymalonate, ethyl 3-oxo-3-phenylpropanoate, pentane-2,4-dione or ethyl 3-oxobutanoate.

The biologically active compounds of pyrimidine, dihydropyrimidinone, and dihydroimidazole have been synthesized in excellent yield under free solvent conditions. The antibacterial evaluation of the products showed a high inhibitory effect. Reaction of 2-guanidinobenzothiazole with several active methylene compounds has revealed formation of the corresponding pyrimidine, dihydropyrimidinone, and dihydroimidazole derivatives under free solvent conditions in very good yield. All compounds have been characterized on the basis of IR, 1H NMR, 13C NMR, mass spectrometry, and X-ray.

The reaction of 4-oxo-3,4-dihydroquinazolinyl-2-guanidine 1 with several active methylene compounds has revealed formation of the corresponding hydropyrimidine and dihydropyrimidnone (DHPMs) derivatives via cycloaddition reaction mechanism. Satisfactory results were obtained with good yields, short time, and simplicity in the experimental procedure. Reaction with ketones in DMF proceeded via (5+1) heterocyclization and resulted in the formation of 2-amino-4-(het)aryl-4,6-dihydro-1(3)(11)H-[1,3,5]triazino[2,1-b]quinazolin-6-ones 8, 9, 10, 11, 12, 13, respectively. All compounds have been characterized based on IR, 1H-NMR, and mass spectrum.

A novel synthesis of pyrazolopyrimidine derivatives was reported wherein 5-amino-1-benzoyl-3-(methylthio)-1H-pyrazole-4-carbonitrile was treated with formic acid, formamide, thioacetamide, carbon disulfide, and phenylisocyanate and phenylisothiocyanate.

3‐Oxime‐4‐phenyl‐1(H)(l,5)benzodiazepin‐2‐one 2 was prepared and treated with malononitrile, arylidenenitriles, and bidentates to give the corresponding spiro‐3,3′‐isoxazolo‐, thiadiazino‐, and triazino‐1,5‐benzodiazepines 3–7. 3‐Bromo‐3‐cyano‐4‐phenyl‐l(H)(l,5)benzodiazepin‐2‐one 9a and 3‐bromo‐3‐cyano‐4‐(4′‐bromophenyl)‐1(H)(l,5)benzodiazepin‐2‐one 9b were synthesized via the bromination of 3‐cyano‐4‐phenyl‐1(H)(l,5)benzodiazepin‐2‐one 8. Compounds 9a,b were reacted with bidentates or cyclopentanone to afford spiro piprazine, quinoxaline, thiazine, thiadiazine, imidazole, and cyclopentafuran derivatives 10–16. Treatment of compound 1 with p‐tolyldiazonium chloride gave 3‐(p‐tolylazo)‐4‐phenyl‐1(H)(1,5)‐benzodiazepin‐2‐one 17, which in turn treated with nitriles, cyclopentanone, and S,S‐acetal derivative to give the corresponding spiro pyrazole, cyclopentapyrazole, and thiadiazole derivatives 18–21.

3-cyano-1,11-dihydro-4,5-diphenyl-2-thioxopyrido[2,3-b](1,5)benzodiazepine 2 and 3-(2′-cyano-1′-phenyl-2′-ethanethiocarboxamide)-4-phenyl-1(H)(1,5)benzodiazepin2-one 3 were prepared via the reaction of 1,3-dihydro-4-phenyl-(1,5)benzodiazepin-2-one 1 with benzylidenecyanothioacetamide. Compound 2 was treated with halo compounds to give the corresponding S-alkylated compounds 4 a−c, which underwent as intramolecular ring closure to thieno[3,2.5,6]pyrido[2,3-b](1,5)benzodiazepines 5 a−c under PTC conditions. One-pot syntheis of compounds 5 a−c was achieved via the reaction of compound 2 with the appropriate halo compound under PTC conditions. Compound 1 and 1-ethyl-4-phenyl-(1,5)benzodiazepin-2-one 9 were treated with carbon disulfide or phenylisothiocyanate and active nitriles to afford 4-thioxothiopyrano[4,3-b](1,5)benzodiazepines 8 and 10–14. Treatment of compound 10 with phenylisothiocyanate or acetic anhydride yielded oxazino-and pyrimido[4,5-b]thiopyrano-[4′,3′-b′](1,5)benzodiazepine 15 and 17. The rea...

5-Amino-3-anilino-1H-pyrazole-4-carbonitrile 1 was alkylated with various halo reagents under phase transfer conditions to give the corresponding imidazopyrazole derivatives 2a, 2b, 2c, 3, 4, 5, 6. Pyrazolo[1,5-a] pyrimidine derivatives 11, 12, 13, 14 were prepared by treating compound 1 with different dicarbonyl reagents, namely, diethymalonate, ethyl 3-oxo-3-phenylpropanoate, pentane-2,4-dione or ethyl 3-oxobutanoate.

Reaction of dicyandiamide with series of amino acids afforded guanidinyl pyrazolones , respectively. Although reaction of dicyandiamide with urea, acetamide, bezamide, allantion, p-aminobenzoic acid, sulphanilic acid, and adenine gave biguanides , respectively. All compounds have been characterized on the basis of IR and 1H-NMR.

[1,3-Dihydro-4-phenyl(1,5)benzodiazepin-2-ylidene]malononitrile 1 a was treated with formaline and some different primary amines to give the corresponding pyrimido(1,5)benzodiazepines 2 a - d . Treatment of compound 1 a with halo reagents yielded the corresponding pyrrolobenzodiazepines 3 a , b . The reaction of compound 1 a with active methylenes, bidentates, S,S- and N,S-acetals afforded the corresponding spiro(1,5)-benzodiazepines 4 a - c -8 a , b , respectively.

3,4-Diamino-2,5-dicarbethoxythieno[2,3-b]thiophene ( 1 ) was allowed to react with NaNO 2 and active methylenes to afford the corresponding azo compounds 2a-c . Hydrazonyl chloride 2a was treated with carbon disulfide, phenyl isothiocyanate, benzonitrile, benzyl cyanide, malononitrile, benzalaniline, ethyl mercaptoacetate, and ethyl glycinate to give 1,3,4-thiadiazolyl-, s-triazolyl-, 1,3,4-thiadiazinyl-, 1,3,4-triazinylthieno[2,3-b]thiophenes 3-6 respectively. The reaction of 2b,c with urea, thiourea, and guanidine afforded pyrimidinyl- and thiazinylazothieno [2,3-b]thiophenes 7-10 respectively. Bithiazolylthieno[2,3-b]thiophenes 11 and 13 were synthesized by treating compound 1 with CS 2 along with halo compounds. The addition of S,S-, N,S-, and N,O-acetals to the Schiff base 14 afforded compounds 15-17 respectively.

Compounds (IIIa), (VII), (XI), and (XV) have the highest antibacterial activity of the presented compounds.

The reaction of 4-oxo-3,4-dihydroquinazolinyl-2-guanidine 1 with several active methylene compounds has revealed formation of the corresponding hydropyrimidine and dihydropyrimidnone (DHPMs) derivatives via cycloaddition reaction mechanism. Satisfactory results were obtained with good yields, short time, and simplicity in the experimental procedure. Reaction with ketones in DMF proceeded via (5+1) heterocyclization and resulted in the formation of 2-amino-4-(het)aryl-4,6-dihydro-1(3)(11)H-[1,3,5]triazino[2,1-b]quinazolin-6-ones 8, 9, 10, 11, 12, 13, respectively. All compounds have been characterized based on IR, 1H-NMR, and mass spectrum.

1,3-Dihydro-4-phenyl-1,5-benzodiazepin-2-one 1 was treated with bromine in 1:1 molar ratio to get the corresponding 3-bromo derivative 2 which in turn reacted with different nucleophiles to get the corresponding 3-substituted derivatives 3–11. The cyclized compounds 4a , 5a , 7a,b , and 9a–c were achieved on refluxing compounds 4, 5, 6a,b , or 8 a–c respectively in diphenyl ether. Compound 1 was benzoylated with benzoyl chloride to give the corresponding 1-benzoyl derivative 12 which reacted with bromine in 1:2 molar ratio to yield the corresponding 3,3-dibromo derivative 13. Spiro benzodiazepines 14a–d–16 were obtained by reacting compound 13 with the proper bidentates. Compound 1 was treated with formaldehyde and secondary amines or thiols to give Mannich bases or sulphides 17–21, respectively.

A new series of tetrahydronaphthalene, isothiachromene, isochromene and isoquinoline derivatives were synthesized by reacting cyclohexylidenemalononitrile with active nitriles, active halo compounds, carbon disulfide, aldehydes, isothiocyanates and isocyanates, respectively.

3,4-Diamino-2,5-dicarbethoxythieno(2.3-b)thiophene 1 reacted with malononitrile or ethyl cyanoacetate to afford bis(thienopyrimidin-4-one) derivatives 2a.b The reaction of compound 1 with o-aminothiophenol, o-aminophenol or o-phenylenediamine gave benzothiazolyl-, benzoxazolyl-, benzoimidazolylthienothiophene 3a-c, Chloroacetylation of compound 1 and reacting the resulting compound 4 with malononitrile furnished thienopyrolopyrimidine 6. Fusion of compound 1 with formamide yielded bis(thienopyrimidine) 7 which reacted with POCI3/PCl5 to yield the corresponding chloro derivative 8 which was converted into the corresponding hydrazine derivative 9. Treatment of compound 1 with CS2, NaOH and 1,2 dibromoethane produced the corresponding 1.3 dithiolane 11 which also treated with chloroacetyl chloride or ethyl mercaptoacetate to get the corresponding β-lactame 12 or thiazolidinone 13. On reacting compound 1 with CS2, NaOH and (CH3)2S04 produced the corresponding bi(dithiocarbamate methyl ester) 14 which...

The reaction of 3-hydroxy-3(2-oxocyclohexyl)indolin-2-one 1 with some active methylene, bidentates, phenylisocyanate, phenylisothiocyanate, carbon disulfide, benzaldehyde, ketoketene S,S-acetal, cyanoketene S,S-acetal, active halo compounds or benzylidenemalononitrile affords a series of new spiro heterocyclic systems.

3,4-Diamino-2,5-dicarbethoxythieno(2,3b)thiophene (1) was reacted with triethylonhoformate to afford compound 2. The reaction of compounds 2 or 3 with S,S-acetals and N,S-acetals, afforded compounds 4–6. Treatment of compound 1 with 2,5-dimethoxytetrahydrofuran gave the corresponding bipyrrolyl derivative 7, which was reacted with hydrazine hydrate to get the corresponding hydrazide derivative 8. Treating compound 8 with sodium nitrite afforded the corresponding carboazide derivative 9, which in turn cyclized to compound 10. Compound 12 was obtained via the reaction of compound 1 with PhNCS or through treating compound 11 with CS2 PhNH2, and KOH. Also, compound 13 was prepared through treatment of compound 12 with Lawesson's reagent or via the reaction of compound 11 with CS, followed by treating the resulting compound 14 with PhNH2. The reaction of compounds 1 or 3 with Lawesson's reagent gave compound 15. Benzoylation of compound 1 afforded compound 16, which treated with NH3 gave compound 17. ...

2,3-Dimercaptoquinoxaline 1 was allowed to react with some dihalo compounds and chloroanil using PTC technique to afford the corresponding polyfused quinoxalines 2a-d. The reaction of compound 1 with different monohalo compounds under the same PTC conditions or in refluxing ethanol in presence of piperidine catalyst gave (1,4)dithiino-, thieno-, (1,4)thiazino-, and pyrroloquinoxalines 3a-5b. The addition of compound 1 to α,β-unsaturated nitriles was investigated to give the corresponding (1,5)dithiapinoquinoxalines 6a-7b and thiapinoquinoxalines 8a,b. The treatment of compound 1 with active nitriles furnished the corresponding thienoquinoxalines 9a-c and pyridazinoquinoxaline 10.

A new series of pyrano, oxazino, triazolo, oxazolo, furano, and 3-substituted(1,5)benzodiazepines were obtained from thereaction of lH(alkyl)-2,3-dihydro-4-methyl-1,5-benzodiazepin-2-ones with the proper reagents.

5,5-Dibronio-3-phenyl-2-thioxo-4-thiazolidinone 2, was reacted with bidentates, or with CS2 and active methylenes under FTC conditions to afford the corresponding spiro compounds 4a-h or 5a-e. 5-ethoxymethylene-3-phenyl-2-thioxo-4-thiazolidinone 3 was treated with diamino or aminomercapto compounds to give the desired products 6a-d. Treatment of compound 3 with malononitrile gave compound 7. Reaction of compound 7 with some active methylenes affords the corresponding spiro cyclopentenes 8a-c.

Novel heterocyclic compounds were prepared by the reaction of 2-acetyl-2-oxopropylidene s,s-acetal with different amino compounds namely, hydrazine hydrate, phenylhydrazine, guanidine hydrochloride, thiosemicarbazide, o-phenylenediamine, o-aminophenol or o-amino-thiophenol in different molar ratios.

The reaction of anilinomethylenemalononitrile 1 or 1,4-di (malononitrilemethyleneamino) benzene 7 with some reactive halo compounds in a one-pot reaction under PTC conditions affords a new series of pyrrole and pyridinone compounds. The reaction of compounds 1 or 7 with ethyl chloroformate gives the corresponding esters which underwent cyclization on reaction with different amino compounds affording the pyrimidinone derivatives.

Reaction of aminopyrazolecarbonitrile (I) with formic acid, formamide, thioacetamide, carbon disulfide and iso(thio)cyanates provides access to a variety of pyrazolo-fused pyrimidines.

A variety of new dihydroimidazole and benzoimidazotriazine derivatives is synthesized by acid-catalyzed reaction of 2-guanidinobenzimidazole (I) with active halogenated methylene compounds or ketones, respectively.

The pharmacodynamic properties1-3 of substituted amino pyrazines as well as their importance in the synthesis of pteridine and other polyfused heterocyclic systems is well known4,5. In this investigation we aim to prepare a new series of condensed heterocyclic systems containing the pyrazine nucleus.

Reaction of 2-guanidinobenzimidazole with halogenated active methylenes and ketones gave dihydroimidazole and 3,4-dihydrobenzo[4,5]imidazo [1,2-a][1,3,5]triazin derivatives in very good yield. The anti-bacterial evaluation of the newly synthesized products against broad spectrum of bacteria was performed. Most of products showed high inhibitory effect. All compounds have been characterized based on IR, (1)H NMR, (13)C NMR and Mass spectra.

2-Guanidinobenzimidazole condenses with benzaldehyde in the presence of hydrochloric acid to form 2-amino-3,4-dihydro-4-phenyl-1,3,5-triazino[1,2-a]benzimidazole, which was isolated as its hydrochloride, C15H14N5+·Cl−. The positive charge of the cation is formally placed on the double-bonded N atom of the dihydrotriazine ring. The six-membered dihydrotriazine that is fused with the benzimidazole ring system is relatively flat (r.m.s. deviation = 0.106 Å), with the methine C atom deviating most [0.164 (1) Å] from the mean-square plane. The phenyl ring connected to the methine C atom is disordered over two positions in a 0.558 (1):0.442 (1) ratio; the two orientations are aligned at 85.1 (1) and 89.6 (1)° with respect to the dihydrotriazine ring. In the crystal, adjacent cations and anions are linked by N—H...N and N—H...Cl hydrogen bonds, generating a double chain running along the b axis.

The inverse electron demand hetero-Diels-Alder reaction of arylmethylenepyrazolones with enamines results in the selective formation of 3,4-dihydro-2H-pyran derivatives. These cycloadducts under thermodynamic conditions, are transformed via the zwitterion, which can be captured in the presence of tetracyanoethylene (TCE), as the more stable Michael-type adducts. The zwitterion could also be the intermediate for the cyclic adducts.

The pharmacodynamic properties1-3 of substituted amino pyrazines as well as their importance in the synthesis of pteridine and other polyfused heterocyclic systems is well known4,5. In this investigation we aim to prepare a new series of condensed heterocyclic systems containing the pyrazine nucleus.

Novel heterocyclic compounds were prepared by the reaction of 2-acetyl-2-oxopropylidene s,s-acetal with different amino compounds namely, hydrazine hydrate, phenylhydrazine, guanidine hydrochloride, thiosemicarbazide, o-phenylenediamine, o-aminophenol or o-amino-thiophenol in different molar ratios.

The reaction of 2-Coumarylidenemalononitriles 1a,b with some active methylene, bidentates and ketoketene S, S or N, S acetals affords a series of new spiro heterocyclic systems.