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The arylhydrazones were treated with ethyl iodide, ethyl chloroacetate to afford the alkyl derivatives, which cyclized to the pyrazole derivatives, also, arylhydrazones were reacted with ethyl chlo...

A new series of quinoline derivatives 5–12 were efficiently synthesized via one-pot multicomponent reaction (MCR) of resorcinol, aromatic aldehydes, β-ketoesters, and aliphatic/aromatic amines under solvent-free conditions. All products were obtained in excellent yields, pure at low-cost processing, and short time. The structures of all compounds were characterized by means of spectral and elemental analyses. In addition, all the synthesized compounds 5–12 were in vitro screened for their antioxidant and antibacterial activity. Moreover, in silico molecular docking studies of the new quinoline derivatives with the target enzymes, human NAD (P)H dehydrogenase (quinone 1) and DNA gyrase, were achieved to endorse their binding affinities and to understand ligand–enzyme possible intermolecular interactions. Compound 9 displayed promising antioxidant and antibacterial activity, as well as it was found to have the highest negative binding energy of -9.1 and -9.3 kcal/mol for human NAD (P)H dehydrogenase (quinone 1) and DNA gyrase, respectively. Further, it complied with the Lipinski’s rule of five, Veber, and Ghose. Therefore, the quinoline analogue 9 could be promising chemical scaffold for the development of future drug candidates as antioxidant and antibacterial agents.

The elaboration of new small molecules that target phosphodiesterase enzymes (PDEs), especially those of type 5 (PDE5), is an interesting and emerging topic nowadays. A new series of heterocycle-based aminothiazoles were designed and synthesized from the key intermediate, 3-oxo-N-(thiazol-2-yl)butanamide (a PDE5 inhibitor that retains its amidic function), as an essential pharmacophoric moiety. The PDE5 inhibitors prevent the degradation of cyclic guanosine monophosphate, thereby causing severe hypotension as a marked side effect. Hence, an in vivo testing of the target compounds was conducted to verify its relation with arterial blood pressure. Utilizing sildenafil as the reference drug, Compounds 5, 10a, and 11b achieved 100% inhibitions of PDE5 without significantly lowering the mean arterial blood pressures (115.95 ± 2.91, 110.3 ± 2.84, and 78.3 ± 2.57, respectively). The molecular docking study revealed that the tested compounds exhibited docking poses that were similar to that of sildenafil (exploiting the amide functionality that interacted with GLN:817:A). The molecular shape and electrostatic similarity revealed a comparable physically achievable electrostatic potential with the reference drug, sildenafil. Therefore, these concomitant results revealed that the tested compounds exerted sildenafil-like inhibitory effects (although without its known drawbacks) on blood circulation, thus suggesting that the tested compounds might represent a cornerstone of beneficial drug candidates for the safe treatment for erectile dysfunction.

In the last few years we and others reported a variety of synthesis of heteroaromatics that have been developed utilizing β–oxoanilides as readily obtainable compounds. In this study, treatment of 3-Oxobutanamides 1 with phenyl isocyanate at room temperature in basic medium and DMF afforded thiocarbamoyl derivative 3 through intermediate 2 upon treatment with dilute HCl. The non-isolable potassium salt 2 was allowed to react with α-halo carbonyl compounds such as ethyl chloroacetate and chloroacetonitrile in dry DMF at room temperature to furnished thiophene 6 and thiazole derivative 9 respectively. Compound 6 was treated with hydrazine hydrate in ethanol to yield thiophene-5-carbohydrazide derivative 7. Also, compound 1 reacted with malononitrile and sulfur element in refluxing absolute ethanol and triethylamine to yield thiophene derivative 11, which reacted with formic acid and α-chloro acetylchloride to give thieno[2,3-d]pyrimidine derivative 12 and chloro acetamide derivative 13. Treatment of compound 13 with ammonium thiocyanate led to thiazolo[3,2-a]thieno[2,3-d]pyrimidine derivative 15 through non-isolable 14. Also, condensation of 1 with malononitrile and ethylene diamine afforded the pyridine derivative 17 and 1,4-diazepine derivative 18. The structures and formulas of all the synthesized compounds were supported by spectral data. Some of the synthesized compounds were evaluated for their antibacterial and antioxidant activity. These compounds showed different degrees of activity.

Covalent organic frameworks (COFs) are new generation of porous materials constructed from light elements (such as carbon, oxygen and nitrogen) linked via covalent bonds. Herein, one-pot synthesis of the composite of a COF and two-dimensional (2D) nanomaterials (graphene oxide (GO), graphitic carbon nitride (g-C3N4), and boron nitride (BN)) was reported. Melamine is poly-condensed with terephthaldehyde in the presence of GO, g-C3N4, and BN leading to the formation of a series of highly cross-linked microporous hierarchical porous amine networks. The thermal behavior, surface morphology, and crystalline structure were studied using thermogravimetric analysis (TGA), differential thermal analysis (DTA), scanning electron microscopy (SEM), X-ray diffraction (XRD), and transmission electron microscopy (TEM). The prepared COF nanocomposites possessed a high surface area of 42-509 m2 g−1 with a hierarchical porous structure and high thermal stability. COF nanocomposites (COF@GO, COF@g-C3N4, and COF@BN) were explored as an adsorbent for dye removal anionic dyes (Eosin dye and fluorescein) and cationic dyes (Fuchsine, and methylene blue). The composite materials exhibit high adsorption efficiency of 100% with excellent selectivity compared to the pristine COF. The synergic effect of COF and 2D nanomaterials improves the adsorption performance of the materials.

2-Aminopyridine-3-carbonitrile derivative 1 reacted with each of malononitrile, ethyl cyanacetate, benzylidenemalononitrile, diethyl malonate, and ethyl acetoacetate to give the corresponding [1,8]naphthyridine derivatives 3, 5, 8, 11, and 14, respectively. Further annulations of 3, 5, and 8 gave the corresponding pyrido[2,3-b][1,8]naphthyridine-3-carbonitrile derivative 17, pyrido[2,3-h][1,6]naphthyridine-3-carbonitrile derivatives 18 and 19, respectively. The reaction of 1 with formic acid, formamide, acetic anhydride, urea or thiourea, and 4-isothiocyanatobenzenesulfonamide gave the pyridopyrimidine derivatives 20a,b, 21, 22a,b, and 26, respectively. Treatment of compound 1 with sulfuric acid afforded the amide derivative 27. Compound 27 reacted with 4-chlorobenzaldehyde and 1H-indene-1,3(2H)-dione to give the pyridopyrimidine derivative 28 and spiro derivative 30, respectively. In addition, compound 1 reacted with halo compounds afforded the pyrrolopyridine derivatives 32 and 34. Finally, treatment of 1 with hydrazine hydrate gave the pyrazolopyridine derivative 35. The structures of the newly synthesized compounds were established by elemental and spectral data.

Condensation of β-Oxoanilide 1 with active methylene derivatives 2a,bafforded the pyridine derivative 5, and with crotononitrile afforded the pyridine 8. Compounds 9 and 11a-c were obtained by reaction of 1 with malononitrile dimer and arylidinemalononitrile 10a-10c. In contrast, when compound 1 reacted with ethoxymethylen malononitrile afforded the pyridine derivative 13. On the other hand, treatment of 1 with anthranilic acid gave the quinoline derivative 14. Also, reactions of 1 with isothiocyanate derivatives afforded compounds 16-18. The reaction of 1 with chalcone derivative afforded the pyridine derivative 22. Treatment of compound 1 with thiourea produced pyrimidine derivative 23. Furthermore, compound 1 converted into pyrimidinethione 24a and pyrimidinone 24b on treatment with a mixture of aromatic aldehydes and thiourea or urea respectively. Reaction of 24a with hydrazonyl halide, thiosemicarbazide and arylidinecyanothioacetamide afforded compounds 26, 28 and 29. Compound 29 was treated with chloroacetonitrile to afford compound 30. Six compounds from the newly synthesized were screened for antibacterial and antifungal activity against bacteria staphylococcus aureus, bacillus cereus and klebsiella pneumonia and fungi aspergillus flavus and aspergillus ochraceous, respectively. Some of the tested compounds showed significant antimicrobial activity. IR, 1H NMR, mass spectral data, and elemental analysis elucidated the structures of all the newly synthesized compounds.

β-Oxoanilide 1 reacted with acetyl isothiocyanate and ethoxycarbonyl isothiocyanate to givepyridine derivatives 6a,b and pyrimidinethiol 8 respectively. While with arylidine malononitrile gave the pyran derivative 12. Similarly, treatment of 1 with arylidine cyanoacetamide or arylidine cyanothioacetamide afforded the pyridine derivatives 13a,b, 14a,b respectively. Condensation of 1 with aromatic aldehyde obtained the cyclohexenones 19a-c. The reaction of 1 with a mixture of aromatic aldehyde and urea or thiourea gave the pyrimidine derivatives 23a,b. Treatment of compound 1 with arylidine acetophenone yield the cyclohexene derivatives 26a,b. Reaction of 1 with a mixture of ethyl cyanoacetate and sulfur yield the thiophene derivative 27. Which was reacted with formamide, potassium thiocyanate and hydrazine to afford the thienopyrimidines 28, 29 and the hydrazide derivative 30. respectively.

Ethyl 5-cyano-6-mercaptonicotinate derivatives 1a,b reacted with the N-[4-(aminosulfonyl) phenyl]-2-chloroacetamide derivatives 2a,b to give the ethyl 6-[(2-{[4-(aminosulfonyl) phenyl]amino}-2-oxoethyl)thio]nicotinate derivatives 3a–d. Cyclization of 3a–d afforded the corresponding ethyl 3-amino-2-({[4-(aminosulfonyl)phenyl]amino}carbonylthieno[2,3-b] pyridine-5-carboxylate derivatives 4a–d. Ethyl 3-[4-(amino-sulfonyl)phenyl]-4-oxopyrido [3′,2′:4,5]thieno[3,2-d]pyrimidine-8-carboxylate derivatives 5a–d and ethyl 3-[4-(amino- sulfonyl)phenyl]-4-oxopyrido[3′,2′:4,5]thieno[3,2-d][1,2,3]-triazine-8-carboxylate derivat- ives 6a–d were prepared from 4a–d. Reaction of 1a,b with chloroacetonitrile (7) and condensation of the thus formed 3-aminothienopyridines 8a,b with dimethylformamide-dimethylacetal (DMF-DMA) yielded the corresponding ethyl 2-cyano-3-{[(N, N-dimethylamino)methylene]amino}thieno[2,3-b]pyridine-5-carboxylate derivatives 9a,b. Reaction of compounds 9a,b with the sulfadiazine (10) gave ethyl 4-{[4-...

N-1-Naphthyl-3-oxobutanamide (1) reacts with arylidinecyanothioacetamide 2a–c in ethanol/piperidine solution under reflux to yield the pyridine-2(1H)-thiones 6a–c. Compound 6a reacts with α-haloketones 7a–e to give the 6-thio-N-1-naphthyl-nicotinamides derivatives 8a–e, which cyclized to thieno[2,3-b]pyridine derivatives 9a–e. The reaction of compound 9a with hydrazine hydrate and formamide gives the thieno[2,3-b]pyridine carbohydrazide derivative 10 and pyridothienopyrimidine derivative 11, respectively. Reaction of 9a with benzoyl isothiocyanate gave thiourea derivative 12. Compound 12, upon treatment with alcoholic NaOH, gave pyridothienopyrimidine 13. Saponifications of 9a gave the amino acid 15, which affords 16 when refluxed in Ac2O. Treatment of compound 16 with AcONH4/AcOH gave 17. Diazotization and self-coupling of 9b gave the pyridothienotriazine 18. Also, diazotization of the ortho-aminohydrazide 10 give the corresponding azide 19, which was subjected to Curtius rearrangement in boiling xylene ...

The reactivity of Isothiocyanatoazobenzene 2 towards some nucleophiles was investigated. Thus, reaction of isothiocyanate 2 with aromatic amines gave thioureas 3a–d . The reaction of compound 3a with arylidenemalononitriles 4a,b afforded the corresponding 1,3-pyrimidines 7a , b . Thiosemicarbazide 8 and ethyl thiocarbamate 9 were synthesized by interaction of isothiocyanate 2 with hydrazine hydrate and ethanol, respectively. Cyclocondensation of isothiocyanate 2 with 2-aminophenol and anthranilic acid produced the novel benzoxazole 11 and quinazolinone 13 derivatives , respectively. Finally, treatment of isothiocyanatoazobenzene 2 with compounds 14 and 17 afforded the novel thioureas 15 and 18 derivatives, respectively. The structures of the synthesized compounds were established from their analytical and spectral data.

Condensation of 1,3-diphenylpyrazole-4-carboxaldehyde (1) with some cyclic and heterocyclic active methylene derivatives afforded the condensation products 2-5. The reaction of 1 with benzoylglycine afforded the key intermediate 4-[(1,3-diphenyl-1H-pyrazol-4-yl)methylene]-2-phenyl-1,3-oxazol-5(4H)-one (6). Also, 1 reacted with malononitrile to give 7. The later reacted with 1H-indene-1,3(2H)-dione to give 9. The oxazolone 6 reacted with some aromatic and heteroaromatic amine derivatives to yield 5-[(1H-pyrazol-4-yl)methylene]-3,5-dihydro-4H-imidazol-4-one derivatives 11a,b, 12, 13 and 15. Reacting the oxazolone 6 with acetylacetone, ethyl acetoacetate, 5,5-dimethylcyclohexane-1,3-dione and 1H-indane-1,3-(2H)-dionegave the 1H-pyrazol-4-ylmethylenepyrrolidine-2,4-dione, 1H-pyrazol-4-ylmethylenepyrrol-3-one, 1H-pyrazol-4-ylmethyleneindole-3,4-dione and 1H-pyrazol-4-ylmethyleneindeno[1,2-b]pyrrole-3,4-dione derivatives 18-21 respectively. Antibacterial activity of some of the newly synthesized compounds was studded.

Condensation of 2-cyanomethyl-4-thiazolinone 1 with 1,3-diphenyl-pyrazole-4-carboxaldehyde 2 in ethanol containing a few drops of piperidine yielded the novel methylene derivative 3 . Compound 3 was refluxed with malononitrile to give the corresponding thiazolo[ [3] , [2] ]pyridine derivative 5 . Also, treatment of compound 3 with benzylidenemalononitriles gave the thiazolo[ [3] , [2] ]pyridine derivatives 6a–e . Refluxing of compound 6d with triethyl orthoformate furnished the ethoxymethylideneamino derivative 7 . Formic acid and malononitrile were reacted with compound 6d to produce thiazolo[ [3] , [2] ][ [1] , [8] ]naphthyridine derivative 8 and 11 , respectively. Condensation of 2 with cyanoacetohydrazide in ethanol containing piperidine as catalyst gave the hydrazone derivative 12 which, on treatment with salicyaldehyde and 2-cyano-3-(4-fluorophenyl)acrylic acid ethyl ester, yielded the novel chromene 13 and pyridinone 14 , respectively. Structures of the synthesized compounds have been esta...

The novel cyanothioformamides 2a-d were prepared by treatment of isothiocyanatosulfonamides 1a-d with potassium cyanide at room temperature. Cyclocondensation of compounds 2b,c with phenyl isocyanate as electrophile furnished the corresponding imidazolidines 3a,b. The reactivity of compound 3a towards some nitrogen nucleophiles was investigated. Thus, the thiosemicarbazone 4 and imidazo[4,5-b]quinoxaline 6 were synthesized by condensation of compound 3a with thiosemicarbazide and o-phenylenediamine, respectively. Treatment of 3a with hydrochloric acid afforded compound 7. Our investigation was extended to include the reactivity of cyanothioformamide 2 towards o-aminophenol, anthranilic acid, and o-phenylenediamine and yielded the corresponding heterocycles 9, 11 and 13 derivatives, respectively. Structures of the synthesized compounds were established by their elemental analysis and spectral data.

2-Aminopyridine-3-carbonitrile derivative 1 reacted with each of malononitrile, ethyl cyanacetate, benzylidenemalononitrile, diethyl malonate, and ethyl acetoacetate to give the corresponding [1,8]naphthyridine derivatives 3, 5, 8, 11, and 14, respectively. Further annulations of 3, 5, and 8 gave the corresponding pyrido[2,3-b][1,8]naphthyridine-3-carbonitrile derivative 17, pyrido[2,3-h][1,6]naphthyridine-3-carbonitrile derivatives 18 and 19, respectively. The reaction of 1 with formic acid, formamide, acetic anhydride, urea or thiourea, and 4-isothiocyanatobenzenesulfonamide gave the pyridopyrimidine derivatives 20a,b, 21, 22a,b, and 26, respectively. Treatment of compound 1 with sulfuric acid afforded the amide derivative 27. Compound 27 reacted with 4-chlorobenzaldehyde and 1H-indene-1,3(2H)-dione to give the pyridopyrimidine derivative 28 and spiro derivative 30, respectively. In addition, compound 1 reacted with halo compounds afforded the pyrrolopyridine derivatives 32 and 34. Finally, treatment of 1 with hydrazine hydrate gave the pyrazolopyridine derivative 35. The structures of the newly synthesized compounds were established by elemental and spectral data.

Cyclocondensation of cyanothioformamides (1) with arylhydrazonomalononitriles (2) afforded the novel imidazole derivatives (4a–e) in good yields. Isothiocyanatoazobenzene (6) was allowed to react with potassium cyanide and gave the new cyanothioformamide (7) which was reacted with 4-chlorophenyl isocyanate to yield imidazolidinethione (8). Compound (8) was subjected to react with hydrochloric acid, o-phenylenediamine, 4-methylaniline, and hydrogen sulfide and furnished compounds (10), (11), (12), and (15), respectively. Also, the reactivity of thiohydantoin (15) toward some electrophilic reagents such as N,N-dimethylformamide-dimethylacetal and arylidene-malononitriles was investigated. The structure of the synthesized compounds was established by analytical and spectral data. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:218–225, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20113