Wesam S. Shehab

Synthesis of Some New Pyrimidine Derivatives of Expected Antimicrobial Activity

2-(2-Arylvinyl)-6-methyl-4-mercapto-5-acetylpyrimidine derivatives 3 a − d , were synthesized form the reaction of the appropriate isothiocyanate derivatives 1 with α, β -unsaturated aminoketone 2 . Compound 3 was alkylated with methyl iodide, ethyl chloroacetate and/or bromosugar to afford 6 , 9 , and 22 a − c respectively. Cyanoethylation of 3 b afforded 6 b which upon cyclization with hydrazine hydrate gave pyrazolopyrimidine 7 . Bromination of 6 b gave dibromo compound 8 . Thieno[2,3-d]pyrimidines 10 and 12 were obtained by ring closure of the alkylated product 9 with TEA/EtOH and/or through cyclization of the hydrazide 11 with NaOEt/EtOH. While, Thieno[2,3-d]pyrimidine 14 was obtained directly by alkylation of 3 b with chloroacetone in both TEA/EtOH and Na2CO3 solution. The cycloaddition products 15 and 16 were obtained by reaction of 3b with diethylmaleate and/or maleic anhydride. Formation of 1,3,4-oxadiazole 17 , pyrazoles 18 and 19 where obtained by treating the hydrazide 11 with carbon disulphide, triethyl orthoformate and acetylacetone respectively. While, reaction of 11 with p-chlorobenzaldehyde resulted in the Schiffs base 20 which, cyclizes with thioglycolic acid to afford thiazolidone 21 . Hydrolysis of 22 a − c in TEA/MeOH afforded the free sugar 23 a − c . The structures of all the new compounds were confirmed using IR, 1 H, and 13 C NMR spectra and microanalysis. Selected members of the synthesized compound were screened for antimicrobial activity.

Nanoparticles of manganese oxides as efficient catalyst for the synthesis of pyrano[2,3-d]pyrimidine derivatives and their complexes as potent protease inhibitors

Novel pyrano[2,3-d] pyrimidine derivatives were synthesized via the three-component reaction of thiophene-2-carbaldehyde, malononitrile and barbituric or thiobarbituric acid in the presence of Mn2O3 nanoparticles. This method has been found to be eco-friendly and economical. Compound 1 was used as a precursor for the synthesis of new pyranopyrimidine derivatives 2–5. Moreover, 7-amino-2,3,4,5-tetrahydro-4-oxo-5-(thiophen-2-yl)-2-thioxo-1H-pyrano[2,3-d]pyrimidine-6-carboxamide 4 was then converted into another set of novel compounds 6–8. On the other hand, a series of Mn(II) complexes with pyrano[2,3-d]pyrimidine derivatives have been prepared. The synthesized compounds and its complexes were characterized by elemental analysis, magnetic and spectroscopic methods (IR, XRD, SEM, TEM, 13C, 1HNMR) as well as thermal analysis. The spectrophotometric determinations suggest a distorted octahedral geometry for all complexes. The organic compounds and its chelates as inhibitors exhibited remarkable effects on the enzyme activity of an extracellular toxic protease, KB76 from Brevibacterium otitidis as well as against different bacterial and fungal strains.Graphical abstract

Synthesis and cyclization of β-keto-enol derivatives tethered indole and pyrazole as potential antimicrobial and anticancer activity

Synthesis of biologically active new indole and pyrazole derivatives has earned a substantial position in the pharmaceutical industry. The study aims to synthesize and cyclize β-keto-enol derivatives tethered indole and pyrazole as potential antimicrobial and anticancer activity. Novel derivatives of enolic keto ester 1 have been obtained through Claisen condensation of 3-acetylindole with diethyl oxalate under basic conditions. Spectral data of newly produced compounds were characterized using Fourier transform infrared, hydrogen nuclear magnetic resonance, Carbon-13 nuclear magnetic resonance, and elemental analysis. Few compounds were assessed for their antimicrobial activity, contrary to gram-positive bacterial strains, gram-negative bacterial strain, and antifungal activity that have been approved against Candida albicans. However, compound 2 showed an excellent antimicrobial activity. In vitro antitumor action of few prepared compounds in contradiction to human breast carcinoma cell line, colon cell line, and normal retina cell line was evaluated.Graphical Abstract

Cyclization of pyrazolones: novel synthesis of pyrano, pyrido, pyrimido and spiropyrazole derivatives

Depending on the reaction conditions, two alternative cyclizations are possible for [3 + 3] cyclocondensation of pyrazolone derivative 1a and ethyl cyanoacetate of type pyrano [2,3-c] pyrazol-6(1H)-one 2 and pyrano [2,3-c] pyrazol-4(1H)-one 3. Keeping of enaminic system 3 and benzylidene malononitrile in the presence of catalytic amount of trimethylamine resulted in pyridine cyclization affording pyrazolopyranopyridine derivative 4, not 5. The pyrazolone derivative 6a was obtained as a result of the acid-mediated addition reaction between compound 1a, urea and/or ammonium thiocyanate. In addition, the bispyrazolone of type 6b was obtained from the condensation reaction of urea and pyrazolone derivative. The spiro compound 7 was obtained from the double-addition reaction of pyrazolone to cinnamoyl isothiocyanate. A one-pot three-component condensation of a 3-hydroxybenzaldehyde, pyrazolone 1a, urea and/or thiourea under Biginelli conditions resulted in tetrahydropyrazolo pyrimidine derivatives 8a and 8b, respectively. The acid-mediated reaction of benzaldehyde and pyrazolone derivative 1a in the presence of Ac2O yielded styrylpyrazole derivative 9. The polyfunctionalized product 9 reacted with hydrazine to furnish pyrazolotriazoloe of type 10. Treatment of styrylpyrazole derivative 9 with aniline furnished the aniline derivative 11 and none of the expected polyheterocyclic derivative 12 was obtained. Compound 9 undergoes pyridine cyclization to produce 13 under the effect of urea. N-phenyl pyrazolone converted into pyrano-dipyrazolone derivative 14. Pyran of type 14 underwent a ring transformation upon treatment with urea and/or thiourea to give the same dipyrazolo pyrimidine derivative 15. The newly synthesized compounds were characterized by FT-IR, 1H-NMR, 13C-NMR, ESI/LC-MS and elemental analysis.

Heterocyclization of polarized system: synthesis, antioxidant and anti-inflammatory 4-(pyridin-3-yl)-6-(thiophen-2-yl) pyrimidine-2-thiol derivatives

BackgroundChalcones are intent in the daily diet as a favorable chemotherapeutic compound; on the other hand thiophene moiety is present in a large number of bioactive molecules having diverse biological efficiency.ResultsOur current goal is the synthesis of (E)-1-(pyridin-3-yl)-3-(thiophen-2-yl) prop-2-en-1-one 3 that’s used as a starting compound to synthesize the novel pyrimidine-2-thiol, pyrazole, pyran derivatives. Chalcones 3 was prepared by condensation of 3-acetylpyridine with thiophene 2-carboxaldehyde which reacted with thiourea to obtain pyrimidinthiol derivative 4. Compound 4 was allowed to react with hydrazine hydrate to afford 2-hydrazinylpyrimidine derivative 5. Compound 5 was used as a key intermediate for a facile synthesis of the targets 6 and 7. In contrast, pyranone 8 was obtained by transformation of compound 5. Using as a precursor for the synthesis of new pyrazolo pyrimidine derivatives 9–10. The major incentive behind the preparation of these compounds was the immense biological activities associated to these heterocyclic derivatives.ConclusionsThe newly synthesized compounds (1–4) showed potent anti-inflammatory activities both in vitro and in vivo. They also exhibited promising antioxidant vitalities against α, α-diphenyl-β-picrylhydrazyl scavenging activity and lipid peroxidation. In conclusion, compound 1 showed a hopefully anti-inflammatory and antioxidant activities.