Tamer S. Saleh

Synthesis and analgesic/anti-inflammatory evaluation of fused heterocyclic ring systems incorporating phenylsulfonyl moiety

A series of pyrazolo[1,5-a]pyrimidine, triazolo[1,5-a]pyrimidine, and pyrimido[1,2-a]benzimidazole ring systems incorporating phenylsulfonyl moiety were synthesized via the reaction of 3-(N,N-dimethylamino)-1-aryl-2-(phenylsulfonyl)prop-2-en-1-one derivatives 2a,b with appropriate nitrogen nucleophiles. The analgesic and anti-inflammatory activities of the newly synthesized compound were investigated in vivo. 3-Bromo-2-phenyl-6-(phenylsulfonyl)-7-(4-methylphenyl)pyrazolo[1,5-a]pyrimidine (5e) was found to have an excellent analgesic activity in comparison with indomethacin as a reference drug, while the highest anti-inflammatory effect was observed in the case of 2-(4-bromophenyl)-6-(phenylsulfonyl)-5-(4-methylphenyl)pyrazolo[1,5-a]pyrimidine (5d). From the structure-activity relationship (SAR) point of view, the analgesic/anti-inflammatory activity of pyrazolo[1,5-a]pyrimidine derivatives was found to be much higher than triazolo[1,5-a]pyrimidine and pyrimido[1,2-a]benzimidazole derivatives.

Ultrasound promoted synthesis of substituted pyrazoles and isoxazoles containing sulphone moiety

Novel pyrazoles and isoxazoles were synthesized from the reaction of the carbanions of 1-aryl-2-(phenylsulphonyl)-ethanone with different hydrazonyl halides and 1-aryl-2-bromo-2-hydroximinoethanone in ethanol, respectively. Reactions were carried out under silent and ultrasonic conditions. In general, it was found that ultrasound irradiations enable some reactions to occur which could not be carried out under silent condition in addition to improvement in reaction times. The products were obtained in high yields and their structures were determined by elemental analyses, spectral data and X-ray diffraction.

Single Step Synthesis of New Fused Pyrimidine Derivatives and Their Evaluation as Potent Aurora-A Kinase Inhibitors

A simple, facile, efficient and one pot three-component procedure for the synthesis of pyrazolo[1,5-a]pyrimidines, triazolo[1,5-a]pyrimidines and pyrimido[1,2-a]benzimidazoles ring systems incorporating phenylsulfonyl moiety was developed via the reaction of 1-aryl-2-(phenylsulfonyl)ethanone derivatives 1a-d with the appropriate heterocyclic amine and triethyl orthoformate and evaluated as Aurora-A kinase inhibitors. The cytotoxic activity of the newly synthesized compounds against HST116 colon tumor cell line was investigated. 2,7-Diphenyl-6-(phenylsulfonyl)pyrazolo[1,5-a]pyrimidine (4b) and its p-methoxy analogue 4c were found to be equipotent to Doxorubicin as a reference drug. Molecular modeling study was carried out in order to rationalize the in vitro anti-tumor results.

Synthesis and antimicrobial evaluation of new thiophene and 1,3,4-thiadiazole derivatives

A Facile route to some new thiophene derivatives via the reaction of 3-mercapto-2-(1-methylbenzimidazole-2-carbonyl)-3-phenylaminopropenal (3) with 1-aryl-2-bromoethanones, chloroacetonitrile and ethyl bromoacetate is reported. Reaction of 3 with hydrazonoyl halides afforded 1,3,4-thiadiazole derivatives incorporating a benzimidazole moiety. Antimicrobial and antifungal activities of selected examples of the new products were evaluated.

Synthesis and antimicrobial evaluation of novel pyrazolo〔1,5-a〕pyrimidine triazolo〔1,5-a〕pyrimidine and Pyrimido〔1,2-a〕benzimidazole derivatives

The applicability and synthetic potency of E-1 -(1-methylbenzimidazol-2-yl)-3 -N,N-dimethylaminoprop-2-enone towards some nitrogen nucleophiles was investigated as a convenient route for the synthesis of some novel aminopyrimidine, pyrazolo[1 ,5-a]pyrimidine, triazolo[1 ,5-a]pyrimidine, pyrimido[1,2-a]benzimidazole, and pyrido[2,3-d]pyrimidine derivatives. Some of the newly synthesized compounds were tested in vitro for their antibacterial and antifungal activities, and showed promising results.

An eco-friendly N-sulfonylation of amines using stable and reusable Zn–Al–hydrotalcite solid base catalyst under ultrasound irradiation

Synthetic nanosized Zn-Al-hydrotalcite (Zn-Al-HT) with 20 nm crystallite size and 61 m(2)/g BET-surface area is found to be a mild and efficient catalyst for N-sulfonylation of amines in quantitative yields under ultrasound irradiation. Exclusive synthesis of sulfonamides, using Zn-Al-HT, under ultrasound irradiation, was realized by compatible basic sites of catalyst used. The products were isolated after simple work-up in high yields and purity.

Facile synthesis and in-vitro antitumor activity of some pyrazolo[3,4-b]pyridines and pyrazolo[1,5-a]pyrimidines linked to a thiazolo[3,2-a]benzimidazole moiety.

The key precursor E‐3‐(N,N‐dimethylamino)‐1‐(3‐methylthiazolo[3,2‐a]benzimidazol‐2‐yl)prop‐2‐en‐1‐one 4 was synthesized in good yield using Golds reagent. The reaction of enaminone 4 with 5‐amino‐3‐aryl‐1‐phenylpyrazoles 5a, b in refluxing acetic acid in the presence of sulphuric acid, yielded pyrazolo[3,4‐b]pyridines 7a, b. Similarly, pyrazolo[1,5‐a]pyrimidines 10a, b and 14a–f were prepared by reaction of enaminone 4 with 5‐amino‐1H‐pyrazoles 8a, b and 12a–f, respectively. The structure of pyrazolo[1,5‐a]pyrimidine 10b was determined by X‐ray diffraction. The synthesized compounds were tested for their in‐vitro antitumor activity against the colon cancer cell line CaCo‐2; their cytotoxicity against the normal fibroblast cell line BHK was explored as well. Some of the tested compounds exhibited cell growth inhibitory activity. The significant antitumor activity of compound 14f against the CaCo‐2 cell line (IC50 = 0.5 μg/mL) was coupled with a lower toxicity against BHK (IC50 = 2.3 μg/mL).

Ultrasound assisted one-pot, three-components synthesis of pyrimido[1,2-a]benzimidazoles and pyrazolo[3,4-b]pyridines: A new access via phenylsulfone synthon.

A simple, facile, efficient and three-components procedure for the synthesis of pyrimido[1,2-a]benzimidazoles and pyrazolo[3,4-b]pyridines utilizing phenylsulfone synthon, under ultrasonic irradiation was developed.

Divergent reaction pathways for one-pot, three-component synthesis of novel 4H-pyrano[3,2-h]quinolines under ultrasound irradiation.

The present paper deal with the multi-component condensation of 8-hydroxy quinoline, aromatic aldehydes, and sulfone derivatives catalyzed by p-toluenesulfonic acid for the synthesis of a series of 4H-pyrano[3,2-h]quinoline derivatives in ethanol under ultrasonic irradiations. We provide a series of quinoline derivatives containing sulfone moiety interesting for biological screening tests. The reactions were carried out under both conventional and ultrasonic irradiation conditions. In general, improvement in rates and yields were observed when reactions were carried out under sonication compared with classical silent conditions. Also, also, sonochemical reaction give different reaction pathway other than silent reaction. These remarkable effects appeared in sonicated reactions can be reasonably interpreted in terms of acoustic cavitation phenomenon. Structures of the products were established on analytical and spectral data.

AN EFFICIENT SINGLE STEP SYNTHESIS OF PYRIDAZINE, PYRAZOLO[5,1-c]-1,2,4-TRIAZINE, 1,2,4-TRIAZOLO[5,1-c]-1,2,4-TRIAZINE AND 1,2,4-TRIAZINO[4,3-a]BENZIMIDAZOLE DERIVATIVES

Coupling of E-1-(l-methylbenzimidazol-2-yl)-3-(N,N-dimethylamino)prop-2-enone (1) with the arenediazonium salt gave hydrazonopropanal 5 which underwent cyclocondensation with active methylene compounds to afford substituted pyridazin-6-imine 8 and 11. The enaminone 1 coupled also with the diazonium salts prepared from aminopyrazole, aminotriazole and 2-amino-1H-benzimidazole to afford pyrazolo[5,l-c]-l,2,4-triazine 15, 1,2,4-triazolo[5,1-c]-1,2,4-triazine 19, 1,2,4-triazino[4,3-a]benzimidazole 23 derivatives, respectively.