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Pyrazolo[1,5-a]pyrimidine, triazolo[1,5-a]pyrimidine, and pyrimido[1,2-a]benzimidazole, pyrido[1,2-a]benzimidazole ring systems incorporating phenylsulfonyl moiety were synthesized via the reaction of 3-(N,N-dimethylamino)-1-(thiophen-2-yl)-2-(phenylsulfonyl)prop-2-en-1-one derivatives with the appropriate aminoazoles as 1,3-binucleophiles and 1H-benzimidazol-2-ylacetonitrile using conventional methods as well as microwave irradiation. The regioselectivity of the cyclocondensation reactions was confirmed both experimentally by alternative synthesis of reaction products and theoretically using ab initio quantum chemical calculations namely the Density Functional Theory (DFT). The theoretical work was carried out using the Becke, three parameter, Lee-Yang-Parr hybrid functional (B3LYP) combined with the 6-311++G(d,p) basis set. It was found that the final cyclocondensation reaction product depends mainly on the initial addition to the activated double bond by the nitrogen atom of the 1,3-binucleophiles that has the higher electron density., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

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.

Reaction of E-3-( N, N-dimethylamino)-1-(3-methylthiazolo[3,2- a]benzimidazol-2-yl)prop-2-en-1-one () with some N-nucleophiles, such as anilines , 4-amino- N-pyridin-2-yl-benzenesulfonamide (), 4-amino- N-pyrimidin-2-yl-benzenesulfonamide (), hydrazine, hydroxylamine, thiourea, and guanidine afforded the corresponding arylaminoprop-2-en-1-one derivatives , , the pyrazole, isoxazole, pyrimidinethione and aminopyrimidine derivatives , , , and , respectively. The utility of compound , as a versatile building block, for the synthesis of the pyranone , benzo[ b]furan , and naphtho[1,2- b]furan was also explored via its reaction with 2-benzamidoacetic acid (), 1,4-benzoquinone (), and 1,4-naphthoquinone (), respectively. J. Heterocyclic Chem., (2011). [ABSTRACT FROM AUTHOR]

New fused heterocyclic compounds were synthesized starting from dimethyl terephthalate, as a versatile precursor, via its reactions with the appropriate reagents. The structures of the newly synthesized compounds were supported by their spectral data. Some of the newly synthesized compounds exhibited promising antimicrobial activities. Molecular docking studies were carried out on 4-(5-amino-7-(4-bromophenyl)pyrazolo[1,5- a ]pyrimidine-6-carbonyl) benzoic acid (17) as the most active compound to evaluate its potential interaction molecular docking against Escherichia coli (PDB.ID: 3t88), StReptococcus pneumoniae (PDB.ID: 2wje), AspergIllus flavus (PDB.ID: 4ynt) and Geotrichum candidum (PDB.ID: 1tgh), respectively. Computational calculations at the DFT/B3LYP/6-31G (d) and HF/6-31G (d) level of the theory have been carried out to examine the equilibrium geometry of the pyrazolo[1,5- a ]pyrimidine and harmonic vibrational frequencies, The energy of the HOMO and LUMO and Mullikan atomic charges were also calculated. Image 1 • Synthesis of new series of novel pyrazolo[1,5- a ]pyrimidine derivatives. • Most of the compounds exhibited potent antimicrobial activity. • Molecular modeling and calculation of binding energy of 17 with different proteins. • The quantum chemical calculations were performed for 17 using DFT/B3LYP/6-31G(d) and HF/6-31G(d) methods. [ABSTRACT FROM AUTHOR]