Prompted from the diversity of the wider use and being an integral part of genetic material, an effort was made to synthesize pyrimidine pyrazole derivatives of pharmaceutical interest by oxidative cyclization of chalcones with satisfactory yield and purity. A novel series of 1,3-dimethyl-6-hydroxy-2,4-dioxo-5-(1′-phenyl-3′-aryl-1H-pyrazol-5′-yl)-1,2,3,4-tetrahydropyrimidines (5a–d) and 1,3-diaryl-6-hydroxy-4-oxo-2-thioxo-5-(1′-phenyl-3′-aryl-1H-pyrazol-5′-yl)-1,2,3,4-tetrahydropyrimidines (5e–l) has been synthesized. The structures of these compounds were established on the basis of FT-IR, 1H NMR, 13C NMR, and mass spectral analysis. All the synthesized compounds were screened for their antimicrobial activity against bacteria and fungi. Among all the compounds, 5g was found to be the most active as its MIC was 31.25？μg/mL against S. aureus and B. cereus. The compounds 5h, 5c, and 5e also possess antibacterial activity with MIC values as 62.50, 125.00, and 500.00？μg/mL, respectively. The compounds 5c and 5j were found to have antifungal activity against Aspergillus spp. As antifungal drugs lag behind the antibacterial drugs, therefore we tried in vitro combination of these two compounds with standard antifungal drugs (polyene and azole) against Aspergillus spp. The combination of ketoconazole with 5c and 5j showed synergy at 1？:？8 (6.25？:？50.00？μg/mL) and 1？:？4 (25？:？100？μg/mL) against A. fumigatus (ITCC 4517) and A. fumigatus (VPCI 190/96), respectively. 1. Introduction Nitrogen heterocycles are of special interest as they constitute an important class of natural and nonnatural products, many of which exhibit useful biological activities. Pyrimidine, being an integral part of DNA and RNA, imparts diverse pharmacological properties, such as bactericide, fungicide, vermicide, insecticide, and anticancer and antiviral agents [1]. Certain pyrimidine derivatives are also known to display antimalarial, antifilarial, and antileishmanial activities [2]. The pyrazole derivatives are well known to have antimicrobial [3], antifungal [4], antitubercular [5], anticancer [6], analgesic [7], anti-inflammatory [8], antipyretic [9], anticonvulsant [10], antidepressant [11], muscle relaxing [12], antiulcer [13], antiarrhythmic [14], and antidiabetic [15] activities. With growing application of their synthesis and bioactivity, chemists and biologists in recent years have directed considerable attention to the study of pyrazole derivatives. In view of the above mentioned importance of pyrimidines and pyrazoles, we tried to accommodate these moieties in a single molecular
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