Background: The heterocyclic nucleus pyrimidine is present in several natural and synthetic chemical analogues and has proved its broad medicinal applications. Further, pyrimidine in the form of parent structure or basic skeleton of RNA and DNA is involved in controlling the immune functioning, and in turn, inflammatory reactions. Method: Molecular docking studies of Indomethacin and selected analogues were carried out with COX-2 enzyme (PDB: 4ZOL). The synthesis of derivatives of 4-Phenyl-6-(phenylamino)pyrimidin-2-ol derivatives were begun by following Perkin condensation between substituted acetanilides and substituted aromatic aldehydes to yield an intermediate, which in turn produces the required nucleus for treatment with urea. All synthesized compounds were evaluated for in-vivo and in-vitro anti-inflammatory activity. Result: The docking interaction reflects a good dock score when compared with indomethacine a potent Anti-inflammatory drug. In the majority of the compounds, pyrimidine was able to form hydrogen bonding while the rest of the part was involved in hydrophobic bonding. All compounds were synthesized in good yield and confirmed by physical and spectral studies. In-vitro studies suggested that among all synthesized compounds, 5a and 5e when compared with standard drug Antipyrine while invivo data reflecting that compound 5a, 5c, 5e, and 5h were better in controlling inflammation. Conclusion: The synthetic work and experimental study reveals a good result for compound having more than one electron releasing groups on aniline moiety of pyrimidine, but also the absence of electron withdrawing group favours for better anti-inflammatory activity on the target.