Synthesis of lead compounds is a necessity. Challenges are evolving day by day, Inflammation is a must to consider. A series of new oxazole derivatives were synthesized and evaluated for their anti-inflammatory effects. The new derivatives were synthesized by incorporating an oxazole moiety into a furan molecule as a starting molecule to form furan oxazole amine as an intermediate. In silico evaluation methods were done before synthesis through molecular docking via genetic optimization for ligand docking (GOLD) Suite software with COX-2 enzyme.The prepared compounds showed good activity against standard compounds, theoretically and experimentally.Compounds (P1 and P2) were tested in an in vitro study to inhibit the activity of cyclooxygenase enzyme (COX-2) using RAW 264.7 cell line, and compared to anti-inflammatory drugs (SC560 and Celecoxib).All results of biological experiments were similar to the results of In silico evaluation. These new derivatives were successfully synthesized in good quantities and the chemical composition was confirmed by FTIR, 1HNMR, and 13CNMR spectroscopy.The pharmacokinetic and physicochemical properties of the synthesized compounds were also measured using the Swiss ADME server. The results showed that all the prepared compounds had high oral bioavailability and good absorption in the digestive system and that some compounds had low toxicity.