DiHydroOrotate DeHydrogenase [huDHODH] is a therapeutic target for Rheumatoid arthritis [RA]. Leflunomide [A771726] is a widely used synthetic inhibitor against huDHODH. We to find more efficient lead like compounds. A four featured E-Pharmacophore A1D4H6R7 was built based on the inhibitor A771726. This pharmacophore was validated by checking its ability to identify known highly active inhibitors of huDHODH and assigning higher fitness scores to them. A reverse validation was also performed where random 4 featured pharmacophores were built and its efficiency in identifying actives was compared with our E-Pharmacophore. Our Epharmacophore was very efficient, since it passed both validations by picking the known active molecules with high fitness scores. This validated E- pharmacophore was searched against the KEGG phytochemicals subset database. This search resulted in 18 molecules which were subjected to docking with huDHODH. The molecules with docking score greater than that of A771726 were selected. The docking results were further validated using MM/GBSA which gave similar ranking with high binding free energy values. The four molecules 6-Methoxytaxifolin, Rhamnetin, Rhamnazin and Pinoquercetin were taken for explicit 3ns simulation and it was observed that all four molecules had acceptable RMSD values and stable interactions. Thus our study, suggests four phytomolecules that might inhibit huDHODH more efficiently than A771726. Interestingly, some of the obtained hits have already been proven in vitro anti-inflammatory activity which confirms that, the developed E-pharmacophore can be used to identify novel small molecules against inflammatory target, huDHODH.