Inflammatory diseases are associated with a number of ailments; these disorders could be life threatening like hepatitis, cancer, trauma injury while some decreases the quality of life such as rheumatism, arthritis, tuberculosis etc. Oxa and thiazoles, having unparalleled share in pharmacological activity of especially anti-inflammatory, have arisen as superb templates in drug discovery. Their unique attributes have instigated synthetic chemists to access their innovative analogues by efficient and viable strategies. Insightful insertion of other heterocyclic cores, bicyclic rings and other active functionalities at appropriate sites has greatly enhanced their diversified bioactivities. This research endeavor is made to synthesize some novel anti-inflammatory agents based on oxa/thiazole via green protocol. Hence synthesis of new derivatives of oxa and thiazoles by novel routes focusing green strategy such as DES mediated preparation were carried out by adopting Hantzsch approach. For this purpose, ketones containing simple alkyl to pretentious alkyl functionalities such as tetrahydrocarbazoles and aryl moieties like phenyl and coumarin were used. Besides this, novel amide and thioamide analogues were also synthesized by functionalizing established bioactive heterocycles at their N position and the second step is annulation of these analogous with a series of bioactive ketones. A series of novel oxa and thiazoles each comprising twenty one compounds were synthesized. All new molecules were screened for in vitro anti-inflammatory potential by HRBC membrane stabilization method. Precursors were also subjected to antiinflammatory screening and only those were employed for the synthesis of oxazole and thiazoles which were found comparatively potent. N N NH 2 X R 1 O CH3 N N X R 1 N H X N R 1 N Oxa/ thiazoles N H R H X 2N N R H X 2N Green / Conv. Precursors Characterization of all of the innovative derivatives was done by analytical techniques like FTIR, 1HNMR and MS and CHNS analyser. Compounds 110, 111, 113d, 113b, 113g, 114a, 114b, 114c, 114f, 115b, 115e, 115f, 116d, 117b, 117c, 118a, 118b were found to possess best anti-inflammatory activity.