Imidazo[2,1-b][1,3]thiazine scaffold is the attractive matrix for the design of small molecules with a wide activity spectrum. Therefore, it seemed to be interesting to work out the straightforward and convenient protocol for the synthesis of new hybrid molecules containing diversified imidazo[2,1-b][1,3]thiazine scaffolds linked with potential pharmacophore – pyridine ring and evaluate their drug-like and anti-inflammatory properties. The proposed synthetic approach is based on the utilization of structure-modified imidazolinthiones as starting building block for the formation of imidazo[2,1-b][1,3]thiazine core. The interaction of the last ones in the soft conditions with epichlorohydrin lead to the key 3-hydroxy-imidazo[2,1-b][1,3]thiazines, which were easily transformed to the target (2-pyridinyloxy)substituted imidazo[2,1-b][1,3]thiazines with satisfied yields (53-74%) due to selective nucleophilic substitution by different chloropyridines at room temperature using dry DMF and in the presence of NaH. The structure of compounds was studied and confirmed using ¹H, ¹³C NMR spectroscopy and LC-MS spectrometry. The drug-likeness properties of the synthesized derivatives were determined based on Lipinski and Veber rules and evaluated in silico using the SwisAdme. Almost all tested compounds comply with Lipinski’s rules of five and Veber’s rules, with some exceptions for Mlog P parameter. The anti-inflammatory activity of all synthesized (2-pyridinyloxy)substituted imidazo[2,1-b][1,3]thiazines was studied in vivo using the carrageenin model of edema of hind paws of albino rats. The compounds possess different levels of anti-inflammatory activity (inhibition index was in the range of 3.7 to 39.1 %). The “structure – anti-inflammatory activity” correlation was revealed for the next structure optimization and focused synthesis of imidazo[2,1-b][1,3]thiazine with anti-inflammatory activity.