Convenient Synthesis of 4-pyridinyloxy-Modified imidazo[2,1-b][1,3]thiazines as Potential Anti-inflammatory Agents

Abstract

Novel imidazo[2,1-b][1,3]thiazine derivatives modified with 4-pyridinyloxyl moiety, as potential anti-inflammatory agents are described. Synthetic approach to the preparation of (6-((pyridin-4-yl)oxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazines 3a-f and their benzoanelated analogues 3g-j is based on the interaction of substituted 4-fluoropyridines with 3-hydroxy(benzo)imidazo[2,1-b][1,3]thiazines. The nucleophilic substitution reaction of the fluorine atom occurs selectively at position 4 of the pyridine ring. The drug-like properties of the first synthesized (4-pyridinyloxy)imidazo[2,1-b][1,3]thiazines were predicted in silico using SwissADME. Anti-inflammatory activity was studied in vivo using hind paw edema in white rats (carrageenan test). Compounds with satisfactory drug-like and pharmacological properties have been identified as promising for further structure optimization and in-depth research.