NOVEL EUGLYCEMIC AND HYPOLIPIDEMIC AGENTS - 1

A series of heterocyclyl)ethoxy]benzyl]-2,4-thiazolidinediones have be en synthesized by the condensation of corresponding aldehyde 1 and 2,4 -thiazolidinedione followed by hydrogenation. Both unsaturated thiazol idinedione 2 and its saturated counterpart 3 have shown antihyperglyce mic activity. Many of these compounds have shown superior euglycemic a nd hypolipidemic activity compared to troglitazone (CS 045). The indol e analogue DRF-2189 (3g) was found to be a very potent insulin sensiti zer, comparable to BRL-49653 in genetically obese C57BL/6J-ob/ob and 5 7BL/KsJ-db/db mice. Pharmacokinetic and tissue distribution studies co nducted on BRL-49653 and DRF-2189 (3g) indicate that these drugs are w ell-distributed in target tissues. On the basis of euglycemic activity as well as enhanced selectivity against reduction of triglycerides in plasma, DRF-2189 (3g) has been selected for further evaluation.