Novel antidiabetic and hypolipidemic agents. 5. Hydroxyl versus benzyloxy containing chroman derivatives

Several thiazolidinediones having chroman moieties were synthesized and eva luated for their euglycemic and hypolipidemic activities. Some of the analo gues having an aminoalkyl group as a linker between the chroman ring and 4- [5-(2,4-dioxo-1,3-thiazolidinyl)methyl]phenoxy moiety seem to be better tha n troglitazone. In vitro transactivation assays of PPAR gamma have been car ried out with these glitazones to understand their molecular mechanism. For the first time we have found that some of the unsaturated thiazolidinedion es are superior to their saturated counterpart in the in vivo assay. A more potent thiazolidinedione analogue than troglitazone is reported. Pharmacok inetic studies have shown that protection of the OH group in the chroman mo iety leads to a decrease in metabolism, thereby resulting in a superior pha rmacological profile.