Synthesis of polymeric thiazolidinedione and fibrate conjugates

Abstract

Pioglitazone is a thiazolidinedione (TZD) class of antidiabetic drug acting mainly through activation of PPAR gamma which is a member of family of ligand activated nuclear hormone receptors. Clofibrate is an antilipemic drug acting through activation of PPAR alpha. Despite the impressive antidiabetic activity of TZD, several side effects are implicated to use of this drug on some patient. Dual acting PPAR(alpha/gamma agonists have received increased attention to improve the profiles of the PPAR gamma agonists. Hence, we describe here synthesis of TZD and/or fibrate derivatives-containing homo- or copolymers, poly(TZD) 7, poly(TZD-MAA) 8, poly(TZD-FA) 9, poly(FA) 10, and poly(FA-MAA) 11. The contents of TZD unit in copolymers, poly(TZD-MAA) 8 and poly (TZD-FA) 9 were 25 and 19 mol %, respectively. The number average molecular weights of the polymers determined by GPC were in range from 466 to 12600 and the polydispersity indices were in the range of 1.2 similar to 13.3.