4844 T3D4789 Troglitazone Troglitazone was withdrawn in 2000 due to risk of hepatotoxicity. It was superseded by pioglitazone and rosiglitazone. 97322-87-7 5591 C24H27NO5S White powder. 184-186°C Absorbed rapidly. Food increases the extent of absorption by 30% to 85%. Troglitazone is a thiazolidinedione antidiabetic agent that lowers blood glucose by improving target cell response to insulin. It has a unique mechanism of action that is dependent on the presence of insulin for activity. Troglitazone decreases hepatic glucose output and increases insulin dependent glucose disposal in skeletal muscle. Its mechanism of action is thought to involve binding to nuclear receptors (PPAR) that regulate the transcription of a number of insulin responsive genes critical for the control of glucose and lipid metabolism. Troglitazone is a ligand to both PPAR‘± and PPAR‘_, with a highter affinity for PPAR‘_. The drug also contains an ‘±-tocopheroyl moiety, potentially giving it vitamin E-like activity. Troglitazone has been shown to reduce inflammation, and is associated with a decrase in nuclear factor kappa-B (NF-‘_B) and a concomitant increase in its inhibitor (I‘_B). NF-‘_B is an important cellular transcription regulator for the immune response. Unlike sulfonylureas, troglitazone is not an insulin secretagogue. A sulfate conjugate metabolite (Metabolite 1) and a quinone metabolite (Metabolite 3) have been detected in the plasma of healthy males. A glucuronide conjugate (Metabolite 2) has been detected in the urine and also in negligible amounts in the plasma. In healthy volunteers and in patients with type 2 diabetes, the steady-state concentration of Metabolite 1 is six to seven times that of troglitazone and Metabolite 3. In in vivo drug interaction studies, troglitazone has been shown to induce cytochrome P450 CYP3A4 at clinically relevant doses. Half Life: 16-34 hours No indication of carcinogenicity to humans (not listed by IARC). For the treatment of Type II diabetes mellitus. It is used alone or in combination with a sulfonylurea, metformin, or insulin as an adjunct to diet and exercise. 2014-09-11T05:16:39Z 2014-12-24T20:26:57Z Troglitazone 9753 DB00197 true CC1=C(O)C(C)=C2CCC(C)(COC3=CC=C(CC4SC(=O)N=C4O)C=C3)OC2=C1C C24H27NO5S InChI=1/C24H27NO5S/c1-13-14(2)21-18(15(3)20(13)26)9-10-24(4,30-21)12-29-17-7-5-16(6-8-17)11-19-22(27)25-23(28)31-19/h5-8,19,26H,9-12H2,1-4H3,(H,25,27,28) InChIKey=GXPHKUHSUJUWKP-UHFFFAOYNA-N 441.54 441.160993669 Exogenous Solid 3.6 5389 <p>Krishnamurthi Vyas, Chebiyyam Prabhakar, Sreenivas Dharmaraja Rao, Mamillapalli Ramabadhra Sarma, Om Gaddam Reddy, Rajagopalan Ramanujam, Ranjan Chakrabarti, &#8220;Polymorphic forms of troglitazone having enhanced anti-diabetic activity and a process for their preparation.&#8221; U.S. Patent US5700820, issued June, 1992.</p>