Reddy K A, Lohray B B, Bhushan V, Reddy A S, Rao Mamidi N V, Reddy P P, Saibaba V, Reddy N J, Suryaprakash A, Misra P, Vikramadithyan R K, Rajagopalan R
Medicinal and Organic Chemistry, Clinical Research, Pharmacology, Dr. Reddy's Research Foundation, Bollaram Road, Miyapur, Hyderabad 500 050, India.
J Med Chem. 1999 Aug 26;42(17):3265-78. doi: 10.1021/jm9805541.
Several thiazolidinediones having chroman moieties were synthesized and evaluated for their euglycemic and hypolipidemic activities. Some of the analogues 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 than troglitazone. In vitro transactivation assays of PPARgamma have been carried out with these glitazones to understand their molecular mechanism. For the first time we have found that some of the unsaturated thiazolidinediones are superior to their saturated counterpart in the in vivo assay. A more potent thiazolidinedione analogue than troglitazone is reported. Pharmacokinetic studies have shown that protection of the OH group in the chroman moiety leads to a decrease in metabolism, thereby resulting in a superior pharmacological profile.
合成了几种具有色满部分的噻唑烷二酮类化合物，并对其降血糖和降血脂活性进行了评估。一些在色满环和4-[5-(2,4-二氧代-1,3-噻唑烷-1-基)甲基]苯氧基部分之间具有氨基烷基作为连接基的类似物似乎比曲格列酮更好。已用这些格列酮进行了PPARγ的体外反式激活测定，以了解其分子机制。首次发现一些不饱和噻唑烷二酮类化合物在体内试验中优于其饱和对应物。报道了一种比曲格列酮更有效的噻唑烷二酮类似物。药代动力学研究表明，色满部分中羟基的保护导致代谢降低，从而产生更好的药理学特征。
