Novel Antidiabetic and Hypolipidemic Agents. 3. Benzofuran-Containing Thiazolidinediones

Abstract

Several thiazolidinedione derivatives having 5-hydroxy-2,3-dihydro-2, 2,4,6,7-pentamethylbenzofuran moieties and their 5-benzyloxy derivatives and 5-hydroxy-2,4,6,7-tetramethylbenzofuran moieties were synthesized and evaluated in db/db mice. Insertion of an N-Me group into the linker between thiazolidinedione and substituted benzofuran pharmacophores showed considerable improvement in their euglycemic activity. Further improvement has been observed when a pyrrolidine moiety is introduced in the structure to give 5-[4-[N-[3(R/S)-5-benzyloxy-2,3-dihydro-2,2,4,6, 7-pentamethylbenzofuran-3-ylmethyl]-(2S)-pyrrolidin-2- ylmethoxy]pheny lene]thiazolidine-2,4-dione (21a). At a 100 mg/kg/day dose of the maleate salt, compound 21a reduced the plasma glucose and triglyceride to the level of lean littermate, i.e. 8 +/- 1 mM, and is the most potent and efficacious compound reported in this series.

Comparative Design, In Silico Dockingand Predictive ADME/ TOX Properties of Some Novel 2, 4-hydroxy Derivatives of Thiazolidine-2, 4-diones as PPARγ Modulator

“…The data sets of true and binding decoys for PPARγ used in this study were collected from the available literature 20 as well as from the publically available dataset, DUD [21][22][23][24] . The PPAR γ actives (164) were mixed with decoys (3127) to form a single library of 3291 molecules.…”

“…Docking program and the molecular docking protocol have been validated through virtual screening enrichment study using the decoy and active sets available from DUD and literature. [20][21][22][23][24] Further the designed molecules were also subjected to predictive ADME-TOX studies.…”

Progress in the chemistry of 4‐ thiazolidinones

“…Thiazolidinones derivatives CP-060 (9) and its analogues being antidiabetic drugs are used for the treatment of diabetes [29].…”

Synthesis and Anticonvulsant Screening of Some Novel Derivatives of Substituted Benzofuran

“…During recent years, there has been intense investigation of different classes of benzofuran compounds and many of them were found to be pharmacologically active. The substituted benzofurans have attracted much attention due to their prominent utilization as antimicrobial [1][2] , anti-inflammatory 3-4 , anticonvulsant 5-6 , antitumor [7][8] , Anti-HIV 9 , Antidiabetic 10 and antitubercular 11 , activity probably resulting from its planar and compact structure. Benzofurans, heterocyclic compounds of varied biological activities were found to be one of the new classes of anticonvulsant agents as revealed by literature survey [5][6] .…”