Crystal structure of 2-amino-N-(2-fluoro-phen-yl)-4,5,6,7-tetra-hydro-1-benzo-thio-phene-3-carboxamide.

In the title compound, C15H15FN2OS, the dihedral angle between the planes of the benzo-thio-phene ring system and the fluoro-benzene ring is 3.74 (14)°. The six-membered ring of the benzo-thio-phene moiety adopts a half-chair conformation. The mol-ecular conformation is consolidated by intra-molecular N-H⋯F and N-H⋯O hydrogen bonds. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds, generating C(6) [001] chains.

Recent advances in the synthesis of some bioactive peptides and peptidomimetics.

This review focuses on the synthetic progress of some naturally occurring cyclic peptides and depsipeptides apart from the development of peptidomimetics incorporating unnatural amino acids that have not been covered in the earlier reviews.

Dual PPAR-alpha and -gamma activators derived from novel benzoxazinone containing thiazolidinediones having antidiabetic and hypolipidemic potential.

2,4-Thiazolidinedione derivatives of 1,3-benzoxazinone were synthesized and evaluated for their PPAR-alpha and -gamma dual activation. DRF-2519, a compound obtained through SAR of TZD derivatives of benzoxazinone, has shown potent dual PPAR activation. In ob/ob mice, it showed better efficacy than the comparator molecules. In fat fed rat model, it showed significant improvement in lipid parameters, which was better than fibrates.

Highly efficient CuI-catalyzed coupling of aryl bromides with oxazolidinones using Buchwald's protocol: a short route to linezolid and toloxatone.

[reaction: see text] Coupling of a variety of substituted aryl bromides with oxazolidinones has been achieved using the Buchwald protocol for the amidation of aryl halides. This procedure is exemplified by the synthesis of two medicinally important molecules, linezolid and toloxatone.

Synthesis and biological activity of novel pyrimidinone containing thiazolidinedione derivatives.

A series of pyrimidinone derivatives of thiazolidinediones were synthesized. Their biological activity were evaluated in insulin resistant, hyperglycemic and obese db/db mice. In vitro PPARgamma transactivation assay was performed in HEK 293T cells. PMT13 showed the best biological activity in this series. PMT13 (5-[4-[2-[2-ethyl-4-methyl-6-oxo-1,6-dihydro-1-pyrimidinyl]ethoxy]phenylmethyl]thiazolidine-2,4-dione) showed better plasma glucose, triglyceride and insulin-lowering activity in db/db mice than rosiglitazone and pioglitazone. PMT13 showed better PPARgamma transactivation than the standard compounds. Pharmacokinetic study in Wistar rats showed good systemic exposure of PMT13. Twenty-eight day oral toxicity study in Wistar rats did not show any treatment-related adverse effects.

Novel euglycemic and hypolipidemic agents. 1.

A series of [[(heterocyclyl)ethoxy]benzyl]-2,4-thiazolidinediones have been synthesized by the condensation of corresponding aldehyde 1 and 2,4-thiazolidinedione followed by hydrogenation. Both unsaturated thiazolidinedione 2 and its saturated counterpart 3 have shown antihyperglycemic activity. Many of these compounds have shown superior euglycemic and hypolipidemic activity compared to troglitazone (CS 045). The indole analogue DRF-2189 (3g) was found to be a very potent insulin sensitizer, comparable to BRL-49653 in genetically obese C57BL/6J-ob/ob and 57BL/KsJ-db/db mice. Pharmacokinetic and tissue distribution studies conducted on BRL-49653 and DRF-2189 (3g) indicate that these drugs are well-distributed in target tissues. On the basis of euglycemic activity as well as enhanced selectivity against reduction of triglycerides in plasma, DRF-2189 (3g) has been selected for further evaluation.

Novel euglycemic and hypolipidemic agents: Part-2. Antioxidant moiety as structural motif.

Several thiazolidinediones having antioxidant moities in their structural motif have been synthesised and evaluated for their euglycemic and hypolipidemic activities. A few of them have been found to be superior to troglitazone.