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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.

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Enzyme inhibiting activity X 0220Synthesis and SAR/3D-QSAR Studies on the COX-2 Inhibitory Activity of 1,5-Diarylpyrazoles to Validate the Modified Pharmacophore. -The SAR study mainly involves variations at positions C-3 (R 2 ) and C-5 (Ar) as well as at the N 1 of the pyrazole ring (R 1 ). Several small hydrophobic groups at or around the para-position of C-5 phenyl exhibit impressive COX-2 inhibitory potency, cf. derivatives (Ia)-(Ic). In general, the sulfonamide analogues with CHF 2 at C-3 are found to be more potent than those having a CF3 group. -(SINGH*, S. K.; SAIBABA, V.; RAO, K. S.; REDDY, P. G.; DAGA, P. R.; RAJJAK, S. A.; MISRA, P.; RAO, Y. K.; Eur. J. Med. Chem. 40 (2005) 10, 977-990; Chem.-Discovery Res., Dr. Reddy's Lab. Ltd., Hyderabad 500 049, India; Eng.) -H. Haber 08-215