Over expression of 11 -HSD 1 in key metabolic tissues is related to the development of type 2 diabetes, obesity, hypertension and metabolic syndrome. Nephrotoxicity of corosolic acid (selective inhibitor of 11 -HSD 1) is recently reported, which is one of the major drawback. Therefore, it is of great interest to find out the selective 11 -HSD 1 inhibitors without nephrotoxicity. Using crystal structures of 11 -HSD 1 in complex with inhibitors as a source of structural information, a combined structure-based virtual screening approach followed by PASS toxicity prediction, Lipinski's rule and...

A new series of imidazo 2,1-b] 1,3,4]thiadiazoles 5(a-g), 6(a-g), 9(a-i) and 12(a-h) were synthesized. Among them, 23 compounds 5a, 5b, 5e, 5d, 5f, 5g, 6a, 6b, 6c, 6d, 6e, 9b, 9d, 9f, 9g, 9h, 9i, 12b, 12c, 12d, 12e, 12g, and 12h were evaluated at National Cancer Institute for single dose in vitro primary cytotoxicity assay. Compound 5b, 5e, 6c, 6d, 6e, 12c, 12d and 12e were further screened for 5-log dose molar range as they have shown prominent cell growth inhibition at 10-5 M concentration against variety of cell lines. Compound 5e shows significant inhibition against Leukemia HL-60 cell...