Discovery and Pharmacology of a Novel Somatostatin Subtype 5 (SSTR5) Antagonist: Synergy with DPP-4 Inhibition.

We report new SSTR5 antagonists with enhanced potency, subtype selectivity, and minimal off-target activities as compared to previously reported compounds. Starting from the reported SSTR5 antagonist , we systematically surveyed changes in the central core and head piece while maintaining the diphenyl tail group constant. From this study the azaspirodecanone emerged as a new highly potent and selective SSTR5 antagonist.

Bis-aryl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1.

3-Aryl-5-phenyl-(1,2,4)-triazoles were identified as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). They are active in both in vitro and an in vivo mouse pharmacodynamic (PD) model. The synthesis and structure activity relationships are presented.

Adamantyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1.

Adamantyl triazoles were identified as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). They are active both in in vitro and in in vivo pharmacodynamic models. The synthesis and structure-activity relationships of these inhibitors are presented.

Design and synthesis of novel antibacterial agents with inhibitory activity against DNA polymerase III.

4-Substituted 2-amino-6-(anilino)pyrimidines have been found to be selective inhibitors of DNA polymerase III, a replicative enzyme known to be essential in the DNA synthesis of Gram-positive bacteria. Among the analogues, 18 displayed an IC(50) of 10 microM against DNA polymerase III from Staphylococcus aureus.

Both coactivator LXXLL motif-dependent and -independent interactions are required for peroxisome proliferator-activated receptor gamma (PPARgamma) function.

Nuclear receptor activation is dependent on recruitment of coactivators, including CREB-binding protein (CBP/p300) and steroid receptor coactivator-1 (SRC-1). A three-dimensional NMR approach was used to probe the coactivator binding interface in the peroxisome proliferator-activated receptor gamma (PPARgamma) ligand binding domain (LBD). In the presence of a CBP peptide, peaks corresponding to 20 residues in helices 3, 4, 5, and 12 of the LBD were attenuated.