Approaches towards the development of chimeric DPP4/ACE inhibitors for treating metabolic syndrome.

Designing drug candidates exhibiting polypharmacology is one of the strategies adopted by medicinal chemists to address multifactorial diseases. Metabolic disease is one such multifactorial disorder characterized by hyperglycaemia, hypertension and dyslipidaemia among others. In this paper we report a new class of molecular framework combining the pharmacophoric features of DPP4 inhibitors with those of ACE inhibitors to afford potent dual inhibitors of DPP4 and ACE.

Discovery of a novel non-steroidal GR antagonist with in vivo efficacy in the olanzapine-induced weight gain model in the rat.

We report the optimization of a series of non-steroidal GR antagonists that led to the identification of compound 7. This compound is efficacious when dosed orally in an olanzapine-induced weight gain model in rats.

RBx-0597, a potent, selective and slow-binding inhibitor of dipeptidyl peptidase-IV for the treatment of type 2 diabetes.

Dipeptidyl peptidase IV (DPP-IV) inhibiton is a well recognized approach to treat Type 2 diabetes. RBx-0597 is a novel DPP-IV inhibitor discovered in our laboratory. The aim of the present study was to characterize the pharmacological profiles of RBx-0597 in vitro and in vivo as an anti-diabetic agent.

Syntheses of pyridine C-nucleosides as analogues of the natural nucleosides dC and dU.

The syntheses of four pyrimidine C-nucleosides are described. These derivatives are designed as mimics of dC and dU, and in that respect, each can form two hydrogen bonds with complementary dG or dA residues. The minor groove O2 carbonyl in each derivative is replaced by a fluorine or a methyl group.

Polaronic semiconductor behavior of long-range charge transfer in DNA oligomers in solution: controlling barriers to long-distance radical cation migration in DNA with thymine analogs.

A series of anthraquinone-linked DNA oligonucleotides was prepared and the efficiency of long-distance radical cation migration was measured. In one set of oligonucleotides, two GG steps are separated by either a TATA or an ATAT bridge. In these two compounds, the efficiency of radical cation migration from GG to GG differs by more than an order of magnitude.

Core-substituted naphthalene bisimides: new fluorophors with tunable emission wavelength for FRET studies.

Highly colored and photoluminescent naphthalene bisimide dyes have been synthesized from 2,6-dichloronaphthalene bisanhydride 1 by means of a stepwise nucleophilic displacement of the two chlorine atoms by alkoxides and/or alkyl amines. The alkoxy-substituted derivatives are yellow dyes with green emission and low photoluminescence quantum yields, whereas the amine-substituted derivatives exhibit a color range from red to blue with strong photoluminescence up to 76%. Structure-property relationships for this class of two-dimensional chromophores were evaluated based on a single-crystal X-ray analysis for dye 5a, the observed solvatochromism, and quantum-chemical calculations.