Metabolism, Excretion, and Mass Balance of Solithromycin in Humans.

Solithromycin, a novel macrolide and the first fluoroketolide, is being developed as a therapy for community-acquired bacterial pneumonia, with a distinct mechanism that provides activity against macrolide-resistant bacteria. The pharmacokinetics, metabolism, and excretion of solithromycin were studied in healthy male subjects after oral administration of a single 800-mg (∼100-μCi) dose of [C]solithromycin. Solithromycin was well tolerated, and absorption from the solution occurred with a median time to peak concentration of 4.

Determination of a dipeptidyl peptidase IV agonist, β-aminoacyl containing thiazolidine derivatives (KR-66223) in rat plasma by liquid chromatography-tandem mass spectrometry.

A sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed for a novel dipeptidyl peptidase IV agonist (DDP-IV) agonist, KR-66223, in rat plasma. It involves liquid-liquid extraction (LLE) followed by HPLC separation and electrospray ionization tandem mass spectrometry. KR-66223 and imipramine (IS) was separated on Gemini-NX C18 column with mixture of acetonitrile-ammonium formate (10mM) (90:10, v/v) as mobile phase.

Discovery of β-aminoacyl containing thiazolidine derivatives as potent and selective dipeptidyl peptidase IV inhibitors.

A series of β-aminoacyl containing thiazolidine derivatives was synthesized and evaluated for their ability to inhibit DPP-IV. Several thiazolidine derivatives with an acid moiety were found to be potent DPP-IV inhibitors. Among them, compound 2da is the most active in this series with an IC(50) value of 1 nM, and it showed excellent selectivity over DPP-IV related enzymes including DPP-2, DPP-8, and DPP-9.

Development of HIV fusion inhibitors.

In the past 25 years, the worldwide AIDS epidemic has grown such that roughly 38 million people were estimated to be living with the disease worldwide at the end of 2003. The introduction of antiretroviral-based therapies, beginning in 1987, has enabled many to live with HIV as a chronic, rather than terminal, disease. However, the emergence and spread of drug-resistant strains highlights the continued need for new therapies with novel modes of action.

Differential receptors create patterns diagnostic for ATP and GTP.

Herein we report the combination of a library of resin-bound sensors along with a multicomponent sensor array. This novel combinatorial array sensor system shows selectivity for nucleotide phosphates in solution. The design of the anchored receptor includes a 1,3,5-trisubstituted-2,4,6-triethylbenzene scaffold coupled with peptide libraries.

Solid and Solution Phase Organic Syntheses of Oligomeric Thioureas.

In order to study supramolecular architectures built from unnatural oligomeric and polymeric structures, one must first have an efficient synthetic strategy to produce them. Oligomers built from thiourea groups should form complex secondary and tertiary structures due to the hydrogen-bonding capabilities of the thioureas. Herein, both solution and solid phase synthetic procedures that yield oligomeric thioureas are described.