Synthesis and Pharmacology of (Pyridin-2-yl)methanol Derivatives as Novel and Selective Transient Receptor Potential Vanilloid 3 Antagonists.

Transient receptor potential vanilloid 3 (TRPV3) is a Ca(2+)- and Na(+)-permeable channel with a unique expression pattern. TRPV3 is found in both neuronal and non-neuronal tissues, including dorsal root ganglia, spinal cord, and keratinocytes. Recent studies suggest that TRPV3 may play a role in inflammation, pain sensation, and skin disorders.

The development of an NMR chemical shift prediction application with the accuracy necessary to grade proton NMR spectra for identity.

We have developed an NMR chemical shift prediction system that enables high throughput automatic grading of NMR spectra. In support of high throughput synthetic efforts for our drug discovery program, a rapid and accurate analysis for identity was needed. The system was designed and implemented to take advantage of the NMR assignments that had been tabulated on internally generated research compounds.

Concise construction of novel bridged bicyclic lactams by sequenced Ugi/RCM/Heck reactions.

Herein we report a concise protocol for the diastereoselective synthesis of novel bridged bicyclic lactams from commercially available components by the sequence of Ugi, ring-closing metathesis (RCM), and Heck reactions. X-ray diffraction studies revealed that the bicyclic products contain varying degrees of pyramidalization of the bridgehead nitrogen atom.