Potency enhancement of the κ-opioid receptor antagonist probe ML140 through sulfonamide constraint utilizing a tetrahydroisoquinoline motif

Optimization of the sulfonamide-based kappa opioid receptor (KOR) antagonist probe molecule ML140 through constraint of the sulfonamide nitrogen within a tetrahydroisoquinoline moiety afforded a marked increase in potency. This strategy, when combined with additional structure-activity relationship exploration, has led to a compound only six-fold less potent than norBNI, a widely utilized KOR antagonist tool compound, but significantly more synthetically accessible. The new optimized probe is suitably potent for use as an in vivo tool to investigate the therapeutic potential of KOR antagonists

A View to the Future: Ultraviolet Studies of the Solar System

We discuss the status of ultraviolet knowledge of Solar System objects. We begin with a short historical survey, followed by a review of knowledge gathered so far and of existing observational assets. The survey indicates that UV observations, along with data collected in other spectral bands, are necessary and in some cases essential to understand the nature of our neighbors in the Solar System. By extension, similar observations are needed to explore the nature of extrasolar planets, to support or reject astro-biology arguments, and to compose and test scenarios for the formation and evolution of planetary systems. We propose a set of observations, describing first the necessary instrumental capabilitites to collect these and outlining what would be the expected scientific return. We identify two immediate programmatic requirements: the establishment of a mineralogic database in the ultraviolet for the characterization of planetary, ring, satellite, and minor planet surfaces, and the development and deployment of small orbital solar radiation monitors. The first would extend the methods of characterizing surfaces of atmosphere-less bodies by adding the UV segment. The latter are needed to establish a baseline against which contemporaneous UV observations of Solar System objects must be compared. We identify two types of UV missions, one appropriate for a two-meter-class telescope using almost off-the-shelf technology that could be launched in the next few years, and another for a much larger (5--20 meter class) instrument that would provide the logical follow-up after a decade of utilizing the smaller facility