Earlier studies showed that (R,S)-alpha-acetamido-N-benzylacetamides (2) containing a five- and six-membered aromatic or heteroaromatic group appended at the C(alpha) site displayed outstanding activity in the maximal electroshock-induced seizure (MES) test in mice. An expanded set of C(alpha)-heteroaromatic analogues of 2 have been prepared and evaluated. The observed findings extended the structure-activity relationships previously discerned for this novel class of anticonvulsants and have validated previous trends. The alpha-furan-2-yl (4), alpha-oxazol-2-yl (18), and alpha-thiazol-2-yl (19) alpha-acetamido-N-benzylacetamides afforded excellent protection against MES-induced seizures in mice. The ED50 and PI values for these adducts rivaled those reported for phenytoin. The outstanding properties provided by 4 led to an in-depth examination of the effect of structural modification at key sites within this compound on biological activity. The pharmacological data in this series indicated that stringent steric and electronic requirements existed for maximal activity and revealed the outstanding activity of (R)-(-)-alpha-acetamido-N-(4-fluorobenzyl)-alpha-(furan-2-yl)aceta mide [(R)-30].

Recent studies have demonstrated that C(alpha)-substituted alpha-acetamido-N-benzylacetamides displayed excellent anticonvulsant activities in mice. Analysis of the structure-activity relationship for this series of compounds has shown that placement of small, electron-rich aromatic and heteroaromatic groups at the C(alpha) site led to pronounced protection against MES-induced seizures. In this note, synthetic protocols are reported for the preparation of three novel nonnaturally occurring electron-deficient C(alpha)-aza aromatic alpha-acetamido-N-benzylacetamides (i.e., pyrid-2-yl (11), pyrazin-2-yl (12), pyrimid-2-yl (13)). Expedient syntheses for 12 and 13 were developed using a phase-transfer, nucleophilic aromatic substitution process. All three adducts exhibited potencies comparable to or greater than phenytoin in the MES test (mice, ip). These findings required us to modify in part the previously proposed structure-activity relationship for this class of anticonvulsants.

ABSTRACT. Synthetic aperture radar (SAR) images of Taylor Valley, Antarctica, were acquired inJanuary 1999 in coordination with ground-based measurements to assess SAR detection of the snowline on dry polar glaciers. We expected significant penetration of the radar wave resulting in an offset of the SAR-detected snowline relative to the true snowline. Results indicated no detectable displacement of the SAR snowline. Snow depths of 15 cm over ice can be detected on the imagery. We hypothesize that the optical depth of thin snowpacks is enhanced by reflection and refraction of the radar beam by internal snow layers. The enhanced optical depth increases the volume scattering, and thereby enhances backscatter sufficiently to be detected by the SAR. Consequently, SAR imagery may be used directly to image the position of transient snowlines in dry polar regions.