Preparation of a Series of 5-Methyl-3-(substituted)-[1,2,4]triazines

Procedures for the synthesis of thirty-six 5-methyl-3-(substituted)-[1,2,4]triazines have been described. These compounds were evaluated for antagonism at metabotropic glutamate receptor subtype 5 (mGluR5). Two compounds, 5b and 3c, were determined to be low micromolar inhibitors of mGluR5.     

A fractal analysis of analyte-estrogen receptor binding and dissociation kinetics using biosensors: environmental effects

A fractal analysis is used to model the binding and dissociation kinetics between analytes in solution and estrogen receptors (ER) immobilized on a sensor chip of a surface plasmon resonance (SPR) biosensor. Both cases are analyzed: unliganded as well as liganded. The influence of different ligands is also analyzed. A better understanding of the kinetics provides physical insights into the interactions and suggests means by which appropriate interactions (to promote correct signaling) and inappropriate interactions such as with xenoestrogens (to minimize inappropriate signaling and signaling deleterious to health) may be better controlled. The fractal approach is applied to analyte-ER interaction data available in the literature. Numerical values obtained for the binding and the dissociation rate coefficients are linked to the degree of roughness or heterogeneity (fractal dimension, D(f)) present on the biosensor chip surface. In general, the binding and the dissociation rate coefficients are very sensitive to the degree of heterogeneity on the surface. For example, the binding rate coefficient, k, exhibits a 4.60 order of dependence on the fractal dimension, D(f), for the binding of unliganded and liganded VDR mixed with GST-RXR in solution to Spp-1 VDRE (1,25-dihydroxyvitamin D(3) receptor element) DNA immobilized on a sensor chip surface (Cheskis and Freedman, Biochemistry 35 (1996) 3300-3318). A single-fractal analysis is adequate in some cases. In others (that exhibit complexities in the binding or the dissociation curves) a dual-fractal analysis is required to obtain a better fit. A predictive relationship is also presented for the ratio K(A)(=k/k(d)) as a function of the ratio of the fractal dimensions (D(f)/D(fd)). This has biomedical and environmental implications in that the dissociation and binding rate coefficients may be used to alleviate deleterious effects or enhance beneficial effects by selective modulation of the surface. The K(A) exhibits a 112-order dependence on the ratio of the fractal dimensions for the ligand effects on VDR-RXR interaction with specific DNA.     

Sample indexed spatial orthogonal frequency division multiplexing

Optical spatial modulation(OSM) is a multiple-transmitter technique that can provide higher data rates with low system complexity as compared with single-input single-output systems. Orthogonal frequency division multiplexing(OFDM) is widely implemented to achieve better spectral efficiency in wireless channels. Asymmetrically clipped optical OFDM(O-OFDM) and DC-biased O-OFDM are two well-known O-OFDM techniques suitable for intensity-modulation direct-detection optical systems. In this work, sample indexed spatial OFDM(SIS-OFDM) is proposed to combine OSM and O-OFDM in a novel way and achieve significant performance gain. By assigning time-domain samples of the O-OFDM transmit symbol to different transmitters, SIS-OFDM achieves much better spectral efficiency and reduces computational complexity at the transmitter as compared with previous work that combines OSM with O-OFDM in the frequency domain. We also consider the impact of optical source biasing on overall performance, and the relative performance of imaging receiver(ImR) versus non-imaging receiver(NImR) design for our proposed SIS-OFDM technique. Results indicate that for an Ntx × Nrx multiple-input multiple-output configuration where Ntx = Nrx = 4, SIS-OFDM using ImR can achieve up to 135 dB of signal-to-noise ratio gain over comparable system using a NImR. Also, using Nsc number of O-OFDM subcarriers provides up to Nsc × log2(Ntx) additional bits per symbol of spectral efficiency over techniques that combine OSM and O-OFDM in the frequency domain.     

Synthesis and evaluation of 1,2,4-methyltriazines as mGluR5 antagonists

In previous studies we showed that 3-(substituted phenylethynyl)-5-methyl[1,2,4]triazine analogues of MPEP were potent antagonists of glutamate-mediated mobilization of internal calcium in an mGluR5 in vitro efficacy assay. In the present study we report the synthesis and evaluation of six 3-(substituted biphenylethynyl)-5-methyl[1,2,4]triazines (5a-f), and five 3-(substituted phenoxyphenylethynyl)-5-methyltriazines (6a-e). Compound 2-(4-fluorophenyl-5-[2-(5-methyl[1,2,4]triazine-3-yl)ethynyl]benzonitrile (5f) with an IC(50) of 28.2 nM was the most potent analogue.