Haiping Yu | Search PubMed

PubMed2006

Design, synthesis, and evaluation of Leu*Ala hydroxyethylene-based non-peptide beta-secretase (BACE) inhibitors.

With the aim of developing small molecular non-peptide beta-secretase (BACE) inhibitors, Leu*Ala hydroxyethylene (HE) was investigated as a scaffold to design and synthesize a series of compounds. Taking advantage of efficient combinatorial synthesis approaches and molecular modeling, extensive structure-activity relationship (SAR) studies were carried out on the N- and C-terminal residues of the Leu*Ala HE scaffold. Isobutyl amine was found to be an optimal C-cap, and suitable hydroxylalkylamines at the 3-position and nitro or methyl(methylsulfonyl)amine at the 5-position of isophthalamide as the N-terminus could form additional hydrogen bonds with BACE active sites and help improve potency. Many new potent non-peptide BACE inhibitors were identified in this study. Among them, compounds 37 and 44 exhibited excellent enzyme-inhibiting potency, comparable to that of OM99-2, and obvious inhibitory effects in cell-based assay with low molecular weights (<600).

Amyloid Precursor Protein Secretases↗

PubMed2005

Comparison of Gd [DTPA-bis (2-aminoethoxy) ethane] polymeric contrast agent with gadodiamide injection for interstitial MR lymphography: experimental study with rabbits.

PURPOSE: To compare the differences between macromolecular and small molecular contrast agents in interstitial magnetic resonance (MR) lymphography. MATERIALS AND METHODS: In two groups of rabbits (N = 12 each), 0.5-mL volumes of 0.5 M and 0.1 M gadodiamide, respectively, were injected subcutaneously into the dorsal feet of both hind legs. After a 24-hour interval, 0.5 mL of Gd [DTPA-bis (2-aminoethoxy) ethane] polymeric contrast agent (Gd-poly-DTPA-EOEA) injection (0.1 M) was injected into the same sites in each rabbit. T1-weighted three-dimensional gradient-echo and maximum intensity projection (MIP) images were obtained before and after the administration of each agent. The nodal maximum short-axis diameter (MSAD) and signal-to-noise ratio (SNR) at each time point were measured. Postmortem measurements of nodal MSADs were also performed. The nodal MSAD measurements obtained by MR lymphography were compared with the postmortem measurements. As an additional control experiment, six rabbits received a subcutaneous injection of 0.5 mL of 0.1 M gadodiamide at the same sites as those described above. This procedure was repeated after a 24-hour interval to determine whether the first injected gadodiamide had any effect on the performance of the subsequently injected agent, by comparing the differences in nodal MSADs obtained by MR lymphography after each injection. RESULTS: Gd-poly-DTPA-EOEA showed a significantly longer enhancement plateau compared to gadodiamide. In comparison with postmortem measurements, nodal measurements by MR lymphography with Gd-poly-DTPA-EOEA at the peak-enhancement phase revealed no significantly different MSADs (P > 0.05), whereas nodal measurements by MR lymphography with gadodiamide showed significantly smaller MSADs (P < 0.05). A comparison of the nodal MSADs measured in two gadodiamide-enhanced MR examinations after the 24-hour interval showed no significant difference (P > 0.05). CONCLUSION: Interstitial MR lymphography with polymeric Gd-poly-DTPA-EOEA enhancer enables more sufficient and reliable visualization of lymph nodes compared to small molecular gadodiamide.

Animals↗

PubMed2004

Optically switchable liquid crystal photonic structures.

Photo-optic materials offer the possibility of light controlled photonic devices, intelligent and environmentally adaptive optical materials. One strategy for creating these materials is the combination of structure formation through holographic photopolymerization and the variable optical properties of liquid crystals. Holographically patterned, polymer stabilized liquid crystals (HPSLCs) have proven to be useful optical materials. By incorporating photo-optic, azobenzene-derived liquid crystal blends into such material systems, we have generated practical photoresponsive optical materials.

Journal Article↗