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(Na0.5Bi0.5)0.94Ba0.06TiO3 (NBBT) ceramics doped with 0.1∼2.0 mol.% Ba (Zr0.05Ti0.95)O3 were investigated in terms of the sintering, microstructure, phase transition, and piezoelectric properties. BZT doping has no remarkable effect on the microstructure and densification within the studied doping content. Up to 2 mol.% BZT can dissolve into the lattice of NBBT ceramics, and the structure symmetry is not changed. However, a significant change in the piezoelectric properties took place. The piezoelectric coefficient d33 for the 0.1 wt.% BZT-doped NBBT ceramics sintered at 1150 °C was found to be 120 pC/N and the electromechanical coupling factor kp = 0.24.

A series of androgen receptor modulators based on 8H-[1,4]oxazino[2,3-f]quinolin-8-ones was synthesized and evaluated in an androgen receptor transcriptional activation assay. The most potent analogues from the series exhibited single-digit nanomolar potency in vitro. Compound 18h demonstrated full efficacy in the maintenance of muscle weight, at 10 mg/kg, with reduced activity in prostate weight in an in vivo model of androgen action.

We have completed the total syntheses of elastase inhibitors YM-47141 and YM-47142, the first natural products containing a vicinal tricarbonyl group. The work establishes the configuration at C(4) of the macrocyclic depsipeptide and demonstrates the generality of the phosphoranylidene-ylide activation and protection methodology employed earlier in syntheses of α-keto amides. Key steps involve the coupling of a carboxylic acid with a phosphorane to form a stable ylide intermediate, which contains the highly electrophilic carbonyl group in protected form. The tricarbonyl unit was unmasked at the final stage of the synthesis by oxidative cleavage of the C=P bond.

An efficient synthesis of the androgen receptor modulator ( R )- 4a having an 8 H -[1,4]oxazino[2,3- f ]quinolin-8-one skeleton is described. Synthesis of this ring system, not readily accessible by classical Knorr cyclization methodology, was accomplished by an ortho -metallation strategy. Thus, lithiation of a pivaloyl-protected 7-amino-3,4-dihydro-1,4-benzoxazine using n -butyllithium allowed the introduction of a trifluoroacetyl group regioselectively at the 8-position. Subsequent Wittig reaction and acid catalyzed cyclization afforded the desired 8 H -[1,4]oxazino[2,3- f ]quinolin-8-one ( R )- 4a in very good overall yield from the corresponding benzoxazine.

The coupling of aryl bromides or iodides with oxindoles using a copper iodide-N,N′-dimethylethylene diamine system is presented. The reaction proceeds efficiently and tolerates a variety of substitution patterns.

New RXR-selective modulators possessing a 6-fluoro trienoic acid moiety (6Z olefin) or a fluorinated/heterocyclic-substituted benzene core ring, were synthesized in an expedient and selective way. A subset of these compounds was evaluated for their metabolic properties (exposure in IRC male mice) and show a dramatic increase of exposure compared to our reference compound, 3 (LG101506).

Retinoid X receptor:peroxisome proliferative-activated receptor (RXR:PPAR) heterodimers play a critical role in the regulation of glucose (RXR/PPARgamma) and lipid metabolism (RXR/PPARalpha). Previously, we described a concise structure-activity relationship study of selective RXR modulators possessing a (2E,4E,6Z)-3-methyl-7-(3,5-dialkyl-6-alkoxyphenyl)-octa-2,4,6-trienoic acid scaffold. These studies were focused on the 2-position alkoxy side chain. We describe here the design and synthesis of a novel series of RXR selective modulators possessing the same aromatic core structure with the addition of a ring locked 6-7-Z-olefin on the trienoic acid moiety. The synthesis and structure-activity relationship studies of these 6,7-locked cyclopentenyl, phenyl, thienyl, furan, and pyridine-trienoic acid derivatives is presented herein.

Previous data have shown that RXR-selective agonists (e.g., 3 and 4) are insulin sensitizers in rodent models of non-insulin-dependent diabetes mellitus (NIDDM). Unfortunately, they also produce dramatic increases in triglycerides and profound suppression of the thyroid hormone axis. Here we describe the design and synthesis of new RXR modulators that retain the insulin-sensitizing activity of RXR agonists but produce substantially reduced side effects. These molecules bind selectively and with high affinity to RXR and, unlike RXR agonists, do not activate RXR homodimers. To further evaluate the antidiabetic activity of these RXR modulators, we have designed a concise and systematic structure-activity relationship around the 2E,4E,6Z-7-aryl-3-methylocta-2,4,6-trienoic acid scaffold. Selected compounds have been evaluated using insulin-resistant rodents (db/db mice) to characterize effects on glucose homeostasis. Our studies demonstrate the effectiveness of RXR modulators in lowering plasma glucose in the db/db mouse model.

The crystallization kinetics of a-Ge thin film induced by a thin Ni layer under thermal annealing and pulsed laser irradiation has been studied. Under thermal annealing, the crystallization temperature and activation energy for crystallization of a-Ge in the a-Ge/Ni bilayer recording film were significantly reduced to 385 °C and 2.4 eV, respectively, due to the fast Ge diffusion in the already formed germanide phases. The reaction exponent m of ∼1.7 for the a-Ge/Ni bilayer corresponds to a crystallization process in which grain growth occurs with nucleation and the nucleation rate decreases with the progress of the grain growth process. Under pulsed laser irradiation, the maximum data-transfer rates of 22, 56, 74, and 112 Mbits/s can be achieved in the write-once blue-ray disk at the recording powers of 3, 4, 5, and 6 mW, respectively.

Addition of trichloronitrosomethane to 1,3-cycloalkadienes gives [2+4] cpclo-adducts. However, reactions with acyclic 1,3-butadienes afford unstable cycloadducts which hydrolyze in water-ether solution to produce N-chloroformyl-3,6-dihydro-l, 2-oxazines. The later compounds are reduced to N-methyl or converted to N-methoxylcarbonyl derivatives in high yields.

Addition of trichloronitrosomethane to 1,3-cycloalkadienes gives [2+4] cpclo-adducts. However, reactions with acyclic 1,3-butadienes afford unstable cycloadducts which hydrolyze in water-ether solution to produce N-chloroformyl-3,6-dihydro-l, 2-oxazines. The later compounds are reduced to N-methyl or converted to N-methoxylcarbonyl derivatives in high yields.