The Effect of Predeformation on Creep Strength of 9% Cr Steel.

Martensitic creep-resistant P92 steel was deformed by different methods of severe plastic deformation such as rotation swaging, high-pressure sliding, and high-pressure torsion at room temperature. These methods imposed significantly different equivalent plastic strains of about 1-30. It was found that rotation swaging led to formation of heterogeneous microstructures with elongated grains where low-angle grain boundaries predominated. Other methods led to formation of ultrafine-grained (UFG) microstructures with high frequency of high-angle grain boundaries. Constant load tensile creep tests at 873 K and initial stresses in the range of 50 to 300 MPa revealed that the specimens processed by rotation swaging exhibited one order of magnitude lower minimum creep rate compared to standard P92 steel. By contrast, UFG P92 steel is significantly softer than standard P92 steel, but differences in their strengths decrease with increasing stress. Microstructural results suggest that creep behavior of P92 steel processed by severe plastic deformation is influenced by the frequency of high-angle grain boundaries and dynamic grain coarsening during creep.

Special ergolines are highly selective, potent antagonists of the chemokine receptor CXCR3: discovery, characterization and preliminary SAR of a promising lead.

The special ergoline 1 is a highly potent, selective antagonist of the chemokine receptor CXCR3. The surprising selectivity of this LSD-related compound can be explained by different electronic and steric properties of the ergoline core structure caused by the urea portion of the molecule. Discovery, biopharmaceutical properties and first derivatives of this promising lead compound are discussed.

Complementary use of ion trap/time-of-flight mass spectrometry in combination with capillary high-pressure liquid chromatography: early characterization of in vivo metabolites of the cathepsin K inhibitor NVP-AAV490 in rat.

Cathepsin K is a cysteine proteinase, primarily expressed in osteoclasts, which has a strong collagenolytic activity and plays an essential role involved in bone matrix degradation. Its inhibition could provide a novel approach to the treatment and prevention of osteoporosis. One structural class of lead compounds in our cathepsin K inhibitors program is based on an arylaminoethyl amide scaffold, which has potential metabolic weak points that might be stabilized by appropriate chemical modification(s). For the identification of potential metabolic "soft spots" and the rational design of improved derivatives, early biotransformation of a potent arylaminoethyl amide cathepsin K inhibitor (NVP-AAV490-NX) was investigated in plasma, urine and liver homogenates of rats after intravenous bolus administration of 10 mg/kg. The detection and identification of metabolites was achieved by high-resolution mass spectrometry (time-of-flight MS) and multi-dimensional mass spectrometry (ion trap MS). Both mass spectrometers were combined with reversed-phase capillary high-performance liquid chromatography columns. It was demonstrated that both mass analyzers complement each other and that, even in the sub-nanogram range, the resulting set of MS data can be successfully used to elucidate most of the metabolic changes unambiguously, solely by mass spectrometric techniques. The proposed metabolite structures were additionally corroborated by exact mass measurement of the protonated molecular ions to confirm the predicted elemental composition, by determination of the number of the exchangeable hydrogen atoms replacing water against deuterium oxide as mobile phase and, in one case, by an MS(3) product ion experiment in order to elucidate the site of conjugation.