Application of a hemodialysis clearance prediction model using quantitative structure-pharmacokinetic relationship analysis.

Hemodialysis (HD) is a method used to remove biogenic substances or blood components that cause disease and some drugs used by patients to treat their diseases. Therefore, dosing schedule must be planned according to HD clearance (CLHD ) when medical treatment is provided to patients receiving HD. We aimed to clarify the physical properties (eg, octanol-water partition coefficient and molecular electronegativity) or pharmacokinetic parameters (eg, volume of distribution) of compounds affecting CLHD and to construct a mathematical model to predict CLHD . The analysis covered individual CLHD data for nine compounds from the literature. The molecular descriptors which are physical properties or pharmacokinetic parameters were calculated using the structural formula of each compound, and searched for factors related to CLHD among the calculated 148 molecular descriptors. Nonlinear mixed-effects model analysis with CLHD as objective variable and molecular descriptors as explanatory variable was conducted to examine the factor affecting CLHD and develop a model for predicting CLHD . The logarithm of the brain/blood partition coefficient was detected as a factor affecting CLHD . The predictive accuracy of CLHD using the constructed mathematical model with the logarithm of the brain/blood partition coefficient as explanatory variable was adequate.

Enantioselective, desymmetrizing, bromolactonization reactions of symmetric olefinic dicarboxylic acids.

The results of studies leading to the development of enantioselective desymmetrizing, bromolactonization reactions of symmetric olefinic dicarboxylic acids, which are promoted by a C3 -symmetric trisimidazoline catalyst, are described. These processes generated carboxylic-acid-containing bromolactones in moderately high enantiomeric excesses. The results of optimization studies showed that reactions in a mixed solvent system of toluene and acetone proceeded with the highest levels of enantioselectivity. NMR studies probing the interactions between the catalyst and dicarboxylic acid substrates, as well as the effect of acetone on the stereochemistry of the process, are also described.

Kinetic resolution of ß-substituted olefinic carboxylic acids by asymmetric bromolactonization.

A strategically novel kinetic resolution of ß-substituted olefinic carboxylic acids is developed by asymmetric bromolactonization using an organocatalyst, 4-tBuPh-tris 1b. The cyclization stage, which provides δ-lactone, is proposed to be operative for discrimination of each enantiomer of carboxylic acids.