Force field for monovalent, divalent, and trivalent cations developed under the solvent boundary potential.

Presented are parameters for mono-, di-, and trivalent cations compatible with the CHARMM additive force field and the TIP3P water model. Thermodynamic perturbation molecular dynamics simulations were performed for the cations located at the center of a TIP3P water sphere under a solvent boundary potential. A series of perturbations generated free energies of hydration indexed by the two Lennard-Jones parameters, ε and R(min).

Quantitative structure-activity relationship of spirosuccinimide type aldose reductase inhibitors diminishing sorbitol accumulation in vivo.

Racemate physicochemical descriptors are employed to probe the quantitative structure-activity relationship of spirosuccinimide type aldose reductase inhibitors and the in vivo inhibitory activity of sorbitol accumulation. The in vivo activity data include the percent inhibition and ED50 assay results on the literature. The derived QSAR equations show that the hydrophobic character of aldose reductase inhibitor is the major contributing factor to enhance in vivo activity.

Quantitative structure and aldose reductase inhibitory activity relationship of 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-4-spiro-3'-pyrrolidine-1,2',3,5'-tetrone derivatives.

We investigate the quantitative structure-activity relationship of spirosuccinimide-fused tetrahydropyrrolo[1,2-a]pyrazine-1,3-dione derivatives acting as aldose reductase inhibitors, which contain a chiral center. The published assay data of 30 training compounds are not for optically pure enantiomer preparations but for racemic mixtures. As the physicochemical descriptors for the QSAR analysis must be evaluated for either (R)-enantiomer or (S)-enantiomer, we devise a new 'racemic' descriptor as the arithmetic mean of the (R)-enantiomer descriptor and the (S)-enantiomer descriptor.