Distribution, drug design

Feil, D. (1991) X-ray diffraction and charge distribution application to the electron density distribution in the hydrogen bond, In TheApplication of Charge Density Research to Chemistry and Drug Design, Jeffrey, G.A. and Piniella, J.F. (Eds.), NATO ASI Series B250, Plenum Press, New York. 

Physiologically based pharmacokinetic models provide a format to analyze relationships between model parameters and physicochemical properties for a series of drug analogues. Quantitative structure-pharmacokinetic relationships based on PB-PK model parameters have been pursued [12,13] and may ultimately prove useful in the drug development process. In this venue, such relationships, through predictions of tissue distribution, could expedite drug design and discovery. 

A set of molecules is needed to extract spatially distributed chemical features for inclusion in drug design. 

A quantitative analysis of the structure-retention relationship can be derived by using the relative solubility of solutes in water. One parameter is the partition coefficient, log P, of the analyte measured as the octanol-water partition distribution. In early work, reversed-phase liquid chromatography was used to measure log P values for drug design. Log P values were later used to predict the retention times in reversed-phase liquid chromatography.The calculation of the molecular properties can be performed with the aid of computational chemical calculations. In this chapter, examples of these quantitative structure-retention relationships are described. 

Ho, C.M.W. RACHEL , RACHEL is developed by Drug Design Methodologies LLC, http //www.newdrugdesign.com and is distributed by Tripos Inc, http //www.tripos.com, 2002. 

The present volume of the series Methods and Principles in Medicinal Chemistry focuses on the impact of pharmacokinetics and metabolism in Drug Design. Pharmacokinetics is the study of the kinetics of absorption, distribution, metabolism, and excretion of drugs and their pharmacologic, therapeutic, or toxic response in animals and man. 

Volume of Distribution General Considerations and Applications to Experimental Pharmacokinetics and Drug Design... 

The next major consideration during optimization for the pharmacokinetic/pharmaceutical phase concerns the design of drugs to overcome barriers during their distribution. Of these barriers, the blood-brain barrier is by far the most important to the drug designer. 

The extended Electron Distribution (XED) force field was first described by Vinter [96]. This force field proposes a different electrostatic treatment of molecules to that found in classical molecular mechanics methods. In classical methods, charges are placed on atomic centers, whereas the XED force field explicitly represents electron anisotropy as an expansion of point charges around each atom. The author claims that it successfully reproduces experimental aromatic ji stacking. Later, others made similar observations [97]. This force field is now available in Cresset BioMoleculaf s software package [95]. Apaya et al. were the first to describe the applicability of electrostatic extrema values in drug design, on a set of PDE III inhibitors [98]. 

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