By Bernard Testa, Han van de Waterbeemd, Gerd Folkers, Richard Guy
During this age of combinatorial chemistry and high-throughput applied sciences, bioactive compounds known as hits are came upon via the hundreds of thousands. even though, the line that leads from hits to guide compounds after which to pharmacokinetically optimized medical and drug applicants is particularly lengthy certainly. therefore, the screening, layout, and optimization of pharmacokinetic homes has turn into the bottleneck and a huge problem in drug study. To shorten the time-consuming develop-ment and excessive expense of attrition of lively compounds finally doomed by means of hidden pharmacokinetic defects, drug researchers are coming to include structure-permeation, structure-distribution, structure-metabolism, and structure-toxicity family members into drug-design recommendations. To this finish, robust organic, physicochemical, and computational methods are being built whose ambitions are to extend the scientific relevance of drug layout, and to cast off once attainable compounds with unfavourable physicochemical homes and pharmacokinetic profiles. Toxicological matters also are of extreme significance during this paradigm.
there has been, therefore, an pressing want for a ebook overlaying this box in an authoritative, didactic, complete, authentic, and conceptual demeanour. during this paintings of special breadth and intensity, overseas experts and working towards specialists from academia and current the main smooth organic, physicochemical, and computational concepts to optimize gastrointestinal absorption, protein binding and distribution, mind permeation, and metabolic profile. The organic thoughts emphasised within the e-book contain cellphone cultures and high-throughput displays. The physicochemical suggestions specialise in the choice and interpretation of solubility, lipophilicity, and comparable molecular homes as elements and predictors of pharmacokinetic bahavior. specific awareness is paid to the lipophilicity profiles of ionized compounds, to lipophilicity measurements in anisotropic media (liposomes/water, IAM columns), and to permeability throughout man made membranes. Computational techniques contain digital screening, molecular modelling, lipophilicity, and H-bonding fields and their value for structure-disposition relations.
This booklet is either approximately theoretical and technological breakthroughs. hence, molecular homes are meditated from a twin viewpoint, specifically a) their interpretation in organic and/or physicochemical phrases, and b) their price in screening, lead optimization, and drug-candidate selection.
as well as its 33 chapters, the booklet features a CD-ROM containing the invited lectures, oral communications and posters (in complete model) provided on the moment LogP Symposium, 'Lipophilicity in Drug Disposition -- sensible and Computational techniques to Molecular houses on the topic of Drug Permeation, Disposition and Metabolism', held on the college of Lausanne in March 2000. Content: