Lead phase, overview

This volume of Topics in Stereochemistry could not be complete without hearing about ferroelectric liquid crystals, where chirality is the essential element behind the wide interest in this mesogenic state. In Chapter 8, Walba, a pioneering contributor to this area, provides a historical overview of the earlier key developments in this field and leads us to the discovery of the unique banana phases. This discussion is followed by a view of the most recent results, which involve, among others, the directed design of chiral ferroelectric banana phases, which display spontaneous polar symmetry breaking in a smectic liquid crystal. 

The information was compiled from paper and on-line research and from direct phone conversations and meetings with industry representatives. The more comprehensive overview of case studies of company substitutions for brominated flame retardants demonstrates both the complexity and feasibility of implementing safer alternatives. Other case studies show how leading retailers are moving to phase-out hazardous materials and how some chemical industries are researching and implementing Green Chemistry alternatives. 

Pharmacokinetics and toxicity have been identified as important causes of costly late-stage failures in drug development. Hence, physicochemical as well as ADMET properties need to be fine-tuned even in the lead optimization phase. Recently developed in silica approaches will further increase model predictivity in this area to improve compound design and to focus on the most promising compounds only. A recent overview on ADME in silica models is given in Ref [128]. 

The confusion between these two characteristics is common in medicinal chemistry. It comes from the usual empirical measurement of the lipophilicity, which is the logarithm of the partition coefficient between 1-octanol and water (log P). This parameter gives a representative overview of a compound absorbed by a lipidic membrane, an essential datum in medicinal chemistry. It is often considered that the higher the log P value is, the more lipophilic the compound is. Acmally, the log P value is only a measurement of relative solubility. Considering that the solubility of a fluorinated substance decreases more in water than in octanol, this measurement leads one to think that fluorinated compounds are more lipophilic. Actually, this represents the relative lack of affinity of fluorinated compounds for both phases. 

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