Undesirable physicochemical properties

In the early days of combinatorial chemistry, there was an emphasis on building very large libraries however, these early approaches were disappointing, with libraries either failing to produce the hit rates expected or resulting in hits that had undesirable physicochemical properties to be considered as lead compounds [6]. More recently, the focus has shifted toward more rationally designed smaller libraries [7]. 

The separation of analytes from undesirable matrix components, or cleanup , of sample extracts can be accomplished through a variety of techniques that take advantage of differences in the physicochemical properties of the analytes from co-extracted matrix components. 

These substances share a set of common physicochemical properties that can lead to undesirable effects on living systems. There is a limited range... 

Cyclodextrins (CDs) have a wide range of application in the pharmaceutical field due to their unique structure, which allows them to include hydrophobic molecules in their apolar cavity and to mask the physicochemical properties of the included molecule. This results in the enhancement of drug bioavailability by improving aqueous solubility and the physical and chemical stability of the drug, masking undesired side effects such as irritation, taste, or odor, and overcoming compatibility problems or interactions between drugs and excipients. 

Once identified, these functional groups can be optionally excluded from future compound acquisitions or library designs unless a competing interest encourages their use. A report on the compound acquisition process at Novartis discusses how compounds are prioritized or eliminated for acquisition based on similarity to the historical collection, as well as physicochemical properties and undesirable functionality. Many of the same themes are presented in other reports on compound selection." ... 

Sol-gel-derived materials are popular for developing sensors.16 40"13 The physicochemical properties within these sol-gel-derived nanocomposites is an important factor in designing platforms for sensing applications.18 20 22 44-53 Factors such as polarity, microviscosity, pore size, pore wall chemistry, microscopic phase separation, partition coefficient, and solubility coefficient can dramatically alter the behavior of active dopants within a nanocomposite and may lead to undesirable properties. 

When a lead compound is first discovered for a particular disease state, it often lacks the required potency and pharmacokinetic properties suitable for making it a viable clinical candidate. These may include undesirable side effects, physicochemical properties, other factors that affect oral bioavailability (see Chapter 9), and adverse metabolic or excretion properties. These undesirable properties could be the result of specific functional groups in the molecule. The medicinal chemist therefore must modify the compound to reduce or eliminate these undesirable features without losing the desired biological activity. Replacement or modification of functional groups with other groups having similar properties is known as isosteric replacement, or bioisosteric replacement. ... 

The effects have been studied of the total or partial substitution of Ni by Cu or Co on the physicochemical properties and catalytic activity of Ni (Co,Cu)-Zn-Al catalysts used for the selective hydrogenation of acetylene. In addition, the influence of the hydrogen concentration in the feed on the activity, selectivity and coke formation on the catalysts has been investigated. The results obtained in this work could be explained by the formation, to different degrees, of bimetallic clusters of Ni-Cu and Ni-Co in the quaternary Ni-Co-Zn-Al and Ni-Cu-Zn-Al catalysts. The formation of these bimetallic clusters would be responsible for the diminution of methane and ethane, both undesirable products. 

---