Chemistry Reference
In-Depth Information
Various approaches can also describe steric properties of substituents. The
simplest is to count the number of atoms or the molecular weight of the
substituent as well as summing the van der Waals radii of the substituents atoms
and even taking into account the distance between attachment points. A simple
approach to predict the hydrogen-bonding potential of a substituent is to simple
encode the number of hydrogen bond acceptors (HBA) and hydrogen bond donors
(HBD).
Often the molecular field of a substituent is characterized as descriptors encoding
pharmacophoric feature points and their relations, orientations or electrostatic
potentials. When possible, conformational flexibility is taking into consideration.
Another interesting approach is the mining of bioisosteric groups from molecular
databases with biological activities yielding a rich resource of chemically feasible
bioisosteric pairs. This yields novel relative orientations and combinations of
substituents permitting even local exploration of the chemical space of interest.
There are procedures for automated extraction of transformation rules for
bioisosteric replacements. The determination of a pair of substituents that are
bioisosterically equivalent is still a challenging area of research. Another area of
interest is the identification of bioisosteric groups based on similarity of group
properties. The challenge of scaffold hopping is a subset of bioisosteric
replacement [232-243].
SCAFFOLD HOPPING
The aim of scaffold hoping is to discover structural novel compounds starting
from known active compounds by modifying the central core structure of the
molecule. The term scaffold describe the core structure of a molecule. The core
structure is the central component of a molecule, the substantial substructure that
contains the molecular material necessary to ensure that the functional groups are
in a desired geometrical arrangement [244-254].
Hit selection and lead generation are major research areas of medicinal chemistry.
Ligand complexity, ligand-binding efficiency, chemical tractability and ligand-
target profile are important parameters in hit selection. More chemistry resources
