Pharmacophore Point Filter The to

iogical drug fragmentation approaches cussed above suggest that the occurrence of a relatively small number of frameworks (ring structures and linkers), an even smaller number of side chains, and a small number of polar groups characterize drugs very well. Although drugs and nondrugs are not completely distinguishable, it has been observed that drugs differ somewhat from nondrugs in their possession of hydrophobic moieties that are well functionalized. Non-, drugs often contain under functionalized hydrophobic groups (Fig. 6.8). Recent work to characterize the druglikeness of molecules focuses more on the presence of key functional groups in molecules.

A simple pharmacophore point filter has been introduced recently (47). It is based on the assumption that druglike molecules should contain at least two distinct pharmacophore groups (47). Four functional motifs have been identified that guarantee hydrogen-bonding capabilities that are essential for the specific interaction of a drug molecule with its biological target (Fig. 6.9). These motifs can be combined to functional groups that are also referred to here as pharmacophore points; they include: amine, amide, alcohol, ketone, sulfone, sulfonamide, carboxylic acid, carbamate, guanidine, amidine, urea, and ester. The following main rules apply to the pharmacophore point filter (PF1):

Figure 6.8. Number of pharmacophore points in drug databases (MDDR + CMC) and reagent databases (ACD).

Figure 6.8. Number of pharmacophore points in drug databases (MDDR + CMC) and reagent databases (ACD).

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