Bioisostere prediction

Further development in the chemistry of oxazolidinone antibacterials was based mainly on the assumption that the 4-pyridyl moiety of one of Dupont s lead compounds, E-3709, might be amenable to replacement by suitably saturated heterocyclic bioisosteres [48]. This assumption was based on an example in which successful replacement of the piperazine ring system in the quinolone antibacterials, such as ciprofloxacin, with a pyridine fragment, such as seen in Win-57273, results in improvement of both the antibacterial and the pharmacokinetic profiles of the compounds. Similarly, as in the case of ciprofloxacin and Win-57273, it was predicted that the presence of a small but highly electron-withdrawing fluorine atom would be tolerated at the meta position(s) of the central phenyl ring, and would confer enhanced antibacterial activity and/or other desirable properties to the targeted oxazolidinones, as shown in Fig. 3. 

Database a web-based tool using quantum chemical topology to predict bioisosteric replacements for drug design. Journal of Chemical Information and Modeling, 49 (6), 1497-1513. 

In addition to the potential of triazoles in mimicking the amide moiety and consequently the peptide bond, their capability to act as bioisosteres of the acyl phosphate and h ns-olefinic moieties has also been predicted [18]. The... 

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