Beilstein J. Org. Chem.2024,20, 859–890, doi:10.3762/bjoc.20.78
well as the impact they have on the physiochemical and biological properties of pharmaceuticals and agrochemicals.
Keywords: bioisosteres; drug discovery; meta-benzene; ortho-benzene; Introduction
The logical and iterative modification of the structure of a drug candidate is a critical part of the
soluble and less lipophilic ortho-isosteres has previously been discussed (see Figure 10–Figure 12). The related 1,4-disubstituted-2-oxa-BCHs (2-oxa-1,4-BCHs) have also been investigated as meta-benzene isosteres (Figure 18) [58]. The exit vector analysis of 2-oxa-1,4-BCHs shows that the substituent
also significantly reduced for both 2- and 3-oxa-1,4-BCHs compared with para-benzene 121 indicating higher metabolic stability.
1,5-Disubstituted bicyclo[3.1.1]heptanes
While only one investigation of BCHeps as potential ortho-benzene isosteres has been reported [46], their potential as meta-benzene
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Graphical Abstract
Figure 1:
Scaffolds commonly reported as bioisosteric replacements of para-substituted benzene and examples p...