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
from both compounds.
The first investigation of 1,2-BCPs as an isosteric replacement for ortho-benzene was reported by Baran, Collins and co-workers [26]. They prepared a wide variety of 1,2-BCPs from a common 2-substituted [1.1.1]propellane building block, propellane 3a (Scheme 1A). Propellane 3a was
1,2-BCH (+)-23 and ortho-benzene telmisartan has been reported by Walker and co-workers (Figure 4) [34]. They found that both the substituent distance d and scaffold carbon distance r of 1,2-BCH (+)-23 closely resemble the ones found in telmisartan. While this agreement extends to the substituent
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Graphical Abstract
Figure 1:
Scaffolds commonly reported as bioisosteric replacements of para-substituted benzene and examples p...
Beilstein J. Org. Chem.2019,15, 2753–2764, doi:10.3762/bjoc.15.266
measurements of representative examples, we demonstrate that ortho-benzene substitution of the arylazopyrazoles drastically increases the Z-isomer stability and allows further tuning of their addressability. This includes the discovery of new azopyrazoles with a Z-isomer thermal half-life of ≈46 years. Such
interactions. The energy-minimized structures for the Z-isomer of representative photoswitches are shown in Figure S2 (Supporting Information File 1). The proximity of the ortho-benzene substituents to the heteroaryl ring in the Z-isomer either stabilizes the Z-isomer ground state via noncovalent interactions
improve the performance of azoarene photoswitches – ortho-substitution of the benzene ring(s) and replacement of one of the benzenes for a pyrazole (to give an arylazopyrazole) – into a single switch unit. We show that ortho-benzene substitution of the arylazopyrazoles drastically increases the Z-isomer
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Graphical Abstract
Figure 1:
a) Tetra ortho-substituted azobenzenes represent a significant advance in terms of Z-isomer stabili...