(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

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

A combinatorial approach to improving the performance of azoarene photoswitches

• Joaquin Calbo,
• Aditya R. Thawani,
• Rosina S. L. Gibson,
• Andrew J. P. White and
• Matthew J. Fuchter

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