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. 2024 Feb 26;63(9):e202316557.
doi: 10.1002/anie.202316557. Epub 2024 Jan 22.

Spiro[3.3]heptane as a Saturated Benzene Bioisostere

Kateryna Prysiazhniuk  1 , Oleksandr P Datsenko  1 , Oleksandr Polishchuk  1 , Stanislav Shulha  1 , Oleh Shablykin  1   2 , Yelyzaveta Nikandrova  3 , Kateryna Horbatok  3 , Iryna Bodenchuk  3 , Petro Borysko  3 , Dmytro Shepilov  3 , Iryna Pishel  3 , Vladimir Kubyshkin  1 , Pavel K Mykhailiuk  1
Affiliations

Spiro[3.3]heptane as a Saturated Benzene Bioisostere

Kateryna Prysiazhniuk et al. Angew Chem Int Ed Engl. .

Abstract

The spiro[3.3]heptane core, with the non-coplanar exit vectors, was shown to be a saturated benzene bioisostere. This scaffold was incorporated into the anticancer drug sonidegib (instead of the meta-benzene), the anticancer drug vorinostat (instead of the phenyl ring), and the anesthetic drug benzocaine (instead of the para-benzene). The patent-free saturated analogs obtained showed a high potency in the corresponding biological assays.

Keywords: Bioisostere; Cyclobutane; Medicinal Chemistry; Spiro[3.3]Heptane; Spirocycles.

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