Unlocking therapeutic potential: the role of adamantane in drug discovery

Chianna Dane; Grace A. Cumbers; Beau Allen; Andrew P. Montgomery; Jonathan J. Danon; Michael Kassiou

doi:10.1071/CH24075

RESEARCH ARTICLE (Open Access)

Previous Contents Vol 77(8)

Unlocking therapeutic potential: the role of adamantane in drug discovery

Chianna Dane ^A , Grace A. Cumbers

^A , Beau Allen ^A , Andrew P. Montgomery

^A , Jonathan J. Danon

^A and Michael Kassiou

^A ^*

+ Author Affiliations

- Author Affiliations

^A School of Chemistry, Faculty of Science, University of Sydney, Sydney, NSW 2006, Australia.

^* Correspondence to: michael.kassiou@sydney.edu.au

Handling Editor: Curt Wentrup

Australian Journal of Chemistry 77, CH24075 https://doi.org/10.1071/CH24075

Submitted: 30 May 2024 Accepted: 12 July 2024 Published online: 2 August 2024

© 2024 The Author(s) (or their employer(s)). Published by CSIRO Publishing. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND)

Abstract

The unique structural and physicochemical properties of adamantane and its derivatives have attracted considerable attention in the field of medicinal chemistry. Substituting phenyl rings for adamantane or its derivatives has provided a promising strategy to introduce lipophilicity and escape the ‘flat land’ of modern drug discovery. Additionally, the unique three-dimensional structure of adamantane facilitates the precise positioning of substituents allowing for a more effective exploration of drug targets. Evidently, we have seen an increased use of adamantane in pharmaceutically relevant molecules. The following Account highlights our group’s research in five drug discovery programs over the past 15 years showcasing the use of adamantane and its analogues in these studies.

Keywords: adamantane, cannabinoid receptors, CNS, medicinal chemistry, NMDA receptor, P2X7 receptor, sigma-2 receptor, structure–activity relationships, tau aggregation.

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