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The azulene scaffold from a medicinal chemist's perspective : Physicochemical and in vitro parameters relevant for drug discovery

Abstract
Azulene is a bicyclic scaffold rarely applied in medicinal chemistry. Here we report physicochemical and in vitro parameters relevant for drug discovery for a series of diversely substituted azulenes. We synthesized and characterized several scaffold hopping series of analogously substituted azulenes, indoles and naphthalenes. This enabled a comparison of azulene with the more common scaffolds indole and naphthalene. Our data indicates that undesirably low photostability of azulenes is restricted to certain substitution patterns. Generally, we conclude that azulene is an underused lipophilic bicycle and should be considered as a valuable complement to the collection of medicinal chemistry scaffolds.
Main Authors
Leino, Teppo O. Sieger, Peter Yli-Kauhaluoma, Jari Wallén, Erik A.A. Kley, Jörg T.
Format
Articles Research article
Published
2022
Series
European Journal of Medicinal Chemistry
Subjects
Indole
Naphthalene
Photostability
Scaffold hopping
atsuleeni
lääkesuunnittelu
aromaattiset yhdisteet
lääkekemia
biologinen aktiivisuus
Publication in research information system
https://converis.jyu.fi/converis/portal/detail/Publication/118852176
Publisher
Elsevier
The permanent address of the publication
https://urn.fi/URN:NBN:fi:jyu-202204262374Use this for linking
Review status
Peer reviewed
ISSN
0223-5234
DOI
https://doi.org/10.1016/j.ejmech.2022.114374
Language
English
Published in
European Journal of Medicinal Chemistry
Citation
  • Leino, T. O., Sieger, P., Yli-Kauhaluoma, J., Wallén, E. A., & Kley, J. T. (2022). The azulene scaffold from a medicinal chemist's perspective : Physicochemical and in vitro parameters relevant for drug discovery. European Journal of Medicinal Chemistry, 237, Article 114374. https://doi.org/10.1016/j.ejmech.2022.114374
License
CC BY 4.0Open Access
Funder(s)
Research Council of Finland
Funding program(s)
Postdoctoral Researcher, AoF
Tutkijatohtori, SA
Research Council of Finland
Additional information about funding
T.O.L. acknowledges the Academy of Finland (grant no. 330800) and the Doctoral Programme in Drug Research of the University of Helsinki for financial support.
Copyright© 2022 the Authors

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description Azulene is a bicyclic scaffold rarely applied in medicinal chemistry. Here we report physicochemical and in vitro parameters relevant for drug discovery for a series of diversely substituted azulenes. We synthesized and characterized several scaffold hopping series of analogously substituted azulenes, indoles and naphthalenes. This enabled a comparison of azulene with the more common scaffolds indole and naphthalene. Our data indicates that undesirably low photostability of azulenes is restricted to certain substitution patterns. Generally, we conclude that azulene is an underused lipophilic bicycle and should be considered as a valuable complement to the collection of medicinal chemistry scaffolds.
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spellingShingle The azulene scaffold from a medicinal chemist's perspective : Physicochemical and in vitro parameters relevant for drug discovery Leino, Teppo O. Sieger, Peter Yli-Kauhaluoma, Jari Wallén, Erik A.A. Kley, Jörg T. Indole Naphthalene Photostability Scaffold hopping atsuleeni lääkesuunnittelu aromaattiset yhdisteet lääkekemia biologinen aktiivisuus European Journal of Medicinal Chemistry
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title The azulene scaffold from a medicinal chemist's perspective : Physicochemical and in vitro parameters relevant for drug discovery
title_full The azulene scaffold from a medicinal chemist's perspective : Physicochemical and in vitro parameters relevant for drug discovery
title_fullStr The azulene scaffold from a medicinal chemist's perspective : Physicochemical and in vitro parameters relevant for drug discovery
title_full_unstemmed The azulene scaffold from a medicinal chemist's perspective : Physicochemical and in vitro parameters relevant for drug discovery
title_short The azulene scaffold from a medicinal chemist's perspective : Physicochemical and in vitro parameters relevant for drug discovery
title_sort The azulene scaffold from a medicinal chemists perspective Physicochemical and in vitro parameters relevant for drug discovery
topic Indole Naphthalene Photostability Scaffold hopping atsuleeni lääkesuunnittelu aromaattiset yhdisteet lääkekemia biologinen aktiivisuus
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