Synthesis and characterization of novel classes of PDE10A inhibitors - 1H-1,3-benzodiazoles and imidazo[1,2-a]pyrimidines

New compounds containing [1,2,4]triazolo [1,5-a]pyridine (I), pyrazolo [1,5-a]pyridine (II), 1H-1,3-benzodiazole (III) and imidazo [1,2-a]pyrimidine (IV) backbones were designed and synthesized for PDE10A interaction. Among these compounds, 1H-1,3-benzodiazoles and imidazo [1,2-a]pyrimidines showed...

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Published in:European journal of medicinal chemistry 2018-07, Vol.155, p.96-116
Main Authors: Moszczyński-Pętkowski, Rafał, Majer, Jakub, Borkowska, Małgorzata, Bojarski, Łukasz, Janowska, Sylwia, Matłoka, Mikołaj, Stefaniak, Filip, Smuga, Damian, Bazydło, Katarzyna, Dubiel, Krzysztof, Wieczorek, Maciej
Format: Article
Language:English
Subjects:
1H-1,3-benzodiazoles
Imidazo[1,2-a]pyrimidines
PDE10A
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Summary:New compounds containing [1,2,4]triazolo [1,5-a]pyridine (I), pyrazolo [1,5-a]pyridine (II), 1H-1,3-benzodiazole (III) and imidazo [1,2-a]pyrimidine (IV) backbones were designed and synthesized for PDE10A interaction. Among these compounds, 1H-1,3-benzodiazoles and imidazo [1,2-a]pyrimidines showed the highest affinity for PDE10A enzyme as well as good metabolic stability. Both classes of compounds were identified as selective and potent PDE10A enzyme inhibitors. [Display omitted] •New classes of PDE10 inhibitors were designed based on Example 1a by BMS.•Four different heterocyclic cores were explored.•Two obtained lead classes of compounds are selective and metabolically stable.•Compound 66 proved to be equally potent and 10-fold more stable than Example 1a.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2018.05.043