Discovery of 1H-pyrazolo[3,4-b]pyridines as potent dual orexin receptor antagonists (DORAs)
Graphical abstract
Section snippets
Acknowledgements
We thank J. Blanz, P. Ramstein, W. Gertsch and F. Blasco for the biotransformation study of compound 13. Furthermore we thank Richard Felber, Sandrine Liverneaux, Andrea Hasler, Alfred Tanner, Thomas Gut, Marc Weibel, Fatma Limam, Marjorie Bourrel, Michael Wright for synthetic support, Dominique Monna, Edi Schuepbach and Daniel Langenegger for in vitro biological data, and Jürgen Wagner for management support and helpful discussions.
References and notes (17)
- et al.
Cell
(1998) - et al.
Neuropeptides
(2013) - et al.
Annu. Rep. Med. Chem.
(2013) - et al.
Proc. Natl. Acad. Sci. U.S.A.
(1998) - et al.
Front. Neuroendicrinol.
(2008) - et al.
Curr. Top. Med. Chem.
(2008) - et al.
Expert Opin. Ther. Pat.
(2010) - et al.
J. Neurogenet.
(2011)
Cited by (14)
One-pot three-component synthesis of novel pyrazolo[3,4-b]pyridines as potent antileukemic agents
2022, European Journal of Medicinal ChemistryCitation Excerpt :Interestingly, literature surveying ascribed several pharmacological activities to pyrazolo[3,4-b]pyridine derivatives, such as antibacterial [11–14], antiviral [15,16], antileishmanial [17], antimalarial [18], antitrypanosomal [19,20], anti-inflammatory [21–23], antioxidant [24] and antiplatelet [25] activities. Moreover, pyrazolo [3,4-b]pyridine-based small molecules were reported for management of diabetic nephropathy [26], neurodegenerative disorders [27–30], hypertension [31], insomnia [32], pulmonary hypertension [33,34] and schizophrenia [35], in addition, they were reported for their inhibitory and antagonistic activities towards phosphodiesterase-4 (PDE4) [36], acetylcholinesterase [37], Prostaglandin E2 receptor 1 (EP1) receptor [38] and A1-adenosine receptor [39,40]. Of particular interest, the anticancer activities of pyrazolo[3,4-b]pyridines stand out as the most significant pharmacological actions.
Selective N7 Alkylation of 7-Azaindazoles
2020, Journal of Organic ChemistryUse of sustainable organic transformations in the construction of heterocyclic scaffolds
2020, Green Approaches in Medicinal Chemistry for Sustainable Drug DesignA practical asymmetric synthesis of ortho-substituted 4-pyrazolyl-2-ethylamines
2019, Tetrahedron LettersCitation Excerpt :1,5-Substituted-(1H-pyrazol-4-yl)ethanamines, also known as ortho-substituted 4-pyrazolyl-2-ethylamines, form an important sub-division of bioactive pyrazoles. For example, recent uses of ortho-substituted 4-pyrazolyl-2-ethylamines include BRPF1 bromodomain inhibitors [1], potent dual orexin receptor antagonists [2] and retinoid-related orphan receptor gamma modulators [3], among others [4]. As part of a medicinal chemistry program aimed at discovering novel antagonists of the transient receptor potential vanilloid 1 (TRPV1, also known as VR1), we required an efficient route to a series of chiral ortho-substituted 4-pyrazolyl-2-ethylamines [5,6].
Choline chloride and lactic acid: A natural deep eutectic solvent for one-pot rapid construction of spiro[indoline-3,4′-pyrazolo[3,4-b]pyridines]
2019, Journal of Molecular LiquidsCitation Excerpt :Structures embedded with pyrazolo[3,4-b]pyridine units display potential medicinal properties such as antiplatelet [27], antifungal [28], anticancer [29], antimicrobial and antiproliferative [30]. They have also been found to behave as potent dual orexin receptor antagonists [31], c-Met [32], and selective FGFR kinase inhibitors [33]. Moreover, spirooxindole are also attractive structural units and are encountered in the core structure of bioactive naturally alkaloids as well as they were considered as privileged scaffolds for antiviral drug development [34–36].