Synthesis and biological evaluation of 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives as protein kinase inhibitors

Mourad Chioua; Abdelouahid Samadi; Elena Soriano; Olivier Lozach; Laurent Meijer; José Marco-Contelles

doi:10.1016/j.bmcl.2009.06.099

Synthesis and biological evaluation of 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives as protein kinase inhibitors

Mourad Chioua, Abdelouahid Samadi, Elena Soriano, Olivier Lozach, Laurent Meijer, José Marco-Contelles

Research output: Contribution to journal › Article › peer-review

95 Citations (Scopus)

Abstract

The synthesis and biological evaluation of a number of differently substituted 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives are reported. From the inhibition results on a selection of disease-relevant protein kinases [IC₅₀ (μM) DYRK1A = 11; CDK5 = 0.41; GSK-3 = 1.5] we have observed that 3,6-diamino-4-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4) constitutes a potential new and simple lead compound in the search of drugs for the treatment of Alzheimer's disease.

Original language	English
Pages (from-to)	4566-4569
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	16
DOIs	https://doi.org/10.1016/j.bmcl.2009.06.099
Publication status	Published - Aug 15 2009
Externally published	Yes

Keywords

3,6-Diamino-1H-pyrazolo[3,4-b]pyridine-5-carbonitriles
Alzheimer's disease
CDK5
GSK-3
Kinase inhibitors
Molecular modelling
Pyrazolo[3,4-b]pyridines

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2009.06.099

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title = "Synthesis and biological evaluation of 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives as protein kinase inhibitors",

abstract = "The synthesis and biological evaluation of a number of differently substituted 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives are reported. From the inhibition results on a selection of disease-relevant protein kinases [IC50 (μM) DYRK1A = 11; CDK5 = 0.41; GSK-3 = 1.5] we have observed that 3,6-diamino-4-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4) constitutes a potential new and simple lead compound in the search of drugs for the treatment of Alzheimer's disease.",

keywords = "3,6-Diamino-1H-pyrazolo[3,4-b]pyridine-5-carbonitriles, Alzheimer's disease, CDK5, GSK-3, Kinase inhibitors, Molecular modelling, Pyrazolo[3,4-b]pyridines",

author = "Mourad Chioua and Abdelouahid Samadi and Elena Soriano and Olivier Lozach and Laurent Meijer and Jos{\'e} Marco-Contelles",

note = "Funding Information: M.C. thanks Instituto de Salud Carlos III (Ministerio de Salud y Consumo) for a post-doctoral fellowship. AS thanks CSIC for a I3P Post-doctoral Contract. J.M.C. thanks also MEC (SAF2006-08764-C02-01), Comunidad de Madrid (S/SAL-0275-2006), and ISCIII [Retic RENEVAS (RD06/0026/1002)] for support. J.M.C. thanks Prof. A. Mart{\'i}nez (IQM, CSIC, Spain) for helpful suggestions and discussions. ",

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doi = "10.1016/j.bmcl.2009.06.099",

language = "English",

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AU - Chioua, Mourad

AU - Samadi, Abdelouahid

AU - Soriano, Elena

AU - Lozach, Olivier

AU - Meijer, Laurent

AU - Marco-Contelles, José

N1 - Funding Information: M.C. thanks Instituto de Salud Carlos III (Ministerio de Salud y Consumo) for a post-doctoral fellowship. AS thanks CSIC for a I3P Post-doctoral Contract. J.M.C. thanks also MEC (SAF2006-08764-C02-01), Comunidad de Madrid (S/SAL-0275-2006), and ISCIII [Retic RENEVAS (RD06/0026/1002)] for support. J.M.C. thanks Prof. A. Martínez (IQM, CSIC, Spain) for helpful suggestions and discussions.

PY - 2009/8/15

Y1 - 2009/8/15

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AB - The synthesis and biological evaluation of a number of differently substituted 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives are reported. From the inhibition results on a selection of disease-relevant protein kinases [IC50 (μM) DYRK1A = 11; CDK5 = 0.41; GSK-3 = 1.5] we have observed that 3,6-diamino-4-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4) constitutes a potential new and simple lead compound in the search of drugs for the treatment of Alzheimer's disease.

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Synthesis and biological evaluation of 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives as protein kinase inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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