Synthesis of (2-Aminopyrimidin-4-yl)(pyridin-4-yl)methanone and Derivatives

Francis Giraud; Béatrice Josselin; Sandrine Ruchaud; Fabrice Anizon; Pascale Moreau

doi:10.1055/a-2107-4571

Synthesis, Table of Contents

Synthesis 2023; 55(22): 3825-3832
DOI: 10.1055/a-2107-4571

paper

Synthesis of (2-Aminopyrimidin-4-yl)(pyridin-4-yl)methanone and Derivatives

Francis Giraud∗

^aUniversité Clermont Auvergne, CNRS, Clermont Auvergne INP, ICCF, 63000 Clermont-Ferrand, France

,

Béatrice Josselin

^bSorbonne Université, CNRS, UMR8227, Integrative Biology of Marine Models Laboratory (LBI2M), Station Biologique de Roscoff, 29680 Roscoff, France

^cSorbonne Université, CNRS, FR2424, Plateforme de criblage KISSf (Kinase Inhibitor Specialized Screening Facility), Station Biologique de Roscoff, 29680 Roscoff, France

,

Sandrine Ruchaud

^bSorbonne Université, CNRS, UMR8227, Integrative Biology of Marine Models Laboratory (LBI2M), Station Biologique de Roscoff, 29680 Roscoff, France

,

Fabrice Anizon∗

^aUniversité Clermont Auvergne, CNRS, Clermont Auvergne INP, ICCF, 63000 Clermont-Ferrand, France

,

Pascale Moreau∗

^aUniversité Clermont Auvergne, CNRS, Clermont Auvergne INP, ICCF, 63000 Clermont-Ferrand, France

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Abstract

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Abstract

Pyrido[3,4-g]quinazoline was previously identified as a relevant scaffold for protein kinase inhibition. In order to assess if the planarity of this heterocyclic system was essential to the protein kinase inhibitory potency observed in this series, new compounds were synthesized and evaluated, in which the central cycle was opened to provide (pyridin-4-yl)(pyrimidin-4-yl)methane derivatives, which were prepared from the corresponding ketone precursor. After preparing (2-aminopyrimidin-4-yl)(pyridin-4-yl)methanone, derivatives were synthesized and evaluated toward a panel of protein kinases. The results demonstrated that the planar pyrido[3,4-g]quinazoline tricyclic system was mandatory to maintain the protein kinase inhibitory potency in this series.

Key words

diheteroaryl ketone - pyrido[3,4-g]quinazoline - (pyrimidin-4-yl)(pyridin-4-yl)methanone - Grignard reagents - molecular shape - protein kinase inhibitors

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References

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