Practical approach to N-benzyl derivatives of 2-amino-8-methoxy-4H-chromene-3-carbonitrile by reductive amination: Exploration of their effects against protein kinases and in silico ADME profiling

Autor: Marwa Dhiabi, Ali Bouattour, Mehdi Fakhfakh, Souhir Abid, Ludovic Paquin, Thomas Robert, Stephane Bach, Jean-Pierre Bazureau, Houcine Ammar
Přispěvatelé: Université de Sfax - University of Sfax, Jouf University, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Plate-forme de criblage d'inhibiteurs de protéines kinases=Kinase Inhibitor Specialized Screening facility (KISSf), Fédération de recherche de Roscoff (FR2424), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Intégrative des Modèles Marins (LBI2M), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), One of us (M.D.) wishes to thank the 'Ministère de l'Enseignement Supérieur et de la Recherche de Tunisie' for the grant. Financial support of this program carried out under the French National Cancer Institute 'Cancéropole Grand Ouest' in the 'Molécules Marines, Métabolisme et Cancer' M3C network, is gratefully acknowledged. S. B. and T. R. thank IBiSA (French Infrastructures en Sciences du Vivant: Biologie, Santé et Agronomie) and Biogenouest (Western France life science and environment core facility network supported by the Conseil Régional de Bretagne) for supporting the KISSf screening facility (FR2424, CNRS and Sorbonne Université).
Rok vydání: 2023
Předmět:
Zdroj: Journal of Molecular Structure
Journal of Molecular Structure, 2023, 1274 (Part 1), pp.134319. ⟨10.1016/j.molstruc.2022.134319⟩
ISSN: 0022-2860
Popis: International audience; The synthesis of 2-benzylamino-8-methoxy-4 H-chromene-3-carbonitriles 7(a-e) has been realized in four steps, via reductive amination from the 2-amino-8-methoxy-4 H-chromene-3-carbonitrile 4 as key intermediate platform with para-and meta-substituted benzaldehydes 5(a-e) , in good overall yields. The physicochemical properties of 7(a-e) and also their aldimines 6(a-e) precursors have been determined using the Swiss ADME server platform according to the Lipinski's descriptors. Biological assays with a panel of six protein kinases such as Hs CDK5-p25, Hs CDK9/cyclin T, Hs Pim1, Hs Haspin, Ssc GSK-3a/ β and Ssc CK1 δ/ ε showed that aldimines 6(a,b) and 6e are potentially interesting because they showed good percentage of residual activities against Hs Pim1 and Hs Haspin.
Databáze: OpenAIRE
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