N-benzyl derivatives of 2-amino-8-methoxy-4H-chromene-3-carbonitrile: synthesis via reductive amination, in silico ADME profiling &amp; exploration of their effects against protein kinases.

Bazureau Jean Pierre; Marwa DHIABI; Ali Bouattour; Mehdi Fakhfakh; Souhir Abid; Emmanuelle Limanton; Ludovic Paquin; Thomas Robert; Stéphane Bach; Houcine Ammar

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N-benzyl derivatives of 2-amino-8-methoxy-4H-chromene-3-carbonitrile: synthesis via reductive amination, in silico ADME profiling & exploration of their effects against protein kinases.

Bazureau Jean Pierre

^{*

1},

Marwa DHIABI

²,

Ali Bouattour

³,

Mehdi Fakhfakh

³,

Souhir Abid

⁴,

Emmanuelle Limanton

^{5, 6},

Ludovic Paquin

¹,

Thomas Robert

^{7, 8},

Stéphane Bach

^{7, 8},

Houcine Ammar

¹ Institut des Sciences Chimiques de Rennes, ISCR UMR 6226, groupe CORINT, Université de Rennes 1, Bât. 10A, Campus de Beaulieu, 263 Av. du Gén. Leclerc, CS 74205, 35042 Rennes Cedex (France)
² Laboratoire de Chimie Appliquée: Hétérocycles, Corps Gras et Polymères. Faculté des Sciences de Sfax. Université de Sfax, Route Soukra, BP 1171, 3000 Sfax, Tunisie
³ Laboratoire de Chimie Appliquée: Hétérocycles Corps Gras & Polymères, Université de Sfax, Route Soukra BP 1171, 3000 Sfax (Tunisie)
⁴ Al-Jouf University, Department of Chemistry (Science and Arts): Al Qurayat, Al Jawf, Saudi Arabia
⁵ Institut des Sciences Chimiques de Rennes ISCR UMR CNRS 6226, Université de Rennes 1, Bât. 10A, Campus de Beaulieu, CS 74205, 263 Avenue du Général Leclerc, 35042 Rennes Cedex, France
⁶ S2Wave platform, ScanMAT UAR 2025 CNRS, Université de Rennes 1, Bât. 10A, Campus de Beaulieu, CS 74205, 263 Avenue du Général Leclerc, 35042 Rennes Cedex, France
⁷ Sorbonne Université, CNRS, UMR 8227, Integrative Biology of Marine Models Laboratory (LBI2M), Station Biologique de Roscoff, Place George Tessier, BP 74, 29680 Roscoff, France
⁸ Sorbonne Université, CNRS, FR2424, Plateforme de criblage KISSf (Kinase Inhibitor Specialized Screening facility), Station Biologique de Roscoff, Place George Plessier, BP 74, 29680 Roscoff, France

Academic Editor: Alfredo Berzal-Herranz

Published: 01 November 2022 by MDPI in 8th International Electronic Conference on Medicinal Chemistry session Pharmaceutical development

Abstract:

The synthesis of 2-benzylamino-8-methoxy-4H-chromene-3-carbonitriles 7(a-e) has been realized in four steps, via reductive amination from the 2-amino-8-methoxy-4H-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 HsCDK5-p25, HsCDK9/cyclin T, HsPim1, HsHaspin, SscGSK-3a/b and SscCK1d/e showed that aldimines 6(a,b) and 6e are potentially interesting because they showed good percentage of residual activities against HsPim1 and HsHaspin.