Insights into the crystal structure of two newly synthesized quinoxalines derivatives as potent inhibitor for c-Jun N-terminal kinases

Two new compounds namely, ethyl (2E)-3-(dimethylamino)-2-(3-methoxyquinoxalin-2-yl)propen-2-enoate (II) and ethyl 2-(3-oxo-4-(prop-2-yn-1-yl)-3,4-dihydroquinoxalin-2-yl)-3-phenylpropanoate (III) have been synthesized from ethyl 2-(oxo-3,4-dihydroquinoxalin-2-yl) acetate (I). The compounds were characterized using NMR (1H and 13C), Fourier transform infrared and confirmed by single crystal X-ray diffraction studies. The quinoxaline portion of II is almost planar with the substituent containing the dimethylamino and carboxyethyl groups rotated well out of its mean plane. In the crystal, C—H···O and C—H···N hydrogen bonds as well as C—H···π(ring) interactions form chains having a U-shaped cross-section and running along the c-axis direction. Two sets of pair-wise C—H···O hydrogen bonds connect the chains into corrugated sheets. In III, the three substituents on the dihydroquinoxaline moiety are rotated well out of its mean plane. Three sets of C—H···O hydrogen bonds as well as C—H···π(ring) and π–π-stacking interactions form layers approximately parallel to [001]. These are associated along the c-axis direction by additional C—H···π(ring) interactions. Additionally, the Hirshfeld surface analyses showed that the H···H contact is the most important interaction for both II and III. In addition to this, molecular docking and dynamics studies were carried for these two compounds with the c-Jun N-terminal kinases (JNK1) molecule. Communicated by Ramaswamy H. Sarma. © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Abad N.1 , El Bakri Y. , Lai C.-H.3, 4 , Karthikeyan S. 5 , Ramli Y.6 , Ferfra S.1 , Mague J.T.7 , Essassi E.M.1
Taylor and Francis Ltd.
  • 1 Laboratoire de Chimie Organique Hétérocyclique, Centre de Recherche des Sciences des Médicaments, Pôle de Compétences Pharmacochimie, URAC 21, Faculté des Sciences, Université Mohammed V Rabat, Rabat, Morocco
  • 2 Department of Theoretical and Applied Chemistry, South Ural State University, Chelyabinsk, Russian Federation
  • 3 Department of Medical Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan
  • 4 Department of Medical Education, Chung Shan Medical University Hospital, Taichung, Taiwan
  • 5 Organic Chemistry Department, Science Faculty, RUDN University, Moscow, Russian Federation
  • 6 Medicinal Chemistry Laboratory, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco
  • 7 Department of Chemistry, Tulane University, New Orleans, LA, United States
crystal structure; Hirshfeld surface analysis; molecular docking; molecular dynamics; Quinoxaline
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