1 Supplementary Information Development of Novel Amide–Derivatized 2,4- Bispyridyl Thiophenes as Highly Potent and Selective Dyrk1A Inhibitors. Part II: Identification of the cyclopropylamide moiety as a key modification AUTHOR NAMES Sarah S. Darwish 1 , Mohammad Abdel-Halim 1 , Ahmed K. ElHady 1 , Mohamed Salah 2 , Ashraf H.Abadi 1 , Walter Becker 3 and Matthias Engel 2 AUTHOR ADDRESS 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt 2 Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2.3, D-66123 Saarbrücken, Germany 3 Institute of Pharmacology and Toxicology, Medical Faculty of the RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany
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1H-NMR (500 MHz, DMSO) and 13C-NMR (126 MHz, … · Web viewDevelopment of Novel Amide–Derivatized 2,4-Bispyridyl Thiophenes as Highly Potent and Selective Dyrk1A Inhibitors. Part
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1
Supplementary Information
Development of Novel Amide–Derivatized 2,4-Bispyridyl Thiophenes
as Highly Potent and Selective Dyrk1A Inhibitors. Part II:
Identification of the cyclopropylamide moiety as a key
modification
AUTHOR NAMES
Sarah S. Darwish1, Mohammad Abdel-Halim1, Ahmed K. ElHady1, Mohamed Salah2, Ashraf
H.Abadi1, Walter Becker3 and Matthias Engel2
AUTHOR ADDRESS
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German
University in Cairo, Cairo 11835, Egypt
2Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2.3, D-66123
Saarbrücken, Germany
3Institute of Pharmacology and Toxicology, Medical Faculty of the RWTH Aachen University,
Wendlingweg 2, 52074 Aachen, Germany
Contents1 1H-NMR (500 MHz, DMSO) and 13C-NMR (126 MHz, DMSO) spectra of selected compounds.......2
1 1H-NMR (500 MHz, DMSO) and 13C-NMR (126 MHz, DMSO) spectra of selected compounds
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2 Figure S1
B
AIle165
Ile165
Fig. S1. Comparison between the hydrophobic surface contacts of the acetyl side chain in compound 1b (A) and the cyclopropyl in compound 4b (B) with Ile165 in Dyrk1A. Van der Waals interactions are predicted for 4b, whereas the van der Waals volume of the acetyl moiety in 1b is too small to contact Ile165. Shown are the Connolly surfaces with the following colour coding: green, hydrophobic; magenta, hydrophilic.