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Synthesis, Experimental and Computational Studies of N-(4-amino-6-oxo- 1,6-dihydropyrimidin-5-yl)benzamide

[ Vol. 15 , Issue. 6 ]

Author(s):

Agnieszka A. Kaczor*, Agata Bartyzel, Monika Pitucha, Tomasz M. Wrobel, Sylwia Wozniak and Dariusz Matosiuk   Pages 491 - 502 ( 12 )

Abstract:


Background: Blockade of kainate receptors is an emerging strategy to treat neurodegenerative diseases, including Parkinson's disease as well as to treat epilepsy. In particular, non-competitive antagonists of kainate receptors are promising due to the expected good safety profile. We present here synthesis, experimental and computational studies of N-(4-amino-6-oxo-1,6-dihydropyrimidin-5- yl)benzamide which is an intermediate in the synthesis of hypoxanthine derivatives which were designed as non-competitive antagonists of kainate GluK1/GluK2 receptors.

Method: The title compound was obtained in a five-step synthesis protocol and characterized used X-ray crystallography and experimental and computed spectra.

Results: The presented detailed X-ray studies of the title compound confirm the reaction course. The title compound crystallizes in triclinic P-1 space group. The asymmetric unit comprises two independent molecules of the compound (A and B) and a DMF solvent molecule. The interpretation of IR spectra was facilitated by Potential Energy Distribution (PED) analysis. The low value of HOMO-LUMO gap indicates that the studied compound is relatively reactive.

Conclusion: The title compound is a well-characterized intermediate which will be subjected to cyclization to hypoxanthine derivative designed as non-competitive antagonist of kainate GluK1 and GluK2 receptors.

Keywords:

IR spectra, NMR spectra, PED analysis, theoretical computations, X-ray studies, receptors.

Affiliation:

Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodzki St., PL-20093 Lublin, Department of General and Coordination Chemistry, Faculty of Chemistry, Maria Curie-Sklodowska University, M. Curie-Sklodowskiej Sq. 2, PL-20031 Lublin, Department of Organic Chemistry, Faculty of Pharmacy with Division of Medical Analytics, 4A Chodzki St., PL-20093 Lublin, Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodzki St., PL-20093 Lublin, Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodzki St., PL-20093 Lublin, Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodzki St., PL-20093 Lublin

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