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New 6-Amino-Pyrido[2,3-D]Pyrimidine-2,4-Diones As Novel Agents to Treat Type 2 Diabetes: A Simple and Efficient Synthesis, Α-Glucosidase Inhibition, Molecular Modeling and Kinetic Study Publisher Pubmed



Adib M1 ; Peytam F1 ; Rahmanianjazi M1 ; Mahernia S2, 3 ; Bijanzadeh HR4 ; Jahani M1 ; Mohammadikhanaposhtani M5 ; Imanparast S6 ; Faramarzi MA6 ; Mahdavi M7 ; Larijani B7
Authors
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Authors Affiliations
  1. 1. School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran
  2. 2. Department of Medicinal Chemistry, Drug Design and Development Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Pharmaceutical Sciences Research Center, The Institute of Pharmaceutical Sciences, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Environmental Sciences, Faculty of Natural Resources and Marine Sciences, Tarbiat Modares University, Nur, Mazandaran, Iran
  5. 5. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
  6. 6. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: European Journal of Medicinal Chemistry Published:2018


Abstract

A new series of 6-amino-pyrido[2,3-d]pyrimidine-2,4-dione derivatives 3a–3s were prepared via a facile and efficient reaction from α-azidochalcones and 6-amiouracils. The reactions were performed under mild conditions to produce the corresponding compounds in good to excellent yields. Obtained derivatives 3a–3s were evaluated for α-glucosidase inhibitory activity and all of them exhibited excellent in vitro yeast α-glucosidase inhibition with IC50 values ranging from 78.0 ± 2.0 to 252.4 ± 1.0 μM. For example, the most active compound 3o was around 10-fold more potent than acarbose, a standard drug (IC50 = 750.0 ± 1.5 μM). Kinetic study of compound 3o revealed that it inhibited α-glucosidase in a competitive mode. Molecular modeling studies of the most active compounds 3o, 3i, 3e and 3m were also performed. © 2018 Elsevier Masson SAS
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