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Synthesis, crystal structure and biological activity of novel analogues of tricyclic drugs.

Authors
  • Bieszczad, Bartosz1
  • Siwek, Agata2
  • Wilczek, Marcin3
  • Trzybiński, Damian4
  • Woźniak, Krzysztof4
  • Satała, Grzegorz5
  • Bojarski, Andrzej J5
  • Mieczkowski, Adam6
  • 1 Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland. Electronic address: [email protected] , (Poland)
  • 2 Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland. , (Poland)
  • 3 Department of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland. , (Poland)
  • 4 Biological and Chemical Research Centre, University of Warsaw, Żwirki i Wigury 101, 02-089 Warsaw, Poland. , (Poland)
  • 5 Maj Institute of Pharmacology, Polish Academy of Sciences, 12, Smętna Street, 31-343, Kraków, Poland. , (Poland)
  • 6 Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland. Electronic address: [email protected] , (Poland)
Type
Published Article
Journal
Bioorganic & medicinal chemistry letters
Publication Date
Aug 13, 2020
Volume
30
Issue
21
Pages
127493–127493
Identifiers
DOI: 10.1016/j.bmcl.2020.127493
PMID: 32798652
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

A series of fourteen novel, eight-membered lactam- and dilactam-based analogues of tricyclic drugs were obtained in a simple one-pot procedure. Crystal structures of two compounds were determined by single-crystal X-ray diffraction analysis and their selected structural features were discussed and compared with those of imipramine and dibenzepine. Affinity of developed molecules for histamine receptor H1, serotonin receptors 5-HT1A, 5-HT2A, 5-HT6, 5-HT7, serotonin transporter (SERT) and dopamine receptor D2 was determined. The commercial drug dibenzepine was also checked on these molecular targets, as its mechanism of action is largely unknown. Two derivatives of 11,12-dihydrodibenzo[b,f]azocin-6(5H)-one (7,8) and two of dibenzo[b,f]azocin-6(5H)-one (9,10) were found to be active toward the H1 receptor in sub-micromolar concentrations. Copyright © 2020 Elsevier Ltd. All rights reserved.

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