1. Synthesis and Structure Activity Relationships of Chalcone based Benzocycloalkanone Derivatives as Adenosine A1 and/or A2A Receptor Antagonists
- Author
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Gisella Terre’Blanche, Helena D. Janse van Rensburg, Lesetja J. Legoabe, 12902608 - Legoabe, Lesetja Jan, 10206280 - Terre'Blanche, Gisella, and 23551917 - Janse van Rensburg, Helena Dorothea
- Subjects
Chalcone ,Stereochemistry ,Chemistry, Pharmaceutical ,Acid catalysed aldol condensation reaction ,2-Benzylidene-1-tetralone derivatives ,Chemistry Techniques, Synthetic ,Adenosine A1 Receptor Antagonists ,Ring (chemistry) ,chemistry.chemical_compound ,Structure-Activity Relationship ,Chalcones ,Morpholine ,Drug Discovery ,medicine ,Tetralone ,Humans ,Computer Simulation ,2-Benzylidene-1-indanone derivatives ,Receptor ,Molecular Structure ,Receptor, Adenosine A1 ,Receptors, Adenosine A2 ,Parkinson Disease ,General Medicine ,Adenosine ,Adenosine receptor ,Adenosine A2 Receptor Antagonists ,chemistry ,Neurological conditions ,Selectivity ,medicine.drug - Abstract
Adenosine A1 and/or A2A receptor antagonists hold promise for the potential treatment of neurological conditions, such as Parkinson’s disease. Herein, a total of seventeen benzocycloalkanone derivatives were synthesised and evaluated for affinity towards adenosine receptors (A1 and A2A AR). The obtained results allowed for the conclusion that affinity and/or selectivity of the 2-benzylidene-1-indanone and -tetralone derivatives toward A1 and/or A2A ARs may be modulated by the nature of the substituents (either -OH, -OCH3 or morpholine) attached at position C4 of the 1-indanone core and C5 of the 1-tetralone core as well as the meta (C3’) and/or para (C4’) position(s) on ring B. Several compounds (2a–b, 3b–c and 4a–b) possessed affinity for the A1 and/or A2A AR below 10 µM. Additionally, compounds 2a, 3b and 4a were A1 AR antagonists. These results, once again, confirmed the importance of C4 methoxy-group substitution on ring A in combination with meta (C3’) and/or para (C4’) hydroxyl-group substitution ring B of the 2-benzylidene-1-indanone scaffold leading to drug-like compounds 1h and 1j with affinity in the nanomolar-range.
- Published
- 2020