Drug Res (Stuttg) 2020; 70(06): 243-256
DOI: 10.1055/a-1146-2996
Original Article

Synthesis and Structure Activity Relationships of Chalcone based Benzocycloalkanone Derivatives as Adenosine A1 and/or A2A Receptor Antagonists

Helena D. Janse van Rensburg
1  Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa
,
Lesetja J. Legoabe
1  Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa
,
Gisella Terre’Blanche
1  Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa
2  Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom, South Africa
› Author Affiliations
Funding: This work is based on the research supported in part by the National Research Foundation (NRF) of South Africa (grant number 111814) and the North-West University (NWU).

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 (2ab, 3bc and 4ab) 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.

Supporting Information



Publication History

Received: 02 March 2020

Accepted: 23 March 2020

Publication Date:
29 April 2020 (online)

© Georg Thieme Verlag KG
Stuttgart · New York