Login / Signup

Methoxy substituted 2-benzylidene-1-indanone derivatives as A1 and/or A2A AR antagonists for the potential treatment of neurological conditions.

Helena D Janse van RensburgLesetja J LegoabeDavid D N'DaMietha Magdalena van der Walt
Published in: MedChemComm (2019)
A prior study reported on hydroxy substituted 2-benzylidene-1-indanone derivatives as A1 and/or A2A antagonists for the potential treatment of neurological conditions. A lead compound (1a) was identified with both A1 and A2A affinity in the micromolar range. The current study explored the structurally related methoxy substituted 2-benzylidene-1-indanone derivatives with various substitutions on ring A and B of the benzylidene indanone scaffold in order to enhance A1 and A2A affinity. This led to compounds with both A1 and A2A affinity in the nanomolar range, namely 2c (A1 K i (rat) = 41 nM; A2A K i (rat) = 97 nM) with C4-OCH3 substitution on ring A together with meta (3') hydroxy substitution on ring B and 2e (A1 K i (rat) = 42 nM; A2A K i (rat) = 78 nM) with C4-OCH3 substitution on ring A together with meta (3') and para (4') dihydroxy substitution on ring B. Additionally, 2c is an A1 antagonist. Consequently, the methoxy substituted 2-benzylidene-1-indanone scaffold is highly promising for the design of novel A1 and A2A antagonists.
Keyphrases
  • molecular docking
  • photodynamic therapy
  • oxidative stress
  • light emitting
  • risk assessment
  • mass spectrometry
  • tissue engineering
  • brain injury
  • blood brain barrier
  • capillary electrophoresis
  • replacement therapy