Methoxy substituted 2-benzylidene-1-indanone derivatives as A1 and/or A2A AR antagonists for the potential treatment of neurological conditions
| Autor: | Helena D. Janse van Rensburg, Mietha M. Van der Walt, Lesetja J. Legoabe, Gisella Terre’Blanche |
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| Rok vydání: | 2019 |
| Předmět: |
Pharmacology
010405 organic chemistry Chemistry Stereochemistry Organic Chemistry Antagonist Pharmaceutical Science Ring (chemistry) 01 natural sciences Biochemistry 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry.chemical_compound Drug Discovery Molecular Medicine Lead compound |
| Zdroj: | MedChemComm. 10:300-309 |
| ISSN: | 2040-2511 2040-2503 |
| Popis: | A prior study reported on hydroxy substituted 2-benzylidene-1-indanone derivatives as A(1) and/or A(2A) antagonists for the potential treatment of neurological conditions. A lead compound (1a) was identified with both A(1) and A(2A) 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 A(1) and A(2A) affinity. This led to compounds with both A(1) and A(2A) affinity in the nanomolar range, namely 2c (A(1)K(i) (rat) = 41 nM; A(2A)K(i) (rat) = 97 nM) with C4-OCH(3) substitution on ring A together with meta (3′) hydroxy substitution on ring B and 2e (A(1)K(i) (rat) = 42 nM; A(2A)K(i) (rat) = 78 nM) with C4-OCH(3) substitution on ring A together with meta (3′) and para (4′) dihydroxy substitution on ring B. Additionally, 2c is an A(1) antagonist. Consequently, the methoxy substituted 2-benzylidene-1-indanone scaffold is highly promising for the design of novel A(1) and A(2A) antagonists. |
| Databáze: | OpenAIRE |
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