Background: Neurodegenerative, neurological and mental disorders, as well as substance
abuse have a worldwide high incidence rate, becoming relevant factors that contribute to
premature morbidity and mortality. Dopamine is well known to be involved in these pathologies.
The key focus in the search for new drugs, that alleviate or cure these diseases, is pursuing the design
of compounds with both efficacy and fewer adverse effects in order to obtain novel agents
capable of restoring the homeostasis in the CNS of dopaminergic neurotransmission and counteracting
some of neurodegenerative and neuropsychiatric diseases, such as Parkinson's disease, schizophrenia,
Huntington's chorea and drug addictions.
Methods: the compounds 11,12H-dihydronaphthalene[1,2-b] quinoline 2a and 9-methoxy-11,12Hdihydronaphthalene
[1,2-b] quinoline 2b were designed and synthesized. The organic synthesis was
performed according to the outlined synthesis strategies, together with a pharmacological evaluation
of the male Sprague-Dawley rats.
Results: Compound structures were confirmed by 1H, 13C, DEPT and HETCOR NMR. Pharmacological
testing and computational studies validated the asserted medicinal-chemical approach for
their design, showing compound 2a acting as an atypical dopamine antagonist.
Conclusion: The study showed that compound 2a has an atypical antagonistic action on the central
dopaminergic system. These pharmacological and computational-theoretical results support the
suitability of the medicinal chemical approach in the design of this compound.