“…Additionally, SAR studies showed that the substituted chlorophenyl group at R 1 is suitable for MAO-A inhibition, the Presence of the CN group at R 2 improves the MAO-B specificity, and the acetyl group at R 3 is essential for inhibitory activity (Fig. 13 ) [ 96 ]. Fig.…”
Parkinson’s disease is a neurodegenerative disorder characterized by slow movement, tremors, and stiffness caused due to loss of dopaminergic neurons caused in the brain’s substantia nigra. The concentration of dopamine is decreased in the brain. Parkinson’s disease may be happened because of various genetic and environmental factors. Parkinson’s disease is related to the irregular expression of the monoamine oxidase (MAO) enzyme, precisely type B, which causes the oxidative deamination of biogenic amines such as dopamine. MAO-B inhibitors, available currently in the market, carry various adverse effects such as dizziness, nausea, vomiting, lightheadedness, fainting, etc. So, there is an urgent need to develop new MAO-B inhibitors with minimum side effects. In this review, we have included recently studied compounds (2018 onwards). Agrawal et al
.
reported MAO-B inhibitors with IC
50
0.0051 µM and showed good binding affinity. Enriquez et al
.
reported a compound with IC
50
144 nM and bind with some critical amino acid residue Tyr60, Ile198, and Ile199. This article also describes the structure–activity relationship of the compounds and clinical trial studies of related derivatives. These compounds may be used as lead compounds to develop potent compounds as MAO-B inhibitors.
Graphic Abstract
“…Additionally, SAR studies showed that the substituted chlorophenyl group at R 1 is suitable for MAO-A inhibition, the Presence of the CN group at R 2 improves the MAO-B specificity, and the acetyl group at R 3 is essential for inhibitory activity (Fig. 13 ) [ 96 ]. Fig.…”
Parkinson’s disease is a neurodegenerative disorder characterized by slow movement, tremors, and stiffness caused due to loss of dopaminergic neurons caused in the brain’s substantia nigra. The concentration of dopamine is decreased in the brain. Parkinson’s disease may be happened because of various genetic and environmental factors. Parkinson’s disease is related to the irregular expression of the monoamine oxidase (MAO) enzyme, precisely type B, which causes the oxidative deamination of biogenic amines such as dopamine. MAO-B inhibitors, available currently in the market, carry various adverse effects such as dizziness, nausea, vomiting, lightheadedness, fainting, etc. So, there is an urgent need to develop new MAO-B inhibitors with minimum side effects. In this review, we have included recently studied compounds (2018 onwards). Agrawal et al
.
reported MAO-B inhibitors with IC
50
0.0051 µM and showed good binding affinity. Enriquez et al
.
reported a compound with IC
50
144 nM and bind with some critical amino acid residue Tyr60, Ile198, and Ile199. This article also describes the structure–activity relationship of the compounds and clinical trial studies of related derivatives. These compounds may be used as lead compounds to develop potent compounds as MAO-B inhibitors.
Graphic Abstract
“…Subsequent reduction of the nitro derivative with tin(II) chloride and other reagents [22] in all cases gave N-hydroxyquinoxalines as the products of reductive cyclization. The obtained compounds showed the properties of potent and selective inhibitors of human monoamine oxidase [23]. Herein, we attempted to aply this approach to the synthesis of fused systems containing indazole and quinoxaline rings.…”
A two-stage method for the preparation of
2-(3-carboxymethylindazol-1-yl)anilines using the N-arylation reaction of 3-carboxymethylindazoles with o-nitrohaloarenes and subsequent reduction of
nitro-containing intermediates with tin(II) chloride was developed. The
experimental results showed that the use of the synthesized compounds as
fluorophores in the visible region of the spectrum is promising.
“…Pyrazolo[1,5- a ]quinoxalin-4(5 H )-one is an important scaffold in drug discovery found in various lead molecules such as TLR7 antagonists, anti-tumor agents, and monoamine oxidase inhibitors, but the face of these compounds toward the GPCR superfamily, especially opioid receptors, has been not explored. Opioid receptors participate in the regulation of several behavioral changes and physiological functions.…”
Pyrazolo[1,5-a]quinoxalin-4(5H)-one derivatives as novel
opioid receptor modulators have been synthesized
via copper-catalyzed oxidative [3 + 2]-annulation of quinoxalin-2(1H)-one and oxime-O-acetates. This hydrazine-free
C–C and N–N bond formation strategy starts with the
generation of C2N1 synthon using oxime acetate,
which reacts in a [3 + 2] manner with quinoxalin-2(1H)-one, followed by oxidative aromatization. The synthesized compounds
were tested against opioid receptors, of which eight compounds exhibited
an antagonistic effect with EC50 < 5 μM at various
opioid receptors. Molecular docking studies were performed to identify
the binding of active pyrazolo[1,5-a]quinoxalin-4(5H)-one ligands with hKOR protein. Docking results indicated
that compounds 3d and 3g participate in
hydrogen bonding with the hydroxyl group of T111 of the active site
pocket residue.
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