Untitled

doi:10.1002/ejoc.v2011.32

Cited by 2 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For compounds 2 and 19, solvent free acylation using benzoyl chloride derivatives was performed under microwave irradiation (Figure 1). The aromatic amines (5,8,25) were obtained in excellent yields from reduction of the respective nitro derivatives (6,9,26). Due to their simple structures, many of our compounds have been described previously, but to our knowledge none of them were determined as potent inhibitors for MAO A or B so far.…”

Section: Results and Discussion Chemistrymentioning

confidence: 99%

“…The respective nitro derivative (6,9,26) (6 mmol, 1 eq) was dissolved in dried ethanol (20 mL). After adding Pd/C (0.6 mmol, 0.1 eq) and hydrazine monohydrate (60 mmol, 10 eq), the mixture was refluxed for 2 h and afterwards stirred for another 45 min at room temperature.…”

Section: Methods Dmentioning

confidence: 99%

“…Reagents and solvents for synthesis were purchased from Sigma-Aldrich, VWR Chemicals, Fisher Scientific, Panreac AppliChem, Alfa Aesar and Chemsolute and were used without further purifications (unless stated otherwise). 1 H NMR and 13 C NMR were recorded on a Bruker AMX spectrometer (Bruker, Germany) at 300 and 75 MHz respectively, where either CDCl 3 or DMSOd 6 was used as a solvent. Tetramethylsilane was used as standard and chemical shifts are reported in parts per million (ppm).…”

Section: Reagents and Instrumentationmentioning

confidence: 99%

“…Recently, safinamide as first reversible MAO B inhibitor in PD therapy was approved. [5][6][7] As the imminent therapeutic benefits of MAO inhibitors are nowadays clear, multiple efforts have been made to develop new reversible and irreversible inhibitors. Due to long-term enzyme inactivation by irreversible MAO inhibitors, these can be associated with serious side effects or drug-drug interactions, eg leading to a serotonin syndrome.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

<p>Reversible Small Molecule Inhibitors of MAO A and MAO B with Anilide Motifs</p>

Hagenow¹,

Hagenow²,

Grau³

et al. 2020

DDDT

View full text Add to dashboard Cite

Background: Ligands consisting of two aryl moieties connected via a short spacer were shown to be potent inhibitors of monoamine oxidases (MAO) A and B, which are known as suitable targets in treatment of neurological diseases. Based on this general blueprint, we synthesized a series of 66 small aromatic amide derivatives as novel MAO A/B inhibitors. Methods: The compounds were synthesized, purified and structurally confirmed by spectroscopic methods. Fluorimetric enzymological assays were performed to determine MAO A/B inhibition properties. Mode and reversibility of inhibition was determined for the most potent MAO B inhibitor. Docking poses and pharmacophore models were generated to confirm the in vitro results. Results: N-(2,4-Dinitrophenyl)benzo[d][1,3]dioxole-5-carboxamide (55, ST-2043) was found to be a reversible competitive moderately selective MAO B inhibitor (IC 50 = 56 nM, K i = 6.3 nM), while N-(2,4-dinitrophenyl)benzamide (7, ST-2023) showed higher preference for MAO A (IC 50 = 126 nM). Computational analysis confirmed in vitro binding properties, where the anilides examined possessed high surface complementarity to MAO A/B active sites. Conclusion: The small molecule anilides with different substitution patterns were identified as potent MAO A/B inhibitors, which were active in nanomolar concentrations ranges. These small and easily accessible molecules are promising motifs, especially for newly designed multitargeted ligands taking advantage of these fragments.

show abstract