Novel synthesis of isoindoline/isoindoline-1,3-dione derivatives under solventless conditions and evaluation with the human D2 receptor

Andrade‐Jorge, Erik; Bahena-Herrera, José Raúl; Garcia-Gamez, Jesus; Padilla‐Martínez, Itzia I.; Trujillo‐Ferrara, José G.

doi:10.1007/s00044-017-1942-6

Cited by 14 publications

(5 citation statements)

References 41 publications

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“…Rotational bonds, degree of torsional freedom, atomic partial loads, and non‐polar hydrogen bonds were added and analyzed with AutoDock 1.5.6 tools [35] . Molecular docking was programmed with AutoDock 1.5.6 tools and Raccoon, [36] utilizing a hybrid Lamarckian genetic algorithm [37] with an initial population of 100 randomly placed individuals, as described in our previous reports [24,29,30,38,39] . The enzyme was assigned Kollmann partial charges, and ligands were assigned Gasteiger charges.…”

Section: Methodsmentioning

confidence: 99%

“…[35] Molecular docking was programmed with AutoDock 1.5.6 tools and Raccoon, [36] utilizing a hybrid Lamarckian genetic algorithm [37] with an initial population of 100 randomly placed individuals, as described in our previous reports. [24,29,30,38,39] The enzyme was assigned Kollmann partial charges, and ligands were assigned Gasteiger charges. The grid parameters for EeAChE were 60 Å per side, with the center at X = 42.27, Y = 66.809, and Z =-81.47, and a mesh separation of 0.375 Å.…”

Section: Dockingmentioning

confidence: 99%

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Benzofurans as Acetylcholinesterase Inhibitors for Treating Alzheimer's Disease: Synthesis, in vitro Testing, and in silico Analysis

Coaviche‐Yoval,

Tovar‐Miranda,

Rodríguez

et al. 2024

ChemMedChem

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Alzheimer’s disease (AD) is a neurodegenerative disorder and the leading cause of dementia worldwide. It is characterized by a progressive decline in cholinergic neurotransmission. During the development of AD, acetylcholinesterase (AChE) binds to β‐amyloid peptides to form amyloid fibrils, which aggregate into plaque deposits. These complexes are cytotoxic for the brain, causing impairment of memory, attention, and cognition. AChE inhibitors are the main treatment for AD, but their effect is only palliative. This study aimed to design and synthesize novel benzofuran derivatives and evaluate their inhibition of AChE in vitro and in silico. Results: The seven synthesized benzofuran derivatives inhibited AChE in vitro. Benzofurans hydroxy ester 4, amino ester 5, and amido ester (±)‐7 had the lowest inhibition constant (Ki) values and displayed good affinity for EeAChE in molecular docking. Six derivatives showed competitive inhibition, while the best compound (5: Ki = 36.53 mM) exhibited uncompetitive inhibition. The amino, hydroxyl, amide, and ester groups of the ligands favored interaction with the enzyme by hydrogen bonds. Conclusion: Three benzofurans were promising AChE inhibitors with excellent Ki values. In future research on their their application to AD, 5 will be considered as the base structure.

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Section: Methodsmentioning

confidence: 99%

Section: Dockingmentioning

confidence: 99%

Benzofurans as Acetylcholinesterase Inhibitors for Treating Alzheimer's Disease: Synthesis, in vitro Testing, and in silico Analysis

Coaviche‐Yoval,

Tovar‐Miranda,

Rodríguez

et al. 2024

ChemMedChem

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“…2-(2-(3,4-dimethoxyphenyl)ethyl)isoindoline-1,3-dione was synthesized by employing a reported procedure with slight modifications [ 43 ]. In brief, 491 mg (1.50 mmol) phthalic anhydride and 244 mg (1.00 mmol) 2-(3,4-dimethoxyphenyl)ethylamine were mixed and placed into a 50 mL round-bottom flask, then stirred and heated to gentle melting at 150–200 °C for 15–20 min until a dark-yellow color appeared.…”

Section: Methodsmentioning

confidence: 99%

“…1 H NMR (CDCl 3 , 300 MHz) δ 2.93 (t, H-11), 3.90 (t, H-10), 3.80 (s, H-19), 3.83 (s, H-18), 6.78 (m, H-13,16,17), 7.70 (m, H-5,6), 7.82 (m, H-4,7); 13 C NMR (CDCl 3 , 75 MHz) δ 168.2 (C-1,3), 123.19 (C-4,7), 132.0 (C-5,6), 130.4 (C-8,9), 39.3 (C-10), 34.0 (C-11), 133.9 (C-12), 111.1 (C-13), 148.7 (C-14), 147.6 (C-15), 111.8 (C-16), 120.8 (C-17), 55.7 (C-18,19). ESI (m/z): 334.0956 [M+Na] [ 43 ].…”

Section: Methodsmentioning

confidence: 99%

Crystal structure, DFT calculations and evaluation of 2-(2-(3,4-dimethoxyphenyl)ethyl)isoindoline-1,3-dione as AChE inhibitor

Andrade‐Jorge

Bribiesca-Carlos

Martínez‐Martínez

et al. 2018

Chemistry Central Journal

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Dioxoisoindolines have been included as a pharmacophore group in diverse drug-like molecules with a wide range of biological activity. Various reports have shown that phthalimide derivatives are potent inhibitors of AChE, a key enzyme involved in the deterioration of the cholinergic system during the development of Alzheimer’s disease. In the present study, 2-(2-(3,4-dimethoxyphenyl)ethyl)isoindoline-1,3-dione was synthesized, crystallized and evaluated as an AChE inhibitor. The geometric structure of the crystal and the theoretical compound (from molecular modeling) were analyzed and compared, finding a close correlation. The formation of the C6–H6···O19 interaction could be responsible for the non-negligible out of phenyl plane deviation of the C19 methoxy group, the O3 from the carbonyl group lead to C16–H16···O3i intermolecular interactions to furnish C(9) and C(14) infinite chains within the (− 4 0 9) and (− 3 1 1) families of planes. Finally, the biological experiments reveal that the isoindoline-1,3-dione exerts a good competitive inhibition on AChE (Ki = 0.33–0.93 mM; 95% confidence interval) and has very low acute toxicity (LD50 > 1600 mg/kg) compared to the AChE inhibitors currently approved for clinical use.

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“…Benzoylisoindolines D (Figure 8) were discovered [102] as potent and selective inhibitors of glycine transporter-1 (GlyT1), a mediator of glycine uptake probably involved in the pathophysiology of schizophrenia. Some synthetic polysubstituted isoindolines [103] (Figure 8, E) derivatives were able to bind to the human dopamine receptor, thus suggesting a potential application as antipsychotic agents. Danoprevir (Figure 9), discovered in 2013, [104] is a novel smallmolecule inhibitor of the hepatitis C virus NS3/4A protease, a clinical candidate based on its favorable potency profile against multiple HCV genotypes.…”

Section: Biological Properties Chemical Reactivitymentioning

confidence: 99%

Potentiality and Synthesis of O‐ and N‐Heterocycles: Pd‐Catalyzed Cyclocarbonylative Sonogashira Coupling as a Valuable Route to Phthalans, Isochromans, and Isoindolines

Albano

Aronica

2017

Eur J Org Chem

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Oxygen and Nitrogen-heterocyclic compounds are found in a vast number of natural substrates and biologically active molecules. In particular, phthalan, isochroman and isoindoline scaffolds are present in many classes of products such as antimicotics, antibiotics, antioxidants, pigments and fluorophores. Therefore several procedure dedicated to the buiding of such heterocycles have been developed. In this review a detailed analysis of literature data regarding these nuclei is described. Particular attention has been devoted to their biological and chemical potentialities and a deep investigation on the most important synthetic methods is reported. Cyclocarbonylative Sonogashira reaction of suitable alcohols and amides has been especially considered, since it represents a valuable and atom economic route to construct alkylidene phthalans, isochromans and isoindolines.Gianluigi Albano, born in Bari (Italy) in 1989, studied Chemistry at the University of Pisa (Italy), where he received his Master's Degree in February 2015. In November 2015 he started his PhD studies at the same university, under the supervision of Prof. Lorenzo Di Bari and Dr. Laura Antonella Aronica. His main research topics are focused on the synthesis and characterization of chiral conjugated oligomers for innovative optoelectronic applications and on the development of new protocols for the synthesis of heterocyclic compounds through transition metals-promoted reactions.Laura Antonella Aronica graduated cum laude in Chemistry in 1995 from the University of Pisa. In 1999 she obtained her Ph.D. in Chemical Sciences. During this period she spent six months as research assistant at University of Ottawa with Prof. Howard Alper. She is presently a researcher at the University of Pisa and her major research interests are concerned with organometallic chemistry directed towards organic synthesis and in particular with carbonylative cross coupling reactions and their application to the synthesis of heterocyclic compounds.

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Novel synthesis of isoindoline/isoindoline-1,3-dione derivatives under solventless conditions and evaluation with the human D2 receptor

Cited by 14 publications

References 41 publications

Benzofurans as Acetylcholinesterase Inhibitors for Treating Alzheimer's Disease: Synthesis, in vitro Testing, and in silico Analysis

Benzofurans as Acetylcholinesterase Inhibitors for Treating Alzheimer's Disease: Synthesis, in vitro Testing, and in silico Analysis

Crystal structure, DFT calculations and evaluation of 2-(2-(3,4-dimethoxyphenyl)ethyl)isoindoline-1,3-dione as AChE inhibitor

Potentiality and Synthesis of O‐ and N‐Heterocycles: Pd‐Catalyzed Cyclocarbonylative Sonogashira Coupling as a Valuable Route to Phthalans, Isochromans, and Isoindolines

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