O-Pyrazolylpropynyl-Hydroxylamines as Versatile Intermediates in the Synthesis of Compounds of Pharmacological Interest

Rodríguez‐Franco, María Isabel; Dorronsoro, Isabel; Martínez, Ana

doi:10.1055/s-2001-16768

Cited by 29 publications

(9 citation statements)

References 9 publications

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“…Due to the pathological complexity found in AD, multifunctional molecules with two or more complementary biological activities may represent an important advance for the treatment of this disease. , Continuing with our research on various heterocyclic families with potential application in the AD field, − in recent years we reported the synthesis of multifunctional compounds that combine neuroprotective and AChE inhibition, ,− including a tacrine–melatonin hybrid that is able to reduce amyloid burden and behavioral deficits in a mouse model of AD. ,, …”

Section: Introductionmentioning

confidence: 99%

New Tacrine–4-Oxo-4H-chromene Hybrids as Multifunctional Agents for the Treatment of Alzheimer’s Disease, with Cholinergic, Antioxidant, and β-Amyloid-Reducing Properties

et al. 2012

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By using fragments endowed with interesting and complementary properties for the treatment of Alzheimer’s disease (AD), a new family of tacrine–4-oxo-4H-chromene hybrids has been designed, synthesized, and evaluated biologically. The tacrine fragment was selected for its inhibition of cholinesterases, and the flavonoid scaffold derived from 4-oxo-4H -chromene was chosen for its radical capture and β-secretase 1 (BACE-1) inhibitory activities. At nano- and picomolar concentrations, the new tacrine–4-oxo-4H-chromene hybrids inhibit human acetyl- and butyrylcholinesterase (h-AChE and h-BuChE), being more potent than the parent inhibitor, tacrine. They are also potent inhibitors of human BACE-1, better than the parent flavonoid, apigenin. They show interesting antioxidant properties and could be able to penetrate into the CNS according to the in vitro PAMPA-BBB assay. Among the hybrids investigated, 6-hydroxy-4-oxo- N-{10-[(1,2,3,4-tetrahydroacridin-9-yl)amino]decyl}-4 H-chromene-2-carboxamide (19) shows potent combined inhibition of human BACE-1 and ChEs, as well as good antioxidant and CNS-permeable properties.

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Section: Introductionmentioning

confidence: 99%

New Tacrine–4-Oxo-4H-chromene Hybrids as Multifunctional Agents for the Treatment of Alzheimer’s Disease, with Cholinergic, Antioxidant, and β-Amyloid-Reducing Properties

et al. 2012

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“…19 1-Acyl-4-halopyrazoles have demonstrated their importance as intermediates for palladium-catalyzed Sonogashira cross-coupling reactions leading to compounds of pharmacological interest. 20 Also, the palladium-catalyzed Heck 21 cross-coupling of 1-acyl-4-halopyrazoles has been demonstrated. In addition, another advantage of this methodology is the fact that the acylation of pyrazoles often gives a mixture of N -acylated products, 22 leading to unwanted and often inseparable product mixtures, where our process eliminates this problem.…”

Section: Resultsmentioning

confidence: 99%

Room Temperature ICl-Induced Dehydration/Iodination of 1-Acyl-5-hydroxy-4,5-dihydro-1H-pyrazoles. A Selective Route to Substituted 1-Acyl-4-iodo-1H-pyrazoles

2008

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“…Our study is based on the work of Rodriguez-Franco's group in the field of AD (Martinez et al 2000;Rodríguez-Franco et al 2001Rodríguez-Franco and Fernández-Bachiller 2002) focuses on dual acting drugs, capable of combining AChE inhibition and antioxidant properties in a single small molecule. They have developed this new tacrine-melatonin hybrid, which is a potent inhibitor of human AChE and shows a high oxygen radical absorbance capacity (Rodríguez-Franco et al 2006;Fernández-Bachiller et al 2009).…”

Section: Introductionmentioning

confidence: 99%

A New Tacrine–Melatonin Hybrid Reduces Amyloid Burden and Behavioral Deficits in a Mouse Model of Alzheimer’s Disease

et al. 2009

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Alzheimer's disease (AD) is a progressive degenerative disorder characterized by the presence of amyloid deposits, neurofibrillary tangles and neuron loss. Emerging evidence indicates that antioxidants could be useful either for the prevention or treatment of AD. Tacrine and melatonin are well-known drugs which act as an acetylcholinesterase inhibitor and a free radical scavenger, respectively. In this study, we evaluated the effects of a new tacrine-melatonin hybrid on behavior and the biochemical and neuropathologic changes observed in amyloid precursor protein/presenilin 1 (APP/Ps1) transgenic mice. Our findings showed that direct intracerebral administration of this hybrid decreased amyloid beta peptide (Abeta)-induced cell death and amyloid burden in the brain parenchyma of APP/Ps1 mice. This reduction in Abeta pathology was accompanied by a recovery in cognitive function. Since this tacrine-melatonin hybrid apparently reduces brain Abeta and behavioral deficits, we believe this drug has remarkable and significant neuroprotective effects and might be considered a potential therapeutic strategy in AD.

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O-Pyrazolylpropynyl-Hydroxylamines as Versatile Intermediates in the Synthesis of Compounds of Pharmacological Interest

Cited by 29 publications

References 9 publications

New Tacrine–4-Oxo-4H-chromene Hybrids as Multifunctional Agents for the Treatment of Alzheimer’s Disease, with Cholinergic, Antioxidant, and β-Amyloid-Reducing Properties

New Tacrine–4-Oxo-4H-chromene Hybrids as Multifunctional Agents for the Treatment of Alzheimer’s Disease, with Cholinergic, Antioxidant, and β-Amyloid-Reducing Properties

Room Temperature ICl-Induced Dehydration/Iodination of 1-Acyl-5-hydroxy-4,5-dihydro-1H-pyrazoles. A Selective Route to Substituted 1-Acyl-4-iodo-1H-pyrazoles

A New Tacrine–Melatonin Hybrid Reduces Amyloid Burden and Behavioral Deficits in a Mouse Model of Alzheimer’s Disease

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