Straightforward synthesis of orthogonally protected piperidin-3-ylmethanamine and piperidin-4-ylmethanamine derivatives

Košak, Urban; Brus, Boris; Gobec, Stanislav

doi:10.1016/j.tetlet.2014.02.034

Cited by 14 publications

(9 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The syntheses of intermediates 9 , 10 , 11 , and 12 (see Supplementary Figures 1, 2, 3, and 5) were achieved according to the relevant literature procedures2866.…”

Section: Methodsmentioning

confidence: 99%

Development of an in-vivo active reversible butyrylcholinesterase inhibitor

Košak¹,

Brus²,

Knez³

et al. 2016

Sci Rep

Self Cite

132

102

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is characterized by severe basal forebrain cholinergic deficit, which results in progressive and chronic deterioration of memory and cognitive functions. Similar to acetylcholinesterase, butyrylcholinesterase (BChE) contributes to the termination of cholinergic neurotransmission. Its enzymatic activity increases with the disease progression, thus classifying BChE as a viable therapeutic target in advanced AD. Potent, selective and reversible human BChE inhibitors were developed. The solved crystal structure of human BChE in complex with the most potent inhibitor reveals its binding mode and provides the molecular basis of its low nanomolar potency. Additionally, this compound is noncytotoxic and has neuroprotective properties. Furthermore, this inhibitor moderately crosses the blood-brain barrier and improves memory, cognitive functions and learning abilities of mice in a model of the cholinergic deficit that characterizes AD, without producing acute cholinergic adverse effects. Our study provides an advanced lead compound for developing drugs for alleviating symptoms caused by cholinergic hypofunction in advanced AD.

show abstract

“…The syntheses of intermediates 9 , 10 , 11 , and 12 (see Supplementary Figures 1, 2, 3, and 5) were achieved according to the relevant literature procedures2866.…”

Section: Methodsmentioning

confidence: 99%

Development of an in-vivo active reversible butyrylcholinesterase inhibitor

Košak¹,

Brus²,

Knez³

et al. 2016

Sci Rep

Self Cite

132

102

View full text Add to dashboard Cite

show abstract

“…49 Debenzylation in methanol using cyclohexene and palladium hydroxide on carbon (i.e., Pearlman's catalyst) in catalytic amounts produced the secondary amines 4a, b, which were alkylated with alkyl/ aryl halides in the next step, using either triethylamine or potassium carbonate as the base. Then the 2,3-dihydro-1H-indene derivatives were prepared following the literature procedure that reacts 1H-inden-2(3H)-one with secondary amine 4a or its derivative with a methoxyethyl chain 45 To prepare the nitroxoline part used in the subsequent coupling with the piperidine moiety, 8-hydroxyquinoline-7-carboxylic acid was nitrated with a HNO 3 /H 2 SO 4 mixture, to produce compound 7 in greater yield (98%) compared to almost the same reported procedure (52%).…”

Section: Chemistrymentioning

confidence: 99%

Structure-based development of nitroxoline derivatives as potential multifunctional anti-Alzheimer agents

Knez

Brus

Coquelle

et al. 2015

Bioorganic & Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

“…The drug was synthesized from piperidine-3-carboxylic acid in a 64% overall yield using a modified previously described procedure 17 , 26 (Fig. 4 ).…”

Section: Methodsmentioning

confidence: 99%

Treatment of canine cognitive dysfunction with novel butyrylcholinesterase inhibitor

Pipan

Mihevc

Štrbenc

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

Canine cognitive dysfunction (CCD) is common in aged dogs and has many similarities with Alzheimer’s disease. Unfortunately, like Alzheimer’s disease, CCD cannot be cured. In the present study, we treated dogs with CCD with our newly developed and characterized butyrylcholinesterase inhibitor (BChEi). Seventeen dogs were randomized into two groups (treated with BChEi and untreated) and followed for 6 months at regular check-ups. The dogs’ cognitive status was determined by a Canine Dementia Scale (CADES) questionnaire and two cognitive tests. In dogs with moderate cognitive impairment, treatment caused significant improvement in the clinical rating of cognitive abilities and the performance-based tests of cognitive functioning when compared to the untreated group (p < 0.001). Dogs treated with BChEi showed markedly improved cognitive function with enhanced quality of life. No side effects were observed in the treated dogs with moderate cognitive impairment. According to the results of this preliminary study, there is an indication that novel BChEi may be a promising drug for the treatment of CCD in dogs and may be an interesting candidate for the treatment of Alzheimer's disease in humans. However, further clinical studies are needed to confirm this.

show abstract

Straightforward synthesis of orthogonally protected piperidin-3-ylmethanamine and piperidin-4-ylmethanamine derivatives

Cited by 14 publications

References 12 publications

Development of an in-vivo active reversible butyrylcholinesterase inhibitor

Development of an in-vivo active reversible butyrylcholinesterase inhibitor

Structure-based development of nitroxoline derivatives as potential multifunctional anti-Alzheimer agents

Treatment of canine cognitive dysfunction with novel butyrylcholinesterase inhibitor

Contact Info

Product

Resources

About