- Novel arylalkenylpropargylamines as neuroprotective, potent, and selective monoamine oxidase B inhibitors for the treatment of Parkinson's disease
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To develop novel neuroprotective agents, a library of novel arylalkenylpropargylamines was synthesized and tested for inhibitory activities against monoamine oxidases. From this, a number of highly potent and selective monoamine oxidase B inhibitors were identified. Selected compounds were also tested for neuroprotection in in vitro studies with PC-12 cells treated with 6-OHDA and rotenone, respectively. It was observed that some of the compounds tested yielded a marked increase in survival in PC-12 cells treated with the neurotoxins. This indicates that these propargylamines are able to confer protection against the effects of the toxins and may also be considered as novel disease-modifying anti-Parkinsonian agents, which are much needed for the therapy of Parkinson's disease.
- Huleatt, Paul B.,Khoo, Mui Ling,Chua, Yi Yuan,Tan, Tiong Wei,Liew, Rou Shen,Balogh, Balázs,Deme, Ruth,G?l?ncsér, Flóra,Magyar, Kalman,Sheela, David P.,Ho, Han Kiat,Sperlágh, Beáta,Mátyus, Péter,Chai, Christina L. L.
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p. 1400 - 1419
(2015/03/04)
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- NEW ARYLALKENYLPROPARGYLAMINE DERIVATIVES EXHIBITING NEUROPROTECTIVE ACTION FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
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The invention relates to novel arylalkenylpropargylamine derivatives of general formula (I) or enantiomers or diastereomers thereof or salts, optionally pharmaceutically acceptable salts, or solvates of any of these. The compounds can be used in treating or preventing a disease or condition in a mammal related to monoamine oxidase dysfunction, especially in neurodegenerative diseases, e.g. Parkinson's disease, Alzheimer's disease or Huntington's disease.
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- Microwave-mediated synthesis of an arylboronate library
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A series of arylboronates has been synthesized from the reaction of 2-(2-, (3-, or (4-(bromomethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 1{1-3} respectively with a range of N-, S-, and O-nucleophiles, using microwave-mediated chemistry. For the synthesis of N- and S-substituted boronates, a supported base, PS-NMM, was employed, and many reactions were complete within 15 min. With O-nucleophiles, a mixture of tetrabutylammonium bromide, potassium carbonate, and sodium hydroxide was employed. The resulting aminomethyl, mercaptomethyl, or alkoxy-/phenoxymethyl-arylboronates were subjected to microwave-mediated Suzuki Miyaura coupling reactions to afford a range of biaryls in moderate to good yields. The X-ray structures of five boronates were determined.
- Spencer, John,Baltus, Christine B.,Patel, Hiren,Press, Neil J.,Callear, Samantha K.,Male, Louise,Coles, Simon J.
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experimental part
p. 24 - 31
(2011/04/15)
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