- Lithiation of 2-aryl-2-methyl-1,3-dioxolanes with PMDTA-complexed butyllithium
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The metalation of chloro- and methoxy-substituted acetophenone ketals with butyllithium (BuLi) and with N,N,N',N″,N″-pentamethyldiethylenetriamine-complexed butyllithium (BuLi/PMDTA) has been investigated. The lithio species thus generated were carboxylat
- Nyulasi, Bálint,Németh, András,Porcs-Makkay, Márta,Kupai, József,Lukács, Gyula,Simig, Gyula,Volk, Balázs
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p. 298 - 306
(2017/01/03)
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- Discovery of a long-acting, peripherally selective inhibitor of catechol- O -methyltransferase
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Novel nitrocatechol-substituted heterocycles were designed and evaluated for their ability to inhibit catechol-O-methyltransferase (COMT). Replacement of the pyrazole core of the initial hit 4 with a 1,2,4-oxadiazole ring resulted in a series of compounds endowed with longer duration of COMT inhibition. Incorporation of a pyridine N-oxide residue at position 3 of the 1,2,4-oxadiazole ring led to analogue 37f, which was found to possess activity comparable to entacapone and lower toxicity in comparison to tolcapone. Lead structure 37f was systematically modified in order to improve selectivity and duration of COMT inhibition as well as to minimize toxicity. Oxadiazole 37d (2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4, 6-dimethylpyridine 1-oxide (BIA 9-1067)) was identified as a long-acting, purely peripheral inhibitor, which is currently under clinical evaluation as an adjunct to l-Dopa therapy of Parkinson's disease.
- Kiss, László E.,Ferreira, Humberto S.,Torr?o, Leonel,Bonifácio, Maria Jo?o,Palma, P. Nuno,Soares-Da-Silva, Patrício,Learmonth, David A.
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experimental part
p. 3396 - 3411
(2010/09/05)
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- Aryloxy- and arylthiosubstituted pyrimidines and triazines and derivatives thereof
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The present invention provides novel compounds, and pharmaceutical compositions thereof, and methods of using same in the treatment of affective disorders, anxiety, depression, post-traumatic stress disorders, eating disorders, supranuclear palsey, irrita
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- Aryloxy- and arylthio- fused pyridines and pyrimidines and derivatives
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Novel compounds and pharmaceutical compositions thereof, and methods of using same in treating anxiety, depression, and other psychiatric and neurological disorders. The novel compounds provided by this invention are those of the following formulae: where
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