274925-97-2Relevant academic research and scientific papers
Discovery of a long-acting, peripherally selective inhibitor of catechol- O -methyltransferase
Kiss, László E.,Ferreira, Humberto S.,Torr?o, Leonel,Bonifácio, Maria Jo?o,Palma, P. Nuno,Soares-Da-Silva, Patrício,Learmonth, David A.
supporting information; scheme or table, p. 3396 - 3411 (2010/09/05)
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.
Substituted 2-phenyl-1-(3,4-dihydroxy-5-nitrophenyl)-1-ethanones, their use in the treatment of some central and peripheral nervous system disorders and pharmaceutical compositions containing them
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, (2008/06/13)
New compounds of formula I are described The compounds have potentially valuable pharmaceutical properties in the treatment of some central and peripheral nervous system disorders, where a reduction in the O-methylation of catecholamines may be of therape
Improved method for demethylation of nitro-catechol methyl ethers
Learmonth, David A.,Alves, Paula C.
, p. 641 - 649 (2007/10/03)
Several nitro-catechol compounds, useful as inhibitors of COMT were obtained in excellent yield and purity via an improved procedure for demethylation of the corresponding methyl ethers using aluminium chloride and pyridine in ethyl acetate.
Synthesis of 1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone and derivatives as potent and long-acting peripheral inhibitors of catechol-O-methyltransferase
Learmonth, David A.,Vieira-Coelho, Maria A.,Benes, Jan,Alves, Paula C.,Borges, Nuno,Freitas, Ana P.,Soares-da-Silva, Patrício
, p. 685 - 695 (2007/10/03)
A homologous series of novel nitro-catechol structures (7a-7e) were synthesized and tested as inhibitors of the enzyme catechol-O-methyltransferase (COMT). Increasing chain length was found to have significant impact on both brain penetration and duration
