158641-45-3Relevant academic research and scientific papers
Synthesis of stable isotope labeled anacetrapib, its major metabolites and [14C]anacetrapib
Kuethe, Jeffrey T.,Soli, Eric D.,Royster, Pernilla,Quinn, Catherine A.
, p. 600 - 608 (2013)
Cholesteryl ester transfer protein inhibitors are an important class of compounds designed to treat hypocholesterolemia and prevent cardiovascular disease. Anacetrapib (MK-0859) is currently in phase III trials for the treatment of elevated cholesterol levels and prevention of cardiovascular disease. In order to further support the development of anacetrapib, we prepared [M + 6]MK-0859, which was required in support of an absolute bioavailability study of the active pharmaceutical ingredient (API). Additional support included the synthesis of an internal standard [M + 13] and three stable isotope labeled metabolites, which were used to analyze clinical samples, and [ 14C]MK-0859 to support drug metabolism studies. A labeling strategy for the preparation of [M + 6], [M + 13], and [14C]anacetrapib is described. The preparation of stable isotope labelled metabolites of anacetrapib is also described.
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.
experimental part, 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.
Synthesis and EPR Investigations of Fluorocatecholamines
Stegmann, Hartmut B.,Deuschle, Gabriele,Schuler, Paul
, p. 547 - 556 (2007/10/02)
The synthesis of 3-fluoro and 5-fluoronoradrenaline (3- and 5-fluoronorepinephrine) starting from 4-fluorophenol or 3-fluoroanisole is described.In the first step the second OH group is introduced followed by O-methylation and subsequent introduction of a
