Structure determination, synthesis, and biological evaluation of a metabolite of the selective α1D adrenoceptor antagonist TAK-259
Tetrahedron(2016)
摘要
5-Chloro-1-(5-chloro-2-(methylsulfonyl)benzyl)-2-imino-1,2-dihydropyridine-3-carboxamide hydrochloride (TAK-259) is a novel, selective, and orally active α1D adrenoceptor antagonist with anti-urinary frequency effect. A metabolite (2) of TAK-259 was identified from monkey urine samples. To elucidate the structure of 2, extraction and purification of the metabolite from TAK-259-treated monkey urine was conducted. Structural analysis of the purified compounds using NMR indicated the compound to be 2-amino-5-chloro-1-[5-chloro-2-(methylsulfonyl)benzyl]-4-oxo-1,4-dihydropyridine-3-carboxamide (2a). An authentic sample of compound 2a was synthesized via regioselective alkylation of 4-methoxypyridin-2-amine. The biological activity of metabolite 2a was also evaluated, and the compound found not to possess affinity toward any known α1 adrenoceptor subtype.
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关键词
Metabolite,Isolation,Structure determination,Synthesis,Selective α1D adrenoceptor antagonist,2-Amino-4-oxo-1,4-dihydropyridine-3-carboxamide
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