Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Photochemical Oxidation of 4-Ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (Emorfazone) by Pyrimido[5, 4-g]pteridine 5-Oxide. : An Attempt to Apply a Functional Chemical Model for Biological Oxidations to Drug-metabolism Studies
YOSHIFUMI MAKIKAORU SHIMADAMAGOICHI SAKOYUKIO KITADEKOSAKU HIROTA
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1988 Volume 36 Issue 5 Pages 1714-1720

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Abstract

Irradiation of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (2) (Emorfazone) with ultraviolet (UV)-visible light in the presence of 1, 3, 7, 9-tetrabutyl-2, 4, 6, 8(1H, 3H, 7H, 9H)-pyrimido-[5, 4-g]pteridinetetrone 5-oxide (1a), followed by chromatography of the reaction mixture, resulted in the isolation of 5-(2, 3-dihydro-1, 4-oxazin-4-yl)-4-ethoxy-2-methyl-3(2H)-pyridazinone (3), 4-ethoxy-5-(2-hydroxyethylamino)-2-methyl-3(2H)-pyridazinone (4), 4-ethoxycarbonyl-2-methyl-4-morpholino-3(2H)-pyrazolone (5), 4, 4'-bi[4-ethoxycarbonyl-2-methyl-3(2H)-pyrazolone] (6) and 1, 3, 7, 9-tetrabutyl-2, 4, 6, 8(1H, 3H, 7H, 9H)-pyrimido[5, 4-g]pteridinetetrone (1b). The product 3 is produced as a result of photochemical dehydrogenation of 2 by 1a. The formation of the morpholine-ring-opening product 4, one of the metabolites of 2, was proved to occur via the autoxidation of 3 and subsequent stepwise ring cleavage in the presence of oxygen and moisture. The formation of the novel ring-contracted product 5 involves oxygen-atom transfer from 1a to 2 in an excited state. The dimer 6 was shown to be a secondary product formed by further photolysis of 5.

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