Analysis of 1, 4-Dimorpholino-7-phenylpyrido [3, 4-d] pyridazine (DS-511) and Its Metabolites in Biological Specimens. I. Identification of Metabolites in Rat Urine and Dog Urine and Bile

The metabolic fate of 1, 4-dimorpholino-7-phenylpyrido [3, 4-d] pyridazine (DS-511) was studied in the rat and the dog. Urine and bile were extracted with ethyl acetate before and after enzymatic hydrolysis and separated into lipophilic and hydrophilic fractions. The structures of seven lipophilic a...

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Veröffentlicht in:Chemical & pharmaceutical bulletin 1979/07/25, Vol.27(7), pp.1544-1552
Hauptverfasser: KUWAYAMA, MOTOAKI, MIYAKE, SOHACHIRO, OMURA, KIYOSHI, ITAKURA, KOICHI
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container_issue 7
container_start_page 1544
container_title Chemical & pharmaceutical bulletin
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creator KUWAYAMA, MOTOAKI
MIYAKE, SOHACHIRO
OMURA, KIYOSHI
ITAKURA, KOICHI
description The metabolic fate of 1, 4-dimorpholino-7-phenylpyrido [3, 4-d] pyridazine (DS-511) was studied in the rat and the dog. Urine and bile were extracted with ethyl acetate before and after enzymatic hydrolysis and separated into lipophilic and hydrophilic fractions. The structures of seven lipophilic and two hydrophilic metabolites obtained on thin-layer chromatograms were investigated by comparing their ultraviolet, infrared and nuclear magnetic resonance spectra, Rf values on thin-layer chromatograms and other physicochemical properties with those of synthetic samples. The main metabolites were 7-(4-hydroxyphenyl)-1, 4-dimorpholinopyrido [3, 4-d] pyridazine and 4-[N-carboxymethyl-N-(2-hydroxyethyl) amino]-1-morpholino-7-phenylpyrido [3, 4-d] pyridazine. In addition, 7-(4-hydroxy-3-methoxyphenyl)-1, 4-dimorpholinopyrido [3, 4-d] pyridazine and 7-(4-hydroxy-3-methoxyphenyl)-4-morpholinopyrido [3, 4-d] pyridazin-1 (2H)-one were observed as minor metabolites in the dog and the rat, respectively.
doi_str_mv 10.1248/cpb.27.1544
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I. Identification of Metabolites in Rat Urine and Dog Urine and Bile</title><source>J-STAGE Free</source><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Free Full-Text Journals in Chemistry</source><creator>KUWAYAMA, MOTOAKI ; MIYAKE, SOHACHIRO ; OMURA, KIYOSHI ; ITAKURA, KOICHI</creator><creatorcontrib>KUWAYAMA, MOTOAKI ; MIYAKE, SOHACHIRO ; OMURA, KIYOSHI ; ITAKURA, KOICHI</creatorcontrib><description>The metabolic fate of 1, 4-dimorpholino-7-phenylpyrido [3, 4-d] pyridazine (DS-511) was studied in the rat and the dog. Urine and bile were extracted with ethyl acetate before and after enzymatic hydrolysis and separated into lipophilic and hydrophilic fractions. The structures of seven lipophilic and two hydrophilic metabolites obtained on thin-layer chromatograms were investigated by comparing their ultraviolet, infrared and nuclear magnetic resonance spectra, Rf values on thin-layer chromatograms and other physicochemical properties with those of synthetic samples. The main metabolites were 7-(4-hydroxyphenyl)-1, 4-dimorpholinopyrido [3, 4-d] pyridazine and 4-[N-carboxymethyl-N-(2-hydroxyethyl) amino]-1-morpholino-7-phenylpyrido [3, 4-d] pyridazine. 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Identification of Metabolites in Rat Urine and Dog Urine and Bile</title><author>KUWAYAMA, MOTOAKI ; MIYAKE, SOHACHIRO ; OMURA, KIYOSHI ; ITAKURA, KOICHI</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4234-907d7c84dfbb8a62bdb5dbd0e08c331db82152fc27c0cd5bcbee1306e0de737c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1979</creationdate><topic>Animals</topic><topic>Bile - analysis</topic><topic>Dogs</topic><topic>gas chromatography-mass spectrometry</topic><topic>Male</topic><topic>Morpholines - metabolism</topic><topic>Morpholines - urine</topic><topic>Pyridazines - metabolism</topic><topic>Pyridazines - urine</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KUWAYAMA, MOTOAKI</creatorcontrib><creatorcontrib>MIYAKE, SOHACHIRO</creatorcontrib><creatorcontrib>OMURA, KIYOSHI</creatorcontrib><creatorcontrib>ITAKURA, KOICHI</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Chemical &amp; pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KUWAYAMA, MOTOAKI</au><au>MIYAKE, SOHACHIRO</au><au>OMURA, KIYOSHI</au><au>ITAKURA, KOICHI</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analysis of 1, 4-Dimorpholino-7-phenylpyrido [3, 4-d] pyridazine (DS-511) and Its Metabolites in Biological Specimens. I. Identification of Metabolites in Rat Urine and Dog Urine and Bile</atitle><jtitle>Chemical &amp; pharmaceutical bulletin</jtitle><addtitle>Chem. Pharm. Bull.</addtitle><date>1979</date><risdate>1979</risdate><volume>27</volume><issue>7</issue><spage>1544</spage><epage>1552</epage><pages>1544-1552</pages><issn>0009-2363</issn><eissn>1347-5223</eissn><abstract>The metabolic fate of 1, 4-dimorpholino-7-phenylpyrido [3, 4-d] pyridazine (DS-511) was studied in the rat and the dog. Urine and bile were extracted with ethyl acetate before and after enzymatic hydrolysis and separated into lipophilic and hydrophilic fractions. The structures of seven lipophilic and two hydrophilic metabolites obtained on thin-layer chromatograms were investigated by comparing their ultraviolet, infrared and nuclear magnetic resonance spectra, Rf values on thin-layer chromatograms and other physicochemical properties with those of synthetic samples. 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source J-STAGE Free; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Free Full-Text Journals in Chemistry
subjects Animals
Bile - analysis
Dogs
gas chromatography-mass spectrometry
Male
Morpholines - metabolism
Morpholines - urine
Pyridazines - metabolism
Pyridazines - urine
Rats
title Analysis of 1, 4-Dimorpholino-7-phenylpyrido [3, 4-d] pyridazine (DS-511) and Its Metabolites in Biological Specimens. I. Identification of Metabolites in Rat Urine and Dog Urine and Bile
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