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 |
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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. 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.</description><identifier>ISSN: 0009-2363</identifier><identifier>EISSN: 1347-5223</identifier><identifier>DOI: 10.1248/cpb.27.1544</identifier><identifier>PMID: 540346</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>Animals ; Bile - analysis ; Dogs ; gas chromatography-mass spectrometry ; Male ; Morpholines - metabolism ; Morpholines - urine ; Pyridazines - metabolism ; Pyridazines - urine ; Rats</subject><ispartof>Chemical and Pharmaceutical Bulletin, 1979/07/25, Vol.27(7), pp.1544-1552</ispartof><rights>The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 1979</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4234-907d7c84dfbb8a62bdb5dbd0e08c331db82152fc27c0cd5bcbee1306e0de737c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1883,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/540346$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KUWAYAMA, MOTOAKI</creatorcontrib><creatorcontrib>MIYAKE, SOHACHIRO</creatorcontrib><creatorcontrib>OMURA, KIYOSHI</creatorcontrib><creatorcontrib>ITAKURA, KOICHI</creatorcontrib><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</title><title>Chemical & pharmaceutical bulletin</title><addtitle>Chem. Pharm. Bull.</addtitle><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.</description><subject>Animals</subject><subject>Bile - analysis</subject><subject>Dogs</subject><subject>gas chromatography-mass spectrometry</subject><subject>Male</subject><subject>Morpholines - metabolism</subject><subject>Morpholines - urine</subject><subject>Pyridazines - metabolism</subject><subject>Pyridazines - urine</subject><subject>Rats</subject><issn>0009-2363</issn><issn>1347-5223</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1979</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkVuLFDEQhRvxNq4--epDQBBFe8x10v24u-NlYEVw3SeRJpfqmQzppE16Hsa_5p-ze3tZZaFIUZyvTkFOUTwneEkor96bXi-pXBLB-b1iQRiXpaCU3S8WGOO6pGzFHhdPct5jTAWW7FHxUHDM-GpR_DkNyh-zyyi2iLxDvFy7LqZ-F70LsZRlv4Nw9P0xORvRDzYR9ie6ntVvFwC9Xl-WgpA3SAWLNkNGX2BQelwfICMX0JmLPm6dUR5d9mBcByEv0WYsC2Fw7agMLobp_p3Nb2pAV2m6MVmv4_a_6cx5eFo8aJXP8OymnxRXHz98P_9cXnz9tDk_vSgNp4yXNZZWmorbVutKrai2WlhtMeDKMEasrigRtDVUGmys0EYDEIZXgC1IJg07KV7Nvn2Kvw6Qh6Zz2YD3KkA85EbymmFRsRF8eQfcx0MaPzg3hIu6qlb0mno7UybFnBO0TZ9cp9KxIbiZ8mzGPBsqmynPkX5x43nQHdhbdg5wlNezvM-D2sKtrNLgjIfJitSimuzk_Eyu_-SdSg0E9hdzYbKQ</recordid><startdate>1979</startdate><enddate>1979</enddate><creator>KUWAYAMA, MOTOAKI</creator><creator>MIYAKE, SOHACHIRO</creator><creator>OMURA, KIYOSHI</creator><creator>ITAKURA, KOICHI</creator><general>The Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>1979</creationdate><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</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 & 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 & 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. 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.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>540346</pmid><doi>10.1248/cpb.27.1544</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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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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