Agents for the Treatment of Overactive Detrusor. IX. Synthesis and Pharmacological Properties of Metabolites of N-tert-Butyl-4, 4-diphenyl-2-cyclopentenylamine (FK584) in Human Urine
We synthesized the racemates of five presumed metabolites (1b-f) of (S)-(-)-N-tert-butyl-4, 4-diphenyl-2-cyclopentenylamine hydrochloride (FK584, S(-)-1a), a novel agent for the treatment of overactive detrusor syndrome, in order to confirm the structures of the metabolites and also to evaluate thie...
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| Veröffentlicht in: | Chemical & pharmaceutical bulletin 1996/06/15, Vol.44(6), pp.1188-1195 |
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| creator | TANIGUCHI, Kiyoshi MIYAO, Yasuhiro YAMANO, Katsuhiro YAMAMOTO, Takao TERAI, Takao KUSUNOKI, Takahiro TSUBAKI, Kazunori SHIOKAWA, Youichi |
| description | We synthesized the racemates of five presumed metabolites (1b-f) of (S)-(-)-N-tert-butyl-4, 4-diphenyl-2-cyclopentenylamine hydrochloride (FK584, S(-)-1a), a novel agent for the treatment of overactive detrusor syndrome, in order to confirm the structures of the metabolites and also to evaluate thier inhibitory activity against detrusor contraction. (±)-N-tert-Butyl-4-(4-hydroxyphenyl)- and 4-(4-hydroxy-3-methoxyphenyl)-4-phenyl-2-cyclopenetenyl-amines (1b-e) were synthesized via 5-(4-methoxyphenyl)- and 5-(4-benzyloxy-3-methoxyphenyl)-5-phenyl-2-cyclopenten-1-one (9g, h), respectively. Compounds 1b-f prepared in this study were identical with the metabolites in human urine in gas chromatography-mass specrometry and analytical HPLC. The inhibitory activity of compounds 1b-f against detrusor contraction in vitro induced by electrical field stimulation in guinea-pigs was less potent than that of FK584. |
| doi_str_mv | 10.1248/cpb.44.1188 |
| format | Article |
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IX. Synthesis and Pharmacological Properties of Metabolites of N-tert-Butyl-4, 4-diphenyl-2-cyclopentenylamine (FK584) in Human Urine</title><source>MEDLINE</source><source>J-STAGE (Japan Science & Technology Information Aggregator, Electronic) Freely Available Titles - Japanese</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Free Full-Text Journals in Chemistry</source><creator>TANIGUCHI, Kiyoshi ; MIYAO, Yasuhiro ; YAMANO, Katsuhiro ; YAMAMOTO, Takao ; TERAI, Takao ; KUSUNOKI, Takahiro ; TSUBAKI, Kazunori ; SHIOKAWA, Youichi</creator><creatorcontrib>TANIGUCHI, Kiyoshi ; MIYAO, Yasuhiro ; YAMANO, Katsuhiro ; YAMAMOTO, Takao ; TERAI, Takao ; KUSUNOKI, Takahiro ; TSUBAKI, Kazunori ; SHIOKAWA, Youichi</creatorcontrib><description>We synthesized the racemates of five presumed metabolites (1b-f) of (S)-(-)-N-tert-butyl-4, 4-diphenyl-2-cyclopentenylamine hydrochloride (FK584, S(-)-1a), a novel agent for the treatment of overactive detrusor syndrome, in order to confirm the structures of the metabolites and also to evaluate thier inhibitory activity against detrusor contraction. (±)-N-tert-Butyl-4-(4-hydroxyphenyl)- and 4-(4-hydroxy-3-methoxyphenyl)-4-phenyl-2-cyclopenetenyl-amines (1b-e) were synthesized via 5-(4-methoxyphenyl)- and 5-(4-benzyloxy-3-methoxyphenyl)-5-phenyl-2-cyclopenten-1-one (9g, h), respectively. Compounds 1b-f prepared in this study were identical with the metabolites in human urine in gas chromatography-mass specrometry and analytical HPLC. The inhibitory activity of compounds 1b-f against detrusor contraction in vitro induced by electrical field stimulation in guinea-pigs was less potent than that of FK584.</description><identifier>ISSN: 0009-2363</identifier><identifier>EISSN: 1347-5223</identifier><identifier>DOI: 10.1248/cpb.44.1188</identifier><identifier>PMID: 8814950</identifier><identifier>CODEN: CPBTAL</identifier><language>eng</language><publisher>Tokyo: The Pharmaceutical Society of Japan</publisher><subject>(±)-N-(2-hydroxy-1, 1-dimethylethyl)-4, 4-diphenyl-2-cyclopetenylamine ; (±)-N-tert-butyl-4-(4-hydroxy-3-methoxyphenyl)-4-phenyl-2-cyclopentenylamine ; (±)-N-tert-butyl-4-(4-hydroxyphenyl)4-phenyl-2-cyclopenetenylamine ; Amines - chemical synthesis ; Amines - pharmacology ; Amines - urine ; Animals ; Benzhydryl Compounds - chemical synthesis ; Benzhydryl Compounds - pharmacology ; Benzhydryl Compounds - urine ; Biological and medical sciences ; Biotransformation ; detrusor contraction inhibition ; Electric Stimulation ; FK584 ; Gas Chromatography-Mass Spectrometry ; Guinea Pigs ; Humans ; In Vitro Techniques ; Medical sciences ; metabolite ; Muscarinic Agonists - chemical synthesis ; Muscarinic Agonists - pharmacology ; Muscarinic Agonists - urine ; Muscle Relaxants, Central - chemical synthesis ; Muscle Relaxants, Central - pharmacology ; Pharmacology. Drug treatments ; Stereoisomerism ; Urinary Bladder - drug effects ; Urinary Bladder - physiology ; Urinary system</subject><ispartof>Chemical and Pharmaceutical Bulletin, 1996/06/15, Vol.44(6), pp.1188-1195</ispartof><rights>The Pharmaceutical Society of Japan</rights><rights>1996 INIST-CNRS</rights><rights>Copyright Japan Science and Technology Agency 1996</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5508-90f6803e4fa6dedf6a7bd3ba86f9417ccc2e9dca791ef12927139daffda1683d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3164405$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8814950$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>TANIGUCHI, Kiyoshi</creatorcontrib><creatorcontrib>MIYAO, Yasuhiro</creatorcontrib><creatorcontrib>YAMANO, Katsuhiro</creatorcontrib><creatorcontrib>YAMAMOTO, Takao</creatorcontrib><creatorcontrib>TERAI, Takao</creatorcontrib><creatorcontrib>KUSUNOKI, Takahiro</creatorcontrib><creatorcontrib>TSUBAKI, Kazunori</creatorcontrib><creatorcontrib>SHIOKAWA, Youichi</creatorcontrib><title>Agents for the Treatment of Overactive Detrusor. IX. Synthesis and Pharmacological Properties of Metabolites of N-tert-Butyl-4, 4-diphenyl-2-cyclopentenylamine (FK584) in Human Urine</title><title>Chemical & pharmaceutical bulletin</title><addtitle>Chem. Pharm. Bull.</addtitle><description>We synthesized the racemates of five presumed metabolites (1b-f) of (S)-(-)-N-tert-butyl-4, 4-diphenyl-2-cyclopentenylamine hydrochloride (FK584, S(-)-1a), a novel agent for the treatment of overactive detrusor syndrome, in order to confirm the structures of the metabolites and also to evaluate thier inhibitory activity against detrusor contraction. (±)-N-tert-Butyl-4-(4-hydroxyphenyl)- and 4-(4-hydroxy-3-methoxyphenyl)-4-phenyl-2-cyclopenetenyl-amines (1b-e) were synthesized via 5-(4-methoxyphenyl)- and 5-(4-benzyloxy-3-methoxyphenyl)-5-phenyl-2-cyclopenten-1-one (9g, h), respectively. Compounds 1b-f prepared in this study were identical with the metabolites in human urine in gas chromatography-mass specrometry and analytical HPLC. The inhibitory activity of compounds 1b-f against detrusor contraction in vitro induced by electrical field stimulation in guinea-pigs was less potent than that of FK584.</description><subject>(±)-N-(2-hydroxy-1, 1-dimethylethyl)-4, 4-diphenyl-2-cyclopetenylamine</subject><subject>(±)-N-tert-butyl-4-(4-hydroxy-3-methoxyphenyl)-4-phenyl-2-cyclopentenylamine</subject><subject>(±)-N-tert-butyl-4-(4-hydroxyphenyl)4-phenyl-2-cyclopenetenylamine</subject><subject>Amines - chemical synthesis</subject><subject>Amines - pharmacology</subject><subject>Amines - urine</subject><subject>Animals</subject><subject>Benzhydryl Compounds - chemical synthesis</subject><subject>Benzhydryl Compounds - pharmacology</subject><subject>Benzhydryl Compounds - urine</subject><subject>Biological and medical sciences</subject><subject>Biotransformation</subject><subject>detrusor contraction inhibition</subject><subject>Electric Stimulation</subject><subject>FK584</subject><subject>Gas Chromatography-Mass Spectrometry</subject><subject>Guinea Pigs</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Medical sciences</subject><subject>metabolite</subject><subject>Muscarinic Agonists - chemical synthesis</subject><subject>Muscarinic Agonists - pharmacology</subject><subject>Muscarinic Agonists - urine</subject><subject>Muscle Relaxants, Central - chemical synthesis</subject><subject>Muscle Relaxants, Central - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Stereoisomerism</subject><subject>Urinary Bladder - drug effects</subject><subject>Urinary Bladder - physiology</subject><subject>Urinary system</subject><issn>0009-2363</issn><issn>1347-5223</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkVFv0zAUhS0EGqXwxDOSJRACQYodO4nzODbGJgabxCbxFt06122qxC62M6l_jN-Ho1ZF4sXWvee751o-hLzkbMFzqT7p7XIh5YJzpR6RGReyyoo8F4_JjDFWZ7koxVPyLIQNY3nBKnFCTpTisi7YjPw5XaGNgRrnaVwjvfMIcUgt6gy9eUAPOnYPSM8x-jE4v6BXvxb0584mOHSBgm3p7Rr8ANr1btVp6Omtd1v0scMwmXzHCEvXd3Ff_shi0rLPY9z1mfxIZdZ22zXaVOWZ3uk-zdo41TB0Fum7i2-Fku9pZ-nlOICl9z61n5MnBvqALw73nNxffLk7u8yub75enZ1eZ7oomMpqZkrFBEoDZYutKaFatmIJqjS15JXWOse61VDVHA3P67ziom7BmBZ4qUQr5uTt3nfr3e8RQ2yGLmjse7DoxtBUKk0JVSfw9X_gxo3eprc1XJZMcJanSObkw57S3oXg0TRb3w3gdw1nzZRlk7JspGymLBP96uA5Lgdsj-whvKS_OegQ0r8bD1Z34YgJXkrJioSd77FNiLDCow4pIt3jtJLXhZrWlvtj2v5PTuk2aMVfWZ_AAw</recordid><startdate>1996</startdate><enddate>1996</enddate><creator>TANIGUCHI, Kiyoshi</creator><creator>MIYAO, Yasuhiro</creator><creator>YAMANO, Katsuhiro</creator><creator>YAMAMOTO, Takao</creator><creator>TERAI, Takao</creator><creator>KUSUNOKI, Takahiro</creator><creator>TSUBAKI, Kazunori</creator><creator>SHIOKAWA, Youichi</creator><general>The Pharmaceutical Society of Japan</general><general>Maruzen</general><general>Japan Science and Technology Agency</general><scope>IQODW</scope><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>1996</creationdate><title>Agents for the Treatment of Overactive Detrusor. IX. Synthesis and Pharmacological Properties of Metabolites of N-tert-Butyl-4, 4-diphenyl-2-cyclopentenylamine (FK584) in Human Urine</title><author>TANIGUCHI, Kiyoshi ; MIYAO, Yasuhiro ; YAMANO, Katsuhiro ; YAMAMOTO, Takao ; TERAI, Takao ; KUSUNOKI, Takahiro ; TSUBAKI, Kazunori ; SHIOKAWA, Youichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5508-90f6803e4fa6dedf6a7bd3ba86f9417ccc2e9dca791ef12927139daffda1683d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>(±)-N-(2-hydroxy-1, 1-dimethylethyl)-4, 4-diphenyl-2-cyclopetenylamine</topic><topic>(±)-N-tert-butyl-4-(4-hydroxy-3-methoxyphenyl)-4-phenyl-2-cyclopentenylamine</topic><topic>(±)-N-tert-butyl-4-(4-hydroxyphenyl)4-phenyl-2-cyclopenetenylamine</topic><topic>Amines - chemical synthesis</topic><topic>Amines - pharmacology</topic><topic>Amines - urine</topic><topic>Animals</topic><topic>Benzhydryl Compounds - chemical synthesis</topic><topic>Benzhydryl Compounds - pharmacology</topic><topic>Benzhydryl Compounds - urine</topic><topic>Biological and medical sciences</topic><topic>Biotransformation</topic><topic>detrusor contraction inhibition</topic><topic>Electric Stimulation</topic><topic>FK584</topic><topic>Gas Chromatography-Mass Spectrometry</topic><topic>Guinea Pigs</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Medical sciences</topic><topic>metabolite</topic><topic>Muscarinic Agonists - chemical synthesis</topic><topic>Muscarinic Agonists - pharmacology</topic><topic>Muscarinic Agonists - urine</topic><topic>Muscle Relaxants, Central - chemical synthesis</topic><topic>Muscle Relaxants, Central - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Stereoisomerism</topic><topic>Urinary Bladder - drug effects</topic><topic>Urinary Bladder - physiology</topic><topic>Urinary system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>TANIGUCHI, Kiyoshi</creatorcontrib><creatorcontrib>MIYAO, Yasuhiro</creatorcontrib><creatorcontrib>YAMANO, Katsuhiro</creatorcontrib><creatorcontrib>YAMAMOTO, Takao</creatorcontrib><creatorcontrib>TERAI, Takao</creatorcontrib><creatorcontrib>KUSUNOKI, Takahiro</creatorcontrib><creatorcontrib>TSUBAKI, Kazunori</creatorcontrib><creatorcontrib>SHIOKAWA, Youichi</creatorcontrib><collection>Pascal-Francis</collection><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>TANIGUCHI, Kiyoshi</au><au>MIYAO, Yasuhiro</au><au>YAMANO, Katsuhiro</au><au>YAMAMOTO, Takao</au><au>TERAI, Takao</au><au>KUSUNOKI, Takahiro</au><au>TSUBAKI, Kazunori</au><au>SHIOKAWA, Youichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Agents for the Treatment of Overactive Detrusor. IX. Synthesis and Pharmacological Properties of Metabolites of N-tert-Butyl-4, 4-diphenyl-2-cyclopentenylamine (FK584) in Human Urine</atitle><jtitle>Chemical & pharmaceutical bulletin</jtitle><addtitle>Chem. Pharm. Bull.</addtitle><date>1996</date><risdate>1996</risdate><volume>44</volume><issue>6</issue><spage>1188</spage><epage>1195</epage><pages>1188-1195</pages><issn>0009-2363</issn><eissn>1347-5223</eissn><coden>CPBTAL</coden><abstract>We synthesized the racemates of five presumed metabolites (1b-f) of (S)-(-)-N-tert-butyl-4, 4-diphenyl-2-cyclopentenylamine hydrochloride (FK584, S(-)-1a), a novel agent for the treatment of overactive detrusor syndrome, in order to confirm the structures of the metabolites and also to evaluate thier inhibitory activity against detrusor contraction. (±)-N-tert-Butyl-4-(4-hydroxyphenyl)- and 4-(4-hydroxy-3-methoxyphenyl)-4-phenyl-2-cyclopenetenyl-amines (1b-e) were synthesized via 5-(4-methoxyphenyl)- and 5-(4-benzyloxy-3-methoxyphenyl)-5-phenyl-2-cyclopenten-1-one (9g, h), respectively. Compounds 1b-f prepared in this study were identical with the metabolites in human urine in gas chromatography-mass specrometry and analytical HPLC. The inhibitory activity of compounds 1b-f against detrusor contraction in vitro induced by electrical field stimulation in guinea-pigs was less potent than that of FK584.</abstract><cop>Tokyo</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>8814950</pmid><doi>10.1248/cpb.44.1188</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0009-2363 |
| ispartof | Chemical and Pharmaceutical Bulletin, 1996/06/15, Vol.44(6), pp.1188-1195 |
| issn | 0009-2363 1347-5223 |
| language | eng |
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| source | MEDLINE; J-STAGE (Japan Science & Technology Information Aggregator, Electronic) Freely Available Titles - Japanese; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Free Full-Text Journals in Chemistry |
| subjects | (±)-N-(2-hydroxy-1, 1-dimethylethyl)-4, 4-diphenyl-2-cyclopetenylamine (±)-N-tert-butyl-4-(4-hydroxy-3-methoxyphenyl)-4-phenyl-2-cyclopentenylamine (±)-N-tert-butyl-4-(4-hydroxyphenyl)4-phenyl-2-cyclopenetenylamine Amines - chemical synthesis Amines - pharmacology Amines - urine Animals Benzhydryl Compounds - chemical synthesis Benzhydryl Compounds - pharmacology Benzhydryl Compounds - urine Biological and medical sciences Biotransformation detrusor contraction inhibition Electric Stimulation FK584 Gas Chromatography-Mass Spectrometry Guinea Pigs Humans In Vitro Techniques Medical sciences metabolite Muscarinic Agonists - chemical synthesis Muscarinic Agonists - pharmacology Muscarinic Agonists - urine Muscle Relaxants, Central - chemical synthesis Muscle Relaxants, Central - pharmacology Pharmacology. Drug treatments Stereoisomerism Urinary Bladder - drug effects Urinary Bladder - physiology Urinary system |
| title | Agents for the Treatment of Overactive Detrusor. IX. Synthesis and Pharmacological Properties of Metabolites of N-tert-Butyl-4, 4-diphenyl-2-cyclopentenylamine (FK584) in Human Urine |
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