Potential Neuroleptic Agents, N-[(2-Pyrrolidinyl)methyl]-2, 3-dihydrobenzofuran-7-carboxamide Derivatives
A series of 2, 3-dihydrobenzofuran-7-carboxamides, presenting a stabilized intramolecular hydrogen bond, was synthesized and evaluated in pharmacological models for antipsychotic activity. Among them, N-[(1-butyl-2-pyrrolidinyl)methyl]-2-methyl-5-sulfamoyl-2, 3-dihydrobenzofuran-7-carboxamide (15) s...
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| Veröffentlicht in: | Chemical & pharmaceutical bulletin 1990/06/25, Vol.38(6), pp.1609-1615 |
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| container_title | Chemical & pharmaceutical bulletin |
| container_volume | 38 |
| creator | TAHARA, Tetsuya HAYANO, Kiyoharu MURAKAMI, Shu FUKUDA, Takemi SETOGUCHI, Michihide IKEDA, Kuniki MARUBAYASHI, Nobuhiro |
| description | A series of 2, 3-dihydrobenzofuran-7-carboxamides, presenting a stabilized intramolecular hydrogen bond, was synthesized and evaluated in pharmacological models for antipsychotic activity. Among them, N-[(1-butyl-2-pyrrolidinyl)methyl]-2-methyl-5-sulfamoyl-2, 3-dihydrobenzofuran-7-carboxamide (15) showed an atypical neuroleptic profile similar to that of sulpiride (1) and more lipophilic properties than 1. Compounds 15 was 11 times more potent in antagonistic activity on apomorphine-induced hyperactivity in mice (ED50=30mg/kg, p.o.) and stronger in potentiation of methamphetamine lethality in rats than 1, while it was as weak in inhibitory activity of apomorphine-induced stereotype in rats (ED50>500mg/kg, p.o.) as 1. On the other hand, N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methyl-5-methylthio-2, 3-dihydrobenzofuran-7-carboxamide (30) showed classical neuroleptic profile with a potency comparable to haloperidol in antagonistic activity on apomorphine-induced hyperactivity in mice (ED50=0.65mg/kg, p.o.). The structure-activity relationships were also discussed. |
| doi_str_mv | 10.1248/cpb.38.1609 |
| format | Article |
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Among them, N-[(1-butyl-2-pyrrolidinyl)methyl]-2-methyl-5-sulfamoyl-2, 3-dihydrobenzofuran-7-carboxamide (15) showed an atypical neuroleptic profile similar to that of sulpiride (1) and more lipophilic properties than 1. Compounds 15 was 11 times more potent in antagonistic activity on apomorphine-induced hyperactivity in mice (ED50=30mg/kg, p.o.) and stronger in potentiation of methamphetamine lethality in rats than 1, while it was as weak in inhibitory activity of apomorphine-induced stereotype in rats (ED50>500mg/kg, p.o.) as 1. On the other hand, N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methyl-5-methylthio-2, 3-dihydrobenzofuran-7-carboxamide (30) showed classical neuroleptic profile with a potency comparable to haloperidol in antagonistic activity on apomorphine-induced hyperactivity in mice (ED50=0.65mg/kg, p.o.). The structure-activity relationships were also discussed.</description><identifier>ISSN: 0009-2363</identifier><identifier>EISSN: 1347-5223</identifier><identifier>DOI: 10.1248/cpb.38.1609</identifier><identifier>PMID: 1976442</identifier><identifier>CODEN: CPBTAL</identifier><language>eng</language><publisher>Tokyo: The Pharmaceutical Society of Japan</publisher><subject>2, 3-dihydrobenzofuran-7-carboxamide derivative ; Animals ; Antipsychotic Agents - chemical synthesis ; apomorphine-induced hyperactivity ; benzamide analogue ; Benzofurans - chemical synthesis ; Benzofurans - pharmacology ; Benzofurans - toxicity ; Chemical Phenomena ; Chemistry ; Exact sciences and technology ; Female ; Heterocyclic compounds ; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms ; intramolecular hydrogen bond ; lipophilicity ; Male ; methamphetamine potentiation ; Mice ; Motor Activity - drug effects ; neuroleptic agent ; Organic chemistry ; Preparations and properties ; Pyrrolidines - chemical synthesis ; Pyrrolidines - pharmacology ; Pyrrolidines - toxicity ; Rats ; stereotype ; Stereotyped Behavior - drug effects ; structure-activity relationship</subject><ispartof>Chemical and Pharmaceutical Bulletin, 1990/06/25, Vol.38(6), pp.1609-1615</ispartof><rights>The Pharmaceutical Society of Japan</rights><rights>1991 INIST-CNRS</rights><rights>Copyright Japan Science and Technology Agency 1990</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19295531$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1976442$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>TAHARA, Tetsuya</creatorcontrib><creatorcontrib>HAYANO, Kiyoharu</creatorcontrib><creatorcontrib>MURAKAMI, Shu</creatorcontrib><creatorcontrib>FUKUDA, Takemi</creatorcontrib><creatorcontrib>SETOGUCHI, Michihide</creatorcontrib><creatorcontrib>IKEDA, Kuniki</creatorcontrib><creatorcontrib>MARUBAYASHI, Nobuhiro</creatorcontrib><title>Potential Neuroleptic Agents, N-[(2-Pyrrolidinyl)methyl]-2, 3-dihydrobenzofuran-7-carboxamide Derivatives</title><title>Chemical & pharmaceutical bulletin</title><addtitle>Chem. Pharm. Bull.</addtitle><description>A series of 2, 3-dihydrobenzofuran-7-carboxamides, presenting a stabilized intramolecular hydrogen bond, was synthesized and evaluated in pharmacological models for antipsychotic activity. Among them, N-[(1-butyl-2-pyrrolidinyl)methyl]-2-methyl-5-sulfamoyl-2, 3-dihydrobenzofuran-7-carboxamide (15) showed an atypical neuroleptic profile similar to that of sulpiride (1) and more lipophilic properties than 1. Compounds 15 was 11 times more potent in antagonistic activity on apomorphine-induced hyperactivity in mice (ED50=30mg/kg, p.o.) and stronger in potentiation of methamphetamine lethality in rats than 1, while it was as weak in inhibitory activity of apomorphine-induced stereotype in rats (ED50>500mg/kg, p.o.) as 1. On the other hand, N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methyl-5-methylthio-2, 3-dihydrobenzofuran-7-carboxamide (30) showed classical neuroleptic profile with a potency comparable to haloperidol in antagonistic activity on apomorphine-induced hyperactivity in mice (ED50=0.65mg/kg, p.o.). The structure-activity relationships were also discussed.</description><subject>2, 3-dihydrobenzofuran-7-carboxamide derivative</subject><subject>Animals</subject><subject>Antipsychotic Agents - chemical synthesis</subject><subject>apomorphine-induced hyperactivity</subject><subject>benzamide analogue</subject><subject>Benzofurans - chemical synthesis</subject><subject>Benzofurans - pharmacology</subject><subject>Benzofurans - toxicity</subject><subject>Chemical Phenomena</subject><subject>Chemistry</subject><subject>Exact sciences and technology</subject><subject>Female</subject><subject>Heterocyclic compounds</subject><subject>Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms</subject><subject>intramolecular hydrogen bond</subject><subject>lipophilicity</subject><subject>Male</subject><subject>methamphetamine potentiation</subject><subject>Mice</subject><subject>Motor Activity - drug effects</subject><subject>neuroleptic agent</subject><subject>Organic chemistry</subject><subject>Preparations and properties</subject><subject>Pyrrolidines - chemical synthesis</subject><subject>Pyrrolidines - pharmacology</subject><subject>Pyrrolidines - toxicity</subject><subject>Rats</subject><subject>stereotype</subject><subject>Stereotyped Behavior - drug effects</subject><subject>structure-activity relationship</subject><issn>0009-2363</issn><issn>1347-5223</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkc1r3DAQxUVpSTZpTzkHDCXQQrSVNJItH5ck_YCQ5tCeSjFja5zV4rU3kh3q_vVV2aXpZQbm_Zhh3mPsTIqlVNp-aHb1EuxS5qJ8wRYSdMGNUvCSLYQQJVeQwzE7iXEjhDKigCN2JMsi11otmL8fRupHj112R1MYOtqNvslWD2kYL7M7_uOd4vdzSIp3vp-791sa13P3k6vLDLjz69mFoab-99BOAXte8AZDPfzCrXeUXVPwTzj6J4qv2asWu0hvDv2Uff948-3qM7_9-unL1eqWb8DokZMSzhKYOlcN6jrXBbTOOmOdapzVEqhFLdEYY2UJJAvTFFIhOScQhM3hlL3d792F4XGiOFabYQp9OllJnQsFUFqTqPMDNdVbctUu-C2GuToYk_SLg46xwa5NrzU-_oep0hiQibvec5s44gP9AzAkGzuqUjayNLYCW-X78jemZ3mNoaIe_gBwY4kj</recordid><startdate>19900601</startdate><enddate>19900601</enddate><creator>TAHARA, Tetsuya</creator><creator>HAYANO, Kiyoharu</creator><creator>MURAKAMI, Shu</creator><creator>FUKUDA, Takemi</creator><creator>SETOGUCHI, Michihide</creator><creator>IKEDA, Kuniki</creator><creator>MARUBAYASHI, Nobuhiro</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>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>H94</scope></search><sort><creationdate>19900601</creationdate><title>Potential Neuroleptic Agents, N-[(2-Pyrrolidinyl)methyl]-2, 3-dihydrobenzofuran-7-carboxamide Derivatives</title><author>TAHARA, Tetsuya ; HAYANO, Kiyoharu ; MURAKAMI, Shu ; FUKUDA, Takemi ; SETOGUCHI, Michihide ; IKEDA, Kuniki ; MARUBAYASHI, Nobuhiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j354t-e20d8e35b62ca4b6473fd8d58d2cd8413efa41a5558193e175c712aedd0a30863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>2, 3-dihydrobenzofuran-7-carboxamide derivative</topic><topic>Animals</topic><topic>Antipsychotic Agents - chemical synthesis</topic><topic>apomorphine-induced hyperactivity</topic><topic>benzamide analogue</topic><topic>Benzofurans - chemical synthesis</topic><topic>Benzofurans - pharmacology</topic><topic>Benzofurans - toxicity</topic><topic>Chemical Phenomena</topic><topic>Chemistry</topic><topic>Exact sciences and technology</topic><topic>Female</topic><topic>Heterocyclic compounds</topic><topic>Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms</topic><topic>intramolecular hydrogen bond</topic><topic>lipophilicity</topic><topic>Male</topic><topic>methamphetamine potentiation</topic><topic>Mice</topic><topic>Motor Activity - drug effects</topic><topic>neuroleptic agent</topic><topic>Organic chemistry</topic><topic>Preparations and properties</topic><topic>Pyrrolidines - chemical synthesis</topic><topic>Pyrrolidines - pharmacology</topic><topic>Pyrrolidines - toxicity</topic><topic>Rats</topic><topic>stereotype</topic><topic>Stereotyped Behavior - drug effects</topic><topic>structure-activity relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>TAHARA, Tetsuya</creatorcontrib><creatorcontrib>HAYANO, Kiyoharu</creatorcontrib><creatorcontrib>MURAKAMI, Shu</creatorcontrib><creatorcontrib>FUKUDA, Takemi</creatorcontrib><creatorcontrib>SETOGUCHI, Michihide</creatorcontrib><creatorcontrib>IKEDA, Kuniki</creatorcontrib><creatorcontrib>MARUBAYASHI, Nobuhiro</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>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Chemical & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>TAHARA, Tetsuya</au><au>HAYANO, Kiyoharu</au><au>MURAKAMI, Shu</au><au>FUKUDA, Takemi</au><au>SETOGUCHI, Michihide</au><au>IKEDA, Kuniki</au><au>MARUBAYASHI, Nobuhiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Potential Neuroleptic Agents, N-[(2-Pyrrolidinyl)methyl]-2, 3-dihydrobenzofuran-7-carboxamide Derivatives</atitle><jtitle>Chemical & pharmaceutical bulletin</jtitle><addtitle>Chem. Pharm. Bull.</addtitle><date>1990-06-01</date><risdate>1990</risdate><volume>38</volume><issue>6</issue><spage>1609</spage><epage>1615</epage><pages>1609-1615</pages><issn>0009-2363</issn><eissn>1347-5223</eissn><coden>CPBTAL</coden><abstract>A series of 2, 3-dihydrobenzofuran-7-carboxamides, presenting a stabilized intramolecular hydrogen bond, was synthesized and evaluated in pharmacological models for antipsychotic activity. Among them, N-[(1-butyl-2-pyrrolidinyl)methyl]-2-methyl-5-sulfamoyl-2, 3-dihydrobenzofuran-7-carboxamide (15) showed an atypical neuroleptic profile similar to that of sulpiride (1) and more lipophilic properties than 1. Compounds 15 was 11 times more potent in antagonistic activity on apomorphine-induced hyperactivity in mice (ED50=30mg/kg, p.o.) and stronger in potentiation of methamphetamine lethality in rats than 1, while it was as weak in inhibitory activity of apomorphine-induced stereotype in rats (ED50>500mg/kg, p.o.) as 1. On the other hand, N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methyl-5-methylthio-2, 3-dihydrobenzofuran-7-carboxamide (30) showed classical neuroleptic profile with a potency comparable to haloperidol in antagonistic activity on apomorphine-induced hyperactivity in mice (ED50=0.65mg/kg, p.o.). The structure-activity relationships were also discussed.</abstract><cop>Tokyo</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>1976442</pmid><doi>10.1248/cpb.38.1609</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Chemical and Pharmaceutical Bulletin, 1990/06/25, Vol.38(6), pp.1609-1615 |
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| language | eng |
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| source | J-STAGE Free; MEDLINE; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | 2, 3-dihydrobenzofuran-7-carboxamide derivative Animals Antipsychotic Agents - chemical synthesis apomorphine-induced hyperactivity benzamide analogue Benzofurans - chemical synthesis Benzofurans - pharmacology Benzofurans - toxicity Chemical Phenomena Chemistry Exact sciences and technology Female Heterocyclic compounds Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms intramolecular hydrogen bond lipophilicity Male methamphetamine potentiation Mice Motor Activity - drug effects neuroleptic agent Organic chemistry Preparations and properties Pyrrolidines - chemical synthesis Pyrrolidines - pharmacology Pyrrolidines - toxicity Rats stereotype Stereotyped Behavior - drug effects structure-activity relationship |
| title | Potential Neuroleptic Agents, N-[(2-Pyrrolidinyl)methyl]-2, 3-dihydrobenzofuran-7-carboxamide Derivatives |
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