6-(Alkylamino)-3-aryl-1,2,4-triazolo[3,4-a]phthalazines. A new class of benzodiazepine receptor ligands
Some 6-(alkylamino)-3-aryl-1,2,4-triazolo[3,4-a]phthalazines have been shown to displace diazepam from rat brain specific binding sites, in vitro, with Ki (nM) values comparable to those of reference benzodiazepines and to have anticonvulsant (pentylenetetrazole test, mice) and anticonflict activity...
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| Veröffentlicht in: | Journal of medicinal chemistry 1988-06, Vol.31 (6), p.1115-1123 |
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| container_end_page | 1123 |
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| container_issue | 6 |
| container_start_page | 1115 |
| container_title | Journal of medicinal chemistry |
| container_volume | 31 |
| creator | Tarzia, Giorgio Occelli, Emilio Toja, Emilio Barone, Domenico Corsico, Nerina Gallico, Licia Luzzani, Franco |
| description | Some 6-(alkylamino)-3-aryl-1,2,4-triazolo[3,4-a]phthalazines have been shown to displace diazepam from rat brain specific binding sites, in vitro, with Ki (nM) values comparable to those of reference benzodiazepines and to have anticonvulsant (pentylenetetrazole test, mice) and anticonflict activity (Vogel test, rat) in vivo. Separation between the doses causing anticonflict effects (Vogel test, rat) and those impairing motor coordination (rotarod test, rat) has been shown for N,N-bis(2-methoxyethyl)-3-(4-methoxyphenyl)-1,2,4-triazolo[3,4-a] phthalazin-6-amine (80). This compound, unlike diazepam, was inactive in counteracting the strychnine (mouse) and maximal electroshock (mouse) induced convulsions and in the "aggressive monkey" model. These differences from the classical benzodiazepines in the animal tests indicate that 80 may have some selective anxiolytic activity. |
| doi_str_mv | 10.1021/jm00401a010 |
| format | Article |
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Separation between the doses causing anticonflict effects (Vogel test, rat) and those impairing motor coordination (rotarod test, rat) has been shown for N,N-bis(2-methoxyethyl)-3-(4-methoxyphenyl)-1,2,4-triazolo[3,4-a] phthalazin-6-amine (80). This compound, unlike diazepam, was inactive in counteracting the strychnine (mouse) and maximal electroshock (mouse) induced convulsions and in the "aggressive monkey" model. 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A new class of benzodiazepine receptor ligands</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>Some 6-(alkylamino)-3-aryl-1,2,4-triazolo[3,4-a]phthalazines have been shown to displace diazepam from rat brain specific binding sites, in vitro, with Ki (nM) values comparable to those of reference benzodiazepines and to have anticonvulsant (pentylenetetrazole test, mice) and anticonflict activity (Vogel test, rat) in vivo. Separation between the doses causing anticonflict effects (Vogel test, rat) and those impairing motor coordination (rotarod test, rat) has been shown for N,N-bis(2-methoxyethyl)-3-(4-methoxyphenyl)-1,2,4-triazolo[3,4-a] phthalazin-6-amine (80). This compound, unlike diazepam, was inactive in counteracting the strychnine (mouse) and maximal electroshock (mouse) induced convulsions and in the "aggressive monkey" model. These differences from the classical benzodiazepines in the animal tests indicate that 80 may have some selective anxiolytic activity.</description><subject>Aggression - drug effects</subject><subject>Animals</subject><subject>Anticonvulsants - chemical synthesis</subject><subject>Anticonvulsants - pharmacology</subject><subject>Chemistry</subject><subject>Conflict (Psychology)</subject><subject>Exact sciences and technology</subject><subject>Heterocyclic compounds</subject><subject>Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings</subject><subject>In Vitro Techniques</subject><subject>Ligands</subject><subject>Macaca</subject><subject>Male</subject><subject>Mice</subject><subject>Motor Activity - drug effects</subject><subject>Organic chemistry</subject><subject>Preparations and properties</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Receptors, GABA-A - metabolism</subject><subject>Species Specificity</subject><subject>Structure-Activity Relationship</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1988</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM1rFDEYh4Moda2ePAtzkKrY1DdfM-lxWdSKBUWrB0XCO0mmnW1msiazaPevN2WXxYPgKbw8Dz_CQ8hjBicMOHu1HAAkMAQGd8iMKQ5UapB3yQyAc8prLu6TBzkvAUAwLg7IAdeiVlrPyGVNn8_D9U3AoR_jCyoopptA2TE_lnRKPW5iiN9FOfDH6mq6woCbfvT5pJpXo_9V2YA5V7GrWj9uoiu-XxVeJW_9aoqpCv0lji4_JPc6DNk_2r2H5Mub1xeLM3r-4e27xfycomRyolpaq7kT3nklVMed7lrnGtG0HZeITSssk07WIB1zAlTbecuYcEKfsrZRVhySo-3uKsWfa58nM_TZ-hBw9HGdTaN5SXUK_xWZkrrWShbx5Va0KeacfGdWqR9KJcPA3PY3f_Uv9pPd7LodvNu7u-CFP91xzBZDl3C0fd5rDVO1bOqi0a3W58n_3mNM16YuNZS5-PjZvP_66WzxjTfmdvbZ1kebzTKu01gi__ODfwBsd6cW</recordid><startdate>19880601</startdate><enddate>19880601</enddate><creator>Tarzia, Giorgio</creator><creator>Occelli, Emilio</creator><creator>Toja, Emilio</creator><creator>Barone, Domenico</creator><creator>Corsico, Nerina</creator><creator>Gallico, Licia</creator><creator>Luzzani, Franco</creator><general>American Chemical Society</general><scope>BSCLL</scope><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>7X8</scope></search><sort><creationdate>19880601</creationdate><title>6-(Alkylamino)-3-aryl-1,2,4-triazolo[3,4-a]phthalazines. A new class of benzodiazepine receptor ligands</title><author>Tarzia, Giorgio ; Occelli, Emilio ; Toja, Emilio ; Barone, Domenico ; Corsico, Nerina ; Gallico, Licia ; Luzzani, Franco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a414t-84cc82d3ede535f2d8fbdd737bf24aa7b3c14d4604d1d305bfec113d3891b75c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1988</creationdate><topic>Aggression - drug effects</topic><topic>Animals</topic><topic>Anticonvulsants - chemical synthesis</topic><topic>Anticonvulsants - pharmacology</topic><topic>Chemistry</topic><topic>Conflict (Psychology)</topic><topic>Exact sciences and technology</topic><topic>Heterocyclic compounds</topic><topic>Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings</topic><topic>In Vitro Techniques</topic><topic>Ligands</topic><topic>Macaca</topic><topic>Male</topic><topic>Mice</topic><topic>Motor Activity - drug effects</topic><topic>Organic chemistry</topic><topic>Preparations and properties</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Receptors, GABA-A - metabolism</topic><topic>Species Specificity</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tarzia, Giorgio</creatorcontrib><creatorcontrib>Occelli, Emilio</creatorcontrib><creatorcontrib>Toja, Emilio</creatorcontrib><creatorcontrib>Barone, Domenico</creatorcontrib><creatorcontrib>Corsico, Nerina</creatorcontrib><creatorcontrib>Gallico, Licia</creatorcontrib><creatorcontrib>Luzzani, Franco</creatorcontrib><collection>Istex</collection><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>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tarzia, Giorgio</au><au>Occelli, Emilio</au><au>Toja, Emilio</au><au>Barone, Domenico</au><au>Corsico, Nerina</au><au>Gallico, Licia</au><au>Luzzani, Franco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>6-(Alkylamino)-3-aryl-1,2,4-triazolo[3,4-a]phthalazines. A new class of benzodiazepine receptor ligands</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1988-06-01</date><risdate>1988</risdate><volume>31</volume><issue>6</issue><spage>1115</spage><epage>1123</epage><pages>1115-1123</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>Some 6-(alkylamino)-3-aryl-1,2,4-triazolo[3,4-a]phthalazines have been shown to displace diazepam from rat brain specific binding sites, in vitro, with Ki (nM) values comparable to those of reference benzodiazepines and to have anticonvulsant (pentylenetetrazole test, mice) and anticonflict activity (Vogel test, rat) in vivo. Separation between the doses causing anticonflict effects (Vogel test, rat) and those impairing motor coordination (rotarod test, rat) has been shown for N,N-bis(2-methoxyethyl)-3-(4-methoxyphenyl)-1,2,4-triazolo[3,4-a] phthalazin-6-amine (80). This compound, unlike diazepam, was inactive in counteracting the strychnine (mouse) and maximal electroshock (mouse) induced convulsions and in the "aggressive monkey" model. These differences from the classical benzodiazepines in the animal tests indicate that 80 may have some selective anxiolytic activity.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>2836588</pmid><doi>10.1021/jm00401a010</doi><tpages>9</tpages></addata></record> |
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| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 1988-06, Vol.31 (6), p.1115-1123 |
| issn | 0022-2623 1520-4804 |
| language | eng |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Aggression - drug effects Animals Anticonvulsants - chemical synthesis Anticonvulsants - pharmacology Chemistry Conflict (Psychology) Exact sciences and technology Heterocyclic compounds Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings In Vitro Techniques Ligands Macaca Male Mice Motor Activity - drug effects Organic chemistry Preparations and properties Rats Rats, Inbred Strains Receptors, GABA-A - metabolism Species Specificity Structure-Activity Relationship |
| title | 6-(Alkylamino)-3-aryl-1,2,4-triazolo[3,4-a]phthalazines. A new class of benzodiazepine receptor ligands |
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