The influence of substitution at aromatic part of 1,2,3,4-tetrahydroisoquinoline on in vitro and in vivo 5-HT(1A)/5-HT(2A) receptor activities of its 1-adamantoyloaminoalkyl derivatives
Further structure-activity relationship (SAR) studies with the 1,2,3,4-tetrahydroisoquinoline (THIQ) class of 5-HT(1A) ligands led to the synthesis of new 1-adamantoyloaminoalkyl derivatives. The impact of substituent variations in the aromatic part of THIQ moiety on 5-HT(1A) and 5-HT(2A) receptor a...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2002-01, Vol.10 (1), p.87-95 |
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| creator | Bojarski, Andrzej J Mokrosz, Maria J Minol, Sijka Charakchieva Kozioł, Aneta Wesołowska, Anna Tatarczyńska, Ewa Kłodzińska, Aleksandra Chojnacka-Wójcik, Ewa |
| description | Further structure-activity relationship (SAR) studies with the 1,2,3,4-tetrahydroisoquinoline (THIQ) class of 5-HT(1A) ligands led to the synthesis of new 1-adamantoyloaminoalkyl derivatives. The impact of substituent variations in the aromatic part of THIQ moiety on 5-HT(1A) and 5-HT(2A) receptor affinities, as well as in vivo functional properties of the investigated compounds were discussed. It was found that those modifications reduced the binding affinity for 5-HT(1A) receptors (in comparison with unsubstituted THIQ derivatives); however, the majority of new compounds still remained potent 5-HT(1A) ligands (K(i)=4.9-46 nM) and most of them showed features of partial agonists of postsynaptic 5-HT(1A) receptors. At the same time, their 5-HT(2A) receptor affinity was slightly increased (K(i)=40-1475 nM), which resulted in a loss of 5-HT(2A)/5-HT(1A) selectivity. 5-Br,8-OCH3 derivative-the most potent, mixed 5-HT(1A)/5-HT(2A) ligand-produced activation of presynaptic 5-HT(1A) receptors and showed properties of a 5-HT(2A) receptor antagonist. |
| format | Article |
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The impact of substituent variations in the aromatic part of THIQ moiety on 5-HT(1A) and 5-HT(2A) receptor affinities, as well as in vivo functional properties of the investigated compounds were discussed. It was found that those modifications reduced the binding affinity for 5-HT(1A) receptors (in comparison with unsubstituted THIQ derivatives); however, the majority of new compounds still remained potent 5-HT(1A) ligands (K(i)=4.9-46 nM) and most of them showed features of partial agonists of postsynaptic 5-HT(1A) receptors. At the same time, their 5-HT(2A) receptor affinity was slightly increased (K(i)=40-1475 nM), which resulted in a loss of 5-HT(2A)/5-HT(1A) selectivity. 5-Br,8-OCH3 derivative-the most potent, mixed 5-HT(1A)/5-HT(2A) ligand-produced activation of presynaptic 5-HT(1A) receptors and showed properties of a 5-HT(2A) receptor antagonist.</description><identifier>ISSN: 0968-0896</identifier><identifier>PMID: 11738610</identifier><language>eng</language><publisher>England</publisher><subject>Adamantane - chemistry ; Animals ; In Vitro Techniques ; Isoquinolines - chemistry ; Isoquinolines - pharmacology ; Magnetic Resonance Spectroscopy ; Male ; Mice ; Rats ; Rats, Wistar ; Serotonin Antagonists - chemistry ; Serotonin Antagonists - pharmacology ; Serotonin Receptor Agonists - chemistry ; Serotonin Receptor Agonists - pharmacology ; Structure-Activity Relationship ; Tetrahydroisoquinolines</subject><ispartof>Bioorganic & medicinal chemistry, 2002-01, Vol.10 (1), p.87-95</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11738610$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bojarski, Andrzej J</creatorcontrib><creatorcontrib>Mokrosz, Maria J</creatorcontrib><creatorcontrib>Minol, Sijka Charakchieva</creatorcontrib><creatorcontrib>Kozioł, Aneta</creatorcontrib><creatorcontrib>Wesołowska, Anna</creatorcontrib><creatorcontrib>Tatarczyńska, Ewa</creatorcontrib><creatorcontrib>Kłodzińska, Aleksandra</creatorcontrib><creatorcontrib>Chojnacka-Wójcik, Ewa</creatorcontrib><title>The influence of substitution at aromatic part of 1,2,3,4-tetrahydroisoquinoline on in vitro and in vivo 5-HT(1A)/5-HT(2A) receptor activities of its 1-adamantoyloaminoalkyl derivatives</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>Further structure-activity relationship (SAR) studies with the 1,2,3,4-tetrahydroisoquinoline (THIQ) class of 5-HT(1A) ligands led to the synthesis of new 1-adamantoyloaminoalkyl derivatives. The impact of substituent variations in the aromatic part of THIQ moiety on 5-HT(1A) and 5-HT(2A) receptor affinities, as well as in vivo functional properties of the investigated compounds were discussed. It was found that those modifications reduced the binding affinity for 5-HT(1A) receptors (in comparison with unsubstituted THIQ derivatives); however, the majority of new compounds still remained potent 5-HT(1A) ligands (K(i)=4.9-46 nM) and most of them showed features of partial agonists of postsynaptic 5-HT(1A) receptors. At the same time, their 5-HT(2A) receptor affinity was slightly increased (K(i)=40-1475 nM), which resulted in a loss of 5-HT(2A)/5-HT(1A) selectivity. 5-Br,8-OCH3 derivative-the most potent, mixed 5-HT(1A)/5-HT(2A) ligand-produced activation of presynaptic 5-HT(1A) receptors and showed properties of a 5-HT(2A) receptor antagonist.</description><subject>Adamantane - chemistry</subject><subject>Animals</subject><subject>In Vitro Techniques</subject><subject>Isoquinolines - chemistry</subject><subject>Isoquinolines - pharmacology</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Male</subject><subject>Mice</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Serotonin Antagonists - chemistry</subject><subject>Serotonin Antagonists - pharmacology</subject><subject>Serotonin Receptor Agonists - chemistry</subject><subject>Serotonin Receptor Agonists - pharmacology</subject><subject>Structure-Activity Relationship</subject><subject>Tetrahydroisoquinolines</subject><issn>0968-0896</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kE1OwzAQhbMA0VK4AvIKUakR_kmcZFlVQJEqsck-mjiOakjsYDuRcjRuh0uLZjEz0ptP895VtMQFz2OcF3wR3Tr3iTGmSUFuogUhGcs5wcvopzxKpHTbjVILiUyL3Fg7r_zoldEIPAJrevBKoAGsPwnIhm7YJom99BaOc2ONcuZ7VNp0SgeEDjw0KW8NAt2cl8mgNN6XT2S7fv4b6HaNrBRy8MYiEF6FAyXdia-8QySGBnrQ3sydgT6wofuaO9RIq6bwzSTdXXTdQufk_aWvovL1pdzt48PH2_tue4iHNMFxgmXb1Fyw4LaoGUlZhiVLs7qlUJA8zSjloUIweUpFy4VIWoq5KGreFg1wtooez9jBBpPS-apXTsiuAy3N6KqMsISzhAThw0U41r1sqsGqHuxc_WfNfgF-g3rD</recordid><startdate>200201</startdate><enddate>200201</enddate><creator>Bojarski, Andrzej J</creator><creator>Mokrosz, Maria J</creator><creator>Minol, Sijka Charakchieva</creator><creator>Kozioł, Aneta</creator><creator>Wesołowska, Anna</creator><creator>Tatarczyńska, Ewa</creator><creator>Kłodzińska, Aleksandra</creator><creator>Chojnacka-Wójcik, Ewa</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>200201</creationdate><title>The influence of substitution at aromatic part of 1,2,3,4-tetrahydroisoquinoline on in vitro and in vivo 5-HT(1A)/5-HT(2A) receptor activities of its 1-adamantoyloaminoalkyl derivatives</title><author>Bojarski, Andrzej J ; Mokrosz, Maria J ; Minol, Sijka Charakchieva ; Kozioł, Aneta ; Wesołowska, Anna ; Tatarczyńska, Ewa ; Kłodzińska, Aleksandra ; Chojnacka-Wójcik, Ewa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p540-40efdb6c36109b315370e357bf2a91857226262024852cf6cc4f206c9b6f9da63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adamantane - chemistry</topic><topic>Animals</topic><topic>In Vitro Techniques</topic><topic>Isoquinolines - chemistry</topic><topic>Isoquinolines - pharmacology</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Male</topic><topic>Mice</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Serotonin Antagonists - chemistry</topic><topic>Serotonin Antagonists - pharmacology</topic><topic>Serotonin Receptor Agonists - chemistry</topic><topic>Serotonin Receptor Agonists - pharmacology</topic><topic>Structure-Activity Relationship</topic><topic>Tetrahydroisoquinolines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bojarski, Andrzej J</creatorcontrib><creatorcontrib>Mokrosz, Maria J</creatorcontrib><creatorcontrib>Minol, Sijka Charakchieva</creatorcontrib><creatorcontrib>Kozioł, Aneta</creatorcontrib><creatorcontrib>Wesołowska, Anna</creatorcontrib><creatorcontrib>Tatarczyńska, Ewa</creatorcontrib><creatorcontrib>Kłodzińska, Aleksandra</creatorcontrib><creatorcontrib>Chojnacka-Wójcik, Ewa</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bojarski, Andrzej J</au><au>Mokrosz, Maria J</au><au>Minol, Sijka Charakchieva</au><au>Kozioł, Aneta</au><au>Wesołowska, Anna</au><au>Tatarczyńska, Ewa</au><au>Kłodzińska, Aleksandra</au><au>Chojnacka-Wójcik, Ewa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The influence of substitution at aromatic part of 1,2,3,4-tetrahydroisoquinoline on in vitro and in vivo 5-HT(1A)/5-HT(2A) receptor activities of its 1-adamantoyloaminoalkyl derivatives</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2002-01</date><risdate>2002</risdate><volume>10</volume><issue>1</issue><spage>87</spage><epage>95</epage><pages>87-95</pages><issn>0968-0896</issn><abstract>Further structure-activity relationship (SAR) studies with the 1,2,3,4-tetrahydroisoquinoline (THIQ) class of 5-HT(1A) ligands led to the synthesis of new 1-adamantoyloaminoalkyl derivatives. The impact of substituent variations in the aromatic part of THIQ moiety on 5-HT(1A) and 5-HT(2A) receptor affinities, as well as in vivo functional properties of the investigated compounds were discussed. It was found that those modifications reduced the binding affinity for 5-HT(1A) receptors (in comparison with unsubstituted THIQ derivatives); however, the majority of new compounds still remained potent 5-HT(1A) ligands (K(i)=4.9-46 nM) and most of them showed features of partial agonists of postsynaptic 5-HT(1A) receptors. At the same time, their 5-HT(2A) receptor affinity was slightly increased (K(i)=40-1475 nM), which resulted in a loss of 5-HT(2A)/5-HT(1A) selectivity. 5-Br,8-OCH3 derivative-the most potent, mixed 5-HT(1A)/5-HT(2A) ligand-produced activation of presynaptic 5-HT(1A) receptors and showed properties of a 5-HT(2A) receptor antagonist.</abstract><cop>England</cop><pmid>11738610</pmid><tpages>9</tpages></addata></record> |
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| subjects | Adamantane - chemistry Animals In Vitro Techniques Isoquinolines - chemistry Isoquinolines - pharmacology Magnetic Resonance Spectroscopy Male Mice Rats Rats, Wistar Serotonin Antagonists - chemistry Serotonin Antagonists - pharmacology Serotonin Receptor Agonists - chemistry Serotonin Receptor Agonists - pharmacology Structure-Activity Relationship Tetrahydroisoquinolines |
| title | The influence of substitution at aromatic part of 1,2,3,4-tetrahydroisoquinoline on in vitro and in vivo 5-HT(1A)/5-HT(2A) receptor activities of its 1-adamantoyloaminoalkyl derivatives |
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