Synthesis and structure–activity relationships of N-aryl-piperidine derivatives as potent (partial) agonists for human histamine H3 receptor
This paper reports the synthesis and in vitro biological evaluation of N-aryl-piperidine derivatives as new human histamine H3 receptor agonist. 4-((1H-Imidazol-4-yl)methyl)-1-aryl-piperazine and piperidine derivatives were designed and synthesized as candidate human histamine type 3 agonists. The p...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2010-07, Vol.18 (14), p.5441-5448 |
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| container_title | Bioorganic & medicinal chemistry |
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| creator | Ishikawa, Makoto Furuuchi, Takeshi Yamauchi, Miki Yokoyama, Fumikazu Kakui, Nobukazu Sato, Yasuo |
| description | This paper reports the synthesis and in vitro biological evaluation of N-aryl-piperidine derivatives as new human histamine H3 receptor agonist.
4-((1H-Imidazol-4-yl)methyl)-1-aryl-piperazine and piperidine derivatives were designed and synthesized as candidate human histamine type 3 agonists. The piperazine derivatives were found to have low (or no) affinity for human histamine H3 receptor, whereas the piperidine derivatives showed moderate to high affinity, and their agonistic activity was greatly influenced by substituents on the aromatic ring. Among the piperidine-containing compounds, 17d and 17h were potent human histamine H3 receptor agonists with high selectivity over the closely related human H4 receptor. Our results indicate that appropriate conformational restriction, that is, by the piperidine spacer moiety, favors specific binding to the human histamine H3 receptor. |
| doi_str_mv | 10.1016/j.bmc.2010.04.052 |
| format | Article |
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4-((1H-Imidazol-4-yl)methyl)-1-aryl-piperazine and piperidine derivatives were designed and synthesized as candidate human histamine type 3 agonists. The piperazine derivatives were found to have low (or no) affinity for human histamine H3 receptor, whereas the piperidine derivatives showed moderate to high affinity, and their agonistic activity was greatly influenced by substituents on the aromatic ring. Among the piperidine-containing compounds, 17d and 17h were potent human histamine H3 receptor agonists with high selectivity over the closely related human H4 receptor. Our results indicate that appropriate conformational restriction, that is, by the piperidine spacer moiety, favors specific binding to the human histamine H3 receptor.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmc.2010.04.052</identifier><identifier>PMID: 20541426</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Agonists ; Animals ; Biological and medical sciences ; CHO Cells ; Cricetinae ; Cricetulus ; Histamine Agonists - chemistry ; Histamine Agonists - pharmacology ; Histamine H3 receptor ; Humans ; Medical sciences ; Miscellaneous ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Pharmacology. Drug treatments ; Piperidines - chemistry ; Piperidines - pharmacology ; Receptors, Histamine H3 - metabolism</subject><ispartof>Bioorganic & medicinal chemistry, 2010-07, Vol.18 (14), p.5441-5448</ispartof><rights>2010 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright (c) 2010 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c382t-f7fc235231b3c1d83c88968a5cdfeae4b99af0a9b6a530d2bec5e27a777681c23</citedby><cites>FETCH-LOGICAL-c382t-f7fc235231b3c1d83c88968a5cdfeae4b99af0a9b6a530d2bec5e27a777681c23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0968089610003640$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23054892$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20541426$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ishikawa, Makoto</creatorcontrib><creatorcontrib>Furuuchi, Takeshi</creatorcontrib><creatorcontrib>Yamauchi, Miki</creatorcontrib><creatorcontrib>Yokoyama, Fumikazu</creatorcontrib><creatorcontrib>Kakui, Nobukazu</creatorcontrib><creatorcontrib>Sato, Yasuo</creatorcontrib><title>Synthesis and structure–activity relationships of N-aryl-piperidine derivatives as potent (partial) agonists for human histamine H3 receptor</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>This paper reports the synthesis and in vitro biological evaluation of N-aryl-piperidine derivatives as new human histamine H3 receptor agonist.
4-((1H-Imidazol-4-yl)methyl)-1-aryl-piperazine and piperidine derivatives were designed and synthesized as candidate human histamine type 3 agonists. The piperazine derivatives were found to have low (or no) affinity for human histamine H3 receptor, whereas the piperidine derivatives showed moderate to high affinity, and their agonistic activity was greatly influenced by substituents on the aromatic ring. Among the piperidine-containing compounds, 17d and 17h were potent human histamine H3 receptor agonists with high selectivity over the closely related human H4 receptor. Our results indicate that appropriate conformational restriction, that is, by the piperidine spacer moiety, favors specific binding to the human histamine H3 receptor.</description><subject>Agonists</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>Histamine Agonists - chemistry</subject><subject>Histamine Agonists - pharmacology</subject><subject>Histamine H3 receptor</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Pharmacology. Drug treatments</subject><subject>Piperidines - chemistry</subject><subject>Piperidines - pharmacology</subject><subject>Receptors, Histamine H3 - metabolism</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kT2OFDEQhS0EYpeFA5AgJwgIevBP_4oIrYBFWkEAxFa1u5rxqNtuXO6RJuMEJNyQk-DRDJAR2SV979n1HmOPpdhIIeuXu00_240SeRblRlTqDruUZV0WWnfyLrsUXd0Wou3qC_aAaCeEUGUn77MLJapSlqq-ZD8-HXzaIjni4AdOKa42rRF_ff8JNrm9SwcecYLkgqetW4iHkX8oIB6mYnELRjc4j3zIl32G9ph9iC8hoU_8-QIxOZhecPgavKNEfAyRb9cZPN_mGeaj-EbnJywuKcSH7N4IE-Gj83nFvrx98_n6prj9-O799evbwupWpWJsRqt0pbTstZVDq22bt2yhssOIgGXfdTAK6PoaKi0G1aOtUDXQNE3dyiy9Ys9OvksM31akZGZHFqcJPIaVTJMTbKta1JmUJ9LGQBRxNEt0c97fSGGOLZidyS2YYwtGlCa3kDVPzu5rP-PwV_En9gw8PQNAFqYxgreO_nE6g213NHp14jBnsXcYDVmH3uLgcmLJDMH95xu_AVnrqV8</recordid><startdate>20100715</startdate><enddate>20100715</enddate><creator>Ishikawa, Makoto</creator><creator>Furuuchi, Takeshi</creator><creator>Yamauchi, Miki</creator><creator>Yokoyama, Fumikazu</creator><creator>Kakui, Nobukazu</creator><creator>Sato, Yasuo</creator><general>Elsevier Ltd</general><general>Elsevier</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>7X8</scope></search><sort><creationdate>20100715</creationdate><title>Synthesis and structure–activity relationships of N-aryl-piperidine derivatives as potent (partial) agonists for human histamine H3 receptor</title><author>Ishikawa, Makoto ; Furuuchi, Takeshi ; Yamauchi, Miki ; Yokoyama, Fumikazu ; Kakui, Nobukazu ; Sato, Yasuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c382t-f7fc235231b3c1d83c88968a5cdfeae4b99af0a9b6a530d2bec5e27a777681c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Agonists</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>CHO Cells</topic><topic>Cricetinae</topic><topic>Cricetulus</topic><topic>Histamine Agonists - chemistry</topic><topic>Histamine Agonists - pharmacology</topic><topic>Histamine H3 receptor</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Pharmacology. Drug treatments</topic><topic>Piperidines - chemistry</topic><topic>Piperidines - pharmacology</topic><topic>Receptors, Histamine H3 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ishikawa, Makoto</creatorcontrib><creatorcontrib>Furuuchi, Takeshi</creatorcontrib><creatorcontrib>Yamauchi, Miki</creatorcontrib><creatorcontrib>Yokoyama, Fumikazu</creatorcontrib><creatorcontrib>Kakui, Nobukazu</creatorcontrib><creatorcontrib>Sato, Yasuo</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>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ishikawa, Makoto</au><au>Furuuchi, Takeshi</au><au>Yamauchi, Miki</au><au>Yokoyama, Fumikazu</au><au>Kakui, Nobukazu</au><au>Sato, Yasuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and structure–activity relationships of N-aryl-piperidine derivatives as potent (partial) agonists for human histamine H3 receptor</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2010-07-15</date><risdate>2010</risdate><volume>18</volume><issue>14</issue><spage>5441</spage><epage>5448</epage><pages>5441-5448</pages><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>This paper reports the synthesis and in vitro biological evaluation of N-aryl-piperidine derivatives as new human histamine H3 receptor agonist.
4-((1H-Imidazol-4-yl)methyl)-1-aryl-piperazine and piperidine derivatives were designed and synthesized as candidate human histamine type 3 agonists. The piperazine derivatives were found to have low (or no) affinity for human histamine H3 receptor, whereas the piperidine derivatives showed moderate to high affinity, and their agonistic activity was greatly influenced by substituents on the aromatic ring. Among the piperidine-containing compounds, 17d and 17h were potent human histamine H3 receptor agonists with high selectivity over the closely related human H4 receptor. Our results indicate that appropriate conformational restriction, that is, by the piperidine spacer moiety, favors specific binding to the human histamine H3 receptor.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>20541426</pmid><doi>10.1016/j.bmc.2010.04.052</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
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| subjects | Agonists Animals Biological and medical sciences CHO Cells Cricetinae Cricetulus Histamine Agonists - chemistry Histamine Agonists - pharmacology Histamine H3 receptor Humans Medical sciences Miscellaneous Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Piperidines - chemistry Piperidines - pharmacology Receptors, Histamine H3 - metabolism |
| title | Synthesis and structure–activity relationships of N-aryl-piperidine derivatives as potent (partial) agonists for human histamine H3 receptor |
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