Homologs of Histamine as Histamine H3 Receptor Antagonists: A New Potent and Selective H3 Antagonist, 4(5)-(5-Aminopentyl)-1H-imidazole
The influence of alkyl chain length variation on the histamine H3 receptor activity of histamine homologs 1 was investigated. A series of 4(5)-(omega-aminoalkyl)-1H-imidazoles 1 was prepared with an alkyl chain length varying from one methylene group to 10 methylene groups. Besides the H3 activity,...
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Veröffentlicht in: | Journal of medicinal chemistry 1995-01, Vol.38 (2), p.266-271 |
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creator | Vollinga, Roeland C Menge, Wiro M. P. B Leurs, Rob Timmerman, Hendrik |
description | The influence of alkyl chain length variation on the histamine H3 receptor activity of histamine homologs 1 was investigated. A series of 4(5)-(omega-aminoalkyl)-1H-imidazoles 1 was prepared with an alkyl chain length varying from one methylene group to 10 methylene groups. Besides the H3 activity, the affinities of these compounds for the H1 and H2 receptors were determined. The ethylene chain of histamine is optimal for agonistic activity on all three histamine receptor subtypes. For the H3 receptor, elongation of the alkyl chain from three methylene groups on leads to compounds with antagonistic properties. 4(5)-(5-Aminopentyl)-1H-imidazole (impentamine, 1e) is the most potent and selective H3 antagonist from this series of 4(5)-(omega-aminoalkyl)-1H-imidazoles 1, with a pA2 value of 8.4 (on guinea pig jejunum). A specific antagonistic binding site for this compound is proposed. |
doi_str_mv | 10.1021/jm00002a008 |
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P. B ; Leurs, Rob ; Timmerman, Hendrik</creator><creatorcontrib>Vollinga, Roeland C ; Menge, Wiro M. P. B ; Leurs, Rob ; Timmerman, Hendrik</creatorcontrib><description>The influence of alkyl chain length variation on the histamine H3 receptor activity of histamine homologs 1 was investigated. A series of 4(5)-(omega-aminoalkyl)-1H-imidazoles 1 was prepared with an alkyl chain length varying from one methylene group to 10 methylene groups. Besides the H3 activity, the affinities of these compounds for the H1 and H2 receptors were determined. The ethylene chain of histamine is optimal for agonistic activity on all three histamine receptor subtypes. For the H3 receptor, elongation of the alkyl chain from three methylene groups on leads to compounds with antagonistic properties. 4(5)-(5-Aminopentyl)-1H-imidazole (impentamine, 1e) is the most potent and selective H3 antagonist from this series of 4(5)-(omega-aminoalkyl)-1H-imidazoles 1, with a pA2 value of 8.4 (on guinea pig jejunum). A specific antagonistic binding site for this compound is proposed.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm00002a008</identifier><identifier>PMID: 7830269</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Animals ; Biological and medical sciences ; Guinea Pigs ; Histamine - analogs & derivatives ; Histamine - chemistry ; Histamine - metabolism ; Histamine Agonists ; Histamine and antagonists. Allergy ; Histamine Antagonists ; Imidazoles - chemistry ; Imidazoles - metabolism ; Jejunum ; Magnetic Resonance Spectroscopy ; Medical sciences ; Pharmacology. Drug treatments ; Receptors, Histamine H1 - metabolism ; Receptors, Histamine H2 - metabolism ; Receptors, Histamine H3 - metabolism ; Structure-Activity Relationship</subject><ispartof>Journal of medicinal chemistry, 1995-01, Vol.38 (2), p.266-271</ispartof><rights>1995 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a364t-2a2cc464d2376a7b4a1fc4196981674a8d6aeafe1cf55a3204ebf75eea2d660c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm00002a008$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm00002a008$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>315,781,785,2766,27078,27926,27927,56740,56790</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3388436$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7830269$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vollinga, Roeland C</creatorcontrib><creatorcontrib>Menge, Wiro M. P. B</creatorcontrib><creatorcontrib>Leurs, Rob</creatorcontrib><creatorcontrib>Timmerman, Hendrik</creatorcontrib><title>Homologs of Histamine as Histamine H3 Receptor Antagonists: A New Potent and Selective H3 Antagonist, 4(5)-(5-Aminopentyl)-1H-imidazole</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>The influence of alkyl chain length variation on the histamine H3 receptor activity of histamine homologs 1 was investigated. A series of 4(5)-(omega-aminoalkyl)-1H-imidazoles 1 was prepared with an alkyl chain length varying from one methylene group to 10 methylene groups. Besides the H3 activity, the affinities of these compounds for the H1 and H2 receptors were determined. The ethylene chain of histamine is optimal for agonistic activity on all three histamine receptor subtypes. For the H3 receptor, elongation of the alkyl chain from three methylene groups on leads to compounds with antagonistic properties. 4(5)-(5-Aminopentyl)-1H-imidazole (impentamine, 1e) is the most potent and selective H3 antagonist from this series of 4(5)-(omega-aminoalkyl)-1H-imidazoles 1, with a pA2 value of 8.4 (on guinea pig jejunum). A specific antagonistic binding site for this compound is proposed.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Guinea Pigs</subject><subject>Histamine - analogs & derivatives</subject><subject>Histamine - chemistry</subject><subject>Histamine - metabolism</subject><subject>Histamine Agonists</subject><subject>Histamine and antagonists. Allergy</subject><subject>Histamine Antagonists</subject><subject>Imidazoles - chemistry</subject><subject>Imidazoles - metabolism</subject><subject>Jejunum</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Receptors, Histamine H1 - metabolism</subject><subject>Receptors, Histamine H2 - metabolism</subject><subject>Receptors, Histamine H3 - metabolism</subject><subject>Structure-Activity Relationship</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0E9v0zAYBnALgUYZnDgj-YBgExj8L3bKra3YgjTBYGNX663zZkpJ4mKnwPgCfG0MrcoO-GLZz8-vrIeQx4K_ElyK16ue5yWB8_IOmYhCcqZLru-SSb6VTBqp7pMHKa2yUkKqA3JgS8WlmU7Iryr0oQvXiYaGVm0aoW8HpJBuHSpFP6HH9RginQ0jXIchZ-kNndH3-J2ehxGHkcJQ0wvs0I_tt79v_tGXVB8Vx-yoYLM8MKwzv-mOmahY27c1_AwdPiT3GugSPtrth-TzydvLRcXOPpy-W8zOGCijRyZBeq-NrqWyBuxSg2i8FlMzLYWxGsraAEKDwjdFAUpyjcvGFogga2O4V4fk2XbuOoavG0yj69vksetgwLBJztpc0LTQGb7YQh9DShEbt45tD_HGCe7-1O5u1Z71k93YzbLHem93Pef86S6H5KFrIgy-TXumVFlqZTJjW5ZLwx_7GOIXZ6yyhbs8v3Af51fzxdXpiZtn_3zrwSe3Cps45O7--8HfrHCkWA</recordid><startdate>19950101</startdate><enddate>19950101</enddate><creator>Vollinga, Roeland C</creator><creator>Menge, Wiro M. P. B</creator><creator>Leurs, Rob</creator><creator>Timmerman, Hendrik</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>7X8</scope></search><sort><creationdate>19950101</creationdate><title>Homologs of Histamine as Histamine H3 Receptor Antagonists: A New Potent and Selective H3 Antagonist, 4(5)-(5-Aminopentyl)-1H-imidazole</title><author>Vollinga, Roeland C ; Menge, Wiro M. P. B ; Leurs, Rob ; Timmerman, Hendrik</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a364t-2a2cc464d2376a7b4a1fc4196981674a8d6aeafe1cf55a3204ebf75eea2d660c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Guinea Pigs</topic><topic>Histamine - analogs & derivatives</topic><topic>Histamine - chemistry</topic><topic>Histamine - metabolism</topic><topic>Histamine Agonists</topic><topic>Histamine and antagonists. Allergy</topic><topic>Histamine Antagonists</topic><topic>Imidazoles - chemistry</topic><topic>Imidazoles - metabolism</topic><topic>Jejunum</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Receptors, Histamine H1 - metabolism</topic><topic>Receptors, Histamine H2 - metabolism</topic><topic>Receptors, Histamine H3 - metabolism</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vollinga, Roeland C</creatorcontrib><creatorcontrib>Menge, Wiro M. P. 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B</au><au>Leurs, Rob</au><au>Timmerman, Hendrik</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Homologs of Histamine as Histamine H3 Receptor Antagonists: A New Potent and Selective H3 Antagonist, 4(5)-(5-Aminopentyl)-1H-imidazole</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1995-01-01</date><risdate>1995</risdate><volume>38</volume><issue>2</issue><spage>266</spage><epage>271</epage><pages>266-271</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>The influence of alkyl chain length variation on the histamine H3 receptor activity of histamine homologs 1 was investigated. A series of 4(5)-(omega-aminoalkyl)-1H-imidazoles 1 was prepared with an alkyl chain length varying from one methylene group to 10 methylene groups. Besides the H3 activity, the affinities of these compounds for the H1 and H2 receptors were determined. The ethylene chain of histamine is optimal for agonistic activity on all three histamine receptor subtypes. For the H3 receptor, elongation of the alkyl chain from three methylene groups on leads to compounds with antagonistic properties. 4(5)-(5-Aminopentyl)-1H-imidazole (impentamine, 1e) is the most potent and selective H3 antagonist from this series of 4(5)-(omega-aminoalkyl)-1H-imidazoles 1, with a pA2 value of 8.4 (on guinea pig jejunum). A specific antagonistic binding site for this compound is proposed.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>7830269</pmid><doi>10.1021/jm00002a008</doi><tpages>6</tpages></addata></record> |
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subjects | Animals Biological and medical sciences Guinea Pigs Histamine - analogs & derivatives Histamine - chemistry Histamine - metabolism Histamine Agonists Histamine and antagonists. Allergy Histamine Antagonists Imidazoles - chemistry Imidazoles - metabolism Jejunum Magnetic Resonance Spectroscopy Medical sciences Pharmacology. Drug treatments Receptors, Histamine H1 - metabolism Receptors, Histamine H2 - metabolism Receptors, Histamine H3 - metabolism Structure-Activity Relationship |
title | Homologs of Histamine as Histamine H3 Receptor Antagonists: A New Potent and Selective H3 Antagonist, 4(5)-(5-Aminopentyl)-1H-imidazole |
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