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,...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of medicinal chemistry 1995-01, Vol.38 (2), p.266-271
Hauptverfasser: Vollinga, Roeland C, Menge, Wiro M. P. B, Leurs, Rob, Timmerman, Hendrik
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 271
container_issue 2
container_start_page 266
container_title Journal of medicinal chemistry
container_volume 38
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
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_77123954</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>77123954</sourcerecordid><originalsourceid>FETCH-LOGICAL-a364t-2a2cc464d2376a7b4a1fc4196981674a8d6aeafe1cf55a3204ebf75eea2d660c3</originalsourceid><addsrcrecordid>eNpt0E9v0zAYBnALgUYZnDgj-YBgExj8L3bKra3YgjTBYGNX663zZkpJ4mKnwPgCfG0MrcoO-GLZz8-vrIeQx4K_ElyK16ue5yWB8_IOmYhCcqZLru-SSb6VTBqp7pMHKa2yUkKqA3JgS8WlmU7Iryr0oQvXiYaGVm0aoW8HpJBuHSpFP6HH9RginQ0jXIchZ-kNndH3-J2ehxGHkcJQ0wvs0I_tt79v_tGXVB8Vx-yoYLM8MKwzv-mOmahY27c1_AwdPiT3GugSPtrth-TzydvLRcXOPpy-W8zOGCijRyZBeq-NrqWyBuxSg2i8FlMzLYWxGsraAEKDwjdFAUpyjcvGFogga2O4V4fk2XbuOoavG0yj69vksetgwLBJztpc0LTQGb7YQh9DShEbt45tD_HGCe7-1O5u1Z71k93YzbLHem93Pef86S6H5KFrIgy-TXumVFlqZTJjW5ZLwx_7GOIXZ6yyhbs8v3Af51fzxdXpiZtn_3zrwSe3Cps45O7--8HfrHCkWA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>77123954</pqid></control><display><type>article</type><title>Homologs of Histamine as Histamine H3 Receptor Antagonists: A New Potent and Selective H3 Antagonist, 4(5)-(5-Aminopentyl)-1H-imidazole</title><source>MEDLINE</source><source>American Chemical Society Journals</source><creator>Vollinga, Roeland C ; Menge, Wiro M. 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 &amp; 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&amp;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 &amp; 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 &amp; 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. B</creatorcontrib><creatorcontrib>Leurs, Rob</creatorcontrib><creatorcontrib>Timmerman, Hendrik</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>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vollinga, Roeland C</au><au>Menge, Wiro M. P. 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>
fulltext fulltext
identifier ISSN: 0022-2623
ispartof Journal of medicinal chemistry, 1995-01, Vol.38 (2), p.266-271
issn 0022-2623
1520-4804
language eng
recordid cdi_proquest_miscellaneous_77123954
source MEDLINE; American Chemical Society Journals
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
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-17T23%3A41%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Homologs%20of%20Histamine%20as%20Histamine%20H3%20Receptor%20Antagonists:%20A%20New%20Potent%20and%20Selective%20H3%20Antagonist,%204(5)-(5-Aminopentyl)-1H-imidazole&rft.jtitle=Journal%20of%20medicinal%20chemistry&rft.au=Vollinga,%20Roeland%20C&rft.date=1995-01-01&rft.volume=38&rft.issue=2&rft.spage=266&rft.epage=271&rft.pages=266-271&rft.issn=0022-2623&rft.eissn=1520-4804&rft.coden=JMCMAR&rft_id=info:doi/10.1021/jm00002a008&rft_dat=%3Cproquest_cross%3E77123954%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=77123954&rft_id=info:pmid/7830269&rfr_iscdi=true