Thromboxane synthetase inhibitors and antihypertensive agents. 1. N-[(1H-imidazol-1-yl)alkyl]aryl amides and N-[(1H-1,2,4-triazol-1-yl)alkyl]aryl amides
The title compounds were prepared to investigate their potential as thromboxane synthetase inhibitors as well as antihypertensive agents. Imidazoles VIII and triazoles X were prepared to examine the effects of aromatic substitution, chain length, and heterocycle substitution upon biological activity...
Gespeichert in:
| Veröffentlicht in: | Journal of medicinal chemistry 1986-04, Vol.29 (4), p.523-530 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 530 |
|---|---|
| container_issue | 4 |
| container_start_page | 523 |
| container_title | Journal of medicinal chemistry |
| container_volume | 29 |
| creator | Wright, William B Press, Jeffery B Chan, Peter S Marsico, Joseph W Haug, Margie F Lucas, Judy Tauber, Jess Tomcufcik, Andrew S |
| description | The title compounds were prepared to investigate their potential as thromboxane synthetase inhibitors as well as antihypertensive agents. Imidazoles VIII and triazoles X were prepared to examine the effects of aromatic substitution, chain length, and heterocycle substitution upon biological activity. Imidazoles VIII and triazoles X were thromboxane synthetase inhibitors that did not inhibit prostacyclin formation. The most interesting thromboxane synthetase inhibitors prepared were 4-chloro-, 4-(trifluoromethyl)-, and 4-bromobenzamide derivatives of (1H-imidazol-1-yl)alkylamines with C5-C8 alkyl chains separating the heterocycle from the amide moiety, while the most active antihypertensive agents were 3- or 4-chloro-, -bromo, or -(trifluoromethyl)benzamides with C3 alkyl chains. The best thromboxane synthetase inhibitors in this study were up to 10 times more potent than the standard, dazoxiben (UK 37,248). |
| doi_str_mv | 10.1021/jm00154a017 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_76759704</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>76759704</sourcerecordid><originalsourceid>FETCH-LOGICAL-a354t-69233111876bc94e08e0f4f3e6e144400d736ad1a3afdb7a691f54073f1a79283</originalsourceid><addsrcrecordid>eNp9kc2LFDEQxYMo67h68iz0yQ_cjFVJutN9lPVjhUUHHL2IhOrptJPZ_hiTjGz7l_jnGulh8SAeijq8H6-K9xh7iLBEEPhi1wNgrghQ32ILzAVwVYK6zRYAQnBRCHmX3QthBwAShTxhJ7LKK5CwYL_WWz_29XhNg83CNMStjRRs5oatq10cfchoaNJEt5321kc7BPfDZvTNDjEsM1xm7_mXp3jBXe8a-jl2HPnUPaPuauq-kp-6jJJgZ5sjimfiTPHo3X_4--xOS12wD477lH1683p9fsEvP7x9d_7ykpPMVeRFJaRExFIX9aZSFkoLrWqlLSwqpQAaLQtqkCS1Ta2pqLDNFWjZIulKlPKUPZ599378frAhmt6Fje26FMh4CEYXOq80qAQ-n8GNH0PwtjV77_r0sUEwf3owf_WQ6EdH20Pd2-aGPQafdD7rLkR7fSOTvzKFljo369VHgytclZ_FKyMT_2TmaRPMbjz4IYXyz8u_Ab0fnW8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>76759704</pqid></control><display><type>article</type><title>Thromboxane synthetase inhibitors and antihypertensive agents. 1. N-[(1H-imidazol-1-yl)alkyl]aryl amides and N-[(1H-1,2,4-triazol-1-yl)alkyl]aryl amides</title><source>MEDLINE</source><source>American Chemical Society Journals</source><creator>Wright, William B ; Press, Jeffery B ; Chan, Peter S ; Marsico, Joseph W ; Haug, Margie F ; Lucas, Judy ; Tauber, Jess ; Tomcufcik, Andrew S</creator><creatorcontrib>Wright, William B ; Press, Jeffery B ; Chan, Peter S ; Marsico, Joseph W ; Haug, Margie F ; Lucas, Judy ; Tauber, Jess ; Tomcufcik, Andrew S</creatorcontrib><description>The title compounds were prepared to investigate their potential as thromboxane synthetase inhibitors as well as antihypertensive agents. Imidazoles VIII and triazoles X were prepared to examine the effects of aromatic substitution, chain length, and heterocycle substitution upon biological activity. Imidazoles VIII and triazoles X were thromboxane synthetase inhibitors that did not inhibit prostacyclin formation. The most interesting thromboxane synthetase inhibitors prepared were 4-chloro-, 4-(trifluoromethyl)-, and 4-bromobenzamide derivatives of (1H-imidazol-1-yl)alkylamines with C5-C8 alkyl chains separating the heterocycle from the amide moiety, while the most active antihypertensive agents were 3- or 4-chloro-, -bromo, or -(trifluoromethyl)benzamides with C3 alkyl chains. The best thromboxane synthetase inhibitors in this study were up to 10 times more potent than the standard, dazoxiben (UK 37,248).</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm00154a017</identifier><identifier>PMID: 3959030</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Amides - chemical synthesis ; Amides - pharmacology ; Animals ; Antihypertensive Agents - chemical synthesis ; Antihypertensive Agents - pharmacology ; Imidazoles - chemical synthesis ; Imidazoles - pharmacology ; Male ; Rats ; Rats, Inbred SHR ; Structure-Activity Relationship ; Thromboxane-A Synthase - antagonists & inhibitors ; Triazoles - chemical synthesis ; Triazoles - pharmacology</subject><ispartof>Journal of medicinal chemistry, 1986-04, Vol.29 (4), p.523-530</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a354t-69233111876bc94e08e0f4f3e6e144400d736ad1a3afdb7a691f54073f1a79283</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/jm00154a017$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm00154a017$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3959030$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wright, William B</creatorcontrib><creatorcontrib>Press, Jeffery B</creatorcontrib><creatorcontrib>Chan, Peter S</creatorcontrib><creatorcontrib>Marsico, Joseph W</creatorcontrib><creatorcontrib>Haug, Margie F</creatorcontrib><creatorcontrib>Lucas, Judy</creatorcontrib><creatorcontrib>Tauber, Jess</creatorcontrib><creatorcontrib>Tomcufcik, Andrew S</creatorcontrib><title>Thromboxane synthetase inhibitors and antihypertensive agents. 1. N-[(1H-imidazol-1-yl)alkyl]aryl amides and N-[(1H-1,2,4-triazol-1-yl)alkyl]aryl amides</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>The title compounds were prepared to investigate their potential as thromboxane synthetase inhibitors as well as antihypertensive agents. Imidazoles VIII and triazoles X were prepared to examine the effects of aromatic substitution, chain length, and heterocycle substitution upon biological activity. Imidazoles VIII and triazoles X were thromboxane synthetase inhibitors that did not inhibit prostacyclin formation. The most interesting thromboxane synthetase inhibitors prepared were 4-chloro-, 4-(trifluoromethyl)-, and 4-bromobenzamide derivatives of (1H-imidazol-1-yl)alkylamines with C5-C8 alkyl chains separating the heterocycle from the amide moiety, while the most active antihypertensive agents were 3- or 4-chloro-, -bromo, or -(trifluoromethyl)benzamides with C3 alkyl chains. The best thromboxane synthetase inhibitors in this study were up to 10 times more potent than the standard, dazoxiben (UK 37,248).</description><subject>Amides - chemical synthesis</subject><subject>Amides - pharmacology</subject><subject>Animals</subject><subject>Antihypertensive Agents - chemical synthesis</subject><subject>Antihypertensive Agents - pharmacology</subject><subject>Imidazoles - chemical synthesis</subject><subject>Imidazoles - pharmacology</subject><subject>Male</subject><subject>Rats</subject><subject>Rats, Inbred SHR</subject><subject>Structure-Activity Relationship</subject><subject>Thromboxane-A Synthase - antagonists & inhibitors</subject><subject>Triazoles - chemical synthesis</subject><subject>Triazoles - pharmacology</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1986</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc2LFDEQxYMo67h68iz0yQ_cjFVJutN9lPVjhUUHHL2IhOrptJPZ_hiTjGz7l_jnGulh8SAeijq8H6-K9xh7iLBEEPhi1wNgrghQ32ILzAVwVYK6zRYAQnBRCHmX3QthBwAShTxhJ7LKK5CwYL_WWz_29XhNg83CNMStjRRs5oatq10cfchoaNJEt5321kc7BPfDZvTNDjEsM1xm7_mXp3jBXe8a-jl2HPnUPaPuauq-kp-6jJJgZ5sjimfiTPHo3X_4--xOS12wD477lH1683p9fsEvP7x9d_7ykpPMVeRFJaRExFIX9aZSFkoLrWqlLSwqpQAaLQtqkCS1Ta2pqLDNFWjZIulKlPKUPZ599378frAhmt6Fje26FMh4CEYXOq80qAQ-n8GNH0PwtjV77_r0sUEwf3owf_WQ6EdH20Pd2-aGPQafdD7rLkR7fSOTvzKFljo369VHgytclZ_FKyMT_2TmaRPMbjz4IYXyz8u_Ab0fnW8</recordid><startdate>19860401</startdate><enddate>19860401</enddate><creator>Wright, William B</creator><creator>Press, Jeffery B</creator><creator>Chan, Peter S</creator><creator>Marsico, Joseph W</creator><creator>Haug, Margie F</creator><creator>Lucas, Judy</creator><creator>Tauber, Jess</creator><creator>Tomcufcik, Andrew S</creator><general>American Chemical Society</general><scope>BSCLL</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>19860401</creationdate><title>Thromboxane synthetase inhibitors and antihypertensive agents. 1. N-[(1H-imidazol-1-yl)alkyl]aryl amides and N-[(1H-1,2,4-triazol-1-yl)alkyl]aryl amides</title><author>Wright, William B ; Press, Jeffery B ; Chan, Peter S ; Marsico, Joseph W ; Haug, Margie F ; Lucas, Judy ; Tauber, Jess ; Tomcufcik, Andrew S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a354t-69233111876bc94e08e0f4f3e6e144400d736ad1a3afdb7a691f54073f1a79283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1986</creationdate><topic>Amides - chemical synthesis</topic><topic>Amides - pharmacology</topic><topic>Animals</topic><topic>Antihypertensive Agents - chemical synthesis</topic><topic>Antihypertensive Agents - pharmacology</topic><topic>Imidazoles - chemical synthesis</topic><topic>Imidazoles - pharmacology</topic><topic>Male</topic><topic>Rats</topic><topic>Rats, Inbred SHR</topic><topic>Structure-Activity Relationship</topic><topic>Thromboxane-A Synthase - antagonists & inhibitors</topic><topic>Triazoles - chemical synthesis</topic><topic>Triazoles - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wright, William B</creatorcontrib><creatorcontrib>Press, Jeffery B</creatorcontrib><creatorcontrib>Chan, Peter S</creatorcontrib><creatorcontrib>Marsico, Joseph W</creatorcontrib><creatorcontrib>Haug, Margie F</creatorcontrib><creatorcontrib>Lucas, Judy</creatorcontrib><creatorcontrib>Tauber, Jess</creatorcontrib><creatorcontrib>Tomcufcik, Andrew S</creatorcontrib><collection>Istex</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>Wright, William B</au><au>Press, Jeffery B</au><au>Chan, Peter S</au><au>Marsico, Joseph W</au><au>Haug, Margie F</au><au>Lucas, Judy</au><au>Tauber, Jess</au><au>Tomcufcik, Andrew S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Thromboxane synthetase inhibitors and antihypertensive agents. 1. N-[(1H-imidazol-1-yl)alkyl]aryl amides and N-[(1H-1,2,4-triazol-1-yl)alkyl]aryl amides</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1986-04-01</date><risdate>1986</risdate><volume>29</volume><issue>4</issue><spage>523</spage><epage>530</epage><pages>523-530</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><abstract>The title compounds were prepared to investigate their potential as thromboxane synthetase inhibitors as well as antihypertensive agents. Imidazoles VIII and triazoles X were prepared to examine the effects of aromatic substitution, chain length, and heterocycle substitution upon biological activity. Imidazoles VIII and triazoles X were thromboxane synthetase inhibitors that did not inhibit prostacyclin formation. The most interesting thromboxane synthetase inhibitors prepared were 4-chloro-, 4-(trifluoromethyl)-, and 4-bromobenzamide derivatives of (1H-imidazol-1-yl)alkylamines with C5-C8 alkyl chains separating the heterocycle from the amide moiety, while the most active antihypertensive agents were 3- or 4-chloro-, -bromo, or -(trifluoromethyl)benzamides with C3 alkyl chains. The best thromboxane synthetase inhibitors in this study were up to 10 times more potent than the standard, dazoxiben (UK 37,248).</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>3959030</pmid><doi>10.1021/jm00154a017</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 1986-04, Vol.29 (4), p.523-530 |
| issn | 0022-2623 1520-4804 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_76759704 |
| source | MEDLINE; American Chemical Society Journals |
| subjects | Amides - chemical synthesis Amides - pharmacology Animals Antihypertensive Agents - chemical synthesis Antihypertensive Agents - pharmacology Imidazoles - chemical synthesis Imidazoles - pharmacology Male Rats Rats, Inbred SHR Structure-Activity Relationship Thromboxane-A Synthase - antagonists & inhibitors Triazoles - chemical synthesis Triazoles - pharmacology |
| title | Thromboxane synthetase inhibitors and antihypertensive agents. 1. N-[(1H-imidazol-1-yl)alkyl]aryl amides and N-[(1H-1,2,4-triazol-1-yl)alkyl]aryl amides |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T02%3A05%3A33IST&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=Thromboxane%20synthetase%20inhibitors%20and%20antihypertensive%20agents.%201.%20N-%5B(1H-imidazol-1-yl)alkyl%5Daryl%20amides%20and%20N-%5B(1H-1,2,4-triazol-1-yl)alkyl%5Daryl%20amides&rft.jtitle=Journal%20of%20medicinal%20chemistry&rft.au=Wright,%20William%20B&rft.date=1986-04-01&rft.volume=29&rft.issue=4&rft.spage=523&rft.epage=530&rft.pages=523-530&rft.issn=0022-2623&rft.eissn=1520-4804&rft_id=info:doi/10.1021/jm00154a017&rft_dat=%3Cproquest_cross%3E76759704%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=76759704&rft_id=info:pmid/3959030&rfr_iscdi=true |