Loading…
Esters of isoguvacine as potential prodrugs
The syntheses of the methyl ester, butyl ester, (ethoxycarbonyl)methyl ester, and 11 (acyloxy)methyl esters of the potent gamma-aminobutyric acid agonist isoguvacine (1,2,3,6-tetrahydropyridine-4-carboxylic acid) and described. The chemical stability of the esters and their in vitro rates of hydroly...
Saved in:
Published in: | Journal of medicinal chemistry 1981-03, Vol.24 (3), p.285-289 |
---|---|
Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-a420t-ed8605a7008098e7d778530dfedfa6895cf8f251f7562bcfe5d70515de5e006a3 |
---|---|
cites | |
container_end_page | 289 |
container_issue | 3 |
container_start_page | 285 |
container_title | Journal of medicinal chemistry |
container_volume | 24 |
creator | Falch, Erik Krogsgaard-Larsen, Povl Christensen, Anne Vibeke |
description | The syntheses of the methyl ester, butyl ester, (ethoxycarbonyl)methyl ester, and 11 (acyloxy)methyl esters of the potent gamma-aminobutyric acid agonist isoguvacine (1,2,3,6-tetrahydropyridine-4-carboxylic acid) and described. The chemical stability of the esters and their in vitro rates of hydrolysis under approximately physiological conditions by nonspecific esterases from human serum were examined. A selected number of the esters were tested for antagonism of convulsions induced by bicuculline, isoniazide, and by electroschock. While in the compounds showed only weak activities in the bicuculline and isoniazide tests, a good correlation between in vitro rates of enzymatic hydrolysis and the time of onset of the antagonism of the electroschock-induced convulsions could be found. |
doi_str_mv | 10.1021/jm00135a009 |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_73602290</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>73602290</sourcerecordid><originalsourceid>FETCH-LOGICAL-a420t-ed8605a7008098e7d778530dfedfa6895cf8f251f7562bcfe5d70515de5e006a3</originalsourceid><addsrcrecordid>eNptkE1LAzEQhoMotVZPnoU96aGsTpJNsnu0pbVCQcF68RLSTVK27kdNdkX_vZEtxYOHYQ7vwzvMg9AlhlsMBN9tKwBMmQLIjtAQMwJxkkJyjIYAhMSEE3qKzrzfAgDFhA7QQBDOME6GaDzzrXE-amxU-GbTfaq8qE2kfLRrWlO3hSqjnWu06zb-HJ1YVXpzsd8j9DqfraaLePn08Di9X8YqIdDGRqccmBIAKWSpEVqIlFHQ1mireJqx3KaWMGwF42SdW8O0AIaZNswAcEVH6LrvDYc_OuNbWRU-N2WpatN0XgrKw18ZBHDcg7lrvHfGyp0rKuW-JQb5q0b-URPoq31tt66MPrB7FyGP-7wISr4OsXLvkgsqmFw9v4RZzFdvEyEngb_peZV7uW06Vwcp_17-Aa5AeNk</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>73602290</pqid></control><display><type>article</type><title>Esters of isoguvacine as potential prodrugs</title><source>American Chemical Society</source><creator>Falch, Erik ; Krogsgaard-Larsen, Povl ; Christensen, Anne Vibeke</creator><creatorcontrib>Falch, Erik ; Krogsgaard-Larsen, Povl ; Christensen, Anne Vibeke</creatorcontrib><description>The syntheses of the methyl ester, butyl ester, (ethoxycarbonyl)methyl ester, and 11 (acyloxy)methyl esters of the potent gamma-aminobutyric acid agonist isoguvacine (1,2,3,6-tetrahydropyridine-4-carboxylic acid) and described. The chemical stability of the esters and their in vitro rates of hydrolysis under approximately physiological conditions by nonspecific esterases from human serum were examined. A selected number of the esters were tested for antagonism of convulsions induced by bicuculline, isoniazide, and by electroschock. While in the compounds showed only weak activities in the bicuculline and isoniazide tests, a good correlation between in vitro rates of enzymatic hydrolysis and the time of onset of the antagonism of the electroschock-induced convulsions could be found.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm00135a009</identifier><identifier>PMID: 7265114</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; Anticonvulsants - chemical synthesis ; Anticonvulsants - pharmacology ; Drug Stability ; Esters ; Humans ; Hydrolysis ; Isonicotinic Acids - chemical synthesis ; Mice</subject><ispartof>Journal of medicinal chemistry, 1981-03, Vol.24 (3), p.285-289</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a420t-ed8605a7008098e7d778530dfedfa6895cf8f251f7562bcfe5d70515de5e006a3</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/jm00135a009$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm00135a009$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,27062,27922,27923,56764,56814</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7265114$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Falch, Erik</creatorcontrib><creatorcontrib>Krogsgaard-Larsen, Povl</creatorcontrib><creatorcontrib>Christensen, Anne Vibeke</creatorcontrib><title>Esters of isoguvacine as potential prodrugs</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>The syntheses of the methyl ester, butyl ester, (ethoxycarbonyl)methyl ester, and 11 (acyloxy)methyl esters of the potent gamma-aminobutyric acid agonist isoguvacine (1,2,3,6-tetrahydropyridine-4-carboxylic acid) and described. The chemical stability of the esters and their in vitro rates of hydrolysis under approximately physiological conditions by nonspecific esterases from human serum were examined. A selected number of the esters were tested for antagonism of convulsions induced by bicuculline, isoniazide, and by electroschock. While in the compounds showed only weak activities in the bicuculline and isoniazide tests, a good correlation between in vitro rates of enzymatic hydrolysis and the time of onset of the antagonism of the electroschock-induced convulsions could be found.</description><subject>Animals</subject><subject>Anticonvulsants - chemical synthesis</subject><subject>Anticonvulsants - pharmacology</subject><subject>Drug Stability</subject><subject>Esters</subject><subject>Humans</subject><subject>Hydrolysis</subject><subject>Isonicotinic Acids - chemical synthesis</subject><subject>Mice</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1981</creationdate><recordtype>article</recordtype><recordid>eNptkE1LAzEQhoMotVZPnoU96aGsTpJNsnu0pbVCQcF68RLSTVK27kdNdkX_vZEtxYOHYQ7vwzvMg9AlhlsMBN9tKwBMmQLIjtAQMwJxkkJyjIYAhMSEE3qKzrzfAgDFhA7QQBDOME6GaDzzrXE-amxU-GbTfaq8qE2kfLRrWlO3hSqjnWu06zb-HJ1YVXpzsd8j9DqfraaLePn08Di9X8YqIdDGRqccmBIAKWSpEVqIlFHQ1mireJqx3KaWMGwF42SdW8O0AIaZNswAcEVH6LrvDYc_OuNbWRU-N2WpatN0XgrKw18ZBHDcg7lrvHfGyp0rKuW-JQb5q0b-URPoq31tt66MPrB7FyGP-7wISr4OsXLvkgsqmFw9v4RZzFdvEyEngb_peZV7uW06Vwcp_17-Aa5AeNk</recordid><startdate>198103</startdate><enddate>198103</enddate><creator>Falch, Erik</creator><creator>Krogsgaard-Larsen, Povl</creator><creator>Christensen, Anne Vibeke</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>198103</creationdate><title>Esters of isoguvacine as potential prodrugs</title><author>Falch, Erik ; Krogsgaard-Larsen, Povl ; Christensen, Anne Vibeke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a420t-ed8605a7008098e7d778530dfedfa6895cf8f251f7562bcfe5d70515de5e006a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1981</creationdate><topic>Animals</topic><topic>Anticonvulsants - chemical synthesis</topic><topic>Anticonvulsants - pharmacology</topic><topic>Drug Stability</topic><topic>Esters</topic><topic>Humans</topic><topic>Hydrolysis</topic><topic>Isonicotinic Acids - chemical synthesis</topic><topic>Mice</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Falch, Erik</creatorcontrib><creatorcontrib>Krogsgaard-Larsen, Povl</creatorcontrib><creatorcontrib>Christensen, Anne Vibeke</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>Falch, Erik</au><au>Krogsgaard-Larsen, Povl</au><au>Christensen, Anne Vibeke</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Esters of isoguvacine as potential prodrugs</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1981-03</date><risdate>1981</risdate><volume>24</volume><issue>3</issue><spage>285</spage><epage>289</epage><pages>285-289</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><abstract>The syntheses of the methyl ester, butyl ester, (ethoxycarbonyl)methyl ester, and 11 (acyloxy)methyl esters of the potent gamma-aminobutyric acid agonist isoguvacine (1,2,3,6-tetrahydropyridine-4-carboxylic acid) and described. The chemical stability of the esters and their in vitro rates of hydrolysis under approximately physiological conditions by nonspecific esterases from human serum were examined. A selected number of the esters were tested for antagonism of convulsions induced by bicuculline, isoniazide, and by electroschock. While in the compounds showed only weak activities in the bicuculline and isoniazide tests, a good correlation between in vitro rates of enzymatic hydrolysis and the time of onset of the antagonism of the electroschock-induced convulsions could be found.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>7265114</pmid><doi>10.1021/jm00135a009</doi><tpages>5</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0022-2623 |
ispartof | Journal of medicinal chemistry, 1981-03, Vol.24 (3), p.285-289 |
issn | 0022-2623 1520-4804 |
language | eng |
recordid | cdi_proquest_miscellaneous_73602290 |
source | American Chemical Society |
subjects | Animals Anticonvulsants - chemical synthesis Anticonvulsants - pharmacology Drug Stability Esters Humans Hydrolysis Isonicotinic Acids - chemical synthesis Mice |
title | Esters of isoguvacine as potential prodrugs |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-13T16%3A08%3A32IST&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=Esters%20of%20isoguvacine%20as%20potential%20prodrugs&rft.jtitle=Journal%20of%20medicinal%20chemistry&rft.au=Falch,%20Erik&rft.date=1981-03&rft.volume=24&rft.issue=3&rft.spage=285&rft.epage=289&rft.pages=285-289&rft.issn=0022-2623&rft.eissn=1520-4804&rft_id=info:doi/10.1021/jm00135a009&rft_dat=%3Cproquest_cross%3E73602290%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-a420t-ed8605a7008098e7d778530dfedfa6895cf8f251f7562bcfe5d70515de5e006a3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=73602290&rft_id=info:pmid/7265114&rfr_iscdi=true |