Structure-activity relationship determination within a group of substituted phenyl sulfamate based compounds against the enzyme oestrone sulfatase
ABSTRACT The enzyme oestrone sulfatase (ES) is responsible for the conversion of the stored (sulfated) form of oestrogens to the active form, namely oestrone. In our continuing quest to synthesize potent inhibitors of oestrone sulfatase and to determine the structural requirements for such inhibitio...
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| Veröffentlicht in: | Journal of pharmacy and pharmacology 2003-02, Vol.55 (2), p.211-218 |
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| container_title | Journal of pharmacy and pharmacology |
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| creator | Patel, Chirag K. Galisson, Angelique James, Karen Owen, Caroline P. Ahmed, Sabbir |
| description | ABSTRACT
The enzyme oestrone sulfatase (ES) is responsible for the conversion of the stored (sulfated) form of oestrogens to the active form, namely oestrone. In our continuing quest to synthesize potent inhibitors of oestrone sulfatase and to determine the structural requirements for such inhibition, we have synthesized and evaluated several derivatives of phenyl sulfamate. We report the results of the synthesis and biochemical evaluation of a series of 3‐ and 4‐aminosulfonated derivatives of phenol in an effort to investigate the role of the acid dissociation constant (pKa), and therefore the stability of the phenoxide ion, on the inhibitory activity of compounds against this enzyme. The results showed that there was a strong correlation between the observed pKa and inhibitory activity within the aminosulfonated compounds considered. This suggested that in the inhibition of oestrone sulfatase by these compounds, pKa was an important physicochemical property, and as such, the stability of the O− ion was a crucial factor in the inhibition, and therefore the drug design process. |
| doi_str_mv | 10.1211/002235702586 |
| format | Article |
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The enzyme oestrone sulfatase (ES) is responsible for the conversion of the stored (sulfated) form of oestrogens to the active form, namely oestrone. In our continuing quest to synthesize potent inhibitors of oestrone sulfatase and to determine the structural requirements for such inhibition, we have synthesized and evaluated several derivatives of phenyl sulfamate. We report the results of the synthesis and biochemical evaluation of a series of 3‐ and 4‐aminosulfonated derivatives of phenol in an effort to investigate the role of the acid dissociation constant (pKa), and therefore the stability of the phenoxide ion, on the inhibitory activity of compounds against this enzyme. The results showed that there was a strong correlation between the observed pKa and inhibitory activity within the aminosulfonated compounds considered. This suggested that in the inhibition of oestrone sulfatase by these compounds, pKa was an important physicochemical property, and as such, the stability of the O− ion was a crucial factor in the inhibition, and therefore the drug design process.</description><identifier>ISSN: 0022-3573</identifier><identifier>EISSN: 2042-7158</identifier><identifier>DOI: 10.1211/002235702586</identifier><identifier>PMID: 12631414</identifier><identifier>CODEN: JPPMAB</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Biological and medical sciences ; Enzyme Inhibitors - chemical synthesis ; Enzyme Inhibitors - pharmacology ; General pharmacology ; Medical sciences ; Pharmacology. Drug treatments ; Physicochemical properties. Structure-activity relationships ; Structure-Activity Relationship ; Sulfatases - antagonists & inhibitors ; Sulfonic Acids - chemical synthesis ; Sulfonic Acids - pharmacology</subject><ispartof>Journal of pharmacy and pharmacology, 2003-02, Vol.55 (2), p.211-218</ispartof><rights>2003 Royal Pharmaceutical Society of Great Britain</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4360-94cd3c3a1cd481c0188f2612215b0463c053ebdca9c4a390c11d9e6fdc26ad703</citedby><cites>FETCH-LOGICAL-c4360-94cd3c3a1cd481c0188f2612215b0463c053ebdca9c4a390c11d9e6fdc26ad703</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1211%2F002235702586$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1211%2F002235702586$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14528933$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12631414$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Patel, Chirag K.</creatorcontrib><creatorcontrib>Galisson, Angelique</creatorcontrib><creatorcontrib>James, Karen</creatorcontrib><creatorcontrib>Owen, Caroline P.</creatorcontrib><creatorcontrib>Ahmed, Sabbir</creatorcontrib><title>Structure-activity relationship determination within a group of substituted phenyl sulfamate based compounds against the enzyme oestrone sulfatase</title><title>Journal of pharmacy and pharmacology</title><addtitle>J Pharm Pharmacol</addtitle><description>ABSTRACT
The enzyme oestrone sulfatase (ES) is responsible for the conversion of the stored (sulfated) form of oestrogens to the active form, namely oestrone. In our continuing quest to synthesize potent inhibitors of oestrone sulfatase and to determine the structural requirements for such inhibition, we have synthesized and evaluated several derivatives of phenyl sulfamate. We report the results of the synthesis and biochemical evaluation of a series of 3‐ and 4‐aminosulfonated derivatives of phenol in an effort to investigate the role of the acid dissociation constant (pKa), and therefore the stability of the phenoxide ion, on the inhibitory activity of compounds against this enzyme. The results showed that there was a strong correlation between the observed pKa and inhibitory activity within the aminosulfonated compounds considered. This suggested that in the inhibition of oestrone sulfatase by these compounds, pKa was an important physicochemical property, and as such, the stability of the O− ion was a crucial factor in the inhibition, and therefore the drug design process.</description><subject>Biological and medical sciences</subject><subject>Enzyme Inhibitors - chemical synthesis</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>General pharmacology</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Physicochemical properties. Structure-activity relationships</subject><subject>Structure-Activity Relationship</subject><subject>Sulfatases - antagonists & inhibitors</subject><subject>Sulfonic Acids - chemical synthesis</subject><subject>Sulfonic Acids - pharmacology</subject><issn>0022-3573</issn><issn>2042-7158</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctu1DAUhi0EokNhxxp5AysCvsVJlqiCKaiCSgwgsbEc-6RjSJxgO5TwGDwxHjKirFgd6T_ff64IPaTkGWWUPieEMV5WhJW1vIU2jAhWVLSsb6PNIVXkHD9B92L8QgippJR30QllklNBxQb9ep_CbNIcoNAmue8uLThAr5Mbfdy7CVtIEAbn_yj42qW981jjqzDOEx47HOc2JpfmBBZPe_BLn6W-04NOgFsds2zGYRpnbyPWV9r5mHDaAwb_cxkAjxBTGD2srpQN99GdTvcRHhzjKfrw6uXu7Ly4eLd9ffbiojCCS1I0wlhuuKbGipoaQuu6Y5IyRsuWCMkNKTm01ujGCM0bYii1DcjOGia1rQg_RU_WulMYv815DDW4aKDvtYdxjqripM73qjP4dAVNGGMM0KkpuEGHRVGiDj9Q__4g44-Oded2AHsDH4-egcdHQEej-y5ob1y84UTJ6obzzLGVu3Y9LP9tqt5cnl8y0Ry2KlaTiwl-_DXp8FXJilel-vR2q7a82W13Hz_nHX8DU8ywEQ</recordid><startdate>200302</startdate><enddate>200302</enddate><creator>Patel, Chirag K.</creator><creator>Galisson, Angelique</creator><creator>James, Karen</creator><creator>Owen, Caroline P.</creator><creator>Ahmed, Sabbir</creator><general>Blackwell Publishing Ltd</general><general>Pharmaceutical Press</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>200302</creationdate><title>Structure-activity relationship determination within a group of substituted phenyl sulfamate based compounds against the enzyme oestrone sulfatase</title><author>Patel, Chirag K. ; Galisson, Angelique ; James, Karen ; Owen, Caroline P. ; Ahmed, Sabbir</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4360-94cd3c3a1cd481c0188f2612215b0463c053ebdca9c4a390c11d9e6fdc26ad703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Biological and medical sciences</topic><topic>Enzyme Inhibitors - chemical synthesis</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>General pharmacology</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Physicochemical properties. Structure-activity relationships</topic><topic>Structure-Activity Relationship</topic><topic>Sulfatases - antagonists & inhibitors</topic><topic>Sulfonic Acids - chemical synthesis</topic><topic>Sulfonic Acids - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Patel, Chirag K.</creatorcontrib><creatorcontrib>Galisson, Angelique</creatorcontrib><creatorcontrib>James, Karen</creatorcontrib><creatorcontrib>Owen, Caroline P.</creatorcontrib><creatorcontrib>Ahmed, Sabbir</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 pharmacy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Patel, Chirag K.</au><au>Galisson, Angelique</au><au>James, Karen</au><au>Owen, Caroline P.</au><au>Ahmed, Sabbir</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structure-activity relationship determination within a group of substituted phenyl sulfamate based compounds against the enzyme oestrone sulfatase</atitle><jtitle>Journal of pharmacy and pharmacology</jtitle><addtitle>J Pharm Pharmacol</addtitle><date>2003-02</date><risdate>2003</risdate><volume>55</volume><issue>2</issue><spage>211</spage><epage>218</epage><pages>211-218</pages><issn>0022-3573</issn><eissn>2042-7158</eissn><coden>JPPMAB</coden><abstract>ABSTRACT
The enzyme oestrone sulfatase (ES) is responsible for the conversion of the stored (sulfated) form of oestrogens to the active form, namely oestrone. In our continuing quest to synthesize potent inhibitors of oestrone sulfatase and to determine the structural requirements for such inhibition, we have synthesized and evaluated several derivatives of phenyl sulfamate. We report the results of the synthesis and biochemical evaluation of a series of 3‐ and 4‐aminosulfonated derivatives of phenol in an effort to investigate the role of the acid dissociation constant (pKa), and therefore the stability of the phenoxide ion, on the inhibitory activity of compounds against this enzyme. The results showed that there was a strong correlation between the observed pKa and inhibitory activity within the aminosulfonated compounds considered. This suggested that in the inhibition of oestrone sulfatase by these compounds, pKa was an important physicochemical property, and as such, the stability of the O− ion was a crucial factor in the inhibition, and therefore the drug design process.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>12631414</pmid><doi>10.1211/002235702586</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals; OUP_牛津大学出版社现刊 |
| subjects | Biological and medical sciences Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - pharmacology General pharmacology Medical sciences Pharmacology. Drug treatments Physicochemical properties. Structure-activity relationships Structure-Activity Relationship Sulfatases - antagonists & inhibitors Sulfonic Acids - chemical synthesis Sulfonic Acids - pharmacology |
| title | Structure-activity relationship determination within a group of substituted phenyl sulfamate based compounds against the enzyme oestrone sulfatase |
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