Novel steroid spiro enones: condensation of prednisolone derivatives with diethyl oxalate
In a continuing effort to discover potent anti-inflammatory steroids without systemic side effects, diethyl oxalate was condensed with the 17β-ketol side chain of prednisolone derivatives. Prednisolone gave the most interesting result in forming a novel spiro enone with α-hydroxy and β-carboxylic es...
Gespeichert in:
| Veröffentlicht in: | Steroids 2000-02, Vol.65 (2), p.109-115 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 115 |
|---|---|
| container_issue | 2 |
| container_start_page | 109 |
| container_title | Steroids |
| container_volume | 65 |
| creator | You, Zhengqing Heiman, Ann S Chen, Meiqin Lee, Henry Joung |
| description | In a continuing effort to discover potent anti-inflammatory steroids without systemic side effects, diethyl oxalate was condensed with the 17β-ketol side chain of prednisolone derivatives. Prednisolone gave the most interesting result in forming a novel spiro enone with α-hydroxy and β-carboxylic ester substitutions, and a facile one-pot procedure has been established for the synthesis of this highly functionalized spiro enone structure. The spiro products were tested for their binding potency to the RAW 264.7 macrophage glucocorticoid receptor, for their effect on LPS-induced nitric oxide generation in RAW 264.7 cells, and for their inhibition of rats ear edema induced by croton oil. The new compounds showed weak activities in all of the bioassays. Because the corresponding acid metabolites of two representative spiro enone esters gave no activity in either the binding assay or the nitric oxide generation test, the novel steroids are probably antedrugs. The reduced potency as compared to their parent compounds suggests that the rigid spiro structure is unfavorable to anti-inflammatory activities. Molecular modeling studies confirm that the spiro enones adopt a rigid planar geometry with the ester group in the plane. |
| doi_str_mv | 10.1016/S0039-128X(99)00088-4 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_70839162</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0039128X99000884</els_id><sourcerecordid>70839162</sourcerecordid><originalsourceid>FETCH-LOGICAL-c390t-455fe13d35fe235e85ea81845fd0597591856320778a5c2cb6e05908e1d716833</originalsourceid><addsrcrecordid>eNqFkE1P3DAQQC0Egi3lJ1D5gKr2EGrHcWJzQRVqAQnRQ0GCk2XsiTDK2osnu5R_j5ddUW6cZjTz5kOPkH3ODjnj7Y-_jAld8VrdfNP6O2NMqarZIBOuOlVJ1XabZPKG7JBPiA8FaoWut8kOXyasFhNye5kWMFAcIafgKc5CThRiioBH1KXoIaIdQ4o09XSWwceAaSht6iGHRWktAOlTGO-pDzDePw80_bODHeEz2ertgLC3jrvk-vevq5Oz6uLP6fnJz4vKlRfGqpGyBy68KKEWEpQEq7hqZO-Z1J3UXMlW1KzrlJWudnctlDpTwH3HWyXELvm62jvL6XEOOJppQAfDYCOkOZqOKaF5WxdQrkCXE2KG3sxymNr8bDgzS6fm1alZCjNam1enpilzX9YH5ndT8O-mVhILcLAGLDo79NlGF_A_VzdcqeWe4xUGxcYiQDboAkQHPmRwo_EpfPDJC9JWk7k</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>70839162</pqid></control><display><type>article</type><title>Novel steroid spiro enones: condensation of prednisolone derivatives with diethyl oxalate</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>You, Zhengqing ; Heiman, Ann S ; Chen, Meiqin ; Lee, Henry Joung</creator><creatorcontrib>You, Zhengqing ; Heiman, Ann S ; Chen, Meiqin ; Lee, Henry Joung</creatorcontrib><description>In a continuing effort to discover potent anti-inflammatory steroids without systemic side effects, diethyl oxalate was condensed with the 17β-ketol side chain of prednisolone derivatives. Prednisolone gave the most interesting result in forming a novel spiro enone with α-hydroxy and β-carboxylic ester substitutions, and a facile one-pot procedure has been established for the synthesis of this highly functionalized spiro enone structure. The spiro products were tested for their binding potency to the RAW 264.7 macrophage glucocorticoid receptor, for their effect on LPS-induced nitric oxide generation in RAW 264.7 cells, and for their inhibition of rats ear edema induced by croton oil. The new compounds showed weak activities in all of the bioassays. Because the corresponding acid metabolites of two representative spiro enone esters gave no activity in either the binding assay or the nitric oxide generation test, the novel steroids are probably antedrugs. The reduced potency as compared to their parent compounds suggests that the rigid spiro structure is unfavorable to anti-inflammatory activities. Molecular modeling studies confirm that the spiro enones adopt a rigid planar geometry with the ester group in the plane.</description><identifier>ISSN: 0039-128X</identifier><identifier>EISSN: 1878-5867</identifier><identifier>DOI: 10.1016/S0039-128X(99)00088-4</identifier><identifier>PMID: 10639023</identifier><identifier>CODEN: STEDAM</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Alicyclic compounds, terpenoids, prostaglandins, steroids ; Animals ; Antedrug ; Anti-inflammatory steroid ; Biological and medical sciences ; Bones, joints and connective tissue. Antiinflammatory agents ; Cell Line ; Chemistry ; Cottonseed Oil - adverse effects ; Ear ; Edema - chemically induced ; Edema - drug therapy ; Exact sciences and technology ; Macrophages - chemistry ; Male ; Medical sciences ; Mice ; Models, Molecular ; Molecular Structure ; Nitric Oxide - antagonists & inhibitors ; Nitric Oxide - biosynthesis ; Nitric Oxide Synthase - pharmacology ; Nitric Oxide Synthase Type II ; Organic chemistry ; Oxalates - chemistry ; Pharmacology. Drug treatments ; Prednisolone ; Prednisolone - analogs & derivatives ; Prednisolone - chemical synthesis ; Prednisolone - therapeutic use ; Preparations and properties ; Protein Isoforms - pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid - metabolism ; Spiro Compounds - chemical synthesis ; Spiro Compounds - therapeutic use ; Spiro enone ; Steroids</subject><ispartof>Steroids, 2000-02, Vol.65 (2), p.109-115</ispartof><rights>2000 Elsevier Science Inc.</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-455fe13d35fe235e85ea81845fd0597591856320778a5c2cb6e05908e1d716833</citedby><cites>FETCH-LOGICAL-c390t-455fe13d35fe235e85ea81845fd0597591856320778a5c2cb6e05908e1d716833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0039128X99000884$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1241884$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10639023$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>You, Zhengqing</creatorcontrib><creatorcontrib>Heiman, Ann S</creatorcontrib><creatorcontrib>Chen, Meiqin</creatorcontrib><creatorcontrib>Lee, Henry Joung</creatorcontrib><title>Novel steroid spiro enones: condensation of prednisolone derivatives with diethyl oxalate</title><title>Steroids</title><addtitle>Steroids</addtitle><description>In a continuing effort to discover potent anti-inflammatory steroids without systemic side effects, diethyl oxalate was condensed with the 17β-ketol side chain of prednisolone derivatives. Prednisolone gave the most interesting result in forming a novel spiro enone with α-hydroxy and β-carboxylic ester substitutions, and a facile one-pot procedure has been established for the synthesis of this highly functionalized spiro enone structure. The spiro products were tested for their binding potency to the RAW 264.7 macrophage glucocorticoid receptor, for their effect on LPS-induced nitric oxide generation in RAW 264.7 cells, and for their inhibition of rats ear edema induced by croton oil. The new compounds showed weak activities in all of the bioassays. Because the corresponding acid metabolites of two representative spiro enone esters gave no activity in either the binding assay or the nitric oxide generation test, the novel steroids are probably antedrugs. The reduced potency as compared to their parent compounds suggests that the rigid spiro structure is unfavorable to anti-inflammatory activities. Molecular modeling studies confirm that the spiro enones adopt a rigid planar geometry with the ester group in the plane.</description><subject>Alicyclic compounds, terpenoids, prostaglandins, steroids</subject><subject>Animals</subject><subject>Antedrug</subject><subject>Anti-inflammatory steroid</subject><subject>Biological and medical sciences</subject><subject>Bones, joints and connective tissue. Antiinflammatory agents</subject><subject>Cell Line</subject><subject>Chemistry</subject><subject>Cottonseed Oil - adverse effects</subject><subject>Ear</subject><subject>Edema - chemically induced</subject><subject>Edema - drug therapy</subject><subject>Exact sciences and technology</subject><subject>Macrophages - chemistry</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Models, Molecular</subject><subject>Molecular Structure</subject><subject>Nitric Oxide - antagonists & inhibitors</subject><subject>Nitric Oxide - biosynthesis</subject><subject>Nitric Oxide Synthase - pharmacology</subject><subject>Nitric Oxide Synthase Type II</subject><subject>Organic chemistry</subject><subject>Oxalates - chemistry</subject><subject>Pharmacology. Drug treatments</subject><subject>Prednisolone</subject><subject>Prednisolone - analogs & derivatives</subject><subject>Prednisolone - chemical synthesis</subject><subject>Prednisolone - therapeutic use</subject><subject>Preparations and properties</subject><subject>Protein Isoforms - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Glucocorticoid - metabolism</subject><subject>Spiro Compounds - chemical synthesis</subject><subject>Spiro Compounds - therapeutic use</subject><subject>Spiro enone</subject><subject>Steroids</subject><issn>0039-128X</issn><issn>1878-5867</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1P3DAQQC0Egi3lJ1D5gKr2EGrHcWJzQRVqAQnRQ0GCk2XsiTDK2osnu5R_j5ddUW6cZjTz5kOPkH3ODjnj7Y-_jAld8VrdfNP6O2NMqarZIBOuOlVJ1XabZPKG7JBPiA8FaoWut8kOXyasFhNye5kWMFAcIafgKc5CThRiioBH1KXoIaIdQ4o09XSWwceAaSht6iGHRWktAOlTGO-pDzDePw80_bODHeEz2ertgLC3jrvk-vevq5Oz6uLP6fnJz4vKlRfGqpGyBy68KKEWEpQEq7hqZO-Z1J3UXMlW1KzrlJWudnctlDpTwH3HWyXELvm62jvL6XEOOJppQAfDYCOkOZqOKaF5WxdQrkCXE2KG3sxymNr8bDgzS6fm1alZCjNam1enpilzX9YH5ndT8O-mVhILcLAGLDo79NlGF_A_VzdcqeWe4xUGxcYiQDboAkQHPmRwo_EpfPDJC9JWk7k</recordid><startdate>20000201</startdate><enddate>20000201</enddate><creator>You, Zhengqing</creator><creator>Heiman, Ann S</creator><creator>Chen, Meiqin</creator><creator>Lee, Henry Joung</creator><general>Elsevier Inc</general><general>Elsevier Science</general><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>20000201</creationdate><title>Novel steroid spiro enones: condensation of prednisolone derivatives with diethyl oxalate</title><author>You, Zhengqing ; Heiman, Ann S ; Chen, Meiqin ; Lee, Henry Joung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-455fe13d35fe235e85ea81845fd0597591856320778a5c2cb6e05908e1d716833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Alicyclic compounds, terpenoids, prostaglandins, steroids</topic><topic>Animals</topic><topic>Antedrug</topic><topic>Anti-inflammatory steroid</topic><topic>Biological and medical sciences</topic><topic>Bones, joints and connective tissue. Antiinflammatory agents</topic><topic>Cell Line</topic><topic>Chemistry</topic><topic>Cottonseed Oil - adverse effects</topic><topic>Ear</topic><topic>Edema - chemically induced</topic><topic>Edema - drug therapy</topic><topic>Exact sciences and technology</topic><topic>Macrophages - chemistry</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Models, Molecular</topic><topic>Molecular Structure</topic><topic>Nitric Oxide - antagonists & inhibitors</topic><topic>Nitric Oxide - biosynthesis</topic><topic>Nitric Oxide Synthase - pharmacology</topic><topic>Nitric Oxide Synthase Type II</topic><topic>Organic chemistry</topic><topic>Oxalates - chemistry</topic><topic>Pharmacology. Drug treatments</topic><topic>Prednisolone</topic><topic>Prednisolone - analogs & derivatives</topic><topic>Prednisolone - chemical synthesis</topic><topic>Prednisolone - therapeutic use</topic><topic>Preparations and properties</topic><topic>Protein Isoforms - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Glucocorticoid - metabolism</topic><topic>Spiro Compounds - chemical synthesis</topic><topic>Spiro Compounds - therapeutic use</topic><topic>Spiro enone</topic><topic>Steroids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>You, Zhengqing</creatorcontrib><creatorcontrib>Heiman, Ann S</creatorcontrib><creatorcontrib>Chen, Meiqin</creatorcontrib><creatorcontrib>Lee, Henry Joung</creatorcontrib><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>Steroids</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>You, Zhengqing</au><au>Heiman, Ann S</au><au>Chen, Meiqin</au><au>Lee, Henry Joung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel steroid spiro enones: condensation of prednisolone derivatives with diethyl oxalate</atitle><jtitle>Steroids</jtitle><addtitle>Steroids</addtitle><date>2000-02-01</date><risdate>2000</risdate><volume>65</volume><issue>2</issue><spage>109</spage><epage>115</epage><pages>109-115</pages><issn>0039-128X</issn><eissn>1878-5867</eissn><coden>STEDAM</coden><abstract>In a continuing effort to discover potent anti-inflammatory steroids without systemic side effects, diethyl oxalate was condensed with the 17β-ketol side chain of prednisolone derivatives. Prednisolone gave the most interesting result in forming a novel spiro enone with α-hydroxy and β-carboxylic ester substitutions, and a facile one-pot procedure has been established for the synthesis of this highly functionalized spiro enone structure. The spiro products were tested for their binding potency to the RAW 264.7 macrophage glucocorticoid receptor, for their effect on LPS-induced nitric oxide generation in RAW 264.7 cells, and for their inhibition of rats ear edema induced by croton oil. The new compounds showed weak activities in all of the bioassays. Because the corresponding acid metabolites of two representative spiro enone esters gave no activity in either the binding assay or the nitric oxide generation test, the novel steroids are probably antedrugs. The reduced potency as compared to their parent compounds suggests that the rigid spiro structure is unfavorable to anti-inflammatory activities. Molecular modeling studies confirm that the spiro enones adopt a rigid planar geometry with the ester group in the plane.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>10639023</pmid><doi>10.1016/S0039-128X(99)00088-4</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0039-128X |
| ispartof | Steroids, 2000-02, Vol.65 (2), p.109-115 |
| issn | 0039-128X 1878-5867 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70839162 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Alicyclic compounds, terpenoids, prostaglandins, steroids Animals Antedrug Anti-inflammatory steroid Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Cell Line Chemistry Cottonseed Oil - adverse effects Ear Edema - chemically induced Edema - drug therapy Exact sciences and technology Macrophages - chemistry Male Medical sciences Mice Models, Molecular Molecular Structure Nitric Oxide - antagonists & inhibitors Nitric Oxide - biosynthesis Nitric Oxide Synthase - pharmacology Nitric Oxide Synthase Type II Organic chemistry Oxalates - chemistry Pharmacology. Drug treatments Prednisolone Prednisolone - analogs & derivatives Prednisolone - chemical synthesis Prednisolone - therapeutic use Preparations and properties Protein Isoforms - pharmacology Rats Rats, Sprague-Dawley Receptors, Glucocorticoid - metabolism Spiro Compounds - chemical synthesis Spiro Compounds - therapeutic use Spiro enone Steroids |
| title | Novel steroid spiro enones: condensation of prednisolone derivatives with diethyl oxalate |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-30T03%3A43%3A43IST&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=Novel%20steroid%20spiro%20enones:%20condensation%20of%20prednisolone%20derivatives%20with%20diethyl%20oxalate&rft.jtitle=Steroids&rft.au=You,%20Zhengqing&rft.date=2000-02-01&rft.volume=65&rft.issue=2&rft.spage=109&rft.epage=115&rft.pages=109-115&rft.issn=0039-128X&rft.eissn=1878-5867&rft.coden=STEDAM&rft_id=info:doi/10.1016/S0039-128X(99)00088-4&rft_dat=%3Cproquest_cross%3E70839162%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=70839162&rft_id=info:pmid/10639023&rft_els_id=S0039128X99000884&rfr_iscdi=true |