New Substituted 1,4-Benzoxazine Derivatives with Potential Intracellular Calcium Activity
Substituted 1,4-benzoxazines bearing an amino side chain at the 2-position were prepared and were found to have a moderate activity on intracellular calcium. Of the compounds studied it was found that those which possess a homoveratrylamino moiety exhibited superior potency. The chain length and the...
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| Veröffentlicht in: | Journal of medicinal chemistry 1998-08, Vol.41 (17), p.3142-3158 |
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| container_issue | 17 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 41 |
| creator | Bourlot, Anne-Sophie Sánchez, Isabel Dureng, Georges Guillaumet, Gérald Massingham, Roy Monteil, André Winslow, Eileen Pujol, M. Dolors Mérour, Jean-Yves |
| description | Substituted 1,4-benzoxazines bearing an amino side chain at the 2-position were prepared and were found to have a moderate activity on intracellular calcium. Of the compounds studied it was found that those which possess a homoveratrylamino moiety exhibited superior potency. The chain length and the nature of the amine (4-fluorophenylpiperazine, 4-fluorobenzhydryloxyethylamine, N-substituted homoveratrylamine) is discussed. The 4-benzyl-3,4-dihydro-2-[3-[[2-(3,4-dimethoxyphenyl)ethyl]amino]propyl]-2H-1,4-benzoxazine (3c) is the most potent derivative of the series with a ratio of IC50 values against PE (phenylephrine) and K+ of 2.1. Under these test conditions a ratio near 1 indicates potential intracellular calcium activity while a ratio greater than 100 an action on extracellular calcium influx. |
| doi_str_mv | 10.1021/jm970795t |
| format | Article |
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Dolors ; Mérour, Jean-Yves</creator><creatorcontrib>Bourlot, Anne-Sophie ; Sánchez, Isabel ; Dureng, Georges ; Guillaumet, Gérald ; Massingham, Roy ; Monteil, André ; Winslow, Eileen ; Pujol, M. Dolors ; Mérour, Jean-Yves</creatorcontrib><description>Substituted 1,4-benzoxazines bearing an amino side chain at the 2-position were prepared and were found to have a moderate activity on intracellular calcium. Of the compounds studied it was found that those which possess a homoveratrylamino moiety exhibited superior potency. The chain length and the nature of the amine (4-fluorophenylpiperazine, 4-fluorobenzhydryloxyethylamine, N-substituted homoveratrylamine) is discussed. The 4-benzyl-3,4-dihydro-2-[3-[[2-(3,4-dimethoxyphenyl)ethyl]amino]propyl]-2H-1,4-benzoxazine (3c) is the most potent derivative of the series with a ratio of IC50 values against PE (phenylephrine) and K+ of 2.1. Under these test conditions a ratio near 1 indicates potential intracellular calcium activity while a ratio greater than 100 an action on extracellular calcium influx.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm970795t</identifier><identifier>PMID: 9703461</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>1,4-Benzoxazine ; Animals ; Aorta - drug effects ; Aorta - physiology ; Biological and medical sciences ; Calcium - metabolism ; Calcium Channel Blockers - chemical synthesis ; Calcium Channel Blockers - chemistry ; Calcium Channel Blockers - pharmacology ; Cardiovascular system ; Drug Design ; In Vitro Techniques ; Male ; Medical sciences ; Miscellaneous ; Molecular Structure ; Muscle Contraction - drug effects ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - physiology ; Oxazines - chemical synthesis ; Oxazines - chemistry ; Oxazines - pharmacology ; Pharmacology. Drug treatments ; Phenylephrine - pharmacology ; Rabbits ; Renal Artery - drug effects ; Renal Artery - physiology ; Second Messenger Systems ; Structure-Activity Relationship ; Vasoconstriction - drug effects</subject><ispartof>Journal of medicinal chemistry, 1998-08, Vol.41 (17), p.3142-3158</ispartof><rights>Copyright © 1998 American Chemical Society</rights><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a408t-4768bbca55356e951b04fc4759c4ea8abc794a27b204d6b9eed91508c98156663</citedby><cites>FETCH-LOGICAL-a408t-4768bbca55356e951b04fc4759c4ea8abc794a27b204d6b9eed91508c98156663</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm970795t$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm970795t$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,778,782,2754,27059,27907,27908,56721,56771</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2364190$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9703461$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bourlot, Anne-Sophie</creatorcontrib><creatorcontrib>Sánchez, Isabel</creatorcontrib><creatorcontrib>Dureng, Georges</creatorcontrib><creatorcontrib>Guillaumet, Gérald</creatorcontrib><creatorcontrib>Massingham, Roy</creatorcontrib><creatorcontrib>Monteil, André</creatorcontrib><creatorcontrib>Winslow, Eileen</creatorcontrib><creatorcontrib>Pujol, M. Dolors</creatorcontrib><creatorcontrib>Mérour, Jean-Yves</creatorcontrib><title>New Substituted 1,4-Benzoxazine Derivatives with Potential Intracellular Calcium Activity</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>Substituted 1,4-benzoxazines bearing an amino side chain at the 2-position were prepared and were found to have a moderate activity on intracellular calcium. Of the compounds studied it was found that those which possess a homoveratrylamino moiety exhibited superior potency. The chain length and the nature of the amine (4-fluorophenylpiperazine, 4-fluorobenzhydryloxyethylamine, N-substituted homoveratrylamine) is discussed. The 4-benzyl-3,4-dihydro-2-[3-[[2-(3,4-dimethoxyphenyl)ethyl]amino]propyl]-2H-1,4-benzoxazine (3c) is the most potent derivative of the series with a ratio of IC50 values against PE (phenylephrine) and K+ of 2.1. Under these test conditions a ratio near 1 indicates potential intracellular calcium activity while a ratio greater than 100 an action on extracellular calcium influx.</description><subject>1,4-Benzoxazine</subject><subject>Animals</subject><subject>Aorta - drug effects</subject><subject>Aorta - physiology</subject><subject>Biological and medical sciences</subject><subject>Calcium - metabolism</subject><subject>Calcium Channel Blockers - chemical synthesis</subject><subject>Calcium Channel Blockers - chemistry</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Cardiovascular system</subject><subject>Drug Design</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Molecular Structure</subject><subject>Muscle Contraction - drug effects</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Muscle, Smooth, Vascular - physiology</subject><subject>Oxazines - chemical synthesis</subject><subject>Oxazines - chemistry</subject><subject>Oxazines - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenylephrine - pharmacology</subject><subject>Rabbits</subject><subject>Renal Artery - drug effects</subject><subject>Renal Artery - physiology</subject><subject>Second Messenger Systems</subject><subject>Structure-Activity Relationship</subject><subject>Vasoconstriction - drug effects</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0EtrFEEUBeBClDgmLvwBQi-MELBjvatrmUweBkMMTALRTXG75g7W2I-kqjqvX2-HGWYluLqL83G4HEI-MLrPKGdfl6011FiVX5EJU5yWsqLyNZlQynnJNRdvybuUlpRSwbjYIlsjF1KzCfl5gQ_FbKhTDnnIOC_YF1keYvfcP8Jz6LA4whjuIYd7TMVDyL-Lyz5jlwM0xVmXI3hsmqGBWEyh8WFoiwM_4pCfdsibBTQJ36_vNrk-Ob6afivPf5yeTQ_OS5C0yqU0uqprD0oJpdEqVlO58NIo6yVCBbU3VgI3NadyrmuLOLdM0crbiimttdgmn1e9t7G_GzBl14b08hV02A_JGVEJbZX9L2RGKy6sGOHeCvrYpxRx4W5jaCE-OUbdy95us_doP65Lh7rF-UauBx7zT-sckodmEaHzIW0YF1oyS0dWrlhIGR83McQ_ThthlLu6nDl68Wt6I0-_u9nod1cefHLLfojdOPE_3vsL7i2imA</recordid><startdate>19980813</startdate><enddate>19980813</enddate><creator>Bourlot, Anne-Sophie</creator><creator>Sánchez, Isabel</creator><creator>Dureng, Georges</creator><creator>Guillaumet, Gérald</creator><creator>Massingham, Roy</creator><creator>Monteil, André</creator><creator>Winslow, Eileen</creator><creator>Pujol, M. Dolors</creator><creator>Mérour, Jean-Yves</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>7QP</scope><scope>7X8</scope></search><sort><creationdate>19980813</creationdate><title>New Substituted 1,4-Benzoxazine Derivatives with Potential Intracellular Calcium Activity</title><author>Bourlot, Anne-Sophie ; Sánchez, Isabel ; Dureng, Georges ; Guillaumet, Gérald ; Massingham, Roy ; Monteil, André ; Winslow, Eileen ; Pujol, M. Dolors ; Mérour, Jean-Yves</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a408t-4768bbca55356e951b04fc4759c4ea8abc794a27b204d6b9eed91508c98156663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>1,4-Benzoxazine</topic><topic>Animals</topic><topic>Aorta - drug effects</topic><topic>Aorta - physiology</topic><topic>Biological and medical sciences</topic><topic>Calcium - metabolism</topic><topic>Calcium Channel Blockers - chemical synthesis</topic><topic>Calcium Channel Blockers - chemistry</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Cardiovascular system</topic><topic>Drug Design</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Molecular Structure</topic><topic>Muscle Contraction - drug effects</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Muscle, Smooth, Vascular - physiology</topic><topic>Oxazines - chemical synthesis</topic><topic>Oxazines - chemistry</topic><topic>Oxazines - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenylephrine - pharmacology</topic><topic>Rabbits</topic><topic>Renal Artery - drug effects</topic><topic>Renal Artery - physiology</topic><topic>Second Messenger Systems</topic><topic>Structure-Activity Relationship</topic><topic>Vasoconstriction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bourlot, Anne-Sophie</creatorcontrib><creatorcontrib>Sánchez, Isabel</creatorcontrib><creatorcontrib>Dureng, Georges</creatorcontrib><creatorcontrib>Guillaumet, Gérald</creatorcontrib><creatorcontrib>Massingham, Roy</creatorcontrib><creatorcontrib>Monteil, André</creatorcontrib><creatorcontrib>Winslow, Eileen</creatorcontrib><creatorcontrib>Pujol, M. Dolors</creatorcontrib><creatorcontrib>Mérour, Jean-Yves</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>Calcium & Calcified Tissue Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bourlot, Anne-Sophie</au><au>Sánchez, Isabel</au><au>Dureng, Georges</au><au>Guillaumet, Gérald</au><au>Massingham, Roy</au><au>Monteil, André</au><au>Winslow, Eileen</au><au>Pujol, M. Dolors</au><au>Mérour, Jean-Yves</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>New Substituted 1,4-Benzoxazine Derivatives with Potential Intracellular Calcium Activity</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1998-08-13</date><risdate>1998</risdate><volume>41</volume><issue>17</issue><spage>3142</spage><epage>3158</epage><pages>3142-3158</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>Substituted 1,4-benzoxazines bearing an amino side chain at the 2-position were prepared and were found to have a moderate activity on intracellular calcium. Of the compounds studied it was found that those which possess a homoveratrylamino moiety exhibited superior potency. The chain length and the nature of the amine (4-fluorophenylpiperazine, 4-fluorobenzhydryloxyethylamine, N-substituted homoveratrylamine) is discussed. The 4-benzyl-3,4-dihydro-2-[3-[[2-(3,4-dimethoxyphenyl)ethyl]amino]propyl]-2H-1,4-benzoxazine (3c) is the most potent derivative of the series with a ratio of IC50 values against PE (phenylephrine) and K+ of 2.1. Under these test conditions a ratio near 1 indicates potential intracellular calcium activity while a ratio greater than 100 an action on extracellular calcium influx.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>9703461</pmid><doi>10.1021/jm970795t</doi><tpages>17</tpages></addata></record> |
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| ispartof | Journal of medicinal chemistry, 1998-08, Vol.41 (17), p.3142-3158 |
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| source | MEDLINE; ACS Publications |
| subjects | 1,4-Benzoxazine Animals Aorta - drug effects Aorta - physiology Biological and medical sciences Calcium - metabolism Calcium Channel Blockers - chemical synthesis Calcium Channel Blockers - chemistry Calcium Channel Blockers - pharmacology Cardiovascular system Drug Design In Vitro Techniques Male Medical sciences Miscellaneous Molecular Structure Muscle Contraction - drug effects Muscle, Smooth, Vascular - drug effects Muscle, Smooth, Vascular - physiology Oxazines - chemical synthesis Oxazines - chemistry Oxazines - pharmacology Pharmacology. Drug treatments Phenylephrine - pharmacology Rabbits Renal Artery - drug effects Renal Artery - physiology Second Messenger Systems Structure-Activity Relationship Vasoconstriction - drug effects |
| title | New Substituted 1,4-Benzoxazine Derivatives with Potential Intracellular Calcium Activity |
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