11 beta-amidoalkyl estradiols, a new series of pure antiestrogens
In order to find new antiestrogens, devoid of any agonistic activity, a series of 11 beta-amidoalkyl estradiols were prepared. These compounds have been studied in comparison with tamoxifen (TAM): in vitro, for their relative binding affinities (RBA) for mouse and MCF-7 estrogen receptors (ER) and f...
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| Veröffentlicht in: | The Journal of steroid biochemistry and molecular biology 1992-03, Vol.41 (3-8), p.609-614 |
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| container_issue | 3-8 |
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| container_title | The Journal of steroid biochemistry and molecular biology |
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| creator | Claussner, A Nédélec, L Nique, F Philibert, D Teutsch, G Van de Velde, P |
| description | In order to find new antiestrogens, devoid of any agonistic activity, a series of 11 beta-amidoalkyl estradiols were prepared. These compounds have been studied in comparison with tamoxifen (TAM): in vitro, for their relative binding affinities (RBA) for mouse and MCF-7 estrogen receptors (ER) and for their antiproliferative effect on MCF-7 (estradiol or EGF/PDGF stimulated) and Ly2 human breast cancer cell lines; in vivo, for their uterotrophic/antiuterotrophic activities in the mouse and for their antitumoral activities on MCF-7 tumors implanted in nude mice. The most representative compounds are N-methyl-N-isopropyl-(3,17 beta-dihydroxy-estra-1,3,5(10)-trien-11 beta-yl)- undecanamide (RU 51625) and its 17 alpha-ethynyl derivative (RU 53637). They showed good RBAs for ER and a stronger antiproliferative effect than TAM in vitro. Unlike TAM, these compounds inhibited growth factor stimulated MCF-7 proliferation, and the growth of the TAM resistant cell line Ly2. In vivo, they were completely devoid of uterotrophic activity, when given subcutaneously in mice, but exhibited a slight agonistic effect when administered orally. They showed interesting antitumor activities in nude mice by the percutaneous route, but RU 53637 was significantly more potent than RU 51625 when given orally. |
| doi_str_mv | 10.1016/0960-0760(92)90392-V |
| format | Article |
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These compounds have been studied in comparison with tamoxifen (TAM): in vitro, for their relative binding affinities (RBA) for mouse and MCF-7 estrogen receptors (ER) and for their antiproliferative effect on MCF-7 (estradiol or EGF/PDGF stimulated) and Ly2 human breast cancer cell lines; in vivo, for their uterotrophic/antiuterotrophic activities in the mouse and for their antitumoral activities on MCF-7 tumors implanted in nude mice. The most representative compounds are N-methyl-N-isopropyl-(3,17 beta-dihydroxy-estra-1,3,5(10)-trien-11 beta-yl)- undecanamide (RU 51625) and its 17 alpha-ethynyl derivative (RU 53637). They showed good RBAs for ER and a stronger antiproliferative effect than TAM in vitro. Unlike TAM, these compounds inhibited growth factor stimulated MCF-7 proliferation, and the growth of the TAM resistant cell line Ly2. 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They showed interesting antitumor activities in nude mice by the percutaneous route, but RU 53637 was significantly more potent than RU 51625 when given orally.</description><subject>Alkylation</subject><subject>Amides</subject><subject>Animals</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Cell Division - drug effects</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Estradiol - analogs & derivatives</subject><subject>Estrogen Antagonists - chemical synthesis</subject><subject>Estrogen Antagonists - pharmacology</subject><subject>Estrogen Antagonists - therapeutic use</subject><subject>Female</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Molecular Structure</subject><subject>Neoplasm Transplantation</subject><subject>Structure-Activity Relationship</subject><subject>Transplantation, Heterologous</subject><subject>Uterus - drug effects</subject><subject>Uterus - physiology</subject><issn>0960-0760</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9j0tLxDAUhbNQxnH0HyhkJQpW82geXQ6DLxhwo27LTXIr1bapTYvMv3fE4urA4eM7HELOOLvhjOtbVmiWMaPZZSGuCiYLkb0dkOV_fUSOU_pgjEnJzYIsuNJCSb4ka86pwxEyaOsQofncNRTTOECoY5OuKdAOv2nCocZEY0X7aUAK3Vj_QvEdu3RCDitoEp7OuSKv93cvm8ds-_zwtFlvs55LO2Y6DxCsFMxxVEEpVA6U0dya4LyyXkkvKigsCIO5VdoVnpvcGbDKW4NersjFn7cf4te0ny_bOnlsGugwTqk0wlrDcrMHz2dwci2Gsh_qFoZdOX-WP5VeVwA</recordid><startdate>199203</startdate><enddate>199203</enddate><creator>Claussner, A</creator><creator>Nédélec, L</creator><creator>Nique, F</creator><creator>Philibert, D</creator><creator>Teutsch, G</creator><creator>Van de Velde, P</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>199203</creationdate><title>11 beta-amidoalkyl estradiols, a new series of pure antiestrogens</title><author>Claussner, A ; Nédélec, L ; Nique, F ; Philibert, D ; Teutsch, G ; Van de Velde, P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p138t-64dad8320b1e5d55e5ba576187dbc58c53c2fa98a27e4856b9c174b7a85c87ec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Alkylation</topic><topic>Amides</topic><topic>Animals</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Cell Division - drug effects</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Estradiol - analogs & derivatives</topic><topic>Estrogen Antagonists - chemical synthesis</topic><topic>Estrogen Antagonists - pharmacology</topic><topic>Estrogen Antagonists - therapeutic use</topic><topic>Female</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Molecular Structure</topic><topic>Neoplasm Transplantation</topic><topic>Structure-Activity Relationship</topic><topic>Transplantation, Heterologous</topic><topic>Uterus - drug effects</topic><topic>Uterus - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Claussner, A</creatorcontrib><creatorcontrib>Nédélec, L</creatorcontrib><creatorcontrib>Nique, F</creatorcontrib><creatorcontrib>Philibert, D</creatorcontrib><creatorcontrib>Teutsch, G</creatorcontrib><creatorcontrib>Van de Velde, P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of steroid biochemistry and molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Claussner, A</au><au>Nédélec, L</au><au>Nique, F</au><au>Philibert, D</au><au>Teutsch, G</au><au>Van de Velde, P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>11 beta-amidoalkyl estradiols, a new series of pure antiestrogens</atitle><jtitle>The Journal of steroid biochemistry and molecular biology</jtitle><addtitle>J Steroid Biochem Mol Biol</addtitle><date>1992-03</date><risdate>1992</risdate><volume>41</volume><issue>3-8</issue><spage>609</spage><epage>614</epage><pages>609-614</pages><issn>0960-0760</issn><abstract>In order to find new antiestrogens, devoid of any agonistic activity, a series of 11 beta-amidoalkyl estradiols were prepared. These compounds have been studied in comparison with tamoxifen (TAM): in vitro, for their relative binding affinities (RBA) for mouse and MCF-7 estrogen receptors (ER) and for their antiproliferative effect on MCF-7 (estradiol or EGF/PDGF stimulated) and Ly2 human breast cancer cell lines; in vivo, for their uterotrophic/antiuterotrophic activities in the mouse and for their antitumoral activities on MCF-7 tumors implanted in nude mice. The most representative compounds are N-methyl-N-isopropyl-(3,17 beta-dihydroxy-estra-1,3,5(10)-trien-11 beta-yl)- undecanamide (RU 51625) and its 17 alpha-ethynyl derivative (RU 53637). They showed good RBAs for ER and a stronger antiproliferative effect than TAM in vitro. Unlike TAM, these compounds inhibited growth factor stimulated MCF-7 proliferation, and the growth of the TAM resistant cell line Ly2. In vivo, they were completely devoid of uterotrophic activity, when given subcutaneously in mice, but exhibited a slight agonistic effect when administered orally. They showed interesting antitumor activities in nude mice by the percutaneous route, but RU 53637 was significantly more potent than RU 51625 when given orally.</abstract><cop>England</cop><pmid>1562531</pmid><doi>10.1016/0960-0760(92)90392-V</doi><tpages>6</tpages></addata></record> |
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| identifier | ISSN: 0960-0760 |
| ispartof | The Journal of steroid biochemistry and molecular biology, 1992-03, Vol.41 (3-8), p.609-614 |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Alkylation Amides Animals Antineoplastic Agents - chemical synthesis Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Breast Neoplasms - drug therapy Cell Division - drug effects Drug Screening Assays, Antitumor Estradiol - analogs & derivatives Estrogen Antagonists - chemical synthesis Estrogen Antagonists - pharmacology Estrogen Antagonists - therapeutic use Female Humans Mice Mice, Nude Molecular Structure Neoplasm Transplantation Structure-Activity Relationship Transplantation, Heterologous Uterus - drug effects Uterus - physiology |
| title | 11 beta-amidoalkyl estradiols, a new series of pure antiestrogens |
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