Hydroxamates: Relationships between Structure and Plasma Stability
Hydroxamates are valuable tools for chemical biology as well as interesting leads for medicinal chemistry. Although many hydroxamates display nanomolar activities against metalloproteases, only three hydroxamates have reached the market, among which is the HDAC inhibitor vorinostat. Failures in deve...
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| Veröffentlicht in: | Journal of medicinal chemistry 2009-11, Vol.52 (21), p.6790-6802 |
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| container_end_page | 6802 |
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| container_issue | 21 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 52 |
| creator | Flipo, Marion Charton, Julie Hocine, Akila Dassonneville, Sandrine Deprez, Benoit Deprez-Poulain, Rebecca |
| description | Hydroxamates are valuable tools for chemical biology as well as interesting leads for medicinal chemistry. Although many hydroxamates display nanomolar activities against metalloproteases, only three hydroxamates have reached the market, among which is the HDAC inhibitor vorinostat. Failures in development are generally attributed to lack of selectivity, toxicity, or poor stability. To help medicinal chemists with respect to plasma stability, we have performed the first and preliminary study on structure−plasma stability for hydroxamates. We define some structural rules to predict or improve the plasma stability in the preclinical stage. |
| doi_str_mv | 10.1021/jm900648x |
| format | Article |
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Although many hydroxamates display nanomolar activities against metalloproteases, only three hydroxamates have reached the market, among which is the HDAC inhibitor vorinostat. Failures in development are generally attributed to lack of selectivity, toxicity, or poor stability. To help medicinal chemists with respect to plasma stability, we have performed the first and preliminary study on structure−plasma stability for hydroxamates. 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Med. Chem</addtitle><description>Hydroxamates are valuable tools for chemical biology as well as interesting leads for medicinal chemistry. Although many hydroxamates display nanomolar activities against metalloproteases, only three hydroxamates have reached the market, among which is the HDAC inhibitor vorinostat. Failures in development are generally attributed to lack of selectivity, toxicity, or poor stability. To help medicinal chemists with respect to plasma stability, we have performed the first and preliminary study on structure−plasma stability for hydroxamates. 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Drug treatments</subject><subject>Plasma</subject><subject>Prodrugs - chemical synthesis</subject><subject>Prodrugs - chemistry</subject><subject>Prodrugs - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Stereoisomerism</subject><subject>Structure-Activity Relationship</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0E1Lw0AQBuBFFFurB_-A5OLBQ3RmN5tsvNWiVigo2nuYbDY0JR9lN9H235vS0nrwNPDyzAy8jF0j3CNwfFhWMUAYqPUJG6Lk4AcKglM2BODc5yEXA3bh3BIABHJxzgYYK45ShUP2NN1ktllTRa1xj96nKaktmtotipXzUtP-GFN7X63tdNtZ41GdeR8luYr6kNKiLNrNJTvLqXTmaj9HbP7yPJ9M_dn769tkPPMpQNH6kYwyMrlELZWIM6Mp5HEuTBqhDCCXRmAudJZKJbXQaWyyABQIlWNopEExYne7swsqk5UtKrKbpKEimY5nyTYDARKjOP7-Y7VtnLMmPywgJNvKkkNlvb3Z2VWXViY7yn1HPbjdA3KaytxSrQt3cJwjKB7IoyPtkmXT2bpv45-Hvw9FfzQ</recordid><startdate>20091112</startdate><enddate>20091112</enddate><creator>Flipo, Marion</creator><creator>Charton, Julie</creator><creator>Hocine, Akila</creator><creator>Dassonneville, Sandrine</creator><creator>Deprez, Benoit</creator><creator>Deprez-Poulain, Rebecca</creator><general>American Chemical Society</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>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0003-2863-5721</orcidid><orcidid>https://orcid.org/0000-0002-2777-4538</orcidid><orcidid>https://orcid.org/0000-0002-3318-5297</orcidid></search><sort><creationdate>20091112</creationdate><title>Hydroxamates: Relationships between Structure and Plasma Stability</title><author>Flipo, Marion ; Charton, Julie ; Hocine, Akila ; Dassonneville, Sandrine ; Deprez, Benoit ; Deprez-Poulain, Rebecca</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a413t-757daef51c5839deca629f3eb71540f5e31f3cdb585c3cb9ed408038f16e5e13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Drug Evaluation, Preclinical</topic><topic>Drug Stability</topic><topic>Esterases - blood</topic><topic>Half-Life</topic><topic>Humans</topic><topic>Hydrolysis</topic><topic>Hydrophobic and Hydrophilic Interactions</topic><topic>Hydroxamic Acids - blood</topic><topic>Hydroxamic Acids - chemical synthesis</topic><topic>Hydroxamic Acids - chemistry</topic><topic>Life Sciences</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Pharmaceutical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Plasma</topic><topic>Prodrugs - chemical synthesis</topic><topic>Prodrugs - chemistry</topic><topic>Prodrugs - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Stereoisomerism</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Flipo, Marion</creatorcontrib><creatorcontrib>Charton, Julie</creatorcontrib><creatorcontrib>Hocine, Akila</creatorcontrib><creatorcontrib>Dassonneville, Sandrine</creatorcontrib><creatorcontrib>Deprez, Benoit</creatorcontrib><creatorcontrib>Deprez-Poulain, Rebecca</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>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Flipo, Marion</au><au>Charton, Julie</au><au>Hocine, Akila</au><au>Dassonneville, Sandrine</au><au>Deprez, Benoit</au><au>Deprez-Poulain, Rebecca</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hydroxamates: Relationships between Structure and Plasma Stability</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. 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| fulltext | fulltext |
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| ispartof | Journal of medicinal chemistry, 2009-11, Vol.52 (21), p.6790-6802 |
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| language | eng |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Animals Biological and medical sciences Drug Evaluation, Preclinical Drug Stability Esterases - blood Half-Life Humans Hydrolysis Hydrophobic and Hydrophilic Interactions Hydroxamic Acids - blood Hydroxamic Acids - chemical synthesis Hydroxamic Acids - chemistry Life Sciences Medical sciences Miscellaneous Pharmaceutical sciences Pharmacology. Drug treatments Plasma Prodrugs - chemical synthesis Prodrugs - chemistry Prodrugs - metabolism Rats Rats, Sprague-Dawley Stereoisomerism Structure-Activity Relationship |
| title | Hydroxamates: Relationships between Structure and Plasma Stability |
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