A novel series of highly selective inhibitors of MMP-3
The design and synthesis of a series of highly selective hydroxamate inhibitors of MMP-3 is described. Substitution of a 4-biaryl piperidine sulfonamide core was optimised to give potent inhibitors of MMP-3, with greater than 300-fold selectivity over MMP-1, MMP-2, MMP-9 and MMP-14. The design and s...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2007-12, Vol.17 (24), p.6750-6753 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Whitlock, Gavin A. Dack, Kevin N. Dickinson, Roger P. Lewis, Mark L. |
| description | The design and synthesis of a series of highly selective hydroxamate inhibitors of MMP-3 is described. Substitution of a 4-biaryl piperidine sulfonamide core was optimised to give potent inhibitors of MMP-3, with greater than 300-fold selectivity over MMP-1, MMP-2, MMP-9 and MMP-14.
The design and synthesis of a series of highly selective hydroxamate inhibitors of stromelysin-1 (MMP-3) is described. Substitution of a 4-biaryl piperidine sulfonamide core, which binds at the S1′ subsite of MMP-3, was optimised to give potent inhibitors of MMP-3, with greater than 300-fold selectivity over MMP-1, MMP-2, MMP-9 and MMP-14. Compounds
26 and
27 were identified as having the best balance of pharmacology and properties required for topical drug delivery. |
| doi_str_mv | 10.1016/j.bmcl.2007.10.042 |
| format | Article |
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The design and synthesis of a series of highly selective hydroxamate inhibitors of stromelysin-1 (MMP-3) is described. Substitution of a 4-biaryl piperidine sulfonamide core, which binds at the S1′ subsite of MMP-3, was optimised to give potent inhibitors of MMP-3, with greater than 300-fold selectivity over MMP-1, MMP-2, MMP-9 and MMP-14. Compounds
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The design and synthesis of a series of highly selective hydroxamate inhibitors of stromelysin-1 (MMP-3) is described. Substitution of a 4-biaryl piperidine sulfonamide core, which binds at the S1′ subsite of MMP-3, was optimised to give potent inhibitors of MMP-3, with greater than 300-fold selectivity over MMP-1, MMP-2, MMP-9 and MMP-14. Compounds
26 and
27 were identified as having the best balance of pharmacology and properties required for topical drug delivery.</description><subject>Amino Acids - chemistry</subject><subject>Biological and medical sciences</subject><subject>Combinatorial Chemistry Techniques</subject><subject>Drug Delivery Systems</subject><subject>Hydroxamic Acids - chemical synthesis</subject><subject>Hydroxamic Acids - chemistry</subject><subject>Hydroxamic Acids - pharmacology</subject><subject>Matrix Metalloproteinase Inhibitors</subject><subject>Medical sciences</subject><subject>MMP-3</subject><subject>Models, Molecular</subject><subject>Molecular Structure</subject><subject>Pharmacology. Drug treatments</subject><subject>Protease Inhibitors - chemical synthesis</subject><subject>Protease Inhibitors - chemistry</subject><subject>Protease Inhibitors - pharmacology</subject><subject>Selectivity</subject><subject>Skin, nail, hair, dermoskeleton</subject><subject>Stromelysin</subject><subject>Structure-Activity Relationship</subject><subject>Sulfonamides - chemical synthesis</subject><subject>Sulfonamides - chemistry</subject><subject>Sulfonamides - pharmacology</subject><subject>Topical delivery</subject><subject>Wound healing</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkD1PwzAQhi0EoqXwBxhQFthSzo5jxxILqviSWsHQgc1ynAt1lSbFbiv13-PSSt1gOum95z70EHJNYUiBivv5sFzYZsgAZAyGwNkJ6VMueJpxyE9JH5SAtFD8s0cuQpgDUA6cn5MeLYApKmWfiMek7TbYJAG9w5B0dTJzX7NmG4MG7cptMHHtzJVu1fnf9mTykWaX5Kw2TcCrQx2Q6fPTdPSajt9f3kaP49Rymq9SmVWM1SU1VlJhK05LKU1hayiKyooccqXKjDMsa8o4U7WQRrJcghUFGkuzAbnbr1367nuNYaUXLlhsGtNitw5aAhSCqexfkKosnpNFBNketL4LwWOtl94tjN9qCnpnVc_1zqreWd1l0WocujlsX5cLrI4jB40RuD0AJljT1N601oUjp4QCIVTkHvYcRmcbh14H67C1WDkfZeuqc3_98QOVwJND</recordid><startdate>20071215</startdate><enddate>20071215</enddate><creator>Whitlock, Gavin A.</creator><creator>Dack, Kevin N.</creator><creator>Dickinson, Roger P.</creator><creator>Lewis, Mark L.</creator><general>Elsevier Ltd</general><general>Elsevier</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20071215</creationdate><title>A novel series of highly selective inhibitors of MMP-3</title><author>Whitlock, Gavin A. ; Dack, Kevin N. ; Dickinson, Roger P. ; Lewis, Mark L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-73d22fb1ac716cd41b77a8cf088dc650599b342ebf12429f67a72570c68eac13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Amino Acids - chemistry</topic><topic>Biological and medical sciences</topic><topic>Combinatorial Chemistry Techniques</topic><topic>Drug Delivery Systems</topic><topic>Hydroxamic Acids - chemical synthesis</topic><topic>Hydroxamic Acids - chemistry</topic><topic>Hydroxamic Acids - pharmacology</topic><topic>Matrix Metalloproteinase Inhibitors</topic><topic>Medical sciences</topic><topic>MMP-3</topic><topic>Models, Molecular</topic><topic>Molecular Structure</topic><topic>Pharmacology. Drug treatments</topic><topic>Protease Inhibitors - chemical synthesis</topic><topic>Protease Inhibitors - chemistry</topic><topic>Protease Inhibitors - pharmacology</topic><topic>Selectivity</topic><topic>Skin, nail, hair, dermoskeleton</topic><topic>Stromelysin</topic><topic>Structure-Activity Relationship</topic><topic>Sulfonamides - chemical synthesis</topic><topic>Sulfonamides - chemistry</topic><topic>Sulfonamides - pharmacology</topic><topic>Topical delivery</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Whitlock, Gavin A.</creatorcontrib><creatorcontrib>Dack, Kevin N.</creatorcontrib><creatorcontrib>Dickinson, Roger P.</creatorcontrib><creatorcontrib>Lewis, Mark L.</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>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Whitlock, Gavin A.</au><au>Dack, Kevin N.</au><au>Dickinson, Roger P.</au><au>Lewis, Mark L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel series of highly selective inhibitors of MMP-3</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2007-12-15</date><risdate>2007</risdate><volume>17</volume><issue>24</issue><spage>6750</spage><epage>6753</epage><pages>6750-6753</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>The design and synthesis of a series of highly selective hydroxamate inhibitors of MMP-3 is described. Substitution of a 4-biaryl piperidine sulfonamide core was optimised to give potent inhibitors of MMP-3, with greater than 300-fold selectivity over MMP-1, MMP-2, MMP-9 and MMP-14.
The design and synthesis of a series of highly selective hydroxamate inhibitors of stromelysin-1 (MMP-3) is described. Substitution of a 4-biaryl piperidine sulfonamide core, which binds at the S1′ subsite of MMP-3, was optimised to give potent inhibitors of MMP-3, with greater than 300-fold selectivity over MMP-1, MMP-2, MMP-9 and MMP-14. Compounds
26 and
27 were identified as having the best balance of pharmacology and properties required for topical drug delivery.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>18029177</pmid><doi>10.1016/j.bmcl.2007.10.042</doi><tpages>4</tpages></addata></record> |
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| subjects | Amino Acids - chemistry Biological and medical sciences Combinatorial Chemistry Techniques Drug Delivery Systems Hydroxamic Acids - chemical synthesis Hydroxamic Acids - chemistry Hydroxamic Acids - pharmacology Matrix Metalloproteinase Inhibitors Medical sciences MMP-3 Models, Molecular Molecular Structure Pharmacology. Drug treatments Protease Inhibitors - chemical synthesis Protease Inhibitors - chemistry Protease Inhibitors - pharmacology Selectivity Skin, nail, hair, dermoskeleton Stromelysin Structure-Activity Relationship Sulfonamides - chemical synthesis Sulfonamides - chemistry Sulfonamides - pharmacology Topical delivery Wound healing |
| title | A novel series of highly selective inhibitors of MMP-3 |
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