Chromone 3-phenylcarboxamides as potent and selective MAO-B inhibitors
The present project has been focused on the discovery of new chemical entities (NCEs) for MAO inhibition, based on the development of chromone carboxamides. The chromone-3-carboxamides show high selectivity to MAO-B, with compounds 9 and 12 displaying IC 50 values in nanomolar range. Monoamine oxida...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2011-01, Vol.21 (2), p.707-709 |
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| creator | Gaspar, Alexandra Reis, Joana Fonseca, André Milhazes, Nuno Viña, Dolores Uriarte, Eugenio Borges, Fernanda |
| description | The present project has been focused on the discovery of new chemical entities (NCEs) for MAO inhibition, based on the development of chromone carboxamides. The chromone-3-carboxamides show high selectivity to MAO-B, with compounds
9 and
12 displaying IC
50 values in nanomolar range.
Monoamine oxidase (MAO) is an enzyme, present in mammals in two isoforms MAO-A and MAO-B. These isoforms have a crucial role in neurotransmitters metabolism, representing an attractive drug target in the therapy of neurodegenerative diseases (MAO-B) and depression (MAO-A). In this context, our work has been focused on the discovery of new chemical entities (NCEs) for MAO inhibition, based on the development of chromone carboxamides. Chromone derivatives with a carboxamide function located in position 2- and 3- of the benzo-γ-pyrone core, (compounds
2–
6 and
8–
12) were synthesized, with moderate/good yields, by a one-pot condensation reaction using phosphonium salts as coupling reagents. The synthetic compounds were screened towards human MAO isoforms (
hMAO) to evaluate their potency and selectivity. The chromone-3-carboxamides show high selectivity to
hMAO-B, with compounds
9 and
12 displaying IC
50 values at nanomolar range. |
| doi_str_mv | 10.1016/j.bmcl.2010.11.128 |
| format | Article |
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9 and
12 displaying IC
50 values in nanomolar range.
Monoamine oxidase (MAO) is an enzyme, present in mammals in two isoforms MAO-A and MAO-B. These isoforms have a crucial role in neurotransmitters metabolism, representing an attractive drug target in the therapy of neurodegenerative diseases (MAO-B) and depression (MAO-A). In this context, our work has been focused on the discovery of new chemical entities (NCEs) for MAO inhibition, based on the development of chromone carboxamides. Chromone derivatives with a carboxamide function located in position 2- and 3- of the benzo-γ-pyrone core, (compounds
2–
6 and
8–
12) were synthesized, with moderate/good yields, by a one-pot condensation reaction using phosphonium salts as coupling reagents. The synthetic compounds were screened towards human MAO isoforms (
hMAO) to evaluate their potency and selectivity. The chromone-3-carboxamides show high selectivity to
hMAO-B, with compounds
9 and
12 displaying IC
50 values at nanomolar range.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2010.11.128</identifier><identifier>PMID: 21194943</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>amine oxidase (flavin-containing) ; Animals ; Cell Line ; Chromone ; Chromones - chemistry ; Chromones - pharmacology ; condensation ; drugs ; Humans ; IMAO-B ; Inhibitory Concentration 50 ; metabolism ; Models, Molecular ; Monoamine Oxidase - metabolism ; Monoamine Oxidase Inhibitors - chemistry ; Monoamine Oxidase Inhibitors - pharmacology ; Neurodegenerative diseases ; Neurodegenerative Diseases - drug therapy ; Neurodegenerative Diseases - enzymology ; neurotransmitters ; Protein Isoforms - antagonists & inhibitors ; Protein Isoforms - metabolism ; salts ; Structure-Activity Relationship ; therapeutics</subject><ispartof>Bioorganic & medicinal chemistry letters, 2011-01, Vol.21 (2), p.707-709</ispartof><rights>2010</rights><rights>Copyright © 2010. Published by Elsevier Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c411t-44f81b63e4f4da5d489141ff19cc0e24e23bc03cede4cdeba63044378f4d490b3</citedby><cites>FETCH-LOGICAL-c411t-44f81b63e4f4da5d489141ff19cc0e24e23bc03cede4cdeba63044378f4d490b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X10017531$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21194943$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gaspar, Alexandra</creatorcontrib><creatorcontrib>Reis, Joana</creatorcontrib><creatorcontrib>Fonseca, André</creatorcontrib><creatorcontrib>Milhazes, Nuno</creatorcontrib><creatorcontrib>Viña, Dolores</creatorcontrib><creatorcontrib>Uriarte, Eugenio</creatorcontrib><creatorcontrib>Borges, Fernanda</creatorcontrib><title>Chromone 3-phenylcarboxamides as potent and selective MAO-B inhibitors</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>The present project has been focused on the discovery of new chemical entities (NCEs) for MAO inhibition, based on the development of chromone carboxamides. The chromone-3-carboxamides show high selectivity to MAO-B, with compounds
9 and
12 displaying IC
50 values in nanomolar range.
Monoamine oxidase (MAO) is an enzyme, present in mammals in two isoforms MAO-A and MAO-B. These isoforms have a crucial role in neurotransmitters metabolism, representing an attractive drug target in the therapy of neurodegenerative diseases (MAO-B) and depression (MAO-A). In this context, our work has been focused on the discovery of new chemical entities (NCEs) for MAO inhibition, based on the development of chromone carboxamides. Chromone derivatives with a carboxamide function located in position 2- and 3- of the benzo-γ-pyrone core, (compounds
2–
6 and
8–
12) were synthesized, with moderate/good yields, by a one-pot condensation reaction using phosphonium salts as coupling reagents. The synthetic compounds were screened towards human MAO isoforms (
hMAO) to evaluate their potency and selectivity. The chromone-3-carboxamides show high selectivity to
hMAO-B, with compounds
9 and
12 displaying IC
50 values at nanomolar range.</description><subject>amine oxidase (flavin-containing)</subject><subject>Animals</subject><subject>Cell Line</subject><subject>Chromone</subject><subject>Chromones - chemistry</subject><subject>Chromones - pharmacology</subject><subject>condensation</subject><subject>drugs</subject><subject>Humans</subject><subject>IMAO-B</subject><subject>Inhibitory Concentration 50</subject><subject>metabolism</subject><subject>Models, Molecular</subject><subject>Monoamine Oxidase - metabolism</subject><subject>Monoamine Oxidase Inhibitors - chemistry</subject><subject>Monoamine Oxidase Inhibitors - pharmacology</subject><subject>Neurodegenerative diseases</subject><subject>Neurodegenerative Diseases - drug therapy</subject><subject>Neurodegenerative Diseases - enzymology</subject><subject>neurotransmitters</subject><subject>Protein Isoforms - antagonists & inhibitors</subject><subject>Protein Isoforms - metabolism</subject><subject>salts</subject><subject>Structure-Activity Relationship</subject><subject>therapeutics</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkT1PwzAQhi0EoqXwBxggG1OKL76micQCFV8SiAGQ2CzHuVBXSVzsFNF_j6sURphOsp731d1jxo6Bj4FDer4YF42uxwnfPMAYkmyHDQFTjAXyyS4b8jzlcZbj24AdeL_gHJAj7rNBApBjjmLIbmZzZxvbUiTi5Zzada2VK-yXakxJPlI-WtqO2i5SbRl5qkl35pOix8un-Coy7dwUprPOH7K9StWejrZzxF5vrl9md_HD0-397PIh1gjQxYhVBkUqCCss1aTELAeEqoJca04JUiIKzYWmklCXVKhUhIXFNAs45rwQI3bW9y6d_ViR72RjvKa6Vi3ZlZdZJjiEDP-fFFOcYHAWyKQntbPeO6rk0plGubUELjei5UJuRMuNaAkg-9DJtn5VNFT-Rn7MBuC0ByplpXp3xsvX59AwCb8gUPBpIC56goKwT0NOem2oDccbFzTL0pq_NvgGr0OXTw</recordid><startdate>20110115</startdate><enddate>20110115</enddate><creator>Gaspar, Alexandra</creator><creator>Reis, Joana</creator><creator>Fonseca, André</creator><creator>Milhazes, Nuno</creator><creator>Viña, Dolores</creator><creator>Uriarte, Eugenio</creator><creator>Borges, Fernanda</creator><general>Elsevier Ltd</general><scope>FBQ</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><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20110115</creationdate><title>Chromone 3-phenylcarboxamides as potent and selective MAO-B inhibitors</title><author>Gaspar, Alexandra ; Reis, Joana ; Fonseca, André ; Milhazes, Nuno ; Viña, Dolores ; Uriarte, Eugenio ; Borges, Fernanda</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c411t-44f81b63e4f4da5d489141ff19cc0e24e23bc03cede4cdeba63044378f4d490b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>amine oxidase (flavin-containing)</topic><topic>Animals</topic><topic>Cell Line</topic><topic>Chromone</topic><topic>Chromones - chemistry</topic><topic>Chromones - pharmacology</topic><topic>condensation</topic><topic>drugs</topic><topic>Humans</topic><topic>IMAO-B</topic><topic>Inhibitory Concentration 50</topic><topic>metabolism</topic><topic>Models, Molecular</topic><topic>Monoamine Oxidase - metabolism</topic><topic>Monoamine Oxidase Inhibitors - chemistry</topic><topic>Monoamine Oxidase Inhibitors - pharmacology</topic><topic>Neurodegenerative diseases</topic><topic>Neurodegenerative Diseases - drug therapy</topic><topic>Neurodegenerative Diseases - enzymology</topic><topic>neurotransmitters</topic><topic>Protein Isoforms - antagonists & inhibitors</topic><topic>Protein Isoforms - metabolism</topic><topic>salts</topic><topic>Structure-Activity Relationship</topic><topic>therapeutics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gaspar, Alexandra</creatorcontrib><creatorcontrib>Reis, Joana</creatorcontrib><creatorcontrib>Fonseca, André</creatorcontrib><creatorcontrib>Milhazes, Nuno</creatorcontrib><creatorcontrib>Viña, Dolores</creatorcontrib><creatorcontrib>Uriarte, Eugenio</creatorcontrib><creatorcontrib>Borges, Fernanda</creatorcontrib><collection>AGRIS</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><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gaspar, Alexandra</au><au>Reis, Joana</au><au>Fonseca, André</au><au>Milhazes, Nuno</au><au>Viña, Dolores</au><au>Uriarte, Eugenio</au><au>Borges, Fernanda</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chromone 3-phenylcarboxamides as potent and selective MAO-B inhibitors</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2011-01-15</date><risdate>2011</risdate><volume>21</volume><issue>2</issue><spage>707</spage><epage>709</epage><pages>707-709</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>The present project has been focused on the discovery of new chemical entities (NCEs) for MAO inhibition, based on the development of chromone carboxamides. The chromone-3-carboxamides show high selectivity to MAO-B, with compounds
9 and
12 displaying IC
50 values in nanomolar range.
Monoamine oxidase (MAO) is an enzyme, present in mammals in two isoforms MAO-A and MAO-B. These isoforms have a crucial role in neurotransmitters metabolism, representing an attractive drug target in the therapy of neurodegenerative diseases (MAO-B) and depression (MAO-A). In this context, our work has been focused on the discovery of new chemical entities (NCEs) for MAO inhibition, based on the development of chromone carboxamides. Chromone derivatives with a carboxamide function located in position 2- and 3- of the benzo-γ-pyrone core, (compounds
2–
6 and
8–
12) were synthesized, with moderate/good yields, by a one-pot condensation reaction using phosphonium salts as coupling reagents. The synthetic compounds were screened towards human MAO isoforms (
hMAO) to evaluate their potency and selectivity. The chromone-3-carboxamides show high selectivity to
hMAO-B, with compounds
9 and
12 displaying IC
50 values at nanomolar range.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>21194943</pmid><doi>10.1016/j.bmcl.2010.11.128</doi><tpages>3</tpages></addata></record> |
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| ispartof | Bioorganic & medicinal chemistry letters, 2011-01, Vol.21 (2), p.707-709 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | amine oxidase (flavin-containing) Animals Cell Line Chromone Chromones - chemistry Chromones - pharmacology condensation drugs Humans IMAO-B Inhibitory Concentration 50 metabolism Models, Molecular Monoamine Oxidase - metabolism Monoamine Oxidase Inhibitors - chemistry Monoamine Oxidase Inhibitors - pharmacology Neurodegenerative diseases Neurodegenerative Diseases - drug therapy Neurodegenerative Diseases - enzymology neurotransmitters Protein Isoforms - antagonists & inhibitors Protein Isoforms - metabolism salts Structure-Activity Relationship therapeutics |
| title | Chromone 3-phenylcarboxamides as potent and selective MAO-B inhibitors |
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