Synthesis and evaluation of carbamate and aryl ether substituted pyrazinones as corticotropin releasing factor-1 (CRF1) receptor antagonists
[Display omitted] A series of pyrazinone-based compounds incorporating either carbamate or aryl ether groups was synthesized and evaluated as corticotropin-releasing factor-1 (CRF1) receptor antagonists. Structure–activity relationship studies led to the identification of highly potent CRF1 receptor...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2016-05, Vol.26 (9), p.2184-2187 |
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| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 26 |
| creator | Ahuja, Vijay T. Hartz, Richard A. Molski, Thaddeus F. Mattson, Gail K. Lentz, Kimberley A. Grace, James E. Lodge, Nicholas J. Bronson, Joanne J. Macor, John E. |
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A series of pyrazinone-based compounds incorporating either carbamate or aryl ether groups was synthesized and evaluated as corticotropin-releasing factor-1 (CRF1) receptor antagonists. Structure–activity relationship studies led to the identification of highly potent CRF1 receptor antagonists 14a (IC50=0.74nM) and 14b (IC50=1.9nM). The synthesis, structure–activity relationships and in vitro metabolic stability properties of compounds in this series will be described. |
| doi_str_mv | 10.1016/j.bmcl.2016.03.067 |
| format | Article |
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A series of pyrazinone-based compounds incorporating either carbamate or aryl ether groups was synthesized and evaluated as corticotropin-releasing factor-1 (CRF1) receptor antagonists. Structure–activity relationship studies led to the identification of highly potent CRF1 receptor antagonists 14a (IC50=0.74nM) and 14b (IC50=1.9nM). The synthesis, structure–activity relationships and in vitro metabolic stability properties of compounds in this series will be described.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2016.03.067</identifier><identifier>PMID: 27020524</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Carbamates - chemical synthesis ; Carbamates - metabolism ; Carbamates - pharmacology ; Cell Line, Tumor ; CRF ; CRF1 receptor antagonists ; Depression ; Humans ; Microsomes, Liver - metabolism ; Neuroscience ; Pyrazines - chemical synthesis ; Pyrazines - metabolism ; Pyrazines - pharmacology ; Pyrazinones ; Rats ; Receptors, Corticotropin-Releasing Hormone - antagonists & inhibitors ; Structure-Activity Relationship</subject><ispartof>Bioorganic & medicinal chemistry letters, 2016-05, Vol.26 (9), p.2184-2187</ispartof><rights>2016 Elsevier Ltd</rights><rights>Copyright © 2016 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-85884ab20c5cf5fff07dbc8c1545e36d23fa9746ebdbf08fe92acd5a91cece5c3</citedby><cites>FETCH-LOGICAL-c455t-85884ab20c5cf5fff07dbc8c1545e36d23fa9746ebdbf08fe92acd5a91cece5c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X16302876$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27020524$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ahuja, Vijay T.</creatorcontrib><creatorcontrib>Hartz, Richard A.</creatorcontrib><creatorcontrib>Molski, Thaddeus F.</creatorcontrib><creatorcontrib>Mattson, Gail K.</creatorcontrib><creatorcontrib>Lentz, Kimberley A.</creatorcontrib><creatorcontrib>Grace, James E.</creatorcontrib><creatorcontrib>Lodge, Nicholas J.</creatorcontrib><creatorcontrib>Bronson, Joanne J.</creatorcontrib><creatorcontrib>Macor, John E.</creatorcontrib><title>Synthesis and evaluation of carbamate and aryl ether substituted pyrazinones as corticotropin releasing factor-1 (CRF1) receptor antagonists</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
A series of pyrazinone-based compounds incorporating either carbamate or aryl ether groups was synthesized and evaluated as corticotropin-releasing factor-1 (CRF1) receptor antagonists. Structure–activity relationship studies led to the identification of highly potent CRF1 receptor antagonists 14a (IC50=0.74nM) and 14b (IC50=1.9nM). The synthesis, structure–activity relationships and in vitro metabolic stability properties of compounds in this series will be described.</description><subject>Animals</subject><subject>Carbamates - chemical synthesis</subject><subject>Carbamates - metabolism</subject><subject>Carbamates - pharmacology</subject><subject>Cell Line, Tumor</subject><subject>CRF</subject><subject>CRF1 receptor antagonists</subject><subject>Depression</subject><subject>Humans</subject><subject>Microsomes, Liver - metabolism</subject><subject>Neuroscience</subject><subject>Pyrazines - chemical synthesis</subject><subject>Pyrazines - metabolism</subject><subject>Pyrazines - pharmacology</subject><subject>Pyrazinones</subject><subject>Rats</subject><subject>Receptors, Corticotropin-Releasing Hormone - antagonists & inhibitors</subject><subject>Structure-Activity Relationship</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1rFTEUhoMo9rb6B1xIlnUx0ySTzAe4kUtrhULBD3AXMslJzWUmGZNM4fY3-KPN9VaX0lVCznOewPsi9IaSmhLaXuzqcdZTzcq9Jk1N2u4Z2lDe8qrhRDxHGzK0pOoH_v0Enaa0I4RywvlLdMI6wohgfIN-fdn7_AOSS1h5g-FeTavKLngcLNYqjmpWGf7MVNxPGAoccVrHlF1eMxi87KN6cD54KIqEdYjZ6ZBjWJzHESZQyfk7bJXOIVYUn28_X9F3ZaJhKS9FndVd8C7l9Aq9sGpK8PrxPEPfri6_bq-rm9uPn7YfbirNhchVL_qeq5ERLbQV1lrSmVH3mgouoGkNa6waOt7CaEZLegsDU9oINVBdPhW6OUPnR-8Sw88VUpazSxqmSXkIa5K0G8ggOB_YE9CeiqbtOlFQdkR1DClFsHKJbi6pSUrkoTC5k4fC5KEwSRpZCitLbx_96ziD-bfyt6ECvD8CUAK5dxBl0g68BuNKhFma4P7n_w2SzKrV</recordid><startdate>20160501</startdate><enddate>20160501</enddate><creator>Ahuja, Vijay T.</creator><creator>Hartz, Richard A.</creator><creator>Molski, Thaddeus F.</creator><creator>Mattson, Gail K.</creator><creator>Lentz, Kimberley A.</creator><creator>Grace, James E.</creator><creator>Lodge, Nicholas J.</creator><creator>Bronson, Joanne J.</creator><creator>Macor, John E.</creator><general>Elsevier Ltd</general><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>20160501</creationdate><title>Synthesis and evaluation of carbamate and aryl ether substituted pyrazinones as corticotropin releasing factor-1 (CRF1) receptor antagonists</title><author>Ahuja, Vijay T. ; Hartz, Richard A. ; Molski, Thaddeus F. ; Mattson, Gail K. ; Lentz, Kimberley A. ; Grace, James E. ; Lodge, Nicholas J. ; Bronson, Joanne J. ; Macor, John E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-85884ab20c5cf5fff07dbc8c1545e36d23fa9746ebdbf08fe92acd5a91cece5c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Carbamates - chemical synthesis</topic><topic>Carbamates - metabolism</topic><topic>Carbamates - pharmacology</topic><topic>Cell Line, Tumor</topic><topic>CRF</topic><topic>CRF1 receptor antagonists</topic><topic>Depression</topic><topic>Humans</topic><topic>Microsomes, Liver - metabolism</topic><topic>Neuroscience</topic><topic>Pyrazines - chemical synthesis</topic><topic>Pyrazines - metabolism</topic><topic>Pyrazines - pharmacology</topic><topic>Pyrazinones</topic><topic>Rats</topic><topic>Receptors, Corticotropin-Releasing Hormone - antagonists & inhibitors</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ahuja, Vijay T.</creatorcontrib><creatorcontrib>Hartz, Richard A.</creatorcontrib><creatorcontrib>Molski, Thaddeus F.</creatorcontrib><creatorcontrib>Mattson, Gail K.</creatorcontrib><creatorcontrib>Lentz, Kimberley A.</creatorcontrib><creatorcontrib>Grace, James E.</creatorcontrib><creatorcontrib>Lodge, Nicholas J.</creatorcontrib><creatorcontrib>Bronson, Joanne J.</creatorcontrib><creatorcontrib>Macor, John E.</creatorcontrib><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>Ahuja, Vijay T.</au><au>Hartz, Richard A.</au><au>Molski, Thaddeus F.</au><au>Mattson, Gail K.</au><au>Lentz, Kimberley A.</au><au>Grace, James E.</au><au>Lodge, Nicholas J.</au><au>Bronson, Joanne J.</au><au>Macor, John E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and evaluation of carbamate and aryl ether substituted pyrazinones as corticotropin releasing factor-1 (CRF1) receptor antagonists</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2016-05-01</date><risdate>2016</risdate><volume>26</volume><issue>9</issue><spage>2184</spage><epage>2187</epage><pages>2184-2187</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>[Display omitted]
A series of pyrazinone-based compounds incorporating either carbamate or aryl ether groups was synthesized and evaluated as corticotropin-releasing factor-1 (CRF1) receptor antagonists. Structure–activity relationship studies led to the identification of highly potent CRF1 receptor antagonists 14a (IC50=0.74nM) and 14b (IC50=1.9nM). The synthesis, structure–activity relationships and in vitro metabolic stability properties of compounds in this series will be described.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>27020524</pmid><doi>10.1016/j.bmcl.2016.03.067</doi><tpages>4</tpages></addata></record> |
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| ispartof | Bioorganic & medicinal chemistry letters, 2016-05, Vol.26 (9), p.2184-2187 |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Animals Carbamates - chemical synthesis Carbamates - metabolism Carbamates - pharmacology Cell Line, Tumor CRF CRF1 receptor antagonists Depression Humans Microsomes, Liver - metabolism Neuroscience Pyrazines - chemical synthesis Pyrazines - metabolism Pyrazines - pharmacology Pyrazinones Rats Receptors, Corticotropin-Releasing Hormone - antagonists & inhibitors Structure-Activity Relationship |
| title | Synthesis and evaluation of carbamate and aryl ether substituted pyrazinones as corticotropin releasing factor-1 (CRF1) receptor antagonists |
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