Piperazinebenzylamines as potent and selective antagonists of the human melanocortin-4 receptor
[Display omitted] SAR studies of a series of piperazinebenzylamines resulted in the discovery of potent antagonists of the human melanocortin-4 receptor. Compounds 11c, 11d, and 11l, which had K i values of 21, 14, and 15 nM, respectively, possessed low efficacy in cAMP stimulation (∼15% of α-MSH ma...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2004-11, Vol.14 (22), p.5605-5609 |
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| container_issue | 22 |
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| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 14 |
| creator | Pontillo, Joseph Tran, Joseph A. Fleck, Beth A. Marinkovic, Dragan Arellano, Melissa Tucci, Fabio C. Lanier, Marion Nelson, Jodie Parker, Jessica Saunders, John Murphy, Brian Foster, Alan C. Chen, Chen |
| description | [Display omitted]
SAR studies of a series of piperazinebenzylamines resulted in the discovery of potent antagonists of the human melanocortin-4 receptor. Compounds
11c,
11d, and
11l, which had
K
i values of 21, 14, and 15
nM, respectively, possessed low efficacy in cAMP stimulation (∼15% of α-MSH maximal level) mediated by MC4R, and functioned as antagonists in inhibition of α-MSH-stimulated cAMP release in a dose-dependent manner (
11l, IC
50
=
36
nM). |
| doi_str_mv | 10.1016/j.bmcl.2004.08.055 |
| format | Article |
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SAR studies of a series of piperazinebenzylamines resulted in the discovery of potent antagonists of the human melanocortin-4 receptor. Compounds
11c,
11d, and
11l, which had
K
i values of 21, 14, and 15
nM, respectively, possessed low efficacy in cAMP stimulation (∼15% of α-MSH maximal level) mediated by MC4R, and functioned as antagonists in inhibition of α-MSH-stimulated cAMP release in a dose-dependent manner (
11l, IC
50
=
36
nM).</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2004.08.055</identifier><identifier>PMID: 15482933</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Antagonist ; Benzylamines - chemical synthesis ; Benzylamines - pharmacology ; Biological and medical sciences ; Humans ; MC4 ; Medical sciences ; Melanocortin ; Miscellaneous ; Molecular Structure ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems ; Pharmacology. Drug treatments ; Piperazinebenzylamine ; Piperazines - chemical synthesis ; Piperazines - pharmacology ; Receptor, Melanocortin, Type 4 - antagonists & inhibitors ; Structure-Activity Relationship</subject><ispartof>Bioorganic & medicinal chemistry letters, 2004-11, Vol.14 (22), p.5605-5609</ispartof><rights>2004 Elsevier Ltd</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c382t-2fa5c4cea94e7d3c96d08deacf31c2040384ef7cc831620222f724b539659aea3</citedby><cites>FETCH-LOGICAL-c382t-2fa5c4cea94e7d3c96d08deacf31c2040384ef7cc831620222f724b539659aea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2004.08.055$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16202575$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15482933$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pontillo, Joseph</creatorcontrib><creatorcontrib>Tran, Joseph A.</creatorcontrib><creatorcontrib>Fleck, Beth A.</creatorcontrib><creatorcontrib>Marinkovic, Dragan</creatorcontrib><creatorcontrib>Arellano, Melissa</creatorcontrib><creatorcontrib>Tucci, Fabio C.</creatorcontrib><creatorcontrib>Lanier, Marion</creatorcontrib><creatorcontrib>Nelson, Jodie</creatorcontrib><creatorcontrib>Parker, Jessica</creatorcontrib><creatorcontrib>Saunders, John</creatorcontrib><creatorcontrib>Murphy, Brian</creatorcontrib><creatorcontrib>Foster, Alan C.</creatorcontrib><creatorcontrib>Chen, Chen</creatorcontrib><title>Piperazinebenzylamines as potent and selective antagonists of the human melanocortin-4 receptor</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
SAR studies of a series of piperazinebenzylamines resulted in the discovery of potent antagonists of the human melanocortin-4 receptor. Compounds
11c,
11d, and
11l, which had
K
i values of 21, 14, and 15
nM, respectively, possessed low efficacy in cAMP stimulation (∼15% of α-MSH maximal level) mediated by MC4R, and functioned as antagonists in inhibition of α-MSH-stimulated cAMP release in a dose-dependent manner (
11l, IC
50
=
36
nM).</description><subject>Antagonist</subject><subject>Benzylamines - chemical synthesis</subject><subject>Benzylamines - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Humans</subject><subject>MC4</subject><subject>Medical sciences</subject><subject>Melanocortin</subject><subject>Miscellaneous</subject><subject>Molecular Structure</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems</subject><subject>Pharmacology. Drug treatments</subject><subject>Piperazinebenzylamine</subject><subject>Piperazines - chemical synthesis</subject><subject>Piperazines - pharmacology</subject><subject>Receptor, Melanocortin, Type 4 - antagonists & inhibitors</subject><subject>Structure-Activity Relationship</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE2LFDEQhoMo7uzqH_Agueit23x2d8CLLOoKC3pQ8BYy1dVuhu6kTTILu7_eNDOwN09VBU-9vDyEvOGs5Yx3Hw7tfoG5FYyplg0t0_oZ2XHVqUYqpp-THTMdawajfl-Qy5wPjHHFlHpJLrhWgzBS7oj94VdM7tEH3GN4fJjdUtdMXaZrLBgKdWGkGWeE4u-xXsX9icHnkmmcaLlDendcXKALzi5EiKn40CiaEHAtMb0iLyY3Z3x9nlfk15fPP69vmtvvX79df7ptQA6iNGJyGhSgMwr7UYLpRjaM6GCSHARTTA4Kpx5gkLwTTAgx9ULttTSdNg6dvCLvT7lrin-PmItdfAacaymMx2y7zvScG11BcQIhxZwTTnZNfnHpwXJmN632YDetdtNq2WCr1vr09px-3C84Pr2cPVbg3RlwGdw8JRfA5ydu66z7LejjicPq4t5jshk8BsDRV2PFjtH_r8c_SySXww</recordid><startdate>20041115</startdate><enddate>20041115</enddate><creator>Pontillo, Joseph</creator><creator>Tran, Joseph A.</creator><creator>Fleck, Beth A.</creator><creator>Marinkovic, Dragan</creator><creator>Arellano, Melissa</creator><creator>Tucci, Fabio C.</creator><creator>Lanier, Marion</creator><creator>Nelson, Jodie</creator><creator>Parker, Jessica</creator><creator>Saunders, John</creator><creator>Murphy, Brian</creator><creator>Foster, Alan C.</creator><creator>Chen, Chen</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>7X8</scope></search><sort><creationdate>20041115</creationdate><title>Piperazinebenzylamines as potent and selective antagonists of the human melanocortin-4 receptor</title><author>Pontillo, Joseph ; Tran, Joseph A. ; Fleck, Beth A. ; Marinkovic, Dragan ; Arellano, Melissa ; Tucci, Fabio C. ; Lanier, Marion ; Nelson, Jodie ; Parker, Jessica ; Saunders, John ; Murphy, Brian ; Foster, Alan C. ; Chen, Chen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c382t-2fa5c4cea94e7d3c96d08deacf31c2040384ef7cc831620222f724b539659aea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Antagonist</topic><topic>Benzylamines - chemical synthesis</topic><topic>Benzylamines - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Humans</topic><topic>MC4</topic><topic>Medical sciences</topic><topic>Melanocortin</topic><topic>Miscellaneous</topic><topic>Molecular Structure</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems</topic><topic>Pharmacology. Drug treatments</topic><topic>Piperazinebenzylamine</topic><topic>Piperazines - chemical synthesis</topic><topic>Piperazines - pharmacology</topic><topic>Receptor, Melanocortin, Type 4 - antagonists & inhibitors</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pontillo, Joseph</creatorcontrib><creatorcontrib>Tran, Joseph A.</creatorcontrib><creatorcontrib>Fleck, Beth A.</creatorcontrib><creatorcontrib>Marinkovic, Dragan</creatorcontrib><creatorcontrib>Arellano, Melissa</creatorcontrib><creatorcontrib>Tucci, Fabio C.</creatorcontrib><creatorcontrib>Lanier, Marion</creatorcontrib><creatorcontrib>Nelson, Jodie</creatorcontrib><creatorcontrib>Parker, Jessica</creatorcontrib><creatorcontrib>Saunders, John</creatorcontrib><creatorcontrib>Murphy, Brian</creatorcontrib><creatorcontrib>Foster, Alan C.</creatorcontrib><creatorcontrib>Chen, Chen</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>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pontillo, Joseph</au><au>Tran, Joseph A.</au><au>Fleck, Beth A.</au><au>Marinkovic, Dragan</au><au>Arellano, Melissa</au><au>Tucci, Fabio C.</au><au>Lanier, Marion</au><au>Nelson, Jodie</au><au>Parker, Jessica</au><au>Saunders, John</au><au>Murphy, Brian</au><au>Foster, Alan C.</au><au>Chen, Chen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Piperazinebenzylamines as potent and selective antagonists of the human melanocortin-4 receptor</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2004-11-15</date><risdate>2004</risdate><volume>14</volume><issue>22</issue><spage>5605</spage><epage>5609</epage><pages>5605-5609</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>[Display omitted]
SAR studies of a series of piperazinebenzylamines resulted in the discovery of potent antagonists of the human melanocortin-4 receptor. Compounds
11c,
11d, and
11l, which had
K
i values of 21, 14, and 15
nM, respectively, possessed low efficacy in cAMP stimulation (∼15% of α-MSH maximal level) mediated by MC4R, and functioned as antagonists in inhibition of α-MSH-stimulated cAMP release in a dose-dependent manner (
11l, IC
50
=
36
nM).</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>15482933</pmid><doi>10.1016/j.bmcl.2004.08.055</doi><tpages>5</tpages></addata></record> |
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| ispartof | Bioorganic & medicinal chemistry letters, 2004-11, Vol.14 (22), p.5605-5609 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Antagonist Benzylamines - chemical synthesis Benzylamines - pharmacology Biological and medical sciences Humans MC4 Medical sciences Melanocortin Miscellaneous Molecular Structure Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems Pharmacology. Drug treatments Piperazinebenzylamine Piperazines - chemical synthesis Piperazines - pharmacology Receptor, Melanocortin, Type 4 - antagonists & inhibitors Structure-Activity Relationship |
| title | Piperazinebenzylamines as potent and selective antagonists of the human melanocortin-4 receptor |
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