Design, synthesis, and structure–activity relationship of novel CCR2 antagonists
Discovery of a novel series of 3-aminocyclopentanecarboxamide CCR2 receptor antagonists are presented herein. These compounds demonstrate high affinity and functional inhibition of hCCR2 receptors. A discussion on SAR along with the cross species PK profile for the best analog ( 59) is also included...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2009-03, Vol.19 (6), p.1830-1834 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Kothandaraman, Shankaran Donnely, Karla L. Butora, Gabor Jiao, Richard Pasternak, Alexander Morriello, Gregori J. Goble, Stephen D. Zhou, Changyou Mills, Sander G. MacCoss, Malcolm Vicario, Pasquale P. Ayala, Julia M. DeMartino, Julie A. Struthers, Mary Cascieri, Margaret A. Yang, Lihu |
| description | Discovery of a novel series of 3-aminocyclopentanecarboxamide CCR2 receptor antagonists are presented herein. These compounds demonstrate high affinity and functional inhibition of hCCR2 receptors. A discussion on SAR along with the cross species PK profile for the best analog (
59) is also included.
A series of novel 1-aminocyclopentyl-3-carboxyamides incorporating substituted tetrahydropyran moieties have been synthesized and subsequently evaluated for their antagonistic activity against the human CCR2 receptor. Among them analog
59 was found to posses potent antagonistic activity. |
| doi_str_mv | 10.1016/j.bmcl.2008.12.050 |
| format | Article |
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59) is also included.
A series of novel 1-aminocyclopentyl-3-carboxyamides incorporating substituted tetrahydropyran moieties have been synthesized and subsequently evaluated for their antagonistic activity against the human CCR2 receptor. Among them analog
59 was found to posses potent antagonistic activity.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2008.12.050</identifier><identifier>PMID: 19237282</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Administration, Oral ; Aminocyclopentane carboxamide ; Animals ; Biological and medical sciences ; Bones, joints and connective tissue. Antiinflammatory agents ; CCR2 Antagonist ; Chemistry, Pharmaceutical - methods ; Chemotaxis ; Dogs ; Drug Design ; Humans ; Inhibitory Concentration 50 ; Macaca mulatta ; Medical sciences ; Models, Chemical ; Molecular Structure ; Pharmacology. Drug treatments ; Rats ; Rats, Sprague-Dawley ; Receptors, CCR2 - antagonists & inhibitors ; Receptors, CCR2 - chemistry ; Reductive aminations ; Structure-Activity Relationship</subject><ispartof>Bioorganic & medicinal chemistry letters, 2009-03, Vol.19 (6), p.1830-1834</ispartof><rights>2009</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-905a91da1a6bc76002b62b31878064673cbfa61025c4ed929d1fa688ea48f54c3</citedby><cites>FETCH-LOGICAL-c415t-905a91da1a6bc76002b62b31878064673cbfa61025c4ed929d1fa688ea48f54c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X0801559X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21299034$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19237282$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kothandaraman, Shankaran</creatorcontrib><creatorcontrib>Donnely, Karla L.</creatorcontrib><creatorcontrib>Butora, Gabor</creatorcontrib><creatorcontrib>Jiao, Richard</creatorcontrib><creatorcontrib>Pasternak, Alexander</creatorcontrib><creatorcontrib>Morriello, Gregori J.</creatorcontrib><creatorcontrib>Goble, Stephen D.</creatorcontrib><creatorcontrib>Zhou, Changyou</creatorcontrib><creatorcontrib>Mills, Sander G.</creatorcontrib><creatorcontrib>MacCoss, Malcolm</creatorcontrib><creatorcontrib>Vicario, Pasquale P.</creatorcontrib><creatorcontrib>Ayala, Julia M.</creatorcontrib><creatorcontrib>DeMartino, Julie A.</creatorcontrib><creatorcontrib>Struthers, Mary</creatorcontrib><creatorcontrib>Cascieri, Margaret A.</creatorcontrib><creatorcontrib>Yang, Lihu</creatorcontrib><title>Design, synthesis, and structure–activity relationship of novel CCR2 antagonists</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>Discovery of a novel series of 3-aminocyclopentanecarboxamide CCR2 receptor antagonists are presented herein. These compounds demonstrate high affinity and functional inhibition of hCCR2 receptors. A discussion on SAR along with the cross species PK profile for the best analog (
59) is also included.
A series of novel 1-aminocyclopentyl-3-carboxyamides incorporating substituted tetrahydropyran moieties have been synthesized and subsequently evaluated for their antagonistic activity against the human CCR2 receptor. Among them analog
59 was found to posses potent antagonistic activity.</description><subject>Administration, Oral</subject><subject>Aminocyclopentane carboxamide</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bones, joints and connective tissue. Antiinflammatory agents</subject><subject>CCR2 Antagonist</subject><subject>Chemistry, Pharmaceutical - methods</subject><subject>Chemotaxis</subject><subject>Dogs</subject><subject>Drug Design</subject><subject>Humans</subject><subject>Inhibitory Concentration 50</subject><subject>Macaca mulatta</subject><subject>Medical sciences</subject><subject>Models, Chemical</subject><subject>Molecular Structure</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, CCR2 - antagonists & inhibitors</subject><subject>Receptors, CCR2 - chemistry</subject><subject>Reductive aminations</subject><subject>Structure-Activity Relationship</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM9q3DAQh0VoaTZpXyCH4Et7it2RLMsS9FK2-VMIFEILvQlZlhMtXnmrkRf21nfoG_ZJqmWX5NbTzMD3-zF8hFxQqChQ8XFVdWs7VgxAVpRV0MAJWVAueFlzaF6RBSgBpVT85yk5Q1wBUA6cvyGnVLG6ZZItyMMXh_4xXBW4C-kp73hVmNAXmOJs0xzd399_jE1-69OuiG40yU8Bn_ymmIYiTFs3FsvlA8uZZB6n4DHhW_J6MCO6d8d5Tn7cXH9f3pX3326_Lj_fl5bTJpUKGqNob6gRnW0FAOsE62oqWwmCi7a23WAEBdZY7nrFVE_zLaUzXA4Nt_U5-XDo3cTp1-ww6bVH68bRBDfNqBnwhrVCZpAdQBsnxOgGvYl-beJOU9B7k3ql9yb13qSmTGeTOXR5bJ-7tetfIkd1GXh_BAxaMw7RBOvxmWOUKQU1z9ynA-eyi613UaP1LljX--hs0v3k__fHP_J8knM</recordid><startdate>20090315</startdate><enddate>20090315</enddate><creator>Kothandaraman, Shankaran</creator><creator>Donnely, Karla L.</creator><creator>Butora, Gabor</creator><creator>Jiao, Richard</creator><creator>Pasternak, Alexander</creator><creator>Morriello, Gregori J.</creator><creator>Goble, Stephen D.</creator><creator>Zhou, Changyou</creator><creator>Mills, Sander G.</creator><creator>MacCoss, Malcolm</creator><creator>Vicario, Pasquale P.</creator><creator>Ayala, Julia M.</creator><creator>DeMartino, Julie A.</creator><creator>Struthers, Mary</creator><creator>Cascieri, Margaret A.</creator><creator>Yang, Lihu</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></search><sort><creationdate>20090315</creationdate><title>Design, synthesis, and structure–activity relationship of novel CCR2 antagonists</title><author>Kothandaraman, Shankaran ; Donnely, Karla L. ; Butora, Gabor ; Jiao, Richard ; Pasternak, Alexander ; Morriello, Gregori J. ; Goble, Stephen D. ; Zhou, Changyou ; Mills, Sander G. ; MacCoss, Malcolm ; Vicario, Pasquale P. ; Ayala, Julia M. ; DeMartino, Julie A. ; Struthers, Mary ; Cascieri, Margaret A. ; Yang, Lihu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-905a91da1a6bc76002b62b31878064673cbfa61025c4ed929d1fa688ea48f54c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Administration, Oral</topic><topic>Aminocyclopentane carboxamide</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bones, joints and connective tissue. 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These compounds demonstrate high affinity and functional inhibition of hCCR2 receptors. A discussion on SAR along with the cross species PK profile for the best analog (
59) is also included.
A series of novel 1-aminocyclopentyl-3-carboxyamides incorporating substituted tetrahydropyran moieties have been synthesized and subsequently evaluated for their antagonistic activity against the human CCR2 receptor. Among them analog
59 was found to posses potent antagonistic activity.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>19237282</pmid><doi>10.1016/j.bmcl.2008.12.050</doi><tpages>5</tpages></addata></record> |
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| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2009-03, Vol.19 (6), p.1830-1834 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Administration, Oral Aminocyclopentane carboxamide Animals Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents CCR2 Antagonist Chemistry, Pharmaceutical - methods Chemotaxis Dogs Drug Design Humans Inhibitory Concentration 50 Macaca mulatta Medical sciences Models, Chemical Molecular Structure Pharmacology. Drug treatments Rats Rats, Sprague-Dawley Receptors, CCR2 - antagonists & inhibitors Receptors, CCR2 - chemistry Reductive aminations Structure-Activity Relationship |
| title | Design, synthesis, and structure–activity relationship of novel CCR2 antagonists |
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