Potent MCH-1 receptor antagonists from cis-1,4-diaminocyclohexane-derived indane analogs
Benzimidazole and indane are the two key fragments in our potent and selective MCH-1 receptor (MCHR1) antagonists. To identify novel linkers connecting the two fragments, we investigated diamino-cycloalkane-derived analogs and discovered highly potent antagonists with cis-1,4-diaminocyclohexane as a...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2013-07, Vol.23 (14), p.4216-4220 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Qian, Yimin Conde-Knape, Karin Erickson, Shawn D. Falcioni, Fiorenza Gillespie, Paul Hakimi, Irina Mennona, Francis Ren, Yonglin Salari, Hamid So, Sung-Sau Tilley, Jefferson W. |
| description | Benzimidazole and indane are the two key fragments in our potent and selective MCH-1 receptor (MCHR1) antagonists. To identify novel linkers connecting the two fragments, we investigated diamino-cycloalkane-derived analogs and discovered highly potent antagonists with cis-1,4-diaminocyclohexane as a unique spacer in this chemical class. Structural overlay suggested that cis-1-substituted-4-aminocyclohexane functions as a bioisostere of 4-substituted-piperidine and that the active conformation adopts a U-shaped orientation. |
| doi_str_mv | 10.1016/j.bmcl.2013.05.017 |
| format | Article |
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To identify novel linkers connecting the two fragments, we investigated diamino-cycloalkane-derived analogs and discovered highly potent antagonists with cis-1,4-diaminocyclohexane as a unique spacer in this chemical class. Structural overlay suggested that cis-1-substituted-4-aminocyclohexane functions as a bioisostere of 4-substituted-piperidine and that the active conformation adopts a U-shaped orientation.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2013.05.017</identifier><identifier>PMID: 23743277</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Benzimidazoles - chemistry ; Bioisostere ; Conformation ; Cyclohexanes - chemistry ; Fragment ; GPCR ; Half-Life ; Indans - chemistry ; Indans - metabolism ; Indans - pharmacokinetics ; Isomerism ; MCHR1 antagonist ; Mice ; Protein Binding ; Rats ; Receptors, Pituitary Hormone - antagonists & inhibitors ; Receptors, Pituitary Hormone - metabolism</subject><ispartof>Bioorganic & medicinal chemistry letters, 2013-07, Vol.23 (14), p.4216-4220</ispartof><rights>2013 Elsevier Ltd</rights><rights>Copyright © 2013 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-dc84c1675ee2bf0ae970468d9fe258cd04c43836cec902229feac75fad351f8a3</citedby><cites>FETCH-LOGICAL-c389t-dc84c1675ee2bf0ae970468d9fe258cd04c43836cec902229feac75fad351f8a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X13006033$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23743277$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qian, Yimin</creatorcontrib><creatorcontrib>Conde-Knape, Karin</creatorcontrib><creatorcontrib>Erickson, Shawn D.</creatorcontrib><creatorcontrib>Falcioni, Fiorenza</creatorcontrib><creatorcontrib>Gillespie, Paul</creatorcontrib><creatorcontrib>Hakimi, Irina</creatorcontrib><creatorcontrib>Mennona, Francis</creatorcontrib><creatorcontrib>Ren, Yonglin</creatorcontrib><creatorcontrib>Salari, Hamid</creatorcontrib><creatorcontrib>So, Sung-Sau</creatorcontrib><creatorcontrib>Tilley, Jefferson W.</creatorcontrib><title>Potent MCH-1 receptor antagonists from cis-1,4-diaminocyclohexane-derived indane analogs</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>Benzimidazole and indane are the two key fragments in our potent and selective MCH-1 receptor (MCHR1) antagonists. To identify novel linkers connecting the two fragments, we investigated diamino-cycloalkane-derived analogs and discovered highly potent antagonists with cis-1,4-diaminocyclohexane as a unique spacer in this chemical class. Structural overlay suggested that cis-1-substituted-4-aminocyclohexane functions as a bioisostere of 4-substituted-piperidine and that the active conformation adopts a U-shaped orientation.</description><subject>Animals</subject><subject>Benzimidazoles - chemistry</subject><subject>Bioisostere</subject><subject>Conformation</subject><subject>Cyclohexanes - chemistry</subject><subject>Fragment</subject><subject>GPCR</subject><subject>Half-Life</subject><subject>Indans - chemistry</subject><subject>Indans - metabolism</subject><subject>Indans - pharmacokinetics</subject><subject>Isomerism</subject><subject>MCHR1 antagonist</subject><subject>Mice</subject><subject>Protein Binding</subject><subject>Rats</subject><subject>Receptors, Pituitary Hormone - antagonists & inhibitors</subject><subject>Receptors, Pituitary Hormone - metabolism</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v1DAQhi0EotvCH-CAcuRAwvgrdiQuqAKKVAQHkHqzvONJ8SqJFztb0X-PV1s4wska63nfGT2MveDQceD9m123nXHqBHDZge6Am0dsw1WvWqlAP2YbGHpo7aBuzth5KTsArkCpp-xMSKOkMGbDbr6mlZa1-Xx51fImE9J-Tbnxy-pv0xLLWpoxp7nBWFr-WrUh-jkuCe9xSj_ol1-oDZTjHYUmLqGONeqndFuesSejnwo9f3gv2PcP77_VLddfPn66fHfdorTD2ga0CnlvNJHYjuBpMKB6G4aRhLYYQKGSVvZIOIAQov57NHr0QWo-Wi8v2KtT7z6nnwcqq5tjQZqmeks6FMc1gNFWGv5_tEKit1zoiooTijmVkml0-xxnn-8dB3eU73buKN8d5TvQrsqvoZcP_YftTOFv5I_tCrw9AVSF3EXKrmCkBSnEan51IcV_9f8GWICVZg</recordid><startdate>20130715</startdate><enddate>20130715</enddate><creator>Qian, Yimin</creator><creator>Conde-Knape, Karin</creator><creator>Erickson, Shawn D.</creator><creator>Falcioni, Fiorenza</creator><creator>Gillespie, Paul</creator><creator>Hakimi, Irina</creator><creator>Mennona, Francis</creator><creator>Ren, Yonglin</creator><creator>Salari, Hamid</creator><creator>So, Sung-Sau</creator><creator>Tilley, Jefferson W.</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>20130715</creationdate><title>Potent MCH-1 receptor antagonists from cis-1,4-diaminocyclohexane-derived indane analogs</title><author>Qian, Yimin ; Conde-Knape, Karin ; Erickson, Shawn D. ; Falcioni, Fiorenza ; Gillespie, Paul ; Hakimi, Irina ; Mennona, Francis ; Ren, Yonglin ; Salari, Hamid ; So, Sung-Sau ; Tilley, Jefferson W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-dc84c1675ee2bf0ae970468d9fe258cd04c43836cec902229feac75fad351f8a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Benzimidazoles - chemistry</topic><topic>Bioisostere</topic><topic>Conformation</topic><topic>Cyclohexanes - chemistry</topic><topic>Fragment</topic><topic>GPCR</topic><topic>Half-Life</topic><topic>Indans - chemistry</topic><topic>Indans - metabolism</topic><topic>Indans - pharmacokinetics</topic><topic>Isomerism</topic><topic>MCHR1 antagonist</topic><topic>Mice</topic><topic>Protein Binding</topic><topic>Rats</topic><topic>Receptors, Pituitary Hormone - antagonists & inhibitors</topic><topic>Receptors, Pituitary Hormone - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qian, Yimin</creatorcontrib><creatorcontrib>Conde-Knape, Karin</creatorcontrib><creatorcontrib>Erickson, Shawn D.</creatorcontrib><creatorcontrib>Falcioni, Fiorenza</creatorcontrib><creatorcontrib>Gillespie, Paul</creatorcontrib><creatorcontrib>Hakimi, Irina</creatorcontrib><creatorcontrib>Mennona, Francis</creatorcontrib><creatorcontrib>Ren, Yonglin</creatorcontrib><creatorcontrib>Salari, Hamid</creatorcontrib><creatorcontrib>So, Sung-Sau</creatorcontrib><creatorcontrib>Tilley, Jefferson W.</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>Qian, Yimin</au><au>Conde-Knape, Karin</au><au>Erickson, Shawn D.</au><au>Falcioni, Fiorenza</au><au>Gillespie, Paul</au><au>Hakimi, Irina</au><au>Mennona, Francis</au><au>Ren, Yonglin</au><au>Salari, Hamid</au><au>So, Sung-Sau</au><au>Tilley, Jefferson W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Potent MCH-1 receptor antagonists from cis-1,4-diaminocyclohexane-derived indane analogs</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2013-07-15</date><risdate>2013</risdate><volume>23</volume><issue>14</issue><spage>4216</spage><epage>4220</epage><pages>4216-4220</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>Benzimidazole and indane are the two key fragments in our potent and selective MCH-1 receptor (MCHR1) antagonists. To identify novel linkers connecting the two fragments, we investigated diamino-cycloalkane-derived analogs and discovered highly potent antagonists with cis-1,4-diaminocyclohexane as a unique spacer in this chemical class. Structural overlay suggested that cis-1-substituted-4-aminocyclohexane functions as a bioisostere of 4-substituted-piperidine and that the active conformation adopts a U-shaped orientation.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>23743277</pmid><doi>10.1016/j.bmcl.2013.05.017</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2013-07, Vol.23 (14), p.4216-4220 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Benzimidazoles - chemistry Bioisostere Conformation Cyclohexanes - chemistry Fragment GPCR Half-Life Indans - chemistry Indans - metabolism Indans - pharmacokinetics Isomerism MCHR1 antagonist Mice Protein Binding Rats Receptors, Pituitary Hormone - antagonists & inhibitors Receptors, Pituitary Hormone - metabolism |
| title | Potent MCH-1 receptor antagonists from cis-1,4-diaminocyclohexane-derived indane analogs |
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