Piperidine-Based Nocaine/Modafinil Hybrid Ligands as Highly Potent Monoamine Transporter Inhibitors: Efficient Drug Discovery by Rational Lead Hybridization
Some piperidine-based nocaine/modafinil hybrid ligands have been designed, synthesized, and found to display an improved potency at all three monoamine transporters and particularly for DAT and/or NET. Some highly active and selective monoamine transporter inhibitors with low nanomolar to subnanomol...
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| Veröffentlicht in: | Journal of medicinal chemistry 2004-11, Vol.47 (24), p.5821-5824 |
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| container_issue | 24 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 47 |
| creator | Zhou, Jia He, Rong Johnson, Kenneth M Ye, Yanping Kozikowski, Alan P |
| description | Some piperidine-based nocaine/modafinil hybrid ligands have been designed, synthesized, and found to display an improved potency at all three monoamine transporters and particularly for DAT and/or NET. Some highly active and selective monoamine transporter inhibitors with low nanomolar to subnanomolar potency were identified. Ligands of this type may find important applications as positron emission tomography imaging tools and in the treatment of central nervous system disorders such as depression and sleep apnea. |
| doi_str_mv | 10.1021/jm040117o |
| format | Article |
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Some highly active and selective monoamine transporter inhibitors with low nanomolar to subnanomolar potency were identified. Ligands of this type may find important applications as positron emission tomography imaging tools and in the treatment of central nervous system disorders such as depression and sleep apnea.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm040117o</identifier><identifier>PMID: 15537337</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Animals ; Benzhydryl Compounds - chemical synthesis ; Benzhydryl Compounds - chemistry ; Benzhydryl Compounds - pharmacology ; Biological and medical sciences ; Biological Availability ; Cocaine - pharmacology ; Dopamine Plasma Membrane Transport Proteins ; Drug Design ; In Vitro Techniques ; Ligands ; Medical sciences ; Membrane Glycoproteins - antagonists & inhibitors ; Membrane Transport Modulators ; Membrane Transport Proteins - antagonists & inhibitors ; Modafinil ; Motor Activity - drug effects ; Nerve Endings - drug effects ; Nerve Endings - metabolism ; Nerve Tissue Proteins - antagonists & inhibitors ; Neuropharmacology ; Norepinephrine Plasma Membrane Transport Proteins ; Pharmacology. Drug treatments ; Piperidines - chemical synthesis ; Piperidines - chemistry ; Piperidines - pharmacology ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) ; Psychology. Psychoanalysis. Psychiatry ; Psychopharmacology ; Rats ; Serotonin Plasma Membrane Transport Proteins ; Symporters - antagonists & inhibitors ; Synaptosomes - drug effects ; Synaptosomes - metabolism</subject><ispartof>Journal of medicinal chemistry, 2004-11, Vol.47 (24), p.5821-5824</ispartof><rights>Copyright © 2004 American Chemical Society</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a500t-81837d0c6a26d84a9761170dc55c5161599e31d92bb08b3f59624ac8cdff85f93</citedby><cites>FETCH-LOGICAL-a500t-81837d0c6a26d84a9761170dc55c5161599e31d92bb08b3f59624ac8cdff85f93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm040117o$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm040117o$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>230,314,778,782,883,2754,27065,27913,27914,56727,56777</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16268480$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15537337$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Jia</creatorcontrib><creatorcontrib>He, Rong</creatorcontrib><creatorcontrib>Johnson, Kenneth M</creatorcontrib><creatorcontrib>Ye, Yanping</creatorcontrib><creatorcontrib>Kozikowski, Alan P</creatorcontrib><title>Piperidine-Based Nocaine/Modafinil Hybrid Ligands as Highly Potent Monoamine Transporter Inhibitors: Efficient Drug Discovery by Rational Lead Hybridization</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>Some piperidine-based nocaine/modafinil hybrid ligands have been designed, synthesized, and found to display an improved potency at all three monoamine transporters and particularly for DAT and/or NET. Some highly active and selective monoamine transporter inhibitors with low nanomolar to subnanomolar potency were identified. Ligands of this type may find important applications as positron emission tomography imaging tools and in the treatment of central nervous system disorders such as depression and sleep apnea.</description><subject>Animals</subject><subject>Benzhydryl Compounds - chemical synthesis</subject><subject>Benzhydryl Compounds - chemistry</subject><subject>Benzhydryl Compounds - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Biological Availability</subject><subject>Cocaine - pharmacology</subject><subject>Dopamine Plasma Membrane Transport Proteins</subject><subject>Drug Design</subject><subject>In Vitro Techniques</subject><subject>Ligands</subject><subject>Medical sciences</subject><subject>Membrane Glycoproteins - antagonists & inhibitors</subject><subject>Membrane Transport Modulators</subject><subject>Membrane Transport Proteins - antagonists & inhibitors</subject><subject>Modafinil</subject><subject>Motor Activity - drug effects</subject><subject>Nerve Endings - drug effects</subject><subject>Nerve Endings - metabolism</subject><subject>Nerve Tissue Proteins - antagonists & inhibitors</subject><subject>Neuropharmacology</subject><subject>Norepinephrine Plasma Membrane Transport Proteins</subject><subject>Pharmacology. Drug treatments</subject><subject>Piperidines - chemical synthesis</subject><subject>Piperidines - chemistry</subject><subject>Piperidines - pharmacology</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Rats</subject><subject>Serotonin Plasma Membrane Transport Proteins</subject><subject>Symporters - antagonists & inhibitors</subject><subject>Synaptosomes - drug effects</subject><subject>Synaptosomes - metabolism</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptks1uEzEUhUcIRENhwQsgb0BiMdQ_sWeGBRL0h1RKSmiDYGfdsT2Jw2Qc7EnFsGLbp-i78SS4ZJSAxMqy7-dzj-9xkjwl-BXBlBwtV3iICcncvWRAOMXpMMfD-8kAY0pTKig7SB6FsMQYM0LZw-SAcM4yxrJBcju1a-Otto1J30EwGl04BXF3NHEaKtvYGo26MhJobOfQ6IAgoJGdL-oOTV1rmhZNXONgFe-gmYcmrJ1vjUfnzcKWtnU-vP718wadVpVV9g4_8Zs5OrFBuWvjO1R26BJa6xqo0diA7tvZH38OHycPKqiDedKvh8mns9PZ8Sgdf3h_fvx2nALHuE1zkrNMYyWACp0PochEnAfWinPFiSC8KAwjuqBlifOSVbwQdAgqV7qqcl4V7DB5s9Vdb8qV0Soa9VDLtbcr8J10YOW_lcYu5NxdS8IKTgmJAi96Ae--bUxo5So-0dQ1NMZtgiQFy2kuRARfbkHlXQjeVLsmBMu7OOUuzsg--9vVnuzzi8DzHoCgoK7i_JUNe05QkcfPELl0y9nQmu-7OvivUmQs43I2vZKXXy4mnz-eTeTVXhdUkEu38TGd8B-DvwGVw8d5</recordid><startdate>20041118</startdate><enddate>20041118</enddate><creator>Zhou, Jia</creator><creator>He, Rong</creator><creator>Johnson, Kenneth M</creator><creator>Ye, Yanping</creator><creator>Kozikowski, Alan P</creator><general>American Chemical Society</general><scope>BSCLL</scope><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><scope>5PM</scope></search><sort><creationdate>20041118</creationdate><title>Piperidine-Based Nocaine/Modafinil Hybrid Ligands as Highly Potent Monoamine Transporter Inhibitors: Efficient Drug Discovery by Rational Lead Hybridization</title><author>Zhou, Jia ; He, Rong ; Johnson, Kenneth M ; Ye, Yanping ; Kozikowski, Alan P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a500t-81837d0c6a26d84a9761170dc55c5161599e31d92bb08b3f59624ac8cdff85f93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Benzhydryl Compounds - chemical synthesis</topic><topic>Benzhydryl Compounds - chemistry</topic><topic>Benzhydryl Compounds - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Biological Availability</topic><topic>Cocaine - pharmacology</topic><topic>Dopamine Plasma Membrane Transport Proteins</topic><topic>Drug Design</topic><topic>In Vitro Techniques</topic><topic>Ligands</topic><topic>Medical sciences</topic><topic>Membrane Glycoproteins - antagonists & inhibitors</topic><topic>Membrane Transport Modulators</topic><topic>Membrane Transport Proteins - antagonists & inhibitors</topic><topic>Modafinil</topic><topic>Motor Activity - drug effects</topic><topic>Nerve Endings - drug effects</topic><topic>Nerve Endings - metabolism</topic><topic>Nerve Tissue Proteins - antagonists & inhibitors</topic><topic>Neuropharmacology</topic><topic>Norepinephrine Plasma Membrane Transport Proteins</topic><topic>Pharmacology. Drug treatments</topic><topic>Piperidines - chemical synthesis</topic><topic>Piperidines - chemistry</topic><topic>Piperidines - pharmacology</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Rats</topic><topic>Serotonin Plasma Membrane Transport Proteins</topic><topic>Symporters - antagonists & inhibitors</topic><topic>Synaptosomes - drug effects</topic><topic>Synaptosomes - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Jia</creatorcontrib><creatorcontrib>He, Rong</creatorcontrib><creatorcontrib>Johnson, Kenneth M</creatorcontrib><creatorcontrib>Ye, Yanping</creatorcontrib><creatorcontrib>Kozikowski, Alan P</creatorcontrib><collection>Istex</collection><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>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Jia</au><au>He, Rong</au><au>Johnson, Kenneth M</au><au>Ye, Yanping</au><au>Kozikowski, Alan P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Piperidine-Based Nocaine/Modafinil Hybrid Ligands as Highly Potent Monoamine Transporter Inhibitors: Efficient Drug Discovery by Rational Lead Hybridization</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2004-11-18</date><risdate>2004</risdate><volume>47</volume><issue>24</issue><spage>5821</spage><epage>5824</epage><pages>5821-5824</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>Some piperidine-based nocaine/modafinil hybrid ligands have been designed, synthesized, and found to display an improved potency at all three monoamine transporters and particularly for DAT and/or NET. Some highly active and selective monoamine transporter inhibitors with low nanomolar to subnanomolar potency were identified. Ligands of this type may find important applications as positron emission tomography imaging tools and in the treatment of central nervous system disorders such as depression and sleep apnea.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>15537337</pmid><doi>10.1021/jm040117o</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of medicinal chemistry, 2004-11, Vol.47 (24), p.5821-5824 |
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| language | eng |
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| source | MEDLINE; ACS Publications |
| subjects | Animals Benzhydryl Compounds - chemical synthesis Benzhydryl Compounds - chemistry Benzhydryl Compounds - pharmacology Biological and medical sciences Biological Availability Cocaine - pharmacology Dopamine Plasma Membrane Transport Proteins Drug Design In Vitro Techniques Ligands Medical sciences Membrane Glycoproteins - antagonists & inhibitors Membrane Transport Modulators Membrane Transport Proteins - antagonists & inhibitors Modafinil Motor Activity - drug effects Nerve Endings - drug effects Nerve Endings - metabolism Nerve Tissue Proteins - antagonists & inhibitors Neuropharmacology Norepinephrine Plasma Membrane Transport Proteins Pharmacology. Drug treatments Piperidines - chemical synthesis Piperidines - chemistry Piperidines - pharmacology Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopharmacology Rats Serotonin Plasma Membrane Transport Proteins Symporters - antagonists & inhibitors Synaptosomes - drug effects Synaptosomes - metabolism |
| title | Piperidine-Based Nocaine/Modafinil Hybrid Ligands as Highly Potent Monoamine Transporter Inhibitors: Efficient Drug Discovery by Rational Lead Hybridization |
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