Design, synthesis and pharmacological profile of novel dopamine D2 receptor ligands
The present study describes the synthesis and pharmacological profile of three novel heterocyclic compounds originally designed, on the basis of bioisosterism, as dopamine D2 receptor ligands: 1-[1-(4-chlorophenyl)-1H-pyrazol-4-ylmethyl]-4-phenyl-piperazine (LASSBio-579), 1-phenyl-4-(1-phenyl-1H-[1,...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2003-11, Vol.11 (22), p.4807-4813 |
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| creator | Menegatti, Ricardo Cunha, Anna C Ferreira, Vı́tor F Perreira, Edna F.R El-Nabawi, Ahmed Eldefrawi, Amira T Albuquerque, Edson X Neves, Gilda Rates, Stela M.K Fraga, Carlos A.M Barreiro, Eliezer J |
| description | The present study describes the synthesis and pharmacological profile of three novel heterocyclic compounds originally designed, on the basis of bioisosterism, as dopamine D2 receptor ligands: 1-[1-(4-chlorophenyl)-1H-pyrazol-4-ylmethyl]-4-phenyl-piperazine (LASSBio-579), 1-phenyl-4-(1-phenyl-1H-[1,2,3]triazol-4-ylmethyl)-piperazine (LASSBio-580) and 1-[1-(4-chlorophenyl)-1H-[1,2,3]triazol-4-ylmethyl]-4-phenyl-piperazine (LASSBio-581). Binding studies performed on brain homogenate indicated that all three compounds bind selectively to D2 receptors. In addition, electrophysiological studies carried out in cultured hippocampal neurons suggested that LASSBio-579 and 581 act as D2 agonists, whereas LASSBio-580 acts as a D2 antagonist.
The synthesis and in vitro dopamine receptor ligand profile of new pyrazole and 1,2,3-triazole
N-phenylpiperazines
3–
5 is reported. |
| doi_str_mv | 10.1016/S0968-0896(03)00487-5 |
| format | Article |
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The synthesis and in vitro dopamine receptor ligand profile of new pyrazole and 1,2,3-triazole
N-phenylpiperazines
3–
5 is reported.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/S0968-0896(03)00487-5</identifier><identifier>PMID: 14556797</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Animals ; Biological and medical sciences ; Brain - metabolism ; Catecholaminergic system ; Cell Membrane - metabolism ; Dopamine D2 Receptor Antagonists ; Dose-Response Relationship, Drug ; Drug Design ; Electrophysiology ; Hippocampus - cytology ; Ligands ; Male ; Medical sciences ; Models, Molecular ; Neurons - drug effects ; Neurons - physiology ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Pharmacology. Drug treatments ; Piperazines - chemical synthesis ; Piperazines - chemistry ; Piperazines - metabolism ; Piperazines - pharmacology ; Radioligand Assay ; Rats ; Receptors, Dopamine D1 - metabolism ; Receptors, Dopamine D2 - agonists ; Receptors, Dopamine D2 - metabolism</subject><ispartof>Bioorganic & medicinal chemistry, 2003-11, Vol.11 (22), p.4807-4813</ispartof><rights>2003 Elsevier Ltd</rights><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-87f0a0899de2f1ece5e31857ded46fed813144412366bb8568d978cfcd0a1ccb3</citedby><cites>FETCH-LOGICAL-c393t-87f0a0899de2f1ece5e31857ded46fed813144412366bb8568d978cfcd0a1ccb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0968-0896(03)00487-5$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3552,27931,27932,46002</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15201581$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14556797$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Menegatti, Ricardo</creatorcontrib><creatorcontrib>Cunha, Anna C</creatorcontrib><creatorcontrib>Ferreira, Vı́tor F</creatorcontrib><creatorcontrib>Perreira, Edna F.R</creatorcontrib><creatorcontrib>El-Nabawi, Ahmed</creatorcontrib><creatorcontrib>Eldefrawi, Amira T</creatorcontrib><creatorcontrib>Albuquerque, Edson X</creatorcontrib><creatorcontrib>Neves, Gilda</creatorcontrib><creatorcontrib>Rates, Stela M.K</creatorcontrib><creatorcontrib>Fraga, Carlos A.M</creatorcontrib><creatorcontrib>Barreiro, Eliezer J</creatorcontrib><title>Design, synthesis and pharmacological profile of novel dopamine D2 receptor ligands</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>The present study describes the synthesis and pharmacological profile of three novel heterocyclic compounds originally designed, on the basis of bioisosterism, as dopamine D2 receptor ligands: 1-[1-(4-chlorophenyl)-1H-pyrazol-4-ylmethyl]-4-phenyl-piperazine (LASSBio-579), 1-phenyl-4-(1-phenyl-1H-[1,2,3]triazol-4-ylmethyl)-piperazine (LASSBio-580) and 1-[1-(4-chlorophenyl)-1H-[1,2,3]triazol-4-ylmethyl]-4-phenyl-piperazine (LASSBio-581). Binding studies performed on brain homogenate indicated that all three compounds bind selectively to D2 receptors. In addition, electrophysiological studies carried out in cultured hippocampal neurons suggested that LASSBio-579 and 581 act as D2 agonists, whereas LASSBio-580 acts as a D2 antagonist.
The synthesis and in vitro dopamine receptor ligand profile of new pyrazole and 1,2,3-triazole
N-phenylpiperazines
3–
5 is reported.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Brain - metabolism</subject><subject>Catecholaminergic system</subject><subject>Cell Membrane - metabolism</subject><subject>Dopamine D2 Receptor Antagonists</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Design</subject><subject>Electrophysiology</subject><subject>Hippocampus - cytology</subject><subject>Ligands</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Models, Molecular</subject><subject>Neurons - drug effects</subject><subject>Neurons - physiology</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Pharmacology. Drug treatments</subject><subject>Piperazines - chemical synthesis</subject><subject>Piperazines - chemistry</subject><subject>Piperazines - metabolism</subject><subject>Piperazines - pharmacology</subject><subject>Radioligand Assay</subject><subject>Rats</subject><subject>Receptors, Dopamine D1 - metabolism</subject><subject>Receptors, Dopamine D2 - agonists</subject><subject>Receptors, Dopamine D2 - metabolism</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM1OGzEUha2KqoTQRyjyhgqkTmuPf8azQhV_rYTURejacuzrxNXMeGpPkHh7TBKRJavrxXfuPf4Q-kLJd0qo_LEgrVQVUa28IOySEK6aSnxAM8olrxhr6RGavSHH6CTnf4SQmrf0EzqmXAjZtM0MLW4gh9XwDefnYVqXd8ZmcHhcm9QbG7u4CtZ0eEzRhw5w9HiIT9BhF0fThwHwTY0TWBinmHAXViWcT9FHb7oMn_dzjv7e3T5e_6oe_tz_vv75UFnWsqlSjSemtGsd1J6WHQIYVaJx4Lj04BRllHNOayblcqmEVK5tlPXWEUOtXbI5-rrbW9r930CedB-yha4zA8RN1g2tpaxrVkCxA22KOSfwekyhN-lZU6JfbeqtTf2qShOmtza1KLmz_YHNsgd3SO31FeB8D5hcNPlkBhvygRM1oaL8Y46udhwUHU8Bks42wGDBhSJv0i6Gd6q8AN8Akc4</recordid><startdate>20031103</startdate><enddate>20031103</enddate><creator>Menegatti, Ricardo</creator><creator>Cunha, Anna C</creator><creator>Ferreira, Vı́tor F</creator><creator>Perreira, Edna F.R</creator><creator>El-Nabawi, Ahmed</creator><creator>Eldefrawi, Amira T</creator><creator>Albuquerque, Edson X</creator><creator>Neves, Gilda</creator><creator>Rates, Stela M.K</creator><creator>Fraga, Carlos A.M</creator><creator>Barreiro, Eliezer J</creator><general>Elsevier Ltd</general><general>Elsevier Science</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>20031103</creationdate><title>Design, synthesis and pharmacological profile of novel dopamine D2 receptor ligands</title><author>Menegatti, Ricardo ; Cunha, Anna C ; Ferreira, Vı́tor F ; Perreira, Edna F.R ; El-Nabawi, Ahmed ; Eldefrawi, Amira T ; Albuquerque, Edson X ; Neves, Gilda ; Rates, Stela M.K ; Fraga, Carlos A.M ; Barreiro, Eliezer J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-87f0a0899de2f1ece5e31857ded46fed813144412366bb8568d978cfcd0a1ccb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Brain - metabolism</topic><topic>Catecholaminergic system</topic><topic>Cell Membrane - metabolism</topic><topic>Dopamine D2 Receptor Antagonists</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Design</topic><topic>Electrophysiology</topic><topic>Hippocampus - cytology</topic><topic>Ligands</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Models, Molecular</topic><topic>Neurons - drug effects</topic><topic>Neurons - physiology</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Pharmacology. Drug treatments</topic><topic>Piperazines - chemical synthesis</topic><topic>Piperazines - chemistry</topic><topic>Piperazines - metabolism</topic><topic>Piperazines - pharmacology</topic><topic>Radioligand Assay</topic><topic>Rats</topic><topic>Receptors, Dopamine D1 - metabolism</topic><topic>Receptors, Dopamine D2 - agonists</topic><topic>Receptors, Dopamine D2 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Menegatti, Ricardo</creatorcontrib><creatorcontrib>Cunha, Anna C</creatorcontrib><creatorcontrib>Ferreira, Vı́tor F</creatorcontrib><creatorcontrib>Perreira, Edna F.R</creatorcontrib><creatorcontrib>El-Nabawi, Ahmed</creatorcontrib><creatorcontrib>Eldefrawi, Amira T</creatorcontrib><creatorcontrib>Albuquerque, Edson X</creatorcontrib><creatorcontrib>Neves, Gilda</creatorcontrib><creatorcontrib>Rates, Stela M.K</creatorcontrib><creatorcontrib>Fraga, Carlos A.M</creatorcontrib><creatorcontrib>Barreiro, Eliezer J</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</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Menegatti, Ricardo</au><au>Cunha, Anna C</au><au>Ferreira, Vı́tor F</au><au>Perreira, Edna F.R</au><au>El-Nabawi, Ahmed</au><au>Eldefrawi, Amira T</au><au>Albuquerque, Edson X</au><au>Neves, Gilda</au><au>Rates, Stela M.K</au><au>Fraga, Carlos A.M</au><au>Barreiro, Eliezer J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design, synthesis and pharmacological profile of novel dopamine D2 receptor ligands</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2003-11-03</date><risdate>2003</risdate><volume>11</volume><issue>22</issue><spage>4807</spage><epage>4813</epage><pages>4807-4813</pages><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>The present study describes the synthesis and pharmacological profile of three novel heterocyclic compounds originally designed, on the basis of bioisosterism, as dopamine D2 receptor ligands: 1-[1-(4-chlorophenyl)-1H-pyrazol-4-ylmethyl]-4-phenyl-piperazine (LASSBio-579), 1-phenyl-4-(1-phenyl-1H-[1,2,3]triazol-4-ylmethyl)-piperazine (LASSBio-580) and 1-[1-(4-chlorophenyl)-1H-[1,2,3]triazol-4-ylmethyl]-4-phenyl-piperazine (LASSBio-581). Binding studies performed on brain homogenate indicated that all three compounds bind selectively to D2 receptors. In addition, electrophysiological studies carried out in cultured hippocampal neurons suggested that LASSBio-579 and 581 act as D2 agonists, whereas LASSBio-580 acts as a D2 antagonist.
The synthesis and in vitro dopamine receptor ligand profile of new pyrazole and 1,2,3-triazole
N-phenylpiperazines
3–
5 is reported.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>14556797</pmid><doi>10.1016/S0968-0896(03)00487-5</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Bioorganic & medicinal chemistry, 2003-11, Vol.11 (22), p.4807-4813 |
| issn | 0968-0896 1464-3391 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_71266223 |
| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Animals Biological and medical sciences Brain - metabolism Catecholaminergic system Cell Membrane - metabolism Dopamine D2 Receptor Antagonists Dose-Response Relationship, Drug Drug Design Electrophysiology Hippocampus - cytology Ligands Male Medical sciences Models, Molecular Neurons - drug effects Neurons - physiology Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Piperazines - chemical synthesis Piperazines - chemistry Piperazines - metabolism Piperazines - pharmacology Radioligand Assay Rats Receptors, Dopamine D1 - metabolism Receptors, Dopamine D2 - agonists Receptors, Dopamine D2 - metabolism |
| title | Design, synthesis and pharmacological profile of novel dopamine D2 receptor ligands |
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