title: Further SAR study on 11-O-substituted aporphine analogues: identification of highly potent dopamine D3 receptor ligands.
abstract: A series of new aporphine analogues (aporlogues) were prepared from appropriate aporphine precursors and arylpiperazines using the Click reaction protocol. These compounds displayed good to high affinity at the D(3) receptor, low or no affinity at the D(1) and D(2) receptors. Compounds 7f and 11c stood out as the most potent at the D(3) receptor among our newly synthesized aporlogues with K(i) values of 2.67 and 1.14 nM, respectively. Further assay at the 5-HT(1A) receptor revealed that aporlogues 7f and 11c also showed high affinity at this receptor with K(i) values of 9.68 and 7.59 nM, respectively. They were 3.6- and 6.6-fold more potent at the D(3) over 5-HT(1A) receptors. Such D(3)/5-HT(1A) dual property of these compounds may be useful in the treatment of several brain disorders.
authors.affiliation: Synthetic Organic & Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Na
authors.initials: N
authors.lastname: Ye
authors.forename: QianQian
authors.initials: Q
authors.lastname: Wu
authors.forename: Liyuan
authors.initials: L
authors.lastname: Zhu
authors.forename: Longtai
authors.initials: L
authors.lastname: Zheng
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.forename: Xuechu
authors.initials: X
authors.lastname: Zhen
authors.forename: Ao
authors.initials: A
authors.lastname: Zhang
mesh_terms: D001060:Aporphines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015259:Dopamine Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D057809:HEK293 Cells; D006801:Humans; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C559079:11-((1-(3-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-1H-1,2,3-triazol-4-yl)methoxy)-N-propylnoraporphine; C559080:11-(3-(4-((4-(2-methoxyphenyl)piperazin-1-yl)ethyl)-1H-1,2,3-triazol-1-yl)propoxy)-N-propylnoraporphine; D001060:Aporphines; D015259:Dopamine Agents; D065127:Dopamine D2 Receptor Antagonists; D010879:Piperazines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D044282:Receptor, Serotonin, 5-HT1A; C081279:aporphine