Further characterization of structural requirements for ligands at the dopamine D(2) and D(3) receptor: exploring the thiophene moiety.
The present study describes the synthesis and in vitro pharmacology of a novel series of dopaminergic agents in which the classical phenylethylamine pharmacophore is replaced by a thienylethylamine moiety. In general, the novel compounds showed a moderate affinity for the dopamine (DA) D(2) and D(3) receptors. When the thienylethylamine moiety is fixed in a rigid system, the affinity for the DA receptor is significantly increased. However, in the tricyclic hexahydrothianaphthoxazine structure, the affinity for the DA receptors is diminished.
Dijkstra
Durk
D
Department of Medicinal Chemistry, University of Groningen, Antonius Deusinglaan 1, NL-9713 AV Groningen, The Netherlands. D.Dijkstra@farm.rug.nl
Rodenhuis
Nienke
N
Vermeulen
Erik S
ES
Pugsley
Thomas A
TA
Wise
Lawrence D
LD
Wikström
Håkan V
HV
D000818:Animals; D001667:Binding, Competitive; D001682:Biological Availability; D016466:CHO Cells; D006224:Cricetinae; D018491:Dopamine Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D017551:Microdialysis; D011869:Radioligand Assay; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
C493593:DRD3 protein, human; D018491:Dopamine Agonists; C493595:Drd3 protein, rat; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013876:Thiophenes; C113776:dopamine D2L receptor