Analogues of FAUC 73 revealing new insights into the structural requirements of nonaromatic dopamine D3 receptor agonists.
Employing the nonaromatic D3 agonist FAUC 73 as a lead compound, the dopaminergic enynes 1a,b and the diene 2 (FAUC 206) were synthesized via palladium-catalyzed cross-coupling. FAUC 206 showed remarkable D3 affinity and enhanced selectivity over D4 when compared to the lead compound. To learn more about the bioactive structure of the diene moiety, computational studies including DFT-based conformational analysis and calculations of the magnetic shielding properties were performed. The electrostatic properties of the pharmacophoric pi-systems were visualized by diagnostic MEP maps.
Lenz
Carola
C
Department of Medicinal Chemistry, Emil Fischer Center, Friedrich Alexander University, Schuhstrasse 19, D-91052, Erlangen, Germany.
Boeckler
Frank
F
Hübner
Harald
H
Gmeiner
Peter
P
D000480:Alkynes / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003514:Cyclohexylamines / Q000737:chemistry* / Q000378:metabolism; D018491:Dopamine Agonists / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D013329:Structure-Activity Relationship; D013552:Swine
D000480:Alkynes; D003514:Cyclohexylamines; C493593:DRD3 protein, human; D018491:Dopamine Agonists; C489825:FAUC 73; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3