2,4-Disubstituted pyrroles: synthesis, traceless linking and pharmacological investigations leading to the dopamine D4 receptor partial agonist FAUC 356.
Solution-phase synthesis and a solid-phase supported approach to piperazinylmethyl substituted pyrroles are described. Receptor binding studies and the measurement of D4 ligand efficacy led to the ethynylpyrrole 1d (FAUC 356) exerting selective D4 binding and substantial ligand efficacy (66%, EC(50)=1.9nM). This activity profile might be of interest for the treatment of ADHD.
Department of Medicinal Chemistry, Emil Fischer Center, Friedrich-Alexander University, Schuhstrasse 19, D-91052 Erlangen, Germany.
Markus
M
Bergauer
Harald
H
Hübner
Peter
P
Gmeiner
D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002417:Cattle; D003001:Cloning, Molecular; D006224:Cricetinae; D006801:Humans; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism; D050638:Receptors, Dopamine D4; D011985:Receptors, Serotonin / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013552:Swine
C493599:DRD4 protein, human; C470889:FAUC 356; D010879:Piperazines; D011758:Pyrroles; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D050638:Receptors, Dopamine D4