Binding of 2,4-disubstituted morpholines at human D4 dopamine receptors.
The synthesis of a series of 2,4-disubstituted morpholines is described and their affinities at human dopamine receptors reported. The orally bioavailable 7-azaindole compound 11 has nanomolar affinity at the hD4 receptor with > 1000-fold selectivity over the hD2 receptor.
Showell
G A
GA
Merck, Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Emms
F
F
Marwood
R
R
O'Connor
D
D
Patel
S
S
Leeson
P D
PD
D000284:Administration, Oral; D000818:Animals; D001667:Binding, Competitive; D001682:Biological Availability; D002460:Cell Line; D006801:Humans; D007275:Injections, Intravenous; D008958:Models, Molecular; D009025:Morpholines / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics; D011725:Pyridines / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics; D011869:Radioligand Assay; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050638:Receptors, Dopamine D4; D013134:Spiperone / Q000378:metabolism; D013329:Structure-Activity Relationship; D014316:Tritium
C111612:3-((2-((4-chlorophenoxy)methyl)morpholin-4-yl)methyl)pyrrolo(2,3-b)pyridine; C493599:DRD4 protein, human; C493601:Drd4 protein, rat; D009025:Morpholines; D011725:Pyridines; D017448:Receptors, Dopamine D2; D014316:Tritium; D050638:Receptors, Dopamine D4; D013134:Spiperone