A solution-phase combinatorial synthesis of selective dopamine D4 ligands.
Utilizing combinatorial synthesis and a preparative LC-MS automated chromatography system we have prepared and purified a library of 4-[2-(1,2,4-oxadiazolyl)]piperidines that were designed to be novel and selective dopamine D4 ligands. In one round of synthesis we identified N-4-chlorobenzyl-4-[2-(3-(2-thienyl)-1,2, 4-oxadiazolyl)]piperidine with a Kd of 5 nM for the human D4 receptor.
Williams
J P
JP
Department of Medicinal Chemistry, CombiChem, Inc., San Diego, CA 92121, USA. jwillia9@san.rr.com
Lavrador
K
K
D020650:Combinatorial Chemistry Techniques; D015259:Dopamine Agents / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050638:Receptors, Dopamine D4; D012996:Solutions
C493599:DRD4 protein, human; D015259:Dopamine Agents; D008024:Ligands; D017448:Receptors, Dopamine D2; D012996:Solutions; D050638:Receptors, Dopamine D4