TY - JOUR
T1 - Synthesis and characterization of selective dopamine D2 receptor ligands using aripiprazole as the lead compound
AU - Vangveravong, Suwanna
AU - Zhang, Zhanbin
AU - Taylor, Michelle
AU - Bearden, Melissa
AU - Xu, Jinbin
AU - Cui, Jinquan
AU - Wang, Wei
AU - Luedtke, Robert R.
AU - MacH, Robert H.
N1 - Funding Information:
This research was funded by MH081281 and DA023957 awarded by the National Institutes of Health .
PY - 2011/6/1
Y1 - 2011/6/1
N2 - A series of compounds structurally related to aripiprazole (1), an atypical antipsychotic and antidepressant used clinically for the treatment of schizophrenia, bipolar disorder, and depression, have been prepared and evaluated for affinity at D2-like dopamine receptors. These compounds also share structural elements with the classical D2-like dopamine receptor antagonists, haloperidol, N-methylspiperone, domperidone and benperidol. Two new compounds, 7-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butoxy)- 3,4-dihydroquinolin-2(1H)-one oxalate (6) and 7-(4-(4-(2-(2-fluoroethoxy)phenyl) piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one oxalate (7) were found to (a) bind to the D2 receptor subtype with high affinity (Ki values <0.3 nM), (b) exhibit >50-fold D2 versus D3 receptor binding selectivity and (c) be partial agonists at both the D 2 and D3 receptor subtype.
AB - A series of compounds structurally related to aripiprazole (1), an atypical antipsychotic and antidepressant used clinically for the treatment of schizophrenia, bipolar disorder, and depression, have been prepared and evaluated for affinity at D2-like dopamine receptors. These compounds also share structural elements with the classical D2-like dopamine receptor antagonists, haloperidol, N-methylspiperone, domperidone and benperidol. Two new compounds, 7-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butoxy)- 3,4-dihydroquinolin-2(1H)-one oxalate (6) and 7-(4-(4-(2-(2-fluoroethoxy)phenyl) piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one oxalate (7) were found to (a) bind to the D2 receptor subtype with high affinity (Ki values <0.3 nM), (b) exhibit >50-fold D2 versus D3 receptor binding selectivity and (c) be partial agonists at both the D 2 and D3 receptor subtype.
KW - Aripiprazole
KW - Dopamine D receptor
KW - Dopamine partial agonist
UR - http://www.scopus.com/inward/record.url?scp=79957447359&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2011.04.021
DO - 10.1016/j.bmc.2011.04.021
M3 - Article
C2 - 21536445
AN - SCOPUS:79957447359
SN - 0968-0896
VL - 19
SP - 3502
EP - 3511
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 11
ER -