TY - JOUR
T1 - Synthesis of 2-(2,3-dimethoxyphenyl)-4-(aminomethyl)imidazole analogues and their binding affinities for dopamine D2 and D3 receptors
AU - Huang, Yunsheng
AU - Luedtke, Robert R.
AU - Freeman, Rebekah A.
AU - Wu, Li
AU - Mach, Robert H.
N1 - Funding Information:
This research was supported by PHS grants DA 09142, DA 09147 and DA 12647 from the National Institute on Drug Abuse and by the Scottish Rite Schizophrenia Research Program.
PY - 2001
Y1 - 2001
N2 - A series of 2-(2,3-dimethoxyphenyl)-4-(aminomethyl)imidazole derivatives was prepared and their affinity for dopamine D2 and D3 receptors was measured using in vitro binding assays. Several oxadiazole analogues were also prepared and tested for their affinity for dopamine D2 and D3 receptors. The results of receptor binding studies indicated that the incorporation of an imidazole moiety between the phenyl ring and the basic nitrogen did not significantly increase the selectivity for dopamine D3 receptors, whereas the incorporation of an oxadiazole at the same region resulted in a total loss of affinity for both dopamine receptor subtype binding sites. The most selective compound in this series is 2-(5-bromo-2,3-dimethoxyphenyl)-4-(6,7-dimethoxy-1,2,3, 4-tetrahydroisoquinolinomethyl)imidazole (5i), which has a D3 receptor affinity of 21 nM and a 7-fold selectivity for D3 versus D2 receptors. The binding affinity for σ1 and σ2 receptors was also measured, and the results showed that several analogues were selective σ1 receptor ligands.
AB - A series of 2-(2,3-dimethoxyphenyl)-4-(aminomethyl)imidazole derivatives was prepared and their affinity for dopamine D2 and D3 receptors was measured using in vitro binding assays. Several oxadiazole analogues were also prepared and tested for their affinity for dopamine D2 and D3 receptors. The results of receptor binding studies indicated that the incorporation of an imidazole moiety between the phenyl ring and the basic nitrogen did not significantly increase the selectivity for dopamine D3 receptors, whereas the incorporation of an oxadiazole at the same region resulted in a total loss of affinity for both dopamine receptor subtype binding sites. The most selective compound in this series is 2-(5-bromo-2,3-dimethoxyphenyl)-4-(6,7-dimethoxy-1,2,3, 4-tetrahydroisoquinolinomethyl)imidazole (5i), which has a D3 receptor affinity of 21 nM and a 7-fold selectivity for D3 versus D2 receptors. The binding affinity for σ1 and σ2 receptors was also measured, and the results showed that several analogues were selective σ1 receptor ligands.
UR - http://www.scopus.com/inward/record.url?scp=0035174793&partnerID=8YFLogxK
U2 - 10.1016/S0968-0896(01)00175-4
DO - 10.1016/S0968-0896(01)00175-4
M3 - Article
C2 - 11711286
AN - SCOPUS:0035174793
SN - 0968-0896
VL - 9
SP - 3113
EP - 3122
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 12
ER -