TY - JOUR
T1 - Synthesis and in vitro binding of N-phenyl piperazine analogs as potential dopamine D 3 receptor ligands
AU - Chu, Wenhua
AU - Tu, Zhude
AU - McElveen, Elizabeth
AU - Xu, Jinbin
AU - Taylor, Michelle
AU - Luedtke, Robert R.
AU - MacH, Robert H.
N1 - Funding Information:
This research was funded by grants DA 12647 and DA 16181 awarded by the National Institute on Drug Abuse.
PY - 2005/1/3
Y1 - 2005/1/3
N2 - The synthesis of a series of N-(2-methoxyphenyl)piperazine and N-(2,3-dichlorophenyl)piperazine analogs and their in vitro binding affinities for dopamine D 2, D 3, D 4 are presented. A series of N-(2-methoxyphenyl)piperazine and N-(2,3-dichlorophenyl)piperazine analogs were prepared and their affinities for dopamine D 2, D 3, and D 4 receptors were measured in vitro. Binding studies were also conducted to determine if the compounds bound to sigma (σ 1 and σ 2) and serotonin (5-HT 1A, 5-HT 2A, 5-HT 2B, 5-HT 2C, 5-HT 3, 5-HT 4, 5-HT 5, 5-HT 6, and 5-HT 7) receptors. The results of the current study revealed a number of compounds (12b, 12c, 12e, and 12g) having a high affinity for D 3 (K i at D 3 receptors ranging from 0.3 to 0.9 nM) versus D 2 (K i at D 2 receptors ranging from 40 to 53 nM) receptors and a log P value indicating that they should readily cross the blood brain barrier (log P = 2.6-3.5). All of the compounds evaluated in this study had a high affinity for serotonin 5-HT 1A receptors. These compounds may be useful as probes for studying the behavioral pharmacology of the dopamine D 3 receptor, as well as lead compounds for the development of radiotracers for studying D 3 receptor regulation in vivo with the functional imaging technique, positron emission tomography.
AB - The synthesis of a series of N-(2-methoxyphenyl)piperazine and N-(2,3-dichlorophenyl)piperazine analogs and their in vitro binding affinities for dopamine D 2, D 3, D 4 are presented. A series of N-(2-methoxyphenyl)piperazine and N-(2,3-dichlorophenyl)piperazine analogs were prepared and their affinities for dopamine D 2, D 3, and D 4 receptors were measured in vitro. Binding studies were also conducted to determine if the compounds bound to sigma (σ 1 and σ 2) and serotonin (5-HT 1A, 5-HT 2A, 5-HT 2B, 5-HT 2C, 5-HT 3, 5-HT 4, 5-HT 5, 5-HT 6, and 5-HT 7) receptors. The results of the current study revealed a number of compounds (12b, 12c, 12e, and 12g) having a high affinity for D 3 (K i at D 3 receptors ranging from 0.3 to 0.9 nM) versus D 2 (K i at D 2 receptors ranging from 40 to 53 nM) receptors and a log P value indicating that they should readily cross the blood brain barrier (log P = 2.6-3.5). All of the compounds evaluated in this study had a high affinity for serotonin 5-HT 1A receptors. These compounds may be useful as probes for studying the behavioral pharmacology of the dopamine D 3 receptor, as well as lead compounds for the development of radiotracers for studying D 3 receptor regulation in vivo with the functional imaging technique, positron emission tomography.
KW - Atypical antipsychotics
KW - Dopamine D receptors
UR - http://www.scopus.com/inward/record.url?scp=9644291553&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2004.09.054
DO - 10.1016/j.bmc.2004.09.054
M3 - Article
C2 - 15582454
AN - SCOPUS:9644291553
SN - 0968-0896
VL - 13
SP - 77
EP - 87
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 1
ER -