Syntheses and binding affinities of 6-nitroquipazine analogues for serotonin transporter. Part 2: 4-substituted 6-nitroquipazines.
Eleven 4-substituted derivatives of 6-nitroquipazine were synthesized and evaluated for their abilities to displace [3H]citalopram binding to the rat cortical synaptic membranes. Among them, 4-chloro-6-nitroquipazine was shown to possess the highest binding affinity (K(i=)0.03 nM) which was approximately 6 times higher than that of 6-nitroquipazine (K(i)=0.17 nM) itself. In this paper, we describe the syntheses of 4-substituted 6-nitroquipazine derivatives, the results of corresponding biological evaluation and the SAR study.
Se Lee
Byoung
B
Department of Chemistry, Inha University, 253 Yonghyundong, Namgu, 402-751, Inchon, Republic of Korea
Chu
Soyoung
S
Lee
Bon-Su
BS
Yoon Chi
Dae
D
Song
Yun Seon
YS
Jin
Changbae
C
D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D015283:Citalopram / Q000493:pharmacokinetics; D015195:Drug Design; D005473:Fluoxetine / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008961:Models, Structural; D009419:Nerve Tissue Proteins; D017374:Paroxetine / Q000494:pharmacology; D011814:Quipazine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D013329:Structure-Activity Relationship
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D005473:Fluoxetine; D015283:Citalopram; D017374:Paroxetine; D011814:Quipazine; C031227:6-nitroquipazine