Further SAR study on 11-O-substituted aporphine analogues: identification of highly potent dopamine D3 receptor ligands.

Na Ye, QianQian Wu, Liyuan Zhu, Longtai Zheng, Bo Gao, Xuechu Zhen, Ao Zhang

Synthetic Organic & Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Bioorganic & medicinal chemistry 2011 Mar 15

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A series of new aporphine analogues (aporlogues) were prepared from appropriate aporphine precursors and arylpiperazines using the Click reaction protocol. These compounds displayed good to high affinity at the D(3) receptor, low or no affinity at the D(1) and D(2) receptors. Compounds 7f and 11c stood out as the most potent at the D(3) receptor among our newly synthesized aporlogues with K(i) values of 2.67 and 1.14 nM, respectively. Further assay at the 5-HT(1A) receptor revealed that aporlogues 7f and 11c also showed high affinity at this receptor with K(i) values of 9.68 and 7.59 nM, respectively. They were 3.6- and 6.6-fold more potent at the D(3) over 5-HT(1A) receptors. Such D(3)/5-HT(1A) dual property of these compounds may be useful in the treatment of several brain disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Citation

Na Ye, QianQian Wu, Liyuan Zhu, Longtai Zheng, Bo Gao, Xuechu Zhen, Ao Zhang. Further SAR study on 11-O-substituted aporphine analogues: identification of highly potent dopamine D3 receptor ligands. Bioorganic & medicinal chemistry. 2011 Mar 15;19(6):1999-2008