2176-15-0Relevant academic research and scientific papers
Design, synthesis, and pharmacological evaluation of novel tetrahydroprotoberberine derivatives: Selective inhibitors of dopamine D 1 receptor
Qian, Wangke,Lu, Weijian,Sun, Haifeng,Li, Zeng,Zhu, Liyuan,Zhao, Rui,Zhang, Lei,Zhou, Shengbin,Zhou, Yu,Jiang, Hualiang,Zhen, Xuechu,Liu, Hong
, p. 4862 - 4871 (2012/09/05)
A series of new tetrahydroprotoberberine (THPB) derivatives were designed, synthesized, and tested for their binding affinity towards dopamine (D 1 and D2) and serotonin (5-HT1A and 5-HT 2A) receptors. Many of the THPB compounds exhibited high binding affinity and activity at the dopamine D1 receptor, as well as high selectivity for the D1 receptor over the D2, 5-HT 1A, and 5-HT2A receptors. Among these, compound 19c exhibited a promising D1 receptor binding affinity (Ki = 2.53 nM) and remarkable selectivity versus D2R (inhibition = 81.87%), 5-HT1AR (inhibition = 61.70%), and 5-HT2AR (inhibition = 24.96%). Compared with l-(S)-stepholidine (l-SPD) (D1 Ki = 6.23 nM, D2 Ki = 56.17 nM), compound 19c showed better binding affinity for the D1 receptor (2.5-fold higher) and excellent D2/D1 selectivity. Functional assays found compounds 18j, 18k, and 19c are pure D1 receptor antagonists. These results indicate that removing the C10 hydroxy group and introducing a methoxy group at C11 of the pharmacophore of l-SPD can reverse the function of THPB compounds at the D1 receptor. These results are in accord with molecular docking studies.
