1860-57-7Relevant 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.
1,2,3,4-TETRAHYDROISOQUINOLINE DERIVATIVES HAVING EFFECTS OF PREVENTING AND TREATING DEGENERATIVE AND INFLAMMATORY DISEASES
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Page/Page column 6, (2010/09/05)
Provided are 7-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline derivatives and synthesis methods thereof. The compounds significantly inhibit the production of nitrogen monoxide (NO) and superoxide in an activated microglial cell and expressions of TNF-α, IL-1β inducive NO synthase and cyclooxygenase-2 genes. They also prevent NF-kB shift to a nucleus, decrease reactive oxygen species (ROS), inhibit expression of GTP cyclohydrolase I gene and over-production of tetrahydrobiopterin (BH4), and protect dopaminergic neurons from injury due to activated microglial cells. Consequently, the compounds are effective in treating inflammatory and neurodegenerative diseases.
1,2,3,4-TETRAHYDROISOQUINOLINE DERIVATIVES HAVING EFFECTS OF PREVENTING AND TREATING DEGENERATIVE AND INFLAMMATORY DISEASES
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, (2008/12/06)
Provided are 7-hydroxy-6-methoxy-l,2,3,4-tetrahydroisoquinoline derivatives and synthesis methods thereof. The compounds significantly inhibit the production of nitrogen monoxide (NO) and superoxide in an activated microglial cell and expressions of TNF-α, IL- lβ inducive NO synthase and cyclooxygenase-2 genes. They also prevent NF-kB shift to a nucleus, decrease reactive oxygen species (ROS), inhibit expression of GTP cyclohydrolase I gene and over-production of tetrahydrobiopterin (BH 4 ), and protect dopaminergic neurons from injury due to activated microglial cells. Consequently, the compounds are effective in treating inflammatory and neurodegenerative diseases.
Incorporation of phenethylisoquinolines into colchicine in isolated seeds of Colchicum autumnale
Nasreen, Amber,Gundlach, Heidrun,Zenk, Meinhart H.
, p. 107 - 115 (2007/10/03)
The physiological parameters for application experiments using immature seeds of Colchicum autumnale were optimized, so that incorporation rates in the range of 10% and higher were consistently obtained with intermediate precursors. Application of tritium and 13C-labelled phenethylisoquinolines showed that N-methylation occurs prior to the substitution of ring C and that the free hydroxy group in position 13 of autumnaline is necessary for the phenolic coupling reaction. Autumnaline gives rise to a vast array of metabolites in seeds of this plant.
