63909-38-6Relevant articles and documents
Structure–activity relationship and biological evaluation of berberine derivatives as PCSK9 down-regulating agents
Fan, Tian-Yun,Yang, Yu-Xin,Zeng, Qing-Xuan,Wang, Xue-Lei,Wei, Wei,Guo, Xi-Xi,Zhao, Li-Ping,Song, Dan-Qing,Wang, Yan-Xiang,Wang, Li,Hong, Bin
, (2021/06/01)
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein and its deficiency markedly enhanced the survival rate of patient with cardiovascular diseases (CVDs). Forty berberine (BBR) derivatives were synthesized and evaluated for their activities on down-regulating the transcription of PCSK9 in HepG2 cells, taking BBR as the lead. Structure–activity relationship (SAR) analysis revealed that 2,3-dimethoxy moiety might be beneficial for activity. Among them, 9k displayed the most potent activity with IC50 value of 9.5 ± 0.5 μM, better than that of BBR. Also, it significantly decreased PCSK9 protein level at cellular level, as well as in the liver and serum of mice in vivo. Furthermore, 9k markedly increased LDLR expression and LDL-C clearance via down-regulating PCSK9 protein. The mechanism of action of 9k is targeting HNF1α and/or Sp1 cluster modulation upstream of PCSK9, a different one from BBR. Therefore, 9k might have the potential to be a novel PCSK9 transcriptional inhibitor for the treatment of atherosclerosis, worthy for further investigation.
Vanadium-Catalyzed Oxidative Intramolecular Coupling of Tethered Phenols: Formation of Phenol-Dienone Products
Gilmartin, Philip H.,Kozlowski, Marisa C.
, p. 2914 - 2919 (2020/04/10)
A mild and efficient method for the vanadium-catalyzed intramolecular coupling of tethered free phenols is described. The corresponding phenol-dienone products are prepared directly in good yields with low catalyst loadings. Electronically diverse tethered phenol precursors are well tolerated, and the catalytic method was effectively applied as the key step in syntheses of three natural products and a synthetically useful morphinan alkaloid precursor.
Full-synthetic method of racemic tetrandrine
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Paragraph 0060; 0079, (2019/07/10)
The invention discloses a full-synthetic method of racemic tetrandrine, and belongs to the technical field of drug synthesis. The full-synthetic method of the racemic tetrandrine comprises the steps that a synthetic route adopts a convergence synthesis method, a 5-bromovanillin, namely a compound 1 and 3-hydroxy-4-methoxyphenylacetic acid, namely a compound 5 are taken as starting materials to obtain a compound 4 and a compound 6 respectively, then the compound 4 and the compound 6 are taken as raw materials to synthesize a compound 11, a compound 19 is synthesized from the compound 11, and finally, the compound 11 reacts with the compound 19. The full-synthetic method of the racemic tetrandrine has the advantages that the synthetic efficiency is higher, the yield is higher, and the cost is lower; the reaction conditions are milder, the operation is simple and convenient, the industrial value is higher, and a reference is provided for the full-synthetic method of optical voidness tetrandrine.