75491-93-9

Usage

InChI:InChI=1/C20H19NO4.ClH/c1-23-18-10-15-12(7-17(18)22)4-5-21-11-14-9-20(25-3)19(24-2)8-13(14)6-16(15)21;/h6-11H,4-5H2,1-3H3;1H

Upstream product

• 40225-82-9 (+/-)-discretine 
• 3213-30-7 5-(2-amino-ethyl)-2-methoxy-phenol 
• 322474-09-9 2-(3-hydroxy-4-methoxyphenyl)-1-nitroethane 
• 39816-35-8 2-(3-hydroxy-4-methoxyphenyl)-1-nitroethene 
• 621-59-0 isovanillin 

Relevant academic research and scientific papers

Structure–activity relationship and biological evaluation of berberine derivatives as PCSK9 down-regulating agents

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.

Synthesis and biological evaluation of berberine analogues as novel up-regulators for both low-density-lipoprotein receptor and insulin receptor

Berberine (BBR) is a natural compound with up-regulating activity on both low-density-lipoprotein receptor (LDLR) and insulin receptor (InsR). This one-drug-multiple-target characteristic might be suitable for the treatment of metabolic syndrome. In searching for up-regulators effective for both LDLR and InsR expression, the structure-activity relationship (SAR) analysis for BBR analogues was done. Fourteen BBR analogues were designed, synthesized and biologically evaluated. SAR analysis revealed that appropriate modifications on the phenyl ring A or D of BBR might retain the up-regulatory activities on the expression of both LDLR and InsR. Among these compounds, compound 13a bearing 9-methoxy and 10-hydroxyl on the ring D showed promising activities on either LDLR or InsR gene expression. The 10-hydroxyl of 13a could be an arm to connect proper chemical groups for optimizing drug-bioavailability in vivo. Thus, 13a could be considered to be a parent compound to make pro-drugs for either blood lipids or glucose.