(E)-3-(3,4-diethoxy-5-methoxyphenyl)-1-(pyridin-4-yl)prop-2-en-1-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (E)-3-(3,4-diethoxy-5-methoxyphenyl)-1-(pyridin-4-yl)prop-2-en-1-one
• 英文别名: (E)-3-(3,4-diethoxy-5-methoxyphenyl)-1-pyridin-4-ylprop-2-en-1-one
• 化学式: C₁₉H₂₁NO₄
• 分子量: 327.38
• InChiKey: SQZFPRBIMUDDBG-VOTSOKGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  57.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-乙酰吡啶 、 3,4-diethoxy-5-methoxybenzaldehyde 反应 0.42h， 以9%的产率得到(E)-3-(3,4-diethoxy-5-methoxyphenyl)-1-(pyridin-4-yl)prop-2-en-1-one
  参考文献：
  名称：

  ( E )-3-(3,4,5-Trimethoxyphenyl)-1-(pyridin-4-yl)prop-2-en-1-one, a heterocyclic chalcone is a potent and selective CYP1A1 inhibitor and cancer chemopreventive agent

  摘要：

  The overexpression of CYP1 family of enzymes is reported to be associated with development of human carcinomas. It has been well reported that CYP1A1 specific inhibitors prevents carcinogenesis. Herein, thirteen pyridine-4-yl series of chalcones were synthesized and screened for inhibition of CYP1 isoforms 1A1, 1B1 and 1A2 in Sacchrosomes (TM) and live human HEK293 cells. The structure-activity relationship analysis indicated that chalcones bearing tri-alkoxy groups (8a and 8k) on non-heterocyclic ring displayed selective inhibition of CYP1A1 enzyme, with IC50 values of 58 and 65 nM, respectively. The 3,4,5-trimethoxy substituted derivative 8a have shown > 10-fold selectivity towards CYP1A1 with respect to other enzymes of the CYP1 sub-family and > 100-fold selectivity with respect to CYP2 and CYP3 family of enzymes. The potent and selective CYP1A1 inhibitor 8a displayed antagonism of B[a] P mediated activation of aromatic hydrocarbon receptor (AhR) in yeast cells, and also protected human cells from CYP1A1-mediated B[a] P toxicity in human cells. This potent and selective inhibitor of CYP1A1 enzyme have a potential for development as cancer chemopreventive agent. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.11.009

文献信息

• ( E )-3-(3,4,5-Trimethoxyphenyl)-1-(pyridin-4-yl)prop-2-en-1-one, a heterocyclic chalcone is a potent and selective CYP1A1 inhibitor and cancer chemopreventive agent
  作者：Neill J. Horley、Kenneth J.M. Beresford、Supriya Kaduskar、Prashant Joshi、Glen J.P. McCann、Ketan C. Ruparelia、Ibidapo S. Williams、Linda Gatchie、Vinay R. Sonawane、Sandip B. Bharate、Bhabatosh Chaudhuri

  DOI：10.1016/j.bmcl.2017.11.009

  日期：2017.12

  The overexpression of CYP1 family of enzymes is reported to be associated with development of human carcinomas. It has been well reported that CYP1A1 specific inhibitors prevents carcinogenesis. Herein, thirteen pyridine-4-yl series of chalcones were synthesized and screened for inhibition of CYP1 isoforms 1A1, 1B1 and 1A2 in Sacchrosomes (TM) and live human HEK293 cells. The structure-activity relationship analysis indicated that chalcones bearing tri-alkoxy groups (8a and 8k) on non-heterocyclic ring displayed selective inhibition of CYP1A1 enzyme, with IC50 values of 58 and 65 nM, respectively. The 3,4,5-trimethoxy substituted derivative 8a have shown > 10-fold selectivity towards CYP1A1 with respect to other enzymes of the CYP1 sub-family and > 100-fold selectivity with respect to CYP2 and CYP3 family of enzymes. The potent and selective CYP1A1 inhibitor 8a displayed antagonism of B[a] P mediated activation of aromatic hydrocarbon receptor (AhR) in yeast cells, and also protected human cells from CYP1A1-mediated B[a] P toxicity in human cells. This potent and selective inhibitor of CYP1A1 enzyme have a potential for development as cancer chemopreventive agent. (C) 2017 Elsevier Ltd. All rights reserved.