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Resveratrol derivative, preparation method thereof and application of resveratrol derivative serving as LSD1 inhibitor

A technology of resveratrol and derivatives, applied in antiviral agents, drug combinations, organic chemistry, etc., to achieve strong LSD1 inhibitory activity, high yield, and favorable effects for popularization and application

Active Publication Date: 2016-10-26
XINXIANG MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In order to discover new small-molecule inhibitors of LSD1, a class of resveratrol derivatives was obtained through further structural optimization of resveratrol. Reported inhibitory activity

Method used

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  • Resveratrol derivative, preparation method thereof and application of resveratrol derivative serving as LSD1 inhibitor
  • Resveratrol derivative, preparation method thereof and application of resveratrol derivative serving as LSD1 inhibitor
  • Resveratrol derivative, preparation method thereof and application of resveratrol derivative serving as LSD1 inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] The preparation of embodiment 1 (E)-4-(3,4-dimethoxystyryl) benzyl cyanide (I-1)

[0037]

[0038] The compound 3,4-dimethoxybenzaldehyde (1.66g, 10mmol) and diethyl 4-cyanobenzylphosphonate (2.79g, 11mmol) were dissolved in anhydrous DMF (10mL), stirred in an ice bath Slowly add potassium tert-butoxide (2.24g, 20mmol), and react at room temperature for 3 hours after the addition, slowly add the reaction system into ice water (40mL), a white solid is washed out, suction filtered, washed with water, the solid is collected, and washed with acetone Recrystallized, filtered with suction, and dried in vacuo to obtain 2.21 g of a white solid with a yield of 83.4%. Mp: 102-103°C. 1 H NMR (400MHz, CDCl 3 )δ7.64(d, 2H, J=8.0Hz), 7.58(d, 2H, J=8.0Hz), 7.19(d, 1H, J=16.4Hz), 7.10(m, 2H), 6.98(d, 1H,J=16.4Hz),6.90(d,1H,J=8.0Hz),3.97(s,3H),3.93(s,3H). 13 CNMR (101MHz, CDCl 3 )δ149.76, 149.22, 142.11, 132.48, 132.22, 129.36, 126.59, 124.74, 120.76, 119.17, 111.19, 110.10, 108...

Embodiment 2

[0039] The preparation of embodiment 2 (E)-4-(2-fluoro-4,5-dimethoxystyryl) benzyl cyanide (I-2)

[0040]

[0041] According to the method of Example 1, 2-fluoro-4,5-dimethoxybenzaldehyde (1.84g, 10mmol) was used to replace 3,4-methoxybenzaldehyde to obtain 2.12g of white solid with a yield of 74.9%. Mp: 130-131°C. 1 H NMR (400MHz, CDCl 3 )δ7.66(d, 2H, J=8.0Hz), 7.61(d, 2H, J=8.0Hz), 7.36(d, 1H, J=16.0Hz), 7.06(d, 1H, J=8.0Hz) ,7.04(d,1H,J=16.0Hz),6.69(d,1H,J=12.0Hz),3.95(s,3H),3.92(s,3H). 13 C NMR (101MHz, CDCl 3 )δ156.68,154.24,150.50,150.40,145.64,145.62,142.00,132.51,126.37,126.32,124.47,124.44,119.09,115.29,115.16,110.44,108.35,108.30,100.30,100.02,56.46,56.24.HRMS(ESI)calcd for C 17 h 15 FNO 2 [M+H] + :284.1081,Found:284.1081.

Embodiment 3

[0042] The preparation of embodiment 3 (E)-4-(2-bromo-4,5-dimethoxystyryl) benzyl cyanide (I-3)

[0043]

[0044] According to the method of Example 1, 2-bromo-4,5-dimethoxybenzaldehyde (1.23g, 5mmol) was used to replace 3,4-dimethoxybenzaldehyde to obtain 1.31g of white solid, yield 76.3% . Mp: 149-151°C. 1 H NMR (400MHz, CDCl 3 )δ7.67(d, 2H, J=8.0Hz), 7.63(d, 2H, J=8.0Hz), 7.55(d, 1H, J=16.0Hz), 7.16(s, 1H), 7.08(s, 1H), 6.95(d, 1H, J=16.0Hz), 3.97(s, 3H), 3.92(s, 3H). 13 C NMR (101MHz, CDCl 3 )δ150.10, 148.74, 141.70, 132.55, 130.93, 128.19, 127.31, 126.97, 119.04, 115.74, 115.54, 110.69, 108.68, 56.25, 56.16. HRMS (ESI) calcd for C 17 h 14 BrNNaO 2 [M+Na] + :366.0106,Found:366.0101.

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Abstract

The invention discloses a resveratrol derivative, a synthesizing method thereof and application of the resveratrol derivative serving as a histone lysine specificity demethylase 1 inhibitor and belongs to the field of medicinal chemistry. The formula of the resveratrol derivative is as shown in the specification, wherein R is preferably hydrogen, hydroxyl, methoxy, nitro or halogen, and X represents N atom and C atom. The resveratrol derivative has good inhibitory effect on the histone lysine specificity demethylase 1 and can be used as the candidate for further development or the lead compound to develop medicine for treating diseases such as tumors and AIDS.

Description

technical field [0001] The invention specifically relates to a class of resveratrol derivatives, a preparation method and its application as an inhibitor of histone lysine specific demethylase 1, and belongs to the technical field of medicinal chemistry. Background technique [0002] Histone Lysine Specific Demethylase 1 (LSD1) is the first discovered histone lysine demethylase (Y.Shi et al, Cell, 2004, 29, 941–953). LSD1 is a flavin adenine dinucleotide-dependent demethylase, which acts on different substrates by combining with different molecular partners, thereby producing different biological functions. LSD1 binds to target genes through CoREST, and can specifically remove the single or double methylation of H3K4 (Histone 3, Lysine 4), resulting in gene transcriptional repression. When LSD1 binds to androgen receptor or estrogen receptor, it can specifically remove the mono- or di-methylation of H3K9 (Histone 3, Lysine 9), causing hormone receptor-dependent gene transc...

Claims

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Application Information

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IPC IPC(8): C07C257/18C07D213/58A61P35/00A61P31/18
CPCC07C257/18C07D213/58
Inventor 段迎超关圆圆翟晓雨郑一超刘巍
Owner XINXIANG MEDICAL UNIV
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