Unlock instant, AI-driven research and patent intelligence for your innovation.

sir2 inhibitor

An inhibitor, sir2 technology, applied in the field of Sir2 inhibitors, can solve problems such as poor inhibition effect, and achieve the effect of inhibiting the growth of cancer cells

Inactive Publication Date: 2015-10-28
BOHAI UNIV
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Currently, the IC of Sir2 inhibitors 50 Mostly at the μM level, the inhibitory effect is not good, such as the IC of nicotine on Sirt2 50 100 μM, the IC of chroman-4-one derivatives on Sirt2 50 1.5~10 μM, effective and more potent Sir2 inhibitors are needed to provide the treatment of cancer and Parkinson's disease

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • sir2 inhibitor
  • sir2 inhibitor
  • sir2 inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035]

[0036] The freeze-dried Carba-NMN structural formula is (89 mg, 0.25 mmol) was suspended in 5 ml redistilled dimethyl sulfoxide (DMSO) and 1 ml N,N-dimethylformamide (DMF), sonicated and stirred to dissolve it. Add methylimidazole (415 μl, 5.2 mmol), 2,2 dithiobipyridine ((PyS) 2 ) (286 mg, 0.93 mmol) dissolved in 0.8 ml DMF, triphenylphosphine (PPh 3 ) (341 mg, 1.3 mmol) was dissolved in 0.8 ml DMF, added to the reaction system in sequence, stirred at room temperature for 15 min, and phosphate monoester 6-phenyladenine mononucleotide (555 mg, 0.7 mmol, dissolved in 1.5 ml DMF), stirred at room temperature for 9 h; transferred to a 50 ml centrifuge tube and added 30 ml 0.2 M NaI acetone solution, a precipitate was formed, centrifuged, the precipitate was dissolved in 8 ml water, and dissolved in 15 ml CH 2 Cl 2 Extract 3 times, concentrate the aqueous phase, adjust the pH to 2, put on a DEAE-agarose column (2 M NaCl 1000 ml wash, and then 10 mM NH 4 COOH 1000 ...

Embodiment 2

[0049]

[0050] Using 6-phenyladenine mononucleotide instead of 6-morpholine adenine mononucleotide, the others are the same as in Example 1, and the yield of the obtained target product is 22.9%. 1 H NMR (D 2 O, 400 MHz) δ(ppm) 9.36 (s, 1H), 9.12 (d, J = 6.0 Hz, 1H), 8.63 (d, J = 7.1 Hz, 1H), 8.16 (s, 1H), 8.01 (dd, J = 6.0 Hz, 7.1 Hz, 1H ), 7.93 (s, 1H), 5.83 (m, 2H), 4.3~4.0 (m, 9H), 3.91 (bs, 4H), 3.68 (bs, 4H), 2.60 (ddd, J = 9.4 Hz, 9.4 Hz, 13.3 Hz, 1H), 2.32 (m, 1H), 2.05 (m, 1H); 13 C NMR (D 2 O, 100.6 MHz) 165.1, 153.2, 151.8, 149.7, 145.6, 142.3, 139.9, 139.1, 133.6, 128.6, 118.9, 87.0 (d, J = 8.5 Hz), 86.5, 83.6 (d, J = 8.3 Hz), 77.5, 73.8, 70.6, 70.2, 66.3, 65.3 (d, J = 4.8 Hz), 64.8 (d, J = 4.1 Hz), 45.643.1 (d, J = 8.0 Hz), 28.8; 31 P NMR (D 2 O, 162 MHz) δ(ppm) -11.0 (d, J = 19.4 Hz), -11.3 (d, J = 19.4 Hz); HRMS (ESI) calcd for (C 25 h 32 N 7 o 15 P 2 ) - requires m / z 748.5726, found m / z 748.5732.

[0051] Sir2 inhibitory act...

Embodiment 3

[0053]

[0054] The same method as in Example 1; the difference from Example 1 is that the phosphate monoester used is 6-imidazolium mononucleotide, and the yield is 34.9%. 1 H NMR (D 2 O, 400 MHz) δ(ppm) 9.20 (s, 1H), 9.04 (d, J = 4.0 Hz, 1H), 8.72 (d, J = 8.0 Hz, 1H), 8.66 (br, 2H), 8.59 (s, 1H), 8.04 (dd, J = 4.0 Hz, 8.0 Hz, 1H ), 7.97 (s, 1H), 7.1 (s, 1H), 6.11 (d, J = 5.3 Hz, 1H), 5.9 (d, J = 5.2 Hz, 1H), 4.41 (m, 3H), 4.36 (m, 1H), 4.29 (m, 3H), 4.16 (m, 2H), 3.99 (m, 1H), 2.60 (ddd, J = 9.4 Hz, 9.4 Hz, 13.3 Hz, 1H), 2.32 (m, 1H); 13 C NMR (D 2 O, 100.6 MHz) 164.8, 152.6, 151.7, 145.7, 144.4, 143.9, 142.5, 139.6, 136.9, 133.5, 129.4, 128.4, 121.4, 117.1, 87.5, 86.8 (d, J = 5.7 Hz), 83.7 (d, J = 6.0 Hz), 77.4, 74.2, 70.4, 70.2, 65.2, 64.8, 43.1 (d, J = 8.0 Hz), 28.8; 31 P NMR (D 2 O, 162 MHz) δ(ppm) -10.9 (d, J = 17.8 Hz), -11.2 (d, J = 17.8 Hz); HRMS (ESI) calcd for (C 24 h 27 N 8 o 14 P 2 ) - requires m / z 729.5295, found m / z 729.5222.

...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to a Sir2 inhibitor. A structural formula of the Sir2 inhibitor is as shown in the description, wherein R1 is one of aromatic amine, saturated or unsaturated alkyl, hydroxy and amido; and R2 is one of aryl, saturated or unsaturated alkyl, hydroxy and amino. The compound is the Sir2 inhibitor, can inhibit growth of cancer cells and can be applied to preparation of a medicament for treating cancers of people and other mammals.

Description

technical field [0001] The present invention relates to a Sir2 inhibitor. Background technique [0002] Sir2 (Silent information regulator) is a kind of NAD + (Nicotinamide adenine dinucleotide)-dependent histone deacetylase, involved in the regulation of many life activities, including DNA repair, gene silencing and cell lifespan. Sir2 in NAD + In the presence of acetyl, the acetyl group on histone is removed to generate nicotine and 2-acetyl-ADP (adenosine diphosphate) or 3-acetyl-ADP. Overexpression of Sir2 reduces the activity of the anti-cancer gene p53, and inhibiting Sir2 activity can curb the proliferation of cancer cells. Studies have also shown that inhibiting Sir2 activity can alleviate Parkinson's disease, so inhibiting Sir2 activity is considered to be effective in preventing cancer, Parkinson's disease, and diabetes It is very important in the development of diseases such as ect., and new Sir2 inhibitors need to be developed. [0003] Currently, the IC of S...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/7076A61K31/706A61K31/7068A61P35/00C07H19/207C07H19/056C07H19/10C07H1/00
Inventor 侯淑华刘玉静任冬梅汤立军
Owner BOHAI UNIV