Medicine for inhibiting stearoyl-CoA desaturase 1

A technology of stearoyl coenzyme A and desaturase, which is applied in the field of medicine and biology to inhibit stearoyl coenzyme A desaturase 1. It can solve the problems of no parent ring structure, etc., and achieve obvious effects and obvious inhibition of enzyme activity , the effect of promoting autophagy and apoptosis

Active Publication Date: 2021-07-02
JIANGNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] Currently, the reported small molecule inhibitors of SCD1 mainly include CAY-10566, MF438, A939572, CVT-11127, CVT-12012, T-3764518, PluriSIn 1, SW203668, SW203668, BZ36, SSI-4, etc. (see 1-11 for the structural formula), there is no parent ring structure similar to compound A

Method used

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  • Medicine for inhibiting stearoyl-CoA desaturase 1
  • Medicine for inhibiting stearoyl-CoA desaturase 1
  • Medicine for inhibiting stearoyl-CoA desaturase 1

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Embodiment 1: the preparation of compound

[0029] Synthesis of compound A (formula I structure):

[0030]

[0031] Add 800mg of ICT to a 250mL round bottom flask, add 150mL of acetone, 324mg of 1-bromo-3-methyl-2-butene, 300mg of anhydrous potassium carbonate, reflux at 56°C for 4 hours, cool, evaporate part of the acetone, and leave The reaction solution below was adjusted to PH to 4-5 with 1N HCl, then extracted three times with 100mL dichloromethane, and the organic layer was dried over anhydrous sodium sulfate and separated by silica gel column chromatography (petroleum ether: ethyl acetate=10:1 ) to obtain 130 mg of compound A (yield = 13.71%).

[0032] 1 H NMR (400MHz, Chloroform-d): δ12.75(s, 1H), 8.12(d, J=9.0Hz, 2H), 7.03(d, J=9.1Hz, 2H), 6.31(s, 1H), 6.12(s,1H),5.44(t,J=7.3Hz,1H),5.32(s,1H),4.58(d,J=7.3Hz,2H),3.92(s,3H),3.59(d,J =7.3Hz,2H),1.86(s,3H),1.79(s,3H),1.71(s,3H),1.65(s,3H).

[0033] Synthesis of Compound B:

[0034]

[0035] Add 800mg of...

Embodiment 2

[0042] Effects of compound A, compound B, compound C, and icariin (ICT) on SCD1 enzyme activity in prostate cancer cells:

[0043] SCD1 enzyme activity detection:

[0044] (1) Collect the logarithmic phase cells, adjust the concentration of the cell suspension, and use 4x10 6 One cell / dish is appropriate.

[0045] (2) at 5% CO 2, incubate at 37°C, discard the original medium after the cells have adhered completely, and add 8 mL of 0.2 mM [d31] PA (isotope d31-labeled palmitic acid, linear molecular formula: CD 3 (CD 2 ) 14 CO 2 H) and culture medium with different concentrations of compound A, using SCD1 inhibitor MF-438 as a positive control.

[0046] (3) Discard the supernatant after incubation for 24 hours, wash twice with PBS, add 1ml CH 3 Cells were scraped off with an OH scraper and ultrasonically broken into a lipid extraction bottle.

[0047] (4) Each sample was added with 3ml CH 3 OH, 2ml CHCl 3 , 6mol / L HCl50μl, leak detection, shake for 1h. Then add 2ml C...

Embodiment 3

[0090] Detect the effect of compound A shown in formula I on the proliferation of tumor cells (MCF-7, MDA-MB-231, PC-3, and LNCaP):

[0091] (1) Collect the logarithmic phase cells, adjust the concentration of the cell suspension, preferably 100 μl per well of a 96-well plate, seed the plate to adjust the density of the cells to be tested to 1000-10000 per well, and fill the edge wells with sterile PBS.

[0092] (2) 5% CO 2, incubate the cells at 37°C, discard the original medium after the cells are completely attached, add 100 μl of 10% FBS medium containing 2.5, 5, 10, 20, 40, 80 μM compound A to each well, and the number of multiple wells is 4.

[0093] (3) After incubation for 24 hours, take pictures to record the state of the cells, discard the original culture medium, and add 20 μl of MTT (3-(4,5-dimethylthiazole-2)-2,5- Diphenyltetrazolium bromide, trade name: thiazolium blue).

[0094] (4) After incubation for 4 hours, discard the original culture medium, add 150 μl ...

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Abstract

The invention discloses a medicine for inhibiting stearoyl-CoA desaturase 1, and belongs to the technical field of medical biotechnology. It is found for the first time that the compound with the structure shown in the formula I has the effect of inhibiting stearoyl-CoA desaturase 1, the activity of saturated fatty acid desaturase can be inhibited, the compound plays a role in adjusting fatty acid composition, and an effective new means and a new approach are provided for treating SCD1 drug target diseases.

Description

technical field [0001] The invention relates to a medicine for inhibiting stearoyl-CoA desaturase 1, which belongs to the technical field of medical biotechnology. Background technique [0002] Stearoyl-CoA desaturase 1 (SCD1) is highly expressed in metabolism-related cells and some tumor cells, and SCD1 has become a new drug target for studying such diseases. The study of SCD1 inhibitors is of great significance for inhibiting the synthesis of monounsaturated fatty acids and effectively controlling the occurrence and development of tumors, obesity and various related metabolic syndromes. [0003] The currently reported small molecule inhibitors of SCD1 mainly include CAY-10566, MF438, A939572, CVT-11127, CVT-12012, T-3764518, PluriSIn 1, SW203668, SW203668, BZ36, SSI-4, etc. (see 1- 11), there is no parent ring structure similar to compound A. [0004] [0005] Contents of the invention [0006] The present invention finds that the compound with the structure show...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/352A61P3/04A61P35/00A61P1/16A61P3/06A61P3/10A61P9/10A61P9/00A61P5/48
CPCA61K31/352A61P3/04A61P35/00A61P1/16A61P3/06A61P3/10A61P9/10A61P9/00A61P5/48
Inventor 吴国胜杨晨金忆媛唐春雷陈永泉崔国祯
Owner JIANGNAN UNIV
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