CN103961340A - LSD1 inhibitors and application thereof - Google Patents

Abstract

The present invention relates to a novel LSD1 inhibitor and its application in medicine, especially the application in preparing anti-LSD1 inhibitor medicine and treating tumor, virus infection, blood disease and other medicines. The chemical structural formula of the LSD1 inhibitor is as follows: Compound I: wherein the 2-carbon of the benzene ring is connected to the bromine atom, and the 4,5,3',4'-position carbon is connected to the hydroxyl group. The chemical name in Chinese is: (3′,4′-dihydroxy-phenyl)-(2-bromo-4,5-dihydroxy-phenyl)-methanone; in English: (3′,4′-dihydroxyphenyl) -(2-bromo-4,5-dihydroxyphenyl)methanone. Compound II: wherein the 2,2'-position carbons of the benzene ring are connected to the bromine atom, and the 4,5,4',5'-position carbons are connected to the hydroxyl group. The chemical name in Chinese is: (2′-bromo-4′,5′-dihydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)-methanone; in English: (2′-bromo- 4',5'-dihydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)methanone.

Description

A class of LSD1 inhibitors and applications thereof

technical field

The present invention relates to the technical field of medicines, specifically two novel LSD1 inhibitors (3', 4'-dihydroxy-phenyl)-(2-bromo-4,5-dihydroxy-phenyl)-methanone ( I) and (2'-bromo-4',5'-dihydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)-methanone (II) and its pharmacological activity and pharmaceutical use. The compound and its derivatives can be used as LSD1 inhibitors to prevent and/or treat diseases and symptoms related to the activity of histone demethylase LSD1, especially diseases related to abnormal gene transcription, cell differentiation and proliferation, etc. Such as tumors, viral infections and blood diseases.

Background technique

Malignant tumors seriously affect people's health and have become the second leading cause of human death, second only to cardiovascular and cerebrovascular diseases. According to the statistics of the World Health Organization, more than 10 million cancer patients are newly diagnosed every year in the world, and the total number of cancer deaths worldwide reaches 7 million people every year. With the aggravation of environmental pollution, the incidence of cancer is increasing year by year, showing a trend of multiple occurrences. The WHO 2014 report predicts that global cancer cases will show a rapid growth trend, from 14 million in 2012 to 19 million in 2025. , will reach 24 million by 2035, and the death toll will also increase from 6 million to 10 million per year. In 2012, China had 3.07 million new cancer patients and caused about 2.2 million deaths, accounting for 21.9% and 26.8% of the global total respectively. Cancer has become the leading cause of death among urban and rural residents in my country. Tumors not only seriously threaten the health of the people, bring economic losses to patients and their families, but also cause heavy burdens to the country and society. Finding new anti-tumor drugs with high efficiency, low toxicity, and new mechanisms of action that can selectively kill or inhibit tumor cells has become an important direction for the development of anti-tumor drugs.

Lysine specific demethylase 1 (Lysine specific demethylase1, LSD1) is a flavin adenine dinucleotide (Flavin adenine dinulcleotide, FAD) dependent amine oxidase. LSD1, also known as KIAA0601, KDM1, AOF2, BHC110, p110b and NPAO, was first discovered in 2004 [Shi Y, et al. Cell, 2004, 119(7): 941.]. In the LSD1 structure, there is an N-terminal SWIRM (Swi3p, Rsc8p and Moira) domain, a Tower domain and a C-terminal amine oxidase structure [Aravind L, Iyer L M. Genome Biol, 3, 2002, RESEARCH0039.]. LSD1 is a member of the amine oxidase family, which relies on FAD to catalyze the oxidation reaction to produce a formaldehyde and a demethylated lysine residue to remove the methyl group, and can specifically remove monomethylation and dimethylation Methyl groups at lysine 4 (H3K4) and H3K9 of histone H3. LSD1 regulates gene expression, cell proliferation and differentiation by regulating the activated or repressed chromatin domain, maintains the stability of the body, and plays an important role in cell cycle, apoptosis and other life processes. LSD1 is not only at the center of gene expression regulation network, but also regulates the biological activity of certain proteins. At present, most of the targets regulated by LSD1 are various transcription factors (REST, Gfi-1, Gfi-1b, ZEB1, PIT1, ERα and AR [Forneris F, et al. Trends Biochem Sci, 2008, 33 (4):181.]. LSD1 can also interact with P53, and inhibit the transcriptional activity regulated by P53 by demethylating P53 (the monomethyl and dimethyl groups on K37O can be removed). apoptosis. LSD1 is highly expressed in a variety of tumor cells, including prostate cancer, neuroblastoma, breast cancer, bladder cancer, lung cancer, and colon cancer. LSD1 regulates cell proliferation and differentiation by affecting the expression of factors necessary for cell proliferation and differentiation. It regulates the occurrence and development of tumors, and its imbalance leads to the occurrence of tumors.

Studies have proved that LSD1 has become a new and important drug target for the treatment of tumors, leukemia, and viral diseases, and plays an important role in the prevention and treatment of tumors, viruses, and metabolic diseases. The research on its inhibitors has also become a current research hotspot. Small molecule inhibitors of LSD1 have been proven to be effective lead compounds for the development of tumor therapeutic drugs. There are not many LSD1 inhibitors currently reported, mainly including cyclopropylamines, polyamines, guanidines, ureas, thioureas, cyclic peptides, triazole-dithiocarbamates, etc. These compounds are used as LSD inhibitors have shown good application potential in anti-tumor, anti-virus and treatment of leukemia, but there are no marketed drugs yet. We discovered a series of brominated natural marine natural products from algae with anti-LSD1 activity and synthesized a series of analogues, and found two compounds (3′,4′-dihydroxy-phenyl)-(2-bromo- 4,5-dihydroxy-phenyl)-methanone (I) and (2'-bromo-4',5'-dihydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)- Methanone(II) has strong inhibitory activity against LSD1.

Contents of the invention

The present invention relates to the technical field of medicines, specifically two novel LSD1 inhibitors (3', 4'-dihydroxy-phenyl)-(2-bromo-4,5-dihydroxy-phenyl)-methanone ( I) and (2'-bromo-4',5'-dihydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)-methanone (II) and its pharmacological activity and pharmaceutical use. The compound and its derivatives can be used as LSD1 inhibitors to prevent and/or treat diseases and symptoms related to the activity of histone demethylase LSD1, especially diseases related to abnormal gene transcription, cell differentiation and proliferation, etc. Such as tumors, viral infections, leukemia and other diseases.

The present invention provides two LSD1 inhibitors (3',4'-dihydroxy-phenyl)-(2-bromo-4,5-dihydroxy-phenyl)-methanone (I) and (2'-bromo -4',5'-dihydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)-methanone (II):

The present invention also provides compounds I and II of the present invention for the prevention and/or treatment of diseases and symptoms related to the activity of histone demethylase LSD1, especially those related to abnormal gene transcription, cell differentiation and proliferation, etc. application in disease.

When the compound of the present invention is used as a medicine, it can be used directly or in the form of a pharmaceutical composition. The pharmaceutical composition contains 0.1-99%, preferably 0.5-90%, of the compound of the present invention, and the rest are pharmaceutically acceptable carriers and/or excipients.

The pharmaceutical carrier or excipient is one or more solid, semi-solid and liquid diluents, fillers and pharmaceutical preparation adjuvants. The pharmaceutical composition of the present invention is used in a dose per body weight. The medicine of the present invention can be administered in three forms of injection (intravenous injection, intramuscular injection), oral administration and external application.

The sources of the compounds (I) and (II) are not only natural products, or synthetic products by chemical synthesis or biosynthesis.

The object of the present invention is to provide two novel LSD1 inhibitors (3', 4'-dihydroxy-phenyl)-(2-bromo-4,5-dihydroxy-phenyl)-methanone (I) and (2' -Bromo-4', 5'-dihydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)-methanone (II), the compound and its derivatives can inhibit the activity of LSD1 with For the prevention and/or treatment of diseases and symptoms related to the activity of histone demethylase LSD1, especially diseases related to abnormal gene transcription, cell differentiation and proliferation, such as prostate cancer, neuroblastoma in cancer solid tumors cancer, breast cancer, bladder cancer, gastric cancer, myeloma, lung cancer, colon cancer, hepatitis B virus (HBV) in viral infections, human immunodeficiency virus (HIV) and leukemia in blood diseases.

To achieve the above object, the technical scheme adopted in the present invention is as follows:

1. Compound synthesis and structure identification

Using veratric acid and veratrole as starting materials, PPA as a catalyst, using Friedel-Crafts acylation reaction to synthesize aryl ketone intermediates; then, phenyl ring bromination occurs with bromine in acetic acid to generate brominated intermediates; finally Use boron tribromide to remove the methoxy group to obtain the crude product, then use chloroform and methanol as the eluent, and purify by silica gel column chromatography to obtain a white solid. It was identified as the compound (3′,4′-dihydroxy-phenyl)-(2-bromo-4,5-dihydroxy-phenyl)-methanone (I) [English: (3′ ,4′-dihydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)methanone] and (2′-bromo-4′,5′-dihydroxyphenyl)-(2-bromo-4,5-dihydroxy Phenyl)-methanone (II) [English: (2′-bromo-4′, 5′-dihydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)methanone].

2. Determination of the inhibitory activity of lysine-specific histone methylase 1 (LSD1)

The LSD1 protein with biological activity was obtained by expressing and purifying the E. coli expression system, and the LSD1 activity and the IC ₅₀ value of the inhibitor were detected at 665nm and 615nm wavelengths by PerkinElmer's Lance detection reagent.

Detailed ways

In order to better understand the essence of the present invention, the following will illustrate the compound of the present invention (3', 4'-dihydroxy-phenyl)-(2-bromo-4,5-dihydroxy-benzene) with the examples of the present invention Pharmacological action of (I)-methanone (I) and (2'-bromo-4',5'-dihydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)-methanone (II) results, but the present invention is not limited by this example.

Example 1

(3′,4′-Dihydroxy-phenyl)-(2-bromo-4,5-dihydroxy-phenyl)-methanone (I) and (2′-bromo-4′,5′-dihydroxy Preparation of phenyl)-(2-bromo-4,5-dihydroxyphenyl)-methanone (II).

The synthetic route of the compound is shown in the figure below:

(1) After adding 22.08g (120mmol) of veratrolic acid, 16.92g (120mmol) of veratrole and 100g of polyphosphoric acid into a 500ml three-necked flask, the mixture was reacted under electric stirring at 80°C for 1 hour. The reaction mixture was cooled to 60° C. and 250 ml of ice water was added dropwise to the reactant within 30 min. At this time, a large amount of water-insoluble pink solid appeared in the reactant. After removing water by filtration, the obtained solid was dissolved in 100 ml of dichloromethane, and then the dichloromethane phase was washed 3 times with an equal volume of 3% sodium hydroxide solution and distilled water, respectively. After drying over anhydrous magnesium sulfate, it was concentrated under reduced pressure to obtain a pink solid. The solid was washed three times with petroleum ether, each with 150 ml of petroleum ether. Finally, the solid washed with petroleum ether was evaporated to dryness under reduced pressure to obtain light yellow solid 3 (30.7 g, 85%), white powder, mp 145.3-146.1°C. (lit ⁵ mp147℃); ¹ H NMR (500MHz, CDCl ₃ ) δ3.92(6H,s),3.94(6H,s),6.88(2H,d,J＝8.4Hz),7.36(2H,dd, J＝8.4, 1.7Hz), 7.42 (2H, d, J＝1.7Hz); ¹³ C NMR (125MHz, CDCl ₃ ) δ56.03(CH3), 109.79(C), 112.39(C), 124.69(C) , 130.82 (C), 148.90 (C), 152.61 (C), 194.35 (C=O).

(2) Add 3 g (10 mmol) of light yellow solid 3 into a 250 ml three-necked flask, and add 20 ml of dichloromethane to dissolve. After diluting 0.52ml of bromine with 10ml of dichloromethane, it was slowly added dropwise to the three-necked flask under ice-bath conditions, and the dropwise addition was completed within 1 hour. Then continue to stir the reaction under an ice bath, TLC detects the end point of the reaction, and stops the reaction after the raw material point disappears. The reaction solution was concentrated under reduced pressure to obtain a brown solid. Using petroleum ether: acetone = 8:1, silica gel column purification to obtain white powder 4a (2.43g, 64%), white powder, mp129.9-130.5 ° C, ¹ H NMR (500MHz, CDCl ₃ ) δ3.84 (3H ,s),3.92(3H,s),3.93(3H,s),3.94(3H,s),6.85(1H,d,J＝8.4Hz),6.87(1H,s),7.07(1H,s) ,7.25(1H,dd,J=8.4,1.9Hz),7.54(1H,d,J=1.9Hz); ¹³ C NMR(125MHz,CDCl ₃ )δ56.05(CH ₃ ),56.09(CH ₃ ), 56.19(CH ₃ ), 56.32(CH ₃ ), 110.01(C), 110.65(C), 111.37(C), 112.10(C), 115.81(C), 126.22(C), 129.58(C), 132.85(C ), 148.25(C), 149.29(C), 150.66(C), 153.89(C), 194.25(C=O).

(3) Add 15.1 g (50 mmol) of light yellow solid 3 and 120 ml of acetic acid into a 250 ml three-neck flask, then raise the temperature to 45° C. and stir rapidly to dissolve the solid. After diluting 5.3ml of bromine with 10ml of acetic acid, quickly drop it into the three-necked flask at room temperature, and finish the dropwise addition within 20 minutes. After the bromine was added dropwise, the reaction was continued to be stirred at room temperature. After 1 hour, a light yellow precipitate was precipitated. The end point of the reaction was detected by TLC, and the reaction was stopped after the disappearance of the raw material point. The reaction solution was poured into a separatory funnel filled with 120 ml of saturated saline, and dichloromethane was added for extraction. Add 100ml of dichloromethane each time, extract three times, combine the organic phases, dry over anhydrous magnesium sulfate, and concentrate under reduced pressure to obtain a brown solid. The solid was washed 4 to 6 times with acetone, each with 50 ml of acetone. The resulting solid was evaporated to dryness under reduced pressure to obtain light yellow powder 4b (18.87g, 82%), light yellow powder, mp172.5-173.2°C, ¹ H NMR (500MHz, CDCl ₃ ) δ3.87 (6H, s), 3.94 (6H,s),7.05(4H,s); ¹³ C NMR(125MHz,CDCl ₃ )δ56.26(CH ₃ ),56.33(CH ₃ ),113.22(C),114.00(C),116.37(C) , 131.76 (C), 148.40 (C), 152.01 (C), 194.26 (C=O).

(4) After adding 0.76g (2mmol) of white powder 4a and 30ml of dichloromethane into a 250ml three-necked flask and stirring to dissolve, slowly add 20ml (20mmol) of 1mol/L boron tribromide solution dropwise in an ice bath, within 1h over. Remove the ice and stir the reaction at room temperature. The end point of the reaction was detected by TLC. After the raw material point disappeared, the reaction solution was poured into 100 ml of ice-water mixture to terminate the reaction. The mixture was poured into a 500ml separatory funnel and extracted twice with ethyl acetate, each with 100ml of ethyl acetate. The organic phases were combined, dried with anhydrous magnesium sulfate, and evaporated to dryness under reduced pressure to obtain a brown solid. Using chloroform:methanol=15:1 as the eluent, the silica gel column chromatography was purified to obtain a yellow solid I (0.58g, 89%), a yellow powder , mp83.5-84.2℃, IR (KBr) 3239, 2980, 2879, 1641, 1589, 1506, 1442, 1292, 1188, 1111, 1046, 953, 883, 828, 782, 762, 635cm ^-1 ; ¹ H NMR (500MHz, DMSO-d ₆ ) δ6.71(1H,s),6.80(1H,d,J＝8.3Hz),6.99(1H,s),7.03(1H,dd,J＝8.3,2.0Hz),7.16(1H,d,J＝ 2.0Hz), 9.40(1H,s), 9.52(1H,s), 9.79(1H,s), 9.94(1H,s); ¹³ C NMR(125MHz,DMSO-d ₆ )δ107.28(C), 115.24(C), 115.97(C), 116.56(C), 119.26(C), 123.38(C), 128.07(C), 131.36(C), 144.58(C), 145.14(C), 147.65(C), 151.14(C), 193.21(C=O); EIMSm/z326/324[M] ⁺ (70/70), 245(77), 217/215(43/45), 137(100); HREIMS m/z323 .9649 (calcd for C ₁₃ H ₉ O ₅ Br, 323.9633).

(5), after adding 1.15g (2.5mmol) yellowish powder 4b and 30ml dichloromethane into a 250ml three-necked flask and stirring to dissolve, slowly add 25ml (25mmol) of 1mol/L boron tribromide solution dropwise under ice bath for 1h Added. Remove the ice and stir the reaction at room temperature. The end point of the reaction was detected by TLC. After the raw material point disappeared, the reaction solution was poured into 100 ml of ice-water mixture to terminate the reaction. The mixture was poured into a 500ml separatory funnel and extracted twice with ethyl acetate, each with 100ml of ethyl acetate. The organic phases were combined, dried with anhydrous magnesium sulfate, and evaporated to dryness under reduced pressure to obtain a brown solid. Using chloroform:methanol=15:1 as the eluent, the white solid II (0.9 g, 89%, white powder, mp245.6-245.9℃, IR (KBr) 3254, 2979, 2878, 1652, 1586, 1505, 1418, 1285, 1181, 1041, 880, 796, 768, 661, 646cm ^-1 ; ¹ H NMR (500MHz, DMSO-d ₆ ) δ6.82 (2H,s),7.00(2H,s),9.56(2H,s),10.09(2H,s); ¹³ C NMR(125MHz,DMSO-d ₆ )δ109.57(C),118.25(C), 120.24(C), 129.79(C), 144.55(C), 149.34(C), 192.88(C=O); EIMS m/z406/404/402[M] ⁺ (18/36/19), 326/324 (13/14), 244 (100), 217/215 (70/73); HREIMS m/z 403.8708 (calcd for C ₁₃ H ₈ O ₅ ⁷⁹ Br ⁸¹ Br, 403.8718).

Example 2

Lysine-specific histone methylase 1 (LSD1) inhibitory activity assay

Human recombinant LSD1/CoREST was expressed in Escherichia coli as an independent protein and co-purified using the method reported in the literature (Forneris F et al. Trends Biochem Sci, 2008, 33(4):181-189). Enzyme activity and inhibition experiments refer to methods reported in literature (Forneris F, et al. J. Biol. Chem. 282, 20070-20074), and a screening system was established. Compounds I and II were dissolved in a small amount of DMSO (the weight-to-volume ratio of compound to DMSO: 100mg: 1ml), diluted with buffer solution (50mM Hepes/NaOH with a pH of 7.5), and 2 μL was added to a 30 μL reaction system. Make the final concentrations of 100 μM, 10 μM, 1.0 μM, 0.1 μM, and 0.01 μM respectively, use Lys4 monomethylated histone H3 peptide as a substrate, and measure the fluorescence at 665 nm and 615 nm wavelengths with Lance detection reagent from Perkin Elmer Company The signal intensity was calculated, and the inhibitory activity of the compound on LSD1 was calculated. Compounds (3′,4′-dihydroxy-phenyl)-(2-bromo-4,5-dihydroxy-phenyl)-methanone (I) and (2′-bromo-4′,5′-di The IC ₅₀ values of the inhibitory activity of hydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)-methanone(II) on LSD1 histone methylase were 2.62 μM and 2.22 μM, respectively.

The experimental results show that compounds (I) and (II) have strong inhibitory activity on lysine-specific histone methylase 1 (LSD1), and can be used as LSD1 inhibitors for the prevention and/or treatment of Diseases and symptoms related to the activity of the protein demethylase LSD1, especially those related to abnormal gene transcription, cell differentiation and proliferation, such as tumors, viral infections, leukemia and other diseases.

Example 3

Preparation of compound (I) and (II) injection

Compounds (3′,4′-dihydroxy-phenyl)-(2-bromo-4,5-dihydroxy-phenyl)-methanone (I) and (2′-bromo-4′,5′-di Hydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)-methanone (II) with a small amount of DMSO (weight ratio: 1:0.1-1:0.5, here is 1:0.4) After dissolving, add water for injection as usual (weight ratio is 1:20-1:200, here is 1:200), fine filter, potting and sterilizing to make injection solution.

Example 4

Preparation of compound (I) and (II) powder injection

Compounds (3′,4′-dihydroxy-phenyl)-(2-bromo-4,5-dihydroxy-phenyl)-methanone (I) and (2′-bromo-4′,5′-di Hydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)-methanone (II) with a small amount of DMSO (weight ratio: 1:0.1-1:0.5, here is 1:0.5) After dissolving, dissolve it in sterile water for injection (weight ratio: 1:20-1:60, here is 1:60), stir to dissolve, filter with a sterile suction filter funnel, and then sterile fine filter , divided into ampoules, freeze-dried at low temperature and sealed aseptically to obtain powder injection.

Example 5

Preparation of compound (I) and (II) powder

Compounds (3′,4′-dihydroxy-phenyl)-(2-bromo-4,5-dihydroxy-phenyl)-methanone (I) and (2′-bromo-4′,5′-di Hydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)-methanone (II) was added to excipient (Tween 80:propylene glycol :cyclodextrin:lactose=1:2:4:12 (W/W)), made into powder.

Example 6

Preparation of Compound (I) and (II) Tablets

Compounds (3′,4′-dihydroxy-phenyl)-(2-bromo-4,5-dihydroxy-phenyl)-methanone (I) and (2′-bromo-4′,5′-di Hydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)-methanone (II) according to its and excipient (hypromellose E5: microcrystalline cellulose MCC102: stearic acid Magnesium: (8% povidone K30)=15:15:2:0.1 (W/W)) excipients are added in a weight ratio of 5:1, granulated and compressed into tablets.

Example 7

Preparation of compound (I) and (II) oral liquid

Compounds (3′,4′-dihydroxy-phenyl)-(2-bromo-4,5-dihydroxy-phenyl)-methanone (I) and (2′-bromo-4′,5′-di Hydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)-methanone (II) was added to distilled water containing 20% simple syrup and 0.1% sodium benzoate in mass concentration, and prepared according to conventional oral liquid The concentration is 15μg/mL oral solution.

Example 8

Preparation of compound (I) and (II) capsules

Compounds (3′,4′-dihydroxy-phenyl)-(2-bromo-4,5-dihydroxy-phenyl)-methanone (I) and (2′-bromo-4′,5′-di Hydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)-methanone (II) according to its and excipient (medicinal starch: glucose: hydrolyzed gelatin: glycine=30:10:1: 1 (W/W)) in a ratio of 5:1 by weight to make capsules.

Example 9

Preparation of compound (I) and (II) capsules

Compounds (3′,4′-dihydroxy-phenyl)-(2-bromo-4,5-dihydroxy-phenyl)-methanone (I) and (2′-bromo-4′,5′-di Hydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)-methanone (II) according to its and excipient (medicinal starch: glucose: hydrolyzed gelatin: glycine=30:10:1: 1 (W/W)) in a ratio of 3:1 by weight to make capsules.

Claims (8)

1. A class of LSD1 inhibitors, characterized in that: the LSD1 inhibitors with (3 ', 4 '-dihydroxy-phenyl)-(2-bromo-4,5-dihydroxy-phenyl)-methanone One or both of (I) or (2'-bromo-4', 5'-dihydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)-methanone (II) are Active ingredients, (3',4'-dihydroxy-phenyl)-(2-bromo-4,5-dihydroxy-phenyl)-methanone (I) and (2'-bromo-4',5' The chemical structural formula of -dihydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)-methanone (II) is shown in the figure below: 2. according to the described LSD1 inhibitor of claim 1, it is characterized in that: Compound I: the 2-position carbon of the benzene ring is connected to the bromine atom, and the 4,5,3', 4'-position carbon is connected to the hydroxyl group; the chemical name in Chinese is: (3',4'-dihydroxyl-phenyl)-( 2-bromo-4,5-dihydroxy-phenyl)-methanone; English: (3′,4′-dihydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)methanone; Compound II: the 2,2'-position carbon of the benzene ring is connected to the bromine atom, and the 4,5,4',5'-position carbon is connected to the hydroxyl group; the chemical name in Chinese is: (2'-bromo-4',5'- Dihydroxyphenyl)-(2-bromo-4,5-dihydroxyphenyl)-methanone; English: (2′-bromo-4′,5′-dihydroxyphenyl)-(2-bromo-4,5 -dihydroxyphenyl)methanone; One or two of the compound I and compound II mixed with LSD1 inhibitory activity, the compound I or compound II referred to here can be compound I or compound II itself and the pharmaceutically acceptable compound I or compound II One of chemical equivalents such as salts, esters or ethers, but not limited to the above chemical equivalents. 3. The LSD1 inhibitor according to claim 1 or 2, characterized in that: the compound I or compound II according to claim 1 is derived from natural products or synthetic products by chemical synthesis or biosynthesis. 4. according to the described LSD1 inhibitor of claim 1 or 2, it is characterized in that: One or both of compound I and compound II can be mixed with pharmaceutically acceptable drug carriers and can be made into tablets, capsules, oral liquids, granules, pills or injections for the treatment of related diseases, but not Limited to the above dosage forms. 5. The application of any one of the LSD1 inhibitors according to claim 1-4, characterized in that: one or two of the compound I and the compound II are mixed as an inhibitor of LSD1 histone demethylase , Compound I and Compound II can be used to prevent and/or treat diseases and symptoms related to the activity of histone demethylase LSD1 by inhibiting the activity of LSD1, that is, Compound I and Compound II can be used as active ingredients for the preparation of preventive and/or Or as a drug for treating diseases and symptoms related to the activity of histone demethylase LSD1, or an LSD1 inhibitor as a drug for preventing and/or treating diseases and symptoms related to the activity of histone demethylase LSD1. 6. According to the application according to claim 5, it is characterized in that: said prevention and/or treatment of diseases and symptoms related to the activity of histone demethylase LSD1, especially related to abnormal gene transcription, cell differentiation and proliferation, etc. one or more of these diseases. 7. according to the application described in claim 5, it is characterized in that: the medicine that described compound I and compound II can be used for preparing as active ingredient is prevention and/or treatment tumor medicine, or prevention and/or treatment virus infection medicine, or drugs for the prevention and/or treatment of blood diseases, or LSD1 inhibitors as drugs for the prevention and/or treatment of tumors, or drugs for the prevention and/or treatment of viral infections, or drugs for the prevention and/or treatment of blood diseases; but not limited to these three disease. 8. According to the application according to claim 5, 6 or 7, it is characterized in that: one or both of the compound I and compound II can be mixed with a pharmaceutically acceptable drug carrier and can be prepared to treat related diseases. Tablets, capsules, oral liquids, granules, pills or injections, but not limited to the above dosage forms.