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CN-117304205-B - Benzimidazole ternary fused ring compound, pharmaceutically acceptable salt thereof and application thereof

CN117304205BCN 117304205 BCN117304205 BCN 117304205BCN-117304205-B

Abstract

The invention provides a benzimidazole ternary parallel compound, a pharmaceutically acceptable salt and application thereof, wherein the benzimidazole ternary parallel compound takes TRIM24 as a target point, and the benzimidazole ternary parallel compound with a structure shown in a formula I is designed, so that the benzimidazole ternary parallel compound not only can target TRIM24, but also can target BRPF with the same efficacy. In addition, the compounds also show preliminary inhibition effect on other bromodomains. The compounds show good proliferation inhibition effect on various tumor cell lines, suggesting the potential of the compounds as broad-spectrum antitumor drugs.

Inventors

  • XU YONG
  • CHEN ZHIMING
  • HU QINGQING
  • ZHANG YAN
  • XU HONGRUI
  • ZHANG CHENG
  • ZHUANG XIAOXI
  • HUANG YUMIN
  • LU ZHIFANG
  • WU TONG

Assignees

  • 中国科学院广州生物医药与健康研究院

Dates

Publication Date
20260505
Application Date
20220620

Claims (12)

  1. 1. The benzimidazole ternary fused ring compound is characterized by having a structure shown in the following formula I: ; Wherein X, W is selected from O; Y is selected from-CH-; L is selected from-CH 2 -or-CO-; m is selected from N or-CO-; The connection bond between M and the carbon atom connected with R 1 is represented by S/D, S is a single bond, D is a double bond, the connection bond is a single bond or a double bond, when M is selected from N, the connection bond between M and the carbon atom connected with R 1 is a double bond, when M is selected from-CO-, the connection bond between M and the carbon atom connected with R 1 is a single bond; R 1 is selected from C1-C3 alkoxy, C1-C4 alkyl; R 2 is selected from H and C (R a )(R b )R c , wherein R a is selected from hydrogen, R b is selected from H, C, C6 linear alkyl or a group formed by substituting at least one CH 2 of C1-C6 linear alkyl with O in a non-adjacent mode, R c is selected from hydrogen, or R 2 is selected from any one of the following groups: ; , Wavy lines represent the attachment sites of the groups; r 3 is n-propyloxy; r 4 is hydrogen, C1-C6 alkyl, 、 、 、 、 、 、 Wavy lines represent the attachment sites of the groups.
  2. 2. The benzimidazole-based ternary parallel compound according to claim 1, wherein R 1 is methyl, ethyl or methoxy.
  3. 3. The benzimidazole ternary parallel compound according to claim 1, wherein R 2 is any one of hydrogen, methyl, 、 、 、 、 、 ; 、 Wavy lines represent the attachment sites of the groups.
  4. 4. The benzimidazole tricyclic compound of claim 1, wherein the benzimidazole tricyclic compound has a structure represented by formula Ia: ; Wherein R 1 、R 2 , L and R 4 have the same defined ranges as in formula I.
  5. 5. The benzimidazole-based ternary fused ring compound according to claim 1, wherein the benzimidazole-based ternary fused ring compound has a structure represented by formula Ib: ; Wherein R 2 has the same defined range as in formula I.
  6. 6. The benzimidazole ternary parallel compound is characterized by being any one of the following compounds: 3-methyl-7- (benzenesulfonyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((3, 4-Dimethoxyphenyl) sulfonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3, 7-Dimethyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methyl-5- (3-propoxybenzyl) -7-p-methylbenzenesulfonyl-5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7-Ethylsulfonyl-3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7-Butylsulfonyl-3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((3-Bromo-4-methoxyphenyl) sulfonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((5-Bromo-2-methoxyphenyl) sulfonyl-3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((5-Chloro-2-methoxyphenyl) sulfonyl-3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((2-Methoxyphenyl) sulfonyl-3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((3-Methoxyphenyl) sulfonyl-3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((4-Methoxyphenyl) sulfonyl-3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((2, 3-Dihydrobenzo [ b ] [1,4] dioxin-6-yl) sulfonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((2, 3-Dihydrobenzofuran-5-yl) sulfonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methyl-7- ((2-oxo-2H-chromen-6-yl) sulfonyl) -5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((4-Cyanophenyl) sulfonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((4-Methoxycarbonylphenyl) sulfonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((4-Ethoxycarbonylphenyl) sulfonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methyl-7- ((4-methylsulfonylphenyl) sulfonyl) -5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((4-Bromophenyl) sulfonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((6-Chloropyridin-3-yl) sulfonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((6-Methoxypyridin-3-yl) sulfonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((3, 5-Dichlorophenyl) sulfonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((2, 6-Dichlorophenyl) sulfonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methyl-5- (3-propoxybenzyl) -7- ((1, 3, 5-trimethyl-1H-pyrazol-4-yl) sulfonyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((3, 5-Dimethyl-isoxazol-4-yl) sulfonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((1, 2-Dimethyl-1H-imidazol-4-yl) sulfonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methyl-7- ((1-methyl-1H-pyrazol-3-yl) sulfonyl) -5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methyl-7- ((1-methyl-1H-pyrazol-4-yl) sulfonyl) -5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methyl-7- (morpholinesulfonyl) -5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methyl-7- (piperidine-1-sulfonyl) -5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- (Cyclopropylsulfonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- (Dimethylaminosulfonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methyl-5- (3-propoxybenzyl) -7-propylsulfonyl-5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- (3, 4-Dimethoxybenzoyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- (3, 5-Dimethylisoxazole-4-carbonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7-Cyclopropanecarbonyl-3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- (3, 4-Dimethoxybenzyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methyl-5- (3-propoxybenzyl) -7-propyl-5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methyl-7- (1-methylcyclopropyl) sulfonyl) -5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- (Tert-butylsulphonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- (Isopropylsulfonyl) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methyl-7- (phenylsulfonyl) -5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((3, 4-Dimethoxyphenyl) sulfonamide) -3-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3, 7-Dimethyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methoxy-7-methyl-5- (3-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methoxy-7-methyl-5- (3-propoxybenzoyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 5- (3- (3- (Dimethylamino) propoxy) -5-propoxybenzyl) -3-methyl-5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methyl-5- (3- ((1-methylpiperidin-4-yl) oxy) -5-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 5- (3- (4- (Dimethylamino) butoxy) -5-propoxybenzyl) -3-methyl-5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methyl-5- (3- (piperidine-4-methoxy) -5-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methyl-5- (3- (piperidine-3-methoxy) -5-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methyl-5- (3- ((1-methylpiperidin-4-yl) methoxy) -5-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 3-Methyl-5- (3- ((1-methylpiperidin-3-yl) methoxy) -5-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- (Cyclopropylsulfonyl) -5- (3- (3- (dimethylamino) propoxy) -5-propoxybenzyl) -3-methyl-5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 5- (3- (3- (Dimethylamino) propoxy) -5-propoxybenzyl) -3-methyl-7- ((1, 3, 5-trimethyl-1H-pyrazol-4-yl) sulfonyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((3, 4-Dimethoxyphenyl) sulfonyl) -5- (3- (3- (dimethylamino) propoxy) -5-propoxybenzyl) -3-methyl-5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 5- (3- (3- (Dimethylamino) propoxy) -5-propoxybenzyl) -3-methyl-7-propyl-5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- (Cyclopropylsulfonyl) -3-methyl-5- (3- ((1-methylpiperidin-3-yl) methoxy) -5-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- (Cyclopropanecarbonyl) -3-methyl-5- (3- ((1-methylpiperidin-3-yl) methoxy) -5-propoxybenzyl) -5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one 7- ((3, 4-Dimethoxyphenyl) sulfonyl) -5- (3- (4- (dimethylamino) butoxy) -5-propoxybenzyl) -3-methyl-5, 7-dihydro-6H-imidazo [4',5':4,5] benzo [1,2-d ] isoxazol-6-one.
  7. 7. The benzimidazole ternary parallel compound is characterized by being any one of the following compounds: 3-methyl-5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 3-Methyl-7- (ethylsulfonyl) -5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 7- ((3, 4-Dimethoxyphenyl) sulfonyl) -3-methyl-5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 7- ((3-Bromo-4-methoxyphenyl) sulfonyl) -3-methyl-5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 7- ((4-Methoxyphenyl) sulfonyl) -3-methyl-5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 3-Methyl-5- (3-propoxyphenyl) -7- ((4-trifluoromethoxy) phenyl) sulfonyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 7- ((3-Methoxyphenyl) sulfonyl) -3-methyl-5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 7- ((2, 3-Dihydrobenzo [ b ] [1,4] dioxin-6-yl) sulfonyl) -3-methyl-5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 7- ((2, 3-Dihydrobenzofuran-5-yl) sulfonyl) -3-methyl-5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 3-Methyl-7- ((4- (methylsulfonyl) phenyl) sulfonyl) -5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 7- ((1, 2-Dimethyl-1H-imidazol-4-yl) sulfonyl) -3-methyl-5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 3-Methyl-7- ((1-methyl-1H-pyrazol-3-yl) sulfonyl) -5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 3-Methyl-7- ((1-methyl-1H-pyrazol-4-yl) sulfonyl) -5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 7- ((2-Amino-4-methylthiazol-5-yl) sulfonyl) -3-methyl-5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 3-Methyl-7- (morpholinesulfonyl) -5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 7- (Dimethylaminosulfonyl) -3-methyl-5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 3-Methyl-5- (3-propoxyphenyl) -7- ((trifluoromethyl) sulfonyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 3-Methyl-7- (methylsulfonyl) -5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 7- (Ethylsulfonyl) -3-methyl-5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 3-Methyl-5- (3-propoxyphenyl) -7- (propylsulfonyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 7- (Butylsulfonyl) -3-methyl-5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 7- ((2- (1, 3-Dioxyisoindolin-2-yl) ethyl) sulfonyl) -3-methyl-5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 2- ((3-Methyl-2, 6-dioxo-5- (3-propoxybenzyl) -2,3,5, 6-tetrahydro-7H-imidazo [4',5':4,5] benzo [1,2-d ] oxazol-7-yl) sulfonyl) acetic acid methyl ester 3, 7-Dimethyl-5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 2- (3-Methyl-2, 6-dioxo-5- (3-propoxybenzyl) -2,3,5, 6-tetrahydro-7H-imidazo [4',5':4,5] benzo [1,2-d ] oxazol-7-yl) acetic acid methyl ester 3-Methyl-5- (3-propoxyphenyl) -7-propyl-5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione 7- (3, 4-Dimethoxybenzyl) -3-methyl-5- (3-propoxyphenyl) -5, 7-dihydro-2H-imidazo [4',5':4,5] benzo [1,2-d ] oxazole-2, 6 (3H) -dione.
  8. 8. A pharmaceutically acceptable salt of a benzimidazole-type ternary parallel compound according to any one of claims 1 to 7.
  9. 9. Use of a benzimidazole tri-fused ring compound according to any one of claims 1 to 7 or a pharmaceutically acceptable salt according to claim 8 for the preparation of a bromodomain protein TRIM24 inhibitor.
  10. 10. Use of a benzimidazole tri-fused ring compound according to any one of claims 1 to 7 or a pharmaceutically acceptable salt according to claim 8 for the preparation of a medicament for the treatment of tumors, infections or immune related disorders by inhibition of the TRIM24 bromodomain.
  11. 11. An application of benzimidazole ternary juxtaposition compound or pharmaceutically acceptable salt thereof in preparing bromodomain protein BRPF1 inhibitor, wherein the benzimidazole ternary juxtaposition compound has the following structure: ; Wherein X, W is selected from O; Y is selected from-CH-; l is selected from-CH 2 -; m is selected from N or-CO-; The connection bond between M and the carbon atom connected with R 1 is represented by S/D, S is a single bond, D is a double bond, the connection bond is a single bond or a double bond, when M is selected from N, the connection bond between M and the carbon atom connected with R 1 is a double bond, when M is selected from-CO-, the connection bond between M and the carbon atom connected with R 1 is a single bond; R 1 is selected from C1-C4 alkyl; R 2 is selected from H or Wavy lines represent the attachment sites of the groups; r 3 is n-propyloxy; r 4 is 、 、 、 、 、 、 Wavy lines represent the attachment sites of the groups.
  12. 12. An application of benzimidazole ternary-parallel compound or pharmaceutically acceptable salt thereof in preparing a medicament for treating tumor, infection or immune related diseases by inhibiting BRPF bromine structural domain, the benzimidazole ternary merocyclic compound has the following structure: ; Wherein X, W is selected from O; Y is selected from-CH-; l is selected from-CH 2 -; m is selected from N or-CO-; The connection bond between M and the carbon atom connected with R 1 is represented by S/D, S is a single bond, D is a double bond, the connection bond is a single bond or a double bond, when M is selected from N, the connection bond between M and the carbon atom connected with R 1 is a double bond, when M is selected from-CO-, the connection bond between M and the carbon atom connected with R 1 is a single bond; R 1 is selected from C1-C4 alkyl; R 2 is selected from H or Wavy lines represent the attachment sites of the groups; r 3 is n-propyloxy; r 4 is 、 、 、 、 、 、 Wavy lines represent the attachment sites of the groups.

Description

Benzimidazole ternary fused ring compound, pharmaceutically acceptable salt thereof and application thereof Technical Field The invention belongs to the technical field of chemical medicines, and relates to a benzimidazole ternary fused ring compound, a pharmaceutically acceptable salt thereof and application. Background Epigenetic related targets are one of the most rapidly developed drug research targets in recent years, and are involved in the research of various disease related mechanisms and the research of corresponding chemical drugs, and are rapidly developed as daily life. Epigenetic is proposed relative to classical genetics, the main scientific content of which involves histone modification, histone as the only protein involved in the formation of chromatin structure, modification of its tail has a number of ways, where histone acetylation is considered to be the key to open chromatin structure, promoting gene transcription. Bromodomains (Bromodomain) have chromatin localization functions due to specific recognition of histone tail acetylated lysines, and bromodomains of different proteins can be localized to different chromatin positions due to structural differences. Thus, the bromodomain can serve as a structural protein, mediate the actions of other functional modules of bromodomain-containing proteins (Bromodomain containing protein) or other proteins with chromatin, participate in vital activities such as histone modification, chromatin remodeling, transcription factor recruitment, enhancer or regulator complex assembly, and the like, thereby regulating transcription initiation and elongation. Because bromodomain-containing proteins typically have a variety of other structurally and functionally diverse modules in addition to bromodomain modules. Bromodomains may be coupled to other modules to participate in various life processes, and thus in the development and progression of various diseases, mainly cancer. Thus, inhibition of the bromodomain can interfere with binding of bromodomain-containing protein (Bromodomain containing protein) to chromatin, thereby serving the purpose of impeding disease progression. Bromodomains are the first common sequence found by the Kennison team on different proteins of three species of human, drosophila, yeast origin in 1992. The bromodomain is about 110 amino acids long and has a highly conserved 4-helix bundle tertiary structure. Currently, 61 bromodomains contained in 46 bromodomain-containing proteins have been reported. These bromodomains are classified into 8 subfamilies based on sequence and structural conservation, with TRIM24 and BRPF belonging to the fifth, fourth subfamily. The most effective way to chemically inhibit bromodomain function is to develop small molecule inhibitors that target bromodomains with high efficiency. Since the first 2010, inhibitors JQ1 targeting the second subfamily, BET family proteins, have been of great interest, and have achieved unusual results on BET bromodomain inhibitors, related drugs are now in the clinical stage of research. The good clinical application prospect of the inhibitor targeting the BET bromodomain can indirectly prove that the inhibitor targeting the bromodomain is expected to be a target medicament for clinically treating diseases mainly comprising tumors. Disclosure of Invention Aiming at the defects of the prior art, the invention aims to provide a benzimidazole ternary parallel-ring compound, pharmaceutically acceptable salt and application thereof. To achieve the purpose, the invention adopts the following technical scheme: In one aspect, the invention provides a benzimidazole ternary fused ring compound and pharmaceutically acceptable salts thereof, wherein the benzimidazole ternary fused ring compound has a structure shown in the following formula I: Wherein X, W is selected from O or S; Y is selected from-CH-or N; L is selected from-CH 2 -, -CO-or-SO 2 -; m is selected from N or-CO-; The connection bond between M and the carbon atom connected with R 1 is represented by S/D, S is a single bond, D is a double bond, and the connection bond is a single bond or a double bond; R 1 is selected from H, hydroxy, amino, C1-C3 alkoxy, C1-C3 alkylamino, C1-C4 alkyl, C1-C3 haloalkyl, C1-C3 hydroxyalkyl, C1-C3 aminoalkyl, C1-C3 alkoxyalkyl, C1-C3 alkylaminoalkyl; R 2 is selected from H, -C (R a)(Rb)Rc、-SO2Rd、-CORe; R a、Rb is independently selected from H, hydroxyl, amino, halogen, C1-C6 straight-chain alkyl, C3-C6 branched-chain alkyl, C3-C6 cycloalkyl and C3-C6 heterocycloalkyl, or a group in which at least one CH2 in the C1-C6 straight-chain alkyl and the C3-C6 branched-chain alkyl is replaced by O, N, S in a non-adjacent way, or a group in which at least one hydrogen atom in the C1-C6 straight-chain alkyl, the C3-C6 branched-chain alkyl, the C3-C6 cycloalkyl and the C3-C6 heterocycloalkyl is replaced by halogen; Each R c、Rd、Re is independently selected from H, halogen, or any of the following groups