Imidazolyl and dinitrophenyl derivative and application thereof

Abstract

The present invention relates to compounds of formula (I), stereoisomers thereof, deuterated derivatives thereof, pharmaceutically acceptable salts thereof, pharmaceutically acceptable salts of stereoisomers thereof or pharmaceutically acceptable salts of deuterated derivatives thereof, as well as pharmaceutical compositions containing these compounds and uses thereof.

Description

[0001] Cross-reference to related applications

[0002] This application claims priority to PCT / CN2023 / 099000, filed on 7 June 2023, the entire contents of which are incorporated herein by reference. Technical Field

[0003] This invention relates to compounds for regulating mitochondrial activity, reducing fat content, and treating diseases including diabetes and its related complications, compositions comprising these compounds, and methods of using these compounds. Background Technology

[0004] Obesity has become a global epidemic, affecting more than 600 million people worldwide. Obesity is commonly associated with many metabolic disorders and diseases, such as insulin resistance, type 2 diabetes, and cardiovascular disease. Mitochondria play a crucial role in energy metabolism, and impaired mitochondrial function is linked to obesity.

[0005] Mitochondrial decoupling agents are a class of compounds that dissipate the proton gradient across the inner mitochondrial membrane, leading to reduced efficiency in adenosine triphosphate (ATP) production. This decoupling may result in increased mitochondrial respiration, thereby reducing energy stored as fat and leading to weight loss. The mechanism by which mitochondrial decoupling agents affect energy expenditure makes them an attractive target for the development of drugs to treat obesity.

[0006] Several mitochondrial decoupling agents have been identified and investigated for their potential therapeutic efficacy in treating obesity. The most well-known of these is 2,4-dinitrophenol (DNP), which was previously used for weight loss but was later banned due to its toxicity. However, several novel mitochondrial decoupling agents have been developed, including carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) and 2,3,5-triiodo-L-thyroxine (T3), which have shown promising results in preclinical studies.

[0007] While research suggests that mitochondrial uncoupling agents have potential therapeutic benefits for obesity, concerns remain regarding their safety and potential side effects. Developing safe and effective mitochondrial uncoupling agents for obesity treatment remains an active area of ​​research. Invention Overview

[0009] This application aims to provide a safe and effective mitochondrial decoupling agent.

[0010] The following is the disclosure provided in this application:

[0011] [1]. Compounds of formula (I), their deuterated derivatives, stereoisomers, pharmaceutically acceptable salts of their stereoisomers, or pharmaceutically acceptable salts of their deuterated derivatives:

[0012]

[0013] Each occurrence of R1 is independently selected from hydrogen, deuterium, and -C. 1-6 Alkyl, Halogenated C 1-6 Alkyl and -C 1-6 alkoxyalkyl; the -C 1-6 Alkyl, Halogenated C 1-6 Alkyl or -C 1-6 Alkoxyalkyl groups may optionally be substituted with one or more R 11 replace;

[0014] The R 11 Selected from deuterium, halogens, -C 1-6 Alkyl, -C 2-6 alkenyl, -C 2-6 alkynyl, halogenated C 1-6 Alkyl, -C 1-6 Alkoxyalkyl, -CN, -COOH, -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl), -C(=O)(C 1-6 Alkyl), -S(=O)(C 1-6 Alkyl), -S(=O)2(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-NHC(=O)(C 1-6 alkyl), -N(C) 1-6 Alkyl)C(=O)(C 1-6 Alkyl), -C(=O)O(C 1-6 Alkyl), -OC (=O)(C 1-6 Alkyl groups), -S(=O)NH2, -S(=O)NH(C 1-6 Alkyl), -S(=O)N(C 1-6 Alkyl)2、-NHS(=O)(C 1-6 alkyl), -N(C) 1-6 Alkyl)S(=O)(C 1-6 Alkyl groups), -S(=O)2NH2, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl groups, 2-3-10 membered carbon rings, 3-10 membered heterocycles, 6-10 membered aryl groups, and 5-10 membered heteroaryl groups; when R 11 When it is not deuterium, halogen, or –CN, the R11 It can be optionally replaced by one or more deuterium atoms;

[0015] R2 and R3 are each independently selected from hydrogen, deuterium, halogen, and -C. 1-3 Alkyl, -C 2-3 alkenyl, -C 2-3 alkynyl, -halogenated C 1-3 Alkyl, -C 2-3 Alkoxyalkyl, -CN, -COOH, -NH2, -NH(C 1-3 alkyl), -N(C) 1-3 Alkyl group 2, -OH, -O(C) 1-3 Alkyl), -SH, -S(C 1-3 Alkyl), -C(=O)(C 1-6 Alkyl), -S(=O)(C 1-6 Alkyl), -S(=O)2(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-3 Alkyl), -C(=O)N(C 1-3 Alkyl)2、-NHC(=O)(C 1-3 alkyl), -N(C) 1-3 Alkyl)C(=O)(C 1-3 Alkyl), -C(=O)O(C 1-3 Alkyl), -OC (=O)(C 1-3 Alkyl groups), -S(=O)NH2, -S(=O)NH(C 1-3 Alkyl), -S(=O)N(C 1-3 Alkyl)2、-NHS(=O)(C 1-3 alkyl), -N(C) 1-3 Alkyl)S(=O)(C 1-3 Alkyl groups), -S(=O)2NH2, -S(=O)2NH(C 1-3 Alkyl), -S(=O)2N(C 1-3 alkyl)2、-NHS(=O)2(C 1-3 alkyl), -N(C) 1-3 Alkyl)S(=O)2(C 1-3 Alkyl groups, 3-10 membered carbon rings, 3-10 membered heterocycles, 6-10 membered aryl groups, and 5-10 membered heteroaryl groups; wherein the -C 1-3 Alkyl, -C 1-3 alkenyl, -C 1-3 alkynyl, -halogenated C 1-3 Alkyl, -C 2-3The alkoxyalkyl group, 3-10 membered carbocyclic ring, 3-10 membered heterocyclic ring, 6-10 membered aryl group, or 5-10 membered heteroaryl group may be independently and optionally substituted by one or more substituents selected from deuterium, halogens, and halogenated C. 1-3 Alkyl, -CN, -NH2, -C 1-3 Alkyl, -C 1-3 alkenyl, -C 1-3 alkynyl, -halogenated C 1-3 Alkyl, -C 2-3 Alkoxyalkyl, -CN, -COOH, -NH2, -NH(C 1-3 alkyl), -N(C) 1-3 Alkyl group 2, -OH, -O(C) 1-3 Alkyl), -SH, -S(C 1-3 Alkyl), -C(=O)(C 1-6 Alkyl), -S(=O)(C 1-6 Alkyl), -S(=O)2(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-3 Alkyl), -C(=O)N(C 1-3 Alkyl)2、-NHC(=O)(C 1-3 alkyl), -N(C) 1-3 Alkyl)C(=O)(C 1-3 Alkyl), -C(=O)O(C 1-3 Alkyl), -OC (=O)(C 1-3 Alkyl groups), -S(=O)NH2, -S(=O)NH(C 1-3 Alkyl), -S(=O)N(C 1-3 Alkyl)2、-NHS(=O)(C 1-3 alkyl), -N(C) 1-3 Alkyl)S(=O)(C 1-3 Alkyl groups), -S(=O)2NH2, -S(=O)2NH(C 1-3 Alkyl), -S(=O)2N(C 1-3 alkyl)2、-NHS(=O)2(C 1-3 alkyl), -N(C) 1-3 Alkyl)S(=O)2(C 1-3 Alkyl), 3-10 membered carbon rings, 3-10 membered heterocycles, 6-10 membered aryl and 5-10 membered heteroaryl; wherein when R3 or R2 is not hydrogen, deuterium, halogen or -CN, R3 or R2 may optionally be substituted with one or more deuteriums;

[0016] Optionally, R2 and R3, together with the atoms they are bonded to, form 3-14 membered carbon rings, 3-14 membered heterocycles, 6-12 membered aromatic rings, or 5-14 membered heteroaromatic rings; each ring can be independently bounded by n1 R atoms. S1 replace;

[0017] R S1 Selected from halogens, -C 1-6 Alkyl, -C 2-6 alkenyl, -C 2-6 alkynyl group, -C 1-6 Alkoxyalkyl, halogenated C 1-6 Alkyl, Halogenated C 1-6 Alkoxyalkyl, -CN, -NO2, -N3, oxo, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl), -S(=O)(C 1-6 Alkyl), -S(=O)2(C 1-6 Alkyl), -C(=O)(C 1-6 Alkyl), -C(=O)OH, -C(=O)(OC 1-6 Alkyl), -OC (=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-NHC(=O)(C 1-6 alkyl), -N(C) 1-6 Alkyl)C(=O)(C 1-6 Alkyl), -OC(=O)O(C 1-6 Alkyl), -NHC(=O)(OC 1-6 alkyl), -N(C) 1-6 Alkyl)C(=O)(OC) 1-6 Alkyl), -OC(=O)NH(C 1-6 Alkyl), -OC(=O)N(C 1-6 Alkyl)2, -NHC(=O)NH2, -NHC(=O)NH(C 1-6 Alkyl), -NHC(=O)N(C 1-6 Alkyl)2, -N(C 1-6 Alkyl)C(=O)NH2、-N(C 1-6 alkyl)C(=O)NH(C 1-6 alkyl), -N(C) 1-6 Alkyl)C(=O)N(C 1-6 Alkyl)2、-S(=O)(OC 1-6Alkyl), -OS (=O) (C 1-6 Alkyl groups), -S(=O)NH2, -S(=O)NH(C 1-6 Alkyl), -S(=O)N(C 1-6 Alkyl)2、-NHS(=O)(C 1-6 alkyl), -N(C) 1-6 Alkyl)S(=O)(C 1-6 Alkyl), -S(=O)2(OC 1-6 Alkyl), -OS(=O)2(C 1-6 Alkyl groups), -S(=O)2NH2, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 alkyl)2、-NHS(=O)2(C 1-6 alkyl), -N(C) 1-6 Alkyl)S(=O)2(C 1-6 Alkyl), -OS(=O)2O(C 1-6 Alkyl), -NHS(=O)2O(C 1-6 alkyl), -N(C) 1-6 Alkyl)S(=O)2O(C 1-6 Alkyl groups), -OS(=O)2NH2, -OS(=O)2NH(C 1-6 Alkyl), -OS(=O)2N(C 1-6 Alkyl)2, -NHS(=O)2NH2, -NHS(=O)2NH(C 1-6 Alkyl), -NHS(=O)2N(C 1-6 Alkyl)2, -N(C 1-6 Alkyl)S(=O)2NH2、-N(C 1-6 alkyl)S(=O)2NH(C 1-6 alkyl), -N(C) 1-6 Alkyl)S(=O)2N(C 1-6 alkyl)2, -PH(C 1-6 alkyl), -P(C 1-6 Alkyl)2、-P(=O)H(C 1-6 Alkyl), -P(=O)(C 1-6 Alkyl groups, 2-3-7-membered carbon rings, 3-7-membered heterocycles, 6-10-membered aryl groups, and 5-10-membered heteroaryl groups;

[0018] n1 is selected from 0, 1, 2, 3, 4, 5, and 6;

[0019] Each occurrence of R4 is independently selected from hydrogen, deuterium, halogens, and -C. 1-3 Alkyl, -C 2-3 alkenyl, -C 2-3alkynyl, -halogenated C 1-3 Alkyl, -C 2-3 Alkoxyalkyl, -CN, -COOH, -NH2, -NH(C 1-3 alkyl), -N(C) 1-3 Alkyl group 2, -OH, -O(C) 1-3 Alkyl), -SH, -S(C 1-3 Alkyl), -C(=O)(C 1-6 Alkyl), -S(=O)(C 1-6 Alkyl), -S(=O)2(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-3 Alkyl), -C(=O)N(C 1-3 Alkyl)2、-NHC(=O)(C 1-3 alkyl), -N(C) 1-3 Alkyl)C(=O)(C 1-3 Alkyl), -C(=O)O(C 1-3 Alkyl), -OC (=O)(C 1-3 Alkyl groups), -S(=O)NH2, -S(=O)NH(C 1-3 Alkyl), -S(=O)N(C 1-3 Alkyl)2、-NHS(=O)(C 1-3 alkyl), -N(C) 1-3 Alkyl)S(=O)(C 1-3 Alkyl groups), -S(=O)2NH2, -S(=O)2NH(C 1-3 Alkyl), -S(=O)2N(C 1-3 alkyl)2、-NHS(=O)2(C 1-3 alkyl), -N(C) 1-3 Alkyl)S(=O)2(C 1-3 Alkyl groups, 3-10 membered carbon rings, 3-10 membered heterocycles, 6-10 membered aryl groups, and 5-10 membered heteroaryl groups; wherein the -C 1-3 Alkyl, -C 1-3 alkenyl, -C 1-3 alkynyl, -halogenated C 1-3 Alkyl, -C 2-3 The alkoxyalkyl group, 3-10 membered carbocyclic ring, 3-10 membered heterocyclic ring, 6-10 membered aryl group, or 5-10 membered heteroaryl group may be independently and optionally substituted by one or more substituents selected from deuterium, halogens, and halogenated C. 1-3 Alkyl, -CN, -NH2, -C 1-3 Alkyl, -C 1-3 alkenyl, -C 1-3 alkynyl, -halogenated C 1-3 Alkyl, -C 2-3Alkoxyalkyl, -CN, -COOH, -NH2, -NH(C 1-3 alkyl), -N(C) 1-3 Alkyl group 2, -OH, -O(C) 1-3 Alkyl), -SH, -S(C 1-3 Alkyl), -C(=O)(C 1-6 Alkyl), -S(=O)(C 1-6 Alkyl), -S(=O)2(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-3 Alkyl), -C(=O)N(C 1-3 Alkyl)2、-NHC(=O)(C 1-3 alkyl), -N(C) 1-3 Alkyl)C(=O)(C 1-3 Alkyl), -C(=O)O(C 1-3 Alkyl), -OC (=O)(C 1-3 Alkyl groups), -S(=O)NH2, -S(=O)NH(C 1-3 Alkyl), -S(=O)N(C 1-3 Alkyl)2、-NHS(=O)(C 1-3 alkyl), -N(C) 1-3 Alkyl)S(=O)(C 1-3 Alkyl groups), -S(=O)2NH2, -S(=O)2NH(C 1-3 Alkyl), -S(=O)2N(C 1-3 alkyl)2、-NHS(=O)2(C 1-3 alkyl), -N(C) 1-3 Alkyl)S(=O)2(C 1-3 Alkyl), 3-10 membered carbon rings, 3-10 membered heterocycles, 6-10 membered aryl and 5-10 membered heteroaryl; wherein when R4 is not hydrogen, deuterium, halogen or -CN, R4 may optionally be substituted with one or more deuteriums;

[0020] Each heterocycle independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O, S, S(=O) and S(=O)2;

[0021] Each heteroaryl group independently contains 1, 2, 3, 4, 5 or 6 heteroatoms selected from N, O and S.

[0022] [2]. Compounds of formula (I), their deuterated derivatives, stereoisomers, pharmaceutically acceptable salts of their stereoisomers, or pharmaceutically acceptable salts of their deuterated derivatives, wherein,

[0023] Each occurrence of R1 is independently selected from hydrogen, deuterium, and -C.1-3 Alkyl and -C 2-3 Alkoxyalkyl;

[0024] R1 can be optionally defined by one or more R 11 replace;

[0025] The R 11 Selected from deuterium, -NH(C 1-3 alkyl), -N(C) 1-3 Alkyl)2、-O(C 1-3 alkyl), -S(C 1-3 Alkyl), -C 2-3 Alkoxyalkyl, -C(=O)(C 1-3 Alkyl), -S(=O)(C 1-3 Alkyl), -S(=O)2(C 1-3 Alkyl groups, -C(=O)NH2, -C(=O)N(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-3 Alkyl)2、-NHC(=O)(C 1-3 alkyl), -N(C) 1-3 Alkyl)C(=O)(C 1-3 Alkyl), -S(=O)NH(C 1-3 Alkyl), -S(=O)N(C 1-3 Alkyl)2、-NHS(=O)(C 1-3 alkyl), -N(C) 1-3 Alkyl)S(=O)(C 1-3 Alkyl group), -S(=O)2NH(C 1-3 Alkyl), -S(=O)2N(C 1-3 alkyl)2、-NHS(=O)2(C 1-3 alkyl) and -N(C) 1-3 Alkyl)S(=O)2(C 1-3 Alkyl); the R 11 It can be optionally replaced by one or more -D.

[0026] [3]. A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is described in any one of [1] to [2], wherein,

[0027] Each occurrence of R1 is independently selected from -C 1-3 Alkyl and -C 2-3 Alkoxyalkyl;

[0028] The -C 1-3 Alkyl or -C2-3 The alkoxyalkyl group may optionally be surrounded by 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 R's. 11 replace;

[0029] The R 11 Selected from deuterium, -NH(C 1-3 alkyl), -N(C) 1-3 Alkyl)2、-O(C 1-3 alkyl), -S(C 1-3 Alkyl), -C 2-3 Alkoxyalkyl, -C(=O)(C 1-6 Alkyl), -S(=O)(C 1-6 Alkyl) and -S(=O)2(C 1-6 Alkyl); the R 11 It can be optionally replaced by one or more -D.

[0030] [4]. A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is any one of [1] to [3], wherein,

[0031] Each occurrence of R1 is independently selected from -C 1-3 Alkyl and -C 2-3 Alkoxyalkyl;

[0032] R1 can be arbitrarily divided by 1, 2, 3, 4, 5, 6 or 7 Rs. 11 replace;

[0033] The R 11 Selected from deuterium, -C 2-3 Alkoxyalkyl and -O(C 1-3 Alkyl); the R 11 It can be optionally replaced by one or more -D.

[0034] [5]. A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is any one of [1] to [4], wherein,

[0035] Each occurrence of R1 is independently selected from -CH2D, -CHD2, -CD3, -CH2CH3, -CH2CH2CH3, -CH2CH2CD3, -CH2CD2CD3, -CD2CD2CD3, -CH(CH3)2, -CD(CH3)2, -CD(CD3)(CH3), -CH(CD3)2, -CD(CD3)2,

[0036]

[0037]

[0038]

[0039]

[0040]

[0041] [6]. A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is any one of [1] to [5], wherein,

[0042] Each occurrence of R1 is independently selected from -CD3, -CH2CH3, -CH2CH2CH3, -CH2CH2CD3, -CH2CD2CD3, -CD2CD2CD3, -CH(CH3)2, -CD(CH3)2, -CD(CD3)2,

[0043] [7]. A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is described in any one of [1] to [6], wherein,

[0044] Each occurrence of R1 is independently selected from -CD3.

[0045] [8]. A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is described in any one of [1] to [7], wherein,

[0046] Each occurrence of R1 is independently selected from -C 1-3 Alkyl group; R1 may optionally be substituted with 1, 2, 3, 4, 5, 6 or 7 deuterium atoms.

[0047] [9]. The compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer or pharmaceutically acceptable salt of the deuterated derivative, wherein, is as described in [8], wherein,

[0048] Each occurrence of R1 is independently selected from -CH3, which is replaced by 1, 2 or 3 deuterium atoms.

[0049]

[10] . A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is described in any one of [8] to [9], wherein,

[0050] Each occurrence of R1 is independently selected from -CH2D, -CHD2, -CD3, -CH2CH3, -CH2CH2CH3, -CH2CH2CD3, -CH2CD2CD3, -CD2CD2CD3, -CH(CH3)2, -CD(CH3)2, -CD(CD3)(CH3), -CH(CD3)2, and -CD(CD3)2.

[0051]

[11] . A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is described in any one of [8] to

[10] , wherein,

[0052] Each occurrence of R1 is independently selected from -CD3, -CH2CH3, -CH2CH2CH3, -CH2CH2CD3, -CH2CD2CD3, -CD2CD2CD3, -CH(CH3)2, -CD(CH3)2, and -CD(CD3)2.

[0053]

[12] . A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is any one of [8] to

[11] , wherein,

[0054] Each occurrence of R1 is independently selected from -CD3.

[0055]

[13] . Compounds of formula (I-1), their deuterated derivatives, stereoisomers, pharmaceutically acceptable salts of their stereoisomers, or pharmaceutically acceptable salts of their deuterated derivatives:

[0056]

[0057] R3, R2, or R4 have the same definition as in [1].

[0058]

[14] . A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is any one of [1] to [7], wherein,

[0059] Each occurrence of R1 is independently selected from -C 1-3 Alkyl group, wherein R1 is R 11 Replace; the R 11 Selected from -C 2-3 alkoxyalkyl, the R 11 It can be optionally replaced by one or more deuterium.

[0060]

[15] . A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, which is as described in

[14] , wherein each occurrence of R1 is independently selected from -CH3, -CH2CH3, -CH2CH2CH3, and -CH(CH3)2, wherein R1 is R 11 Replace; the R 11 Selected from -CH2-O-CH3, -CH2-O-CH2-CH3, -CH2-CH2-O-CH3 and -CH(CH3)-O-CH3; the R 11 It can be arbitrarily replaced by 1, 2, 3, 4, 5, 6, or 7 deuteriums.

[0061]

[16] . A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is any one of

[14] to

[15] , wherein,

[0062] Each occurrence of R1 is independently selected from -CH3; said R1 is replaced by -CH2-O-CH3.

[0063]

[17] . A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is any one of

[14] to

[16] , wherein each occurrence of R1 is independently selected from

[0064]

[18] . A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is any one of

[14] to

[17] , wherein each occurrence of R1 is independently selected from

[0065]

[19] . A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is any one of

[14] to

[18] , wherein each occurrence of R1 is independently selected from

[0066]

[20] . Compounds of formula (I-2), their deuterated derivatives, stereoisomers, pharmaceutically acceptable salts of their stereoisomers, or pharmaceutically acceptable salts of their deuterated derivatives:

[0067]

[0068] R3, R2, or R4 have the same definition as in [1].

[0069]

[21] . A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is any one of [1] to [7], wherein,

[0070] Each occurrence of R1 is independently selected from -C 2-3 alkoxyalkyl, wherein R1 is R 11 Replace; the R 11 Selected from -C 2-3 Alkoxyalkyl and -O(C 1-3 alkyl), the R 11 It can be optionally replaced by one or more deuterium.

[0071]

[22] . The compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein, is as described in

[21] , wherein,

[0072] Each occurrence of R1 is independently selected from -CH2-O-CH3, -CH2-O-CH2-CH3, -CH2-CH2-O-CH3, and -CH(CH3)-O-CH3, wherein R1 is controlled by R 11 Replace; the R 11 Selected from -CH2-O-CH3, -CH2-O-CH2-CH3, -CH2-CH2-O-CH3, -CH(CH3)-O-CH3, -O-CH3, -O-CH2-CH3, -O-CH2-CH2-CH3 and -O-CH(CH3)2; the R 11 It can be replaced by 1, 2, 3, 4, 5, 6 or 7 deuteriums.

[0073]

[23] . A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is described in any one of

[21] to

[22] , wherein,

[0074] Each occurrence of R1 is independently selected from -CH2-CH2-O-CH3; said R1 is replaced by -CH2-O-CH3.

[0075]

[24] . A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is described in any one of

[21] to

[23] , wherein,

[0076] Each occurrence of R1 is independently selected

[0077]

[0078]

[25] . A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is described in any one of

[21] to

[24] , wherein,

[0079] Each occurrence of R1 is independently selected

[0080]

[26] . A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is any one of

[21] to

[25] , wherein each occurrence of R1 is independently selected from

[0081]

[27] . Compounds of formula (I-3), their deuterated derivatives, stereoisomers, pharmaceutically acceptable salts of their stereoisomers, or pharmaceutically acceptable salts of their deuterated derivatives:

[0082]

[0083] R3, R2, or R4 have the same definition as in [1].

[0084]

[28] . A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is described in any one of [1] to

[27] , wherein,

[0085] R4 is selected independently each time from -H, -D, halogen, -C. 1-3 Alkyl, Halogenated C 1-3 Alkyl, -C 2-3 Alkoxyalkyl, -C 2-3 alkenyl, -C 2-3 Alkyne group, -CN, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl group 2, -OH, -O(C) 1-3 Alkyl), -O (halogenated C) 1-3 Alkyl), -SH, -S(C 1-3 Alkyl), -C(=O)(C 1-3 Alkyl), -S(=O)(C 1-3 Alkyl), -S(=O)2(C 1-3 Alkyl groups, -C(=O)OH, -C(=O)NH2, -C(=O)NH(C 1-3 Alkyl), -C(=O)N(C 1-3 Alkyl)2、-NHC(=O)(C 1-3 Alkyl groups), -S(=O)NH2, -S(=O)NH(C 1-3 Alkyl), -S(=O)N(C 1-3 Alkyl)2、-NHS(=O)(C 1-3 Alkyl groups), -S(=O)2NH2, -S(=O)2NH(C 1-3 Alkyl), -S(=O)2N(C 1-3 alkyl)2 and -NHS(=O)2(C 1-3 Alkyl); wherein when R4 is not -H, -D, halogen or -CN, R4 may optionally be substituted with one or more deuterium.

[0086]

[29] . A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is any one of [1] to

[28] , wherein,

[0087] R4 is selected independently each time from -H, -D, halogen, -C. 1-3 Alkyl, Halogenated C 1-3 Alkyl, -C 2-3 Alkoxyalkyl, -C 2-3 alkenyl, -C 2-3Alkyne, -CN, -NH2, -C(=O)OH, -NH(C 1-3 alkyl), -N(C) 1-3 Alkyl group 2, -OH, -O(C) 1-3 Alkyl), -O (halogenated C) 1-3 Alkyl), -SH, -S(C 1-3 Alkyl), -C(=O)(C 1-3 Alkyl), -S(=O)(C 1-3 Alkyl) and -S(=O)2(C 1-3 Alkyl); wherein when R4 is not -H, -D, halogen or -CN, R4 may optionally be substituted with one or more deuterium.

[0088]

[30] . A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein it is any one of [1] to

[29] , wherein R4 is independently selected each time from -H, -D, -Cl, -F, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CH2-O-CH3, -CH2-O-CH2-CH3, -CH2-CH2-O-CH3, -CH(CH3)-O-CH3, -CN, -C(=O)OH, -NH2, -NH(CH3), -N(CH3)2, -NH(CH2CH3), -OH, -O-CH3, -O-CH2-CH3, -O-CH2-CH2-CH 3. -O-CH(CH3)2, -O-CF3, -SH, -S-CH3, -S-CH2CH3, -S-CH2CH2CH3, -S-CH(CH3)2, -C(=O)(CH3), -C(= O)(CH2CH3), -C(=O)(CH(CH3)2), -S(=O)(CH3), -S(=O)(CH2CH3), -S(=O)(CH(CH3)2), -S(=O)2(CH3), -S(=O)2(CH2CH3) and -S(=O)2(CH(CH3)2); wherein when R4 is not -H, -D, -Cl, -F, -Br, -CN, R4 may be optionally substituted with one or more deuterium.

[0089]

[31] . A deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of a stereoisomer, or pharmaceutically acceptable salt of a deuterated derivative thereof, wherein R4 is independently selected from -H, -D, -CH3 and -CD3.

[0090]

[32] . A deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of a stereoisomer, or a pharmaceutically acceptable salt of a deuterated derivative thereof, wherein R4 is independently selected from -H.

[0091]

[33] . Deuterated derivatives, stereoisomers, pharmaceutically acceptable salts of the stereoisomers, or pharmaceutically acceptable salts of the deuterated derivatives of compound (II-1):

[0092]

[0093] The definitions of R3 or R2 are the same as in [1].

[0094]

[34] . Deuterated derivatives, stereoisomers, pharmaceutically acceptable salts of the stereoisomers, or pharmaceutically acceptable salts of the deuterated derivatives of compound (II-2):

[0095]

[0096] The definitions of R3 or R2 are the same as in [1].

[0097]

[35] . Deuterated derivatives, stereoisomers, pharmaceutically acceptable salts thereof, pharmaceutically acceptable salts of stereoisomers, or pharmaceutically acceptable salts of deuterated derivatives of compound (II-3):

[0098]

[0099] The definitions of R3 or R2 are the same as in [1].

[0100]

[36] . Deuterated derivatives, stereoisomers, pharmaceutically acceptable salts thereof, pharmaceutically acceptable salts of stereoisomers, or pharmaceutically acceptable salts of deuterated derivatives of compound (I), wherein,

[0101] R2 and R3 are each independently selected from -H, -D, halogen, and -C. 1-3 Alkyl, Halogenated C 1-3 Alkyl, -C 2-3 Alkoxyalkyl, -C 2-3 alkenyl, -C 2-3 Alkyne group, -CN, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3Alkyl group 2, -OH, -O(C) 1-3 Alkyl), -O (halogenated C) 1-3 Alkyl), -SH, -S(C 1-3 Alkyl), -C(=O)(C 1-3 Alkyl), -S(=O)(C 1-3 Alkyl), -S(=O)2(C 1-3 Alkyl groups, -C(=O)OH, -C(=O)NH2, -C(=O)NH(C 1-3 Alkyl), -C(=O)N(C 1-3 Alkyl)2、-NHC(=O)(C 1-3 Alkyl groups), -S(=O)NH2, -S(=O)NH(C 1-3 Alkyl), -S(=O)N(C 1-3 Alkyl)2、-NHS(=O)(C 1-3 Alkyl groups), -S(=O)2NH2, -S(=O)2NH(C 1-3 Alkyl), -S(=O)2N(C 1-3 alkyl)2 and -NHS(=O)2(C 1-3 Alkyl); when R3 or R2 is not -H, -D, halogen or -CN, R3 or R2 may be substituted with one or more deuterium atoms.

[0102]

[37] . Deuterated derivatives, stereoisomers, pharmaceutically acceptable salts thereof, pharmaceutically acceptable salts of stereoisomers, or pharmaceutically acceptable salts of deuterated derivatives of compound (I), wherein,

[0103] R2 and R3 are each independently selected from -H, -D, halogen, and -C. 1-3 Alkyl, Halogenated C 1-3 Alkyl, -C 2-3 Alkoxyalkyl, -C 2-3 alkenyl, -C 2-3 Alkyne, -CN, -NH2, -C(=O)OH, -NH(C 1-3 alkyl), -N(C) 1-3 Alkyl group 2, -OH, -O(C) 1-3 Alkyl), -O (halogenated C) 1-3 Alkyl), -SH, -S(C 1-3 Alkyl), -C(=O)(C 1-3 Alkyl), -S(=O)(C 1-3 Alkyl) and -S(=O)2(C 1-3 Alkyl); when R3 or R2 is not -H, -D, halogen or -CN, R3 or R2 may be substituted with one or more deuterium atoms.

[0104]

[38] . Deuterated derivatives, stereoisomers, pharmaceutically acceptable salts of the compound (I), pharmaceutically acceptable salts of the stereoisomers or pharmaceutically acceptable salts of the deuterated derivatives.

[0105] R2 and R3 are each independently selected from -H, -D, -Cl, -F, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CH2-O-CH3, -CH2-O-CH2-CH3, -CH2-CH2-O-CH3, -CH(CH3)-O-CH3. -CN, -C(=O)OH, -NH2, -NH(CH3), -N(CH3)2, -NH(CH2CH3), -OH, -O-CH3, -O-CH2-CH3, -O-CH2-CH2-CH3 , -O-CH(CH3)2, -O-CF3, -SH, -S-CH3, -S-CH2CH3, -S-CH2CH2CH3, -S-CH(CH3)2, -C(=O)(CH3), -C(=O) (CH2CH3), -C(=O)(CH(CH3)2), -S(=O)(CH3), -S(=O)(CH2CH3), -S(=O)(CH(CH3)2), -S(=O)2(CH3), -S(=O)2(CH2CH3) and -S(=O)2(CH(CH3)2); when R3 or R2 is not -H, -D, -Cl, -F, -Br, -CN, said R3 or R2 may be substituted by one or more deuterium atoms.

[0106]

[39] . Deuterated derivatives, stereoisomers, pharmaceutically acceptable salts thereof, pharmaceutically acceptable salts of stereoisomers, or pharmaceutically acceptable salts of deuterated derivatives of compound (I), wherein,

[0107] R2 and R3 are each independently selected from -H, -D, -CD3, and -CH3.

[0108]

[40] . A deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of a stereoisomer, or pharmaceutically acceptable salt of a deuterated derivative thereof, wherein R3 is selected from -H, -D, -CD3, and -CH3.

[0109]

[41] . A deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of a stereoisomer, or pharmaceutically acceptable salt of a deuterated derivative thereof, wherein R3 is selected from -H.

[0110]

[42] . A deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of a stereoisomer, or pharmaceutically acceptable salt of a deuterated derivative thereof, wherein R2 is selected from -H, -D, -CD3, and -CH3.

[0111]

[43] . A deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of a stereoisomer, or pharmaceutically acceptable salt of a deuterated derivative thereof, wherein R2 is selected from -H.

[0112]

[44] . A deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of a stereoisomer, or pharmaceutically acceptable salt of a deuterated derivative thereof, wherein R3 is selected from -H; R2 is selected from -H.

[0113]

[45] . Deuterated derivatives, stereoisomers, pharmaceutically acceptable salts thereof, pharmaceutically acceptable salts of stereoisomers, or pharmaceutically acceptable salts of deuterated derivatives of compound (I):

[0114]

[0115] Each occurrence of R1 is independently selected from -C 1-3 Alkyl and -C 2-3 Alkoxyalkyl;

[0116] R1 can be 1, 2, or 3 Rs 11 replace;

[0117] The R 11 Selected from deuterium atoms, -C 2-3 Alkoxyalkyl and -O(C 1-3 Alkyl); when R 11 It is -C 2-3 alkoxyalkyl or -O(C) 1-3 When alkyl), the R 11 It can be substituted by one or more deuterium atoms;

[0118] R4 groups are independently selected from -H, -D, halogen, and -C. 1-3 Alkyl, Halogenated C 1-3 Alkyl, -C 2-3 Alkoxyalkyl, -C 2-3 alkenyl, -C 2-3 Alkyne, -CN, -NH2, -C(=O)OH, -NH(C 1-3 alkyl), -N(C) 1-3 Alkyl group 2, -OH, -O(C) 1-3 Alkyl), -O (halogenated C) 1-3Alkyl), -SH, -S(C 1-3 Alkyl), -C(=O)(C 1-3 Alkyl), -S(=O)(C 1-3 Alkyl) and -S(=O)2(C 1-3 Alkyl); when R4 is not -H, -D, halogen, or -CN, R4 may be substituted with one or more deuterium atoms;

[0119] R2 and R3 are each independently selected from -H, -D, halogen, and -C. 1-3 Alkyl, Halogenated C 1-3 Alkyl, -C 2-3 Alkoxyalkyl, -C 2-3 alkenyl, -C 2-3 Alkyne, -CN, -NH2, -C(=O)OH, -NH(C 1-3 alkyl), -N(C) 1-3 Alkyl group 2, -OH, -O(C) 1-3 Alkyl), -O (halogenated C) 1-3 Alkyl), -SH, -S(C 1-3 Alkyl), -C(=O)(C 1-3 Alkyl), -S(=O)(C 1-3 Alkyl) and -S(=O)2(C 1-3 Alkyl); when R3 or R2 is not -H, -D, halogen or -CN, R3 or R2 may be substituted with one or more deuterium atoms.

[0120]

[46] . Deuterated derivatives, stereoisomers, pharmaceutically acceptable salts thereof, pharmaceutically acceptable salts of stereoisomers, or pharmaceutically acceptable salts of deuterated derivatives of compound (I):

[0121]

[0122] Each occurrence of R1 is independently selected from -C 1-3 Alkyl and -C 2-3 Alkoxyalkyl;

[0123] R1 can be 1, 2, or 3 Rs 11 replace;

[0124] The R 11 Selected from deuterium atoms, -C 2-3 Alkoxyalkyl and -O(C 1-3 Alkyl); when R 11 It is -C 2-3 alkoxyalkyl or -O(C) 1-3 When alkyl), the R 11 It can be substituted by one or more deuterium atoms;

[0125] R4 is independently selected from -H, -D, and -C. 1-3 Alkyl; when R4 is -C 1-3 When alkyl, R4 can be substituted with 1, 2, 3, 4, 5 or 6 deuterium atoms;

[0126] R2 and R3 are each independently selected from -H, -D, and -C. 1-3 Alkyl; when R2 or R3 is -C 1-3 When alkyl, R2 or R3 may be substituted with 1, 2, 3, 4, 5 or 6 deuterium atoms.

[0127]

[47] . Deuterated derivatives, stereoisomers, pharmaceutically acceptable salts thereof, pharmaceutically acceptable salts of stereoisomers, or pharmaceutically acceptable salts of deuterated derivatives of compound (I):

[0128]

[0129] Each occurrence of R1 is independently selected from -C 1-3 Alkyl group; the R1 may be substituted with 1, 2, 3, 4, 5, 6 or 7 deuterium atoms;

[0130] R4 is independently selected from -H, -D, and -C. 1-3 Alkyl; when R4 is -C 1-3 When alkyl, R4 can be substituted with 1, 2, 3, 4, 5 or 6 deuterium atoms;

[0131] R2 and R3 are each independently selected from -H, -D, and -C. 1-3 Alkyl; when R2 or R3 is -C 1-3 When alkyl, R2 or R3 may be substituted with 1, 2, 3, 4, 5 or 6 deuterium atoms.

[0132]

[48] . Deuterated derivatives, stereoisomers, pharmaceutically acceptable salts of the deuterated derivative of compound (I), pharmaceutically acceptable salts of the stereoisomers, or pharmaceutically acceptable salts of the deuterated derivative:

[0133]

[0134] Each occurrence of R1 is independently selected from -C 1-3 Alkyl group, wherein R1 is R 11 Replace; the R 11 Selected from -C 2-3 alkoxyalkyl, the R 11 It can be substituted by one or more deuterium atoms;

[0135] R4 is independently selected from -H, -D, and -C. 1-3 Alkyl; when R4 is -C 1-3When alkyl, R4 can be substituted with 1, 2, 3, 4, 5 or 6 deuterium atoms;

[0136] R2 and R3 are each independently selected from -H, -D, and -C. 1-3 Alkyl; when R2 or R3 is -C 1-3 When alkyl, R2 or R3 may be substituted with 1, 2, 3, 4, 5 or 6 deuterium atoms.

[0137]

[49] . Deuterated derivatives, stereoisomers, pharmaceutically acceptable salts of the compound (I-1), pharmaceutically acceptable salts of the stereoisomers, or pharmaceutically acceptable salts of the deuterated derivatives:

[0138]

[0139] R4 is independently selected from -H, -D, and -C. 1-3 Alkyl; when R4 is -C 1-3 When alkyl, R4 can be substituted with 1, 2, 3, 4, 5 or 6 deuterium atoms;

[0140] R2 and R3 are each independently selected from -H, -D, and -C. 1-3 Alkyl; when R2 or R3 is -C 1-3 When alkyl, R2 or R3 may be substituted with 1, 2, 3, 4, 5 or 6 deuterium atoms.

[0141]

[50] . Deuterated derivatives, stereoisomers, pharmaceutically acceptable salts thereof, pharmaceutically acceptable salts of stereoisomers, or pharmaceutically acceptable salts of deuterated derivatives of compound (I-2):

[0142]

[0143] R4 is independently selected from -H, -D, and -C. 1-3 Alkyl; when R4 is -C 1-3 When alkyl, R4 can be substituted with 1, 2, 3, 4, 5 or 6 deuterium atoms;

[0144] R2 and R3 are each independently selected from -H, -D, and -C. 1-3 Alkyl; when R2 or R3 is -C 1-3 When alkyl, R2 or R3 may be substituted with 1, 2, 3, 4, 5 or 6 deuterium atoms.

[0145]

[51] . Deuterated derivatives, stereoisomers, pharmaceutically acceptable salts of the compound (I-3), pharmaceutically acceptable salts of the stereoisomers, or pharmaceutically acceptable salts of the deuterated derivatives:

[0146]

[0147] R4 is independently selected from -H, -D, and -C. 1-3 Alkyl; when R4 is -C 1-3 When alkyl, R4 can be substituted with 1, 2, 3, 4, 5 or 6 deuterium atoms;

[0148] R2 and R3 are each independently selected from -H, -D, and -C. 1-3 Alkyl; when R2 or R3 is -C 1-3 When alkyl, R2 or R3 may be substituted with 1, 2, 3, 4, 5 or 6 deuterium atoms.

[0149]

[52] . A deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of a stereoisomer, or a pharmaceutically acceptable salt of a deuterated derivative of compound (I), wherein the compound is any one of the following formulas:

[0150]

[0151]

[0152]

[0153]

[0154]

[0155]

[0156]

[0157]

[0158]

[0159]

[0160]

[0161]

[0162]

[0163]

[0164]

[0165]

[0166]

[0167]

[0168]

[0169]

[0170]

[0171]

[0172]

[0173]

[0174]

[0175]

[0176]

[53] . A pharmaceutical composition comprising the compound described in [1] to

[52] , a deuterated derivative thereof, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer or a pharmaceutically acceptable salt of the deuterated derivative thereof, and at least one pharmaceutically acceptable excipient.

[0177]

[54] . A method of treating a subject with a mitochondrial-related disease or condition, the method comprising administering to the subject a therapeutically effective amount of the compound described in [1] to

[52] , a deuterated derivative thereof, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, or a pharmaceutically acceptable salt of a deuterated derivative thereof; or the pharmaceutical composition described in

[53] .

[0178]

[55] .

[54] The method wherein the disease is obesity, excessive body fat, diabetes, insulin resistance or intolerance, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hepatic steatosis, type 2 diabetes mellitus (T2DM), dyslipidemia, cardiovascular disease, heart disease or atherosclerosis.

[0179]

[56] . The use of the compounds described in [1] to

[52] , their deuterated derivatives, stereoisomers, pharmaceutically acceptable salts thereof, pharmaceutically acceptable salts of stereoisomers or pharmaceutically acceptable salts of deuterated derivatives; or the pharmaceutical compositions described in

[53] for the manufacture of a medicament for the treatment of mitochondrial-related diseases or conditions.

[0180]

[57] .

[56] The uses described herein, wherein the disease is obesity, excessive body fat, diabetes, insulin resistance or intolerance, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hepatic steatosis, type 2 diabetes mellitus (T2DM), dyslipidemia, cardiovascular disease or heart disease or atherosclerosis.

[0181]

[58] . The use of the compounds described in [1] to

[52] , their deuterated derivatives, stereoisomers, pharmaceutically acceptable salts thereof, pharmaceutically acceptable salts of stereoisomers or pharmaceutically acceptable salts of deuterated derivatives; or the pharmaceutical compositions described in

[53] for the treatment of mitochondrial-related diseases or conditions.

[0182]

[59] .

[58] The uses described herein, wherein the disease is obesity, excessive body fat, diabetes, insulin resistance or intolerance, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hepatic steatosis, type 2 diabetes mellitus (T2DM), dyslipidemia, cardiovascular disease or heart disease or atherosclerosis.

[0183] The beneficial effects of this application are:

[0184] The compounds of formula (I) of this application, their deuterated derivatives, stereoisomers, pharmaceutically acceptable salts thereof, pharmaceutically acceptable salts of stereoisomers, or pharmaceutically acceptable salts of deuterated derivatives provide higher solubility, lower toxicity, and good clinical safety. Attached Figure Description

[0185] Figure 1 : 1H-NMR spectrum of compound 1-1A.

[0186] Figure 2 : 1H-NMR spectrum of compound 1-1B.

[0187] Figure 3 : 1H-NMR spectrum of compound 1.

[0188] Figure 4 : In male ICR mice, plasma DNP C values ​​after administration of compound 1, compound HU6, and DNP were increased max In the figure, "dose" refers to the dosage, and "DNP Plasma Concentration" refers to the DNP plasma concentration.

[0189] definition

[0190] Unless otherwise stated, the terms “halogen” or “halogenated” used interchangeably herein refer to fluorine, chlorine, bromine, or iodine. Preferred halogen groups include -F, -Cl, and -Br.

[0191] Unless otherwise stated, the term "alkyl" as used herein includes straight-chain or branched saturated monovalent hydrocarbon groups. For example, alkyl radicals include methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 3-(2-methyl)butyl, 2-pentyl, 2-methylbutyl, neopentyl, n-hexyl, 2-hexyl, and 2-methylpentyl. (The last part, "in -C," appears to be a typo and can be left as is.) 1-6 C in alkyl 1-6 Defined as a linear or branched arrangement of 1, 2, 3, 4, 5 or 6 carbon atoms in the group.

[0192] Unless otherwise stated, the term "haloalkyl" as used herein refers to an alkyl group substituted with one or more (1, 2, 3, 4, 5, or 6) halogens (-F, -Cl, or -Br). In some embodiments, the haloalkyl group may be replaced with -C 1-6 Halogenated alkyl or halogenated C 1-6 Alkyl groups are used interchangeably, where -C 1-6 Halogenated alkyl or halogenated C 1-6 C in alkyl 1-6 This indicates that the total number of carbon atoms in the alkyl group is 1 to 6. In some embodiments, -C 1-6 Haloalkyl is -C 1-3 Halogenated alkyl groups. In some embodiments, -C 1-3 The haloalkyl group is methyl, ethyl, propyl, or isopropyl, substituted with 1, 2, 3, 4, 5, or 6 -F groups; preferably, -C 1-3 The alkyl halotype is -CF3.

[0193] The term "alkylene" refers to a divalent group obtained by removing an additional hydrogen atom from the aforementioned alkyl group. Examples include methylene (i.e., -CH2-), ethylene (i.e., -CH2-CH2- or -CH(CH3)-), and propylene (i.e., -CH2-CH2-CH2-, -CH(-CH2-CH3)-, or -CH2-CH(CH3)-).

[0194] The term "alkenyl" refers to a straight-chain or branched hydrocarbon group containing one or more double bonds, typically ranging in length from 2 to 20 carbon atoms. For example, "-C 2-6 "Alkenyl" contains 2 to 6 carbon atoms. Alkenyl groups include, but are not limited to, vinyl, propenyl, butenyl, 2-methyl-2-buten-1-yl, heptenyl, octenyl, etc.

[0195] The term "alkynyl" refers to a straight-chain or branched hydrocarbon group containing one or more triple bonds, typically ranging in length from 2 to 20 carbon atoms. For example, "C 2-6 The alkynyl group contains 2 to 6 carbon atoms. Representative alkynyl groups include, but are not limited to, ethynyl, 1-propynyl, 1-butynyl, heptynyl, octyynyl, etc.

[0196] The term "alkoxyalkyl" refers to an oxygen ether formed from the above-mentioned alkyl groups, wherein the total number of carbon atoms is as indicated. Alkoxyalkyl means an alkyl group substituted with -O-alkyl, including but not limited to -CH2-O-CH3, -CH2CH2-O-CH3, -CH2-O-CH2CH3, -CH2(CH3)-O-CH3 and -CH2CH2-O-CH2CH2.

[0197] The term "haloalkoxyalkyl" refers to an alkoxyalkyl group that is substituted with one or more (1, 2, 3, 4, 5, or 6) halogens (-F, -Cl, or -Br). In some embodiments, the haloalkoxyalkyl group may be substituted with -C 1-6 Halogenated alkoxyalkyl or halogenated C 1-6 Alkoxyalkyl groups are used interchangeably, where -C 1-6 Halogenated alkoxyalkyl or halogenated C 1-6 C in alkoxyalkyl 1-6 This indicates that the total number of carbon atoms in the alkoxyalkyl group is 1 to 6. In some embodiments, -C 1-6 Halogenated alkoxyalkyl groups are -C 1-3 Halogenated alkoxyalkyl. In some embodiments, -C 1-3 The haloalkoxyalkyl group is a methoxy, ethoxy, propoxy, or isopropoxy group substituted with 1, 2, 3, 4, 5, or 6 -F groups; preferably, -C 1-3 The haloalkoxyalkyl group is -OCF3.

[0198] Unless otherwise specified, the term "aryl" refers to an unsubstituted or substituted monocyclic or polycyclic aromatic ring system containing a carbon ring atom. Preferred aryl groups are 6-10 membered aromatic ring systems, either monocyclic or bicyclic. Phenyl and naphthyl are preferred aryl groups.

[0199] The interchangeable terms "heterocyclic alkyl" or "heterocyclic group," unless otherwise specified, refer to unsubstituted and substituted monocyclic or polycyclic non-aromatic systems containing one or more heteroatoms, including monocyclic heterocyclic groups, bicyclic heterocyclic groups, bridged heterocyclic groups, fused heterocyclic groups, or spirocyclic groups. Preferred heteroatoms include N, O, and S, including N-oxides, sulfur oxides, and dioxides. Preferably, the ring is a 3- to 10-membered ring that is fully saturated or has one or more degrees of unsaturation. Preferably, it includes one, two, or three degrees of substitution. Examples of these heterocyclic groups include, but are not limited to, aziridine, pyrrolidinyl, piperidinyl, piperazine, oxoperazinyl, oxoperidinyl, oxaziridine, oxaziridine, aziridine, tetrahydrofuranyl, dioxopranyl, tetrahydroimidazolyl, tetrahydrothiazolyl, tetrahydrooxazolyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, thiomorpholinyl sulfoxide, thiomorpholinyl sulfone, and oxadiazolyl.

[0200] The term "heteroaryl" refers to an aromatic ring system containing carbon and at least one heteroatom. Heteroaryls can be monocyclic or polycyclic, substituted or unsubstituted. Monocyclic heteroaryl groups can have 1 to 4 heteroatoms in the ring, while polycyclic heteroaryl groups can contain 1 to 10 heteroatoms. Polycyclic heteroaryl rings can contain fused, spiro, or bridged ring linkages; for example, bicyclic heteroaryl is a polycyclic heteroaryl. Bicyclic heteroaryl rings can contain 8 to 12 ring atoms. Monocyclic heteroaryl rings can contain 5 to 8 ring atoms (carbon and heteroatoms). Examples of heteroaryl groups include, but are not limited to, thienyl, furanyl, imidazolyl, isoxazolyl, oxazolyl, pyrazolyl, pyrroleyl, thiazolyl, thiadiazolyl, triazolyl, pyridinyl, pyridazinyl, indolyl, azaindolyl, indolyl, benzimidazolyl, benzofuranyl, benzothiophene, benzisoxazolyl, benzoxoxazolyl, benzopyrazolyl, benzothiazolyl, benzothiadiazolyl, benzotriazolyl, adenine, quinolinyl, or isoquinolinyl.

[0201] The term "carbocyclic ring" refers to a monocyclic, bicyclic, bridged, fused, or spirocyclic non-aromatic ring system containing only carbon atoms, which may be substituted or unsubstituted. Preferably, the ring is a three- to ten-membered ring and may be fully saturated or have one or more degrees of unsaturation. This definition also includes multiple substitution with one, two, or three substituents. The carbocyclic ring includes, but is not limited to, cycloalkyl, cycloalkenyl, and cycloynyl groups. Exemplary "cycloalkyl" groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups.

[0202] The term "one or more" refers to one or more. In some embodiments, "one or more" refers to 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments, "one or more" refers to 1, 2, 3, 4, 5, or 6. In some embodiments, "one or more" refers to 1, 2, 3, or 4. In some embodiments, "one or more" refers to 1, 2, or 3. In some embodiments, "one or more" refers to 1 or 2. In some embodiments, "one or more" refers to 1. In some embodiments, "one or more" refers to 2. In some embodiments, "one or more" refers to 3. In some embodiments, "one or more" refers to 4. In some embodiments, "one or more" refers to 5. In some embodiments, "one or more" refers to 6.

[0203] In this invention, when one or more substituents are substituted on the ring, it means that each substituent can independently substitute on each ring atom of the ring, including but not limited to ring carbon atoms or ring nitrogen atoms. Furthermore, when the ring is a polycyclic ring, such as a fused ring, a bridged ring, or a spirocyclic ring, each substituent can independently substitute on each ring atom of the polycyclic ring.

[0204] The term "oxo" refers to the formation of a radical by an oxygen atom together with the carbon atom it is attached to.

[0205] The term “composition,” as used herein, is intended to cover products containing a specific amount of a particular ingredient, and any product resulting from a direct or indirect combination of specific amounts of a particular ingredient. Therefore, pharmaceutical compositions containing compounds of the present invention as active ingredients, and methods for preparing said compounds, are also part of this invention. Furthermore, some crystal forms of said compounds may exist in polymorphic forms, which are also intended to be included in this invention. Additionally, some of said compounds may form solvates with water (i.e., hydrates) or common organic solvents, which are also intended to be included within the scope of this invention.

[0206] The term "pharmaceutically acceptable salt" refers to a salt prepared from a pharmaceutically acceptable non-toxic alkali or acid. When the compounds of the present invention are acidic, their corresponding salts can be readily prepared from pharmaceutically acceptable non-toxic alkalis, including inorganic and organic bases. When the compounds of the present invention are basic, their corresponding salts can be readily prepared from pharmaceutically acceptable non-toxic acids, including inorganic and organic acids. Since the compounds of the present invention are intended for pharmaceutical use, they are preferably provided in a substantially pure form, for example, at least 60% pure, more preferably at least 75% pure, and particularly at least 98% pure (% by weight).

[0207] The term “therapeutic effective amount” refers to the amount of compound that is effective in treating the disease or condition.

[0208] The scope of this invention also includes prodrugs of the compounds of this invention. Generally, these prodrugs will be functional derivatives of the compounds that readily convert to the desired compounds in vivo. Therefore, in the treatment methods of this invention, the term "administration" includes the use of compounds specifically disclosed herein or compounds not specifically disclosed but convertible to said compounds in the body of a subject after administration to treat various of the said diseases. Conventional methods for selecting and preparing prodrug derivatives are described, for example, in *Prodrug Design* (1985, Elsevier), edited by H. Bundgaard.

[0209] The definition of any substituent or variable at a specific position in a molecule in this invention should be independent of its definition at other positions in that molecule. Those skilled in the art will understand that the substituents and substitution patterns on the compounds of this invention can be selected as needed to provide chemically stable compounds, and these compounds can be readily synthesized using techniques known in the art and the methods described herein.

[0210] This invention includes one or more chiral centers that the said compounds may contain, thus potentially producing epimers and optical isomers. This invention includes all such possible epimers as racemic mixtures thereof, substantially pure separated enantiomers thereof, all possible geometric isomers, and their pharmaceutically acceptable salts.

[0211] This invention includes all stereoisomers of compounds and their pharmaceutically acceptable salts. Furthermore, mixtures of stereoisomers and the isolation of specific stereoisomers are also included. In the synthesis used to prepare these compounds, or in racemization or epimerization processes known to those skilled in the art, the products of these processes may be mixtures of stereoisomers.

[0212] In this invention, the term "stereoisomer" refers to isomers in which atoms or groups of atoms have the same connection order but different spatial arrangements, including conformational isomers and stereoisomers. Configurational isomers include geometric isomers and optical isomers, with optical isomers mainly including enantiomers and epiomers. This invention encompasses all possible stereoisomers of compounds.

[0213] Some compounds provided by this invention may exist as trans-blocked isomers, which are conformational stereoisomers that occur when the rotation of single bonds in a molecule is blocked or significantly slowed down due to steric interactions with other parts of the molecule. The compounds provided by this invention include all trans-blocked isomers, whether as pure, individual trans-blocked isomer formulations, enriched formulations of each, or non-specific mixtures of each. When the rotational barrier of the single bonds is sufficiently high and the interconversion between conformations is sufficiently slow, isomer species can be isolated and separated.

[0214] This invention aims to include isotopes of all atoms appearing in the compounds. Isotopes include atoms having the same atomic number but different mass numbers. In general embodiments, but not limited to, isotopes of hydrogen include deuterium and tritium. Hydrogen isotopes can be represented as 1H (hydrogen), 2H (deuterium), and 3H (tritium). They are also commonly represented as D for deuterium and T for tritium. In this application, CD3 represents a methyl group where all hydrogen atoms are deuterium. Carbon isotopes include 13C and 14C. The isotope-labeled compounds of this invention can generally be prepared by conventional techniques known to those skilled in the art or by processes similar to those described herein, using suitable isotope-labeling reagents instead of unlabeled reagents.

[0215] Unless otherwise stated, the term "deuterated derivative" herein refers to a compound having the same chemical structure as the reference compound but with one or more hydrogen atoms replaced by deuterium atoms ("D"). It should be recognized that the natural isotopic abundance in the synthesized compound may vary depending on the source of the chemical materials used in the synthesis. Although such variations are small and insignificant, the concentration variations of naturally abundant stable hydrogen isotopes are negligible compared to the degree of stable isotopic substitution in the deuterated derivatives described herein. Therefore, unless otherwise stated, when referring to the "deuterated derivative" of the compounds of the present invention, at least one hydrogen atom is replaced by deuterium, and its natural isotopic abundance is much higher than its natural isotopic abundance (typically about 0.015%). In some embodiments, the deuterated derivatives of the present invention have an isotopic enrichment factor of at least 3500 (52.5% deuterium doping per specified deuterium atom), at least 4500 (67.5% deuterium doping), at least 5000 (75% deuterium doping), at least 5500 (82.5% deuterium doping), at least 6000 (90% deuterium doping), at least 6333.3 (95% deuterium doping), at least 6466.7 (97% deuterium doping), or at least 6600 (99% deuterium doping) per deuterium atom.

[0216] When the compounds of the present invention have tautomers, unless otherwise specified, the present invention includes any possible tautomers and their pharmaceutically acceptable salts and mixtures thereof.

[0217] The pharmaceutical compositions of the present invention comprise the compounds of the present invention (or pharmaceutically acceptable salts thereof) as the active ingredient, a pharmaceutically acceptable carrier, and optionally other therapeutic ingredients or excipients. The compositions include those suitable for oral, rectal, topical, and parenteral (including subcutaneous, intramuscular, and intravenous) administration, although the most suitable route of administration in any given situation will depend on the specific host and the nature and severity of the disease or condition to which the active ingredient is being administered. The pharmaceutical compositions can be conveniently presented in unit dose form and prepared by any method known in the art.

[0218] In practice, the compounds of the present invention, or their prodrugs, metabolites, or pharmaceutically acceptable salts, can be combined with a pharmaceutical carrier in a closely mixed form as the active ingredient according to conventional pharmaceutical formulation techniques. The carrier can take various forms depending on the desired dosage form (e.g., oral or parenteral, including intravenous injection). Therefore, the pharmaceutical compositions of the present invention can be presented as discrete units suitable for oral administration, such as capsules, pouches, or tablets, each unit containing a predetermined amount of the active ingredient. Furthermore, the compositions can be presented as powders, granules, solutions, aqueous liquid suspensions, non-aqueous liquids, water-in-oil emulsions, or oil-in-water liquids. In addition to the common dosage forms listed above, compounds represented by Formula I, or their pharmaceutically acceptable salts, can also be administered by controlled-release means and / or delivery devices. The compositions can be prepared by any pharmaceutical method. Typically, these methods involve associating the active ingredient with a carrier constituting one or more essential components. Typically, the compositions are prepared by uniformly and closely mixing the active ingredient with a liquid carrier or a subdivided solid carrier, or both. The product can then be conveniently formulated into the desired presentation.

[0219] Therefore, the pharmaceutical compositions of the present invention may include a pharmaceutically acceptable carrier and a compound or a pharmaceutically acceptable salt thereof. Compounds of Formula I or pharmaceutically acceptable salts thereof may also be included in the pharmaceutical composition in combination with one or more other therapeutically active compounds.

[0220] The pharmaceutical carrier used can be solid, liquid, or gaseous. Examples of solid carriers include lactose, kaolin, sucrose, talc, gelatin, agar, pectin, gum arabic, magnesium stearate, and stearic acid. Examples of liquid carriers include syrup, peanut oil, olive oil, and water. Examples of gaseous carriers include carbon dioxide and nitrogen. In preparing compositions for oral dosage forms, any convenient pharmaceutical medium can be used. For example, water, ethylene glycol, oil, alcohol, flavoring agents, preservatives, coloring agents, etc., can be used to form oral liquid dosage forms such as suspensions, elixirs, and solutions; while carriers such as starch, sugar, microcrystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrants, etc., can be used to form oral solid dosage forms such as powders, capsules, and tablets. Tablets and capsules are preferred oral dosage units due to their ease of administration, and therefore solid pharmaceutical carriers are used. Tablets can optionally be coated using standard aqueous or non-aqueous techniques.

[0221] Tablets containing the compositions of the present invention can be prepared by compression or molding, and optionally contain one or more excipients or auxiliary ingredients. Compressed tablets can be prepared by compressing a free-flowing active ingredient (e.g., powder or granules) in a suitable machine, optionally mixed with a binder, lubricant, inert diluent, surfactant, or dispersant. Molded tablets can be prepared by molding a mixture of powdered compounds wetted with an inert liquid diluent in a suitable machine. Each tablet preferably contains about 0.05 mg to about 5 g of the active ingredient, and each capsule or pouch preferably contains about 0.05 mg to about 5 g of the active ingredient. For example, formulations intended for oral administration to humans may contain about 0.5 mg to about 5 g of the active ingredient, compounded with a suitable and convenient amount of carrier material, the amount of which may range from about 0.05% to about 95% of the total composition. Unit dosage forms typically contain from about 0.01 mg to about 2 g of the active ingredient, usually in doses of 0.01 mg, 0.02 mg, 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg, 1000 mg, 1500 mg, or 2000 mg.

[0222] This invention relates to pharmaceutical compositions suitable for parenteral administration, which can be prepared as solutions or suspensions of the active ingredient in water. Suitable surfactants, such as hydroxypropyl cellulose, may be included. Dispersions can also be prepared in glycerol, liquid polyethylene glycol, and mixtures thereof in oil. Furthermore, preservatives may be included to prevent harmful microbial growth.

[0223] The pharmaceutical compositions of the present invention suitable for injectable use comprise sterile aqueous solutions or dispersions. Alternatively, the compositions may be in sterile powder form for provisional preparation of such sterile injectable solutions or dispersions. In any case, the final injectable form must be sterile and must flow efficiently for injection. The pharmaceutical compositions must be stable under the conditions of manufacture and storage; therefore, contamination by microorganisms such as bacteria and fungi is preferably prevented. The carrier may be a solvent or dispersion medium containing, for example, water, ethanol, polyols (e.g., glycerol, propylene glycol, and liquid polyethylene glycol), vegetable oils, and suitable mixtures thereof.

[0224] The pharmaceutical compositions of the present invention can be adapted for topical use, such as aerosols, creams, ointments, lotions, powders, etc. Furthermore, the compositions can be adapted for transdermal devices. These formulations can be prepared using compounds of formula I of the present invention or pharmaceutically acceptable salts thereof via conventional processing methods. For example, creams or ointments are prepared by mixing a hydrophilic material with water and then mixing it with about 0.05% to about 10% by weight of a compound to produce a cream or ointment with a desired consistency.

[0225] The pharmaceutical compositions of the present invention are suitable for use in solid forms for rectal administration, wherein the carrier is solid. Preferably, the mixture forms a unit-dose suppository. Suitable carriers include cocoa butter and other materials commonly used in the art. The suppository can be conveniently prepared by first mixing the composition with a softened or melted carrier, then cooling and molding it in a mold.

[0226] In addition to the carrier components described above, the pharmaceutical formulations may also include one or more suitable additional carrier components, such as diluents, buffers, flavoring agents, binders, surfactants, thickeners, lubricants, preservatives (including antioxidants), etc. Furthermore, other excipients may be included to make the formulation isotonic with the blood of the intended receptor. Compositions containing compounds described in Formula I or pharmaceutically acceptable salts thereof may also be prepared in powder or liquid concentrate form.

[0227] Typically, dosage levels of the compound from about 0.001 mg to about 150 mg per kilogram of body weight per day are useful for treating the diseases or conditions mentioned above, or from about 0.05 mg to about 7 g per patient per day. For example, inflammation, cancer, psoriasis, allergies / asthma, immune system disorders and conditions, and central nervous system (CNS) disorders and conditions can be effectively treated with a dosage of the compound from about 0.001 to 50 mg per kilogram of body weight per day, or from about 0.05 mg to about 3.5 g per patient per day.

[0228] However, it is understandable that the specific dosage level for any particular patient will depend on a variety of factors, including age, weight, general health condition, sex, diet, timing of administration, route of administration, excretion rate, combination of drugs, and the severity of the specific disease being treated.

[0229] Unless the context clearly indicates otherwise, when a value is expressed as “about” or “approximately” X, the value of X shall be understood as having an accuracy of ±10%, preferably ±5%, ±2%.

[0230] These and other aspects will become apparent from the following written description of the invention.

[0231] Preparation method

[0232] The compounds of this invention can be synthesized from commercially available reagents using the synthetic methods and reaction schemes described herein. The specific synthetic routes and general schemes outlined below are intended to guide synthetic chemists of ordinary skill levels, who will readily recognize that solvents, concentrations, reagents, protecting groups, the order of synthetic steps, time, temperature, etc., can be modified as needed, entirely within the skill and judgment of those skilled in the art. Example

[0233] The following examples are intended to better illustrate the invention. Unless otherwise expressly stated, all parts and percentages are by weight, and all temperatures are in degrees Celsius. The following abbreviations are used in the examples:

[0234] DMF: N,N-dimethylformamide THF: Tetrahydrofuran EA, EtOAc: Ethyl acetate RT / RT: Room temperature MeOH: Methanol min(s): minutes DCM: Dichloromethane h / hr(s): hours aq: aqueous solution Sat.: saturated Preparative high-performance liquid chromatography (Prep-HPLC)

[0235] Example 1

[0236]

[0237] Ethyl 2-nitro-1H-imidazolium-5-carboxylate (2.00 g, 10.81 mmol), 1-bromo-2-methoxyethane (2.23 g, 16.21 mmol), and KI (359.00 mg, 2.16 mmol) were dissolved in DMF (20 mL), and K₂CO₃ (4.47 g, 32.43 mmol) was added in portions at 0 °C. The resulting mixture was heated to 100 °C and stirred overnight under a nitrogen atmosphere. The mixture was cooled to room temperature, quenched in ice water, and extracted with ethyl acetate. The organic solution was dried over anhydrous sodium sulfate and concentrated. The crude product was purified by silica gel column chromatography (eluting with PE / EtOAc) to give compound 1-1A (1.40 g, 53.8% yield) as a pale yellow solid and compound 1-1B (168.00 mg, 6.5% yield) as a pale yellow oil.

[0238] compound 1-1A: LCMS: m / z=244.3[M+H]+. 1HNMR (400MHz, DMSO-d6, ppm) δ7.77 (s, 1H), 4.61 (t, J=4.8Hz, 2H), 4.38 (q, J=6.8Hz, 2H), 3.71 (t, J=4.8Hz, 2H), 3.31 (s, 3H), 1.37 (t, J=7.2Hz, 3H).

[0239] compound 1-1B: LCMS: m / z=244.0[M+H]+. 1HNMR (400MHz, DMSO-d6, ppm) δ7.70 (s, 1H), 5.13 (t, J=5.2Hz, 2H), 4.37 (q, J=6.8Hz, 2H), 3.61 (t, J=5.2Hz, 2H), 3.23 (s, 3H), 1.39 (t, J=7.2Hz, 3H).

[0240] Compound 1-1A (1.00 g, 5.76 mmol) was dissolved in THF (20 mL), and a solution of NaBH4 (0.65 g, 17.28 mmol) and MeONa (62.20 mg, 1.15 mmol) in MeOH (4 mL) was added dropwise at 0 °C. The mixture was stirred for 3 hours. The reaction was quenched with cold water and extracted with ethyl acetate. The organic solution was dried over anhydrous sodium sulfate and concentrated. The crude product was purified by silica gel column chromatography (eluting with PE / EtOAc) to give compound 1-2 (100 mg, 12.1% yield). LCMS: m / z = 202.0 [M+H] + .

[0241] Compounds 1-2 (100.00 mg, 0.49 mmol) and 1-fluoro-2,4-dinitrobenzene (109.36 mg, 0.58 mmol) were dissolved in dioxane (2 mL), and Cs₂CO₃ (479.22 mg, 1.47 mmol) was added in portions at 0 °C. The resulting mixture was heated to 75 °C and stirred overnight under a nitrogen atmosphere. The mixture was cooled to room temperature, quenched with water, and extracted with ethyl acetate. The organic solution was dried over anhydrous sodium sulfate and concentrated. The crude product was purified by preparative HPLC (C18 column, eluting with MeCN / H₂O) to give compound 1 (102.00 mg, 56.1% yield). LCMS: m / z = 368.2 [M+H] + .

[0242] 1HNMR (400MHz, DMSO-d6, ppm) δ8.77 (d, J=2.8Hz, 1H), 8.54 (dd, J=9.2, 2.8Hz, 1H), 7.79 (d, J=9 .6Hz, 1H), 7.76 (s, 1H), 5.40 (s, 2H), 4.57 (t, J=4.8Hz, 2H), 3.68 (t, J=4.8Hz, 2H), 3.23 (s, 3H).

[0243] The following compounds were synthesized using the steps described above, starting with the corresponding isomers.

[0244]

[0245] Example 2

[0246]

[0247] Compound 3-1 (300 mg, 1.62 mmol) and K₂CO₃ (672 mg, 4.86 mmol) were dissolved in DMF (4 mL), and CD₃I (353 mg, 2.43 mmol) was added. The reaction mixture was heated to 80 °C and stirred overnight. After cooling to room temperature, water (5 mL) was added, followed by extraction with ethyl acetate (3 x 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, concentrated, and the residue was purified by silica gel column chromatography (eluting with PE / EtOAc) to give compound 3-2 (84 mg, 56%) as a white solid. LCMS: m / z = 203.2 [M + H]⁺.

[0248] A solution of compound 3-2 (180 mg, 0.89 mmol) in anhydrous THF (1.0 mL) was added to a solution of NaBH4 (101 mg, 2.67 mmol) in anhydrous THF (1.0 mL) and MeOH (100 μL). The reaction mixture was stirred at 0 °C for 2 hours, and then concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel column chromatography (eluting with PE / EtOAc) to give compound 3-3 (50 mg, 35%) as a white solid. LCMS: m / z = 161.1 [M+H]+.

[0249] Compound 3-3 (50 mg, 0.31 mmol) and 2,4-dinitrofluorobenzene (70 mg, 0.47 mmol) were dissolved in dioxane (1.5 mL), and Cs₂CO₃ (204 mg, 0.62 mmol) was added fractionally at room temperature. The resulting mixture was heated to 75 °C and stirred overnight under a nitrogen atmosphere. The mixture was cooled to room temperature, quenched with water, and extracted with ethyl acetate (3 x 5 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated. The crude product was purified by preparative HPLC (C18 column, eluting with MeCN / H₂O) to give compound 3 (76 mg, 75% yield). LCMS: m / z = 327.1 [M+H]⁺.

[0250] 1HNMR (400MHz, DMSO-d6, ppm) δ 8.77 (d, J=2.8Hz, 1H), 8.54 (dd, J=9.2, 2.8Hz, 1H), 7.825 (d, J=9.6Hz, 1H), 7.77 (s, 1H), 5.40 (s, 2H).

[0251] Pharmacological experiments

[0252] Compound HU6 was synthesized according to the synthesis method of compound A (compound 2) as shown in Table 30-31 of the specification of patent WO2018129258A1.

[0253] DNP It is a metabolite of compound 1 and compound HU6.

[0254] 1. Determination of thermodynamic solubility

[0255] The materials, reagents, plates, and instruments used in the thermodynamic solubility determination experiment are shown in Table 1 below:

[0256] Table 1

[0257]

[0258] Detailed steps

[0259] Preparation of FaSSIF solution, FaSSGF solution and stock solution

[0260] Dissolve 0.42 g NaOH, 3.44 g NaH₂PO₄, and 6.19 g NaCl in 900 mL of ultrapure water. Adjust the pH of the solution to 6.5 with either a 1 N NaOH aqueous solution or a 1 N HCl aqueous solution. Dilute the resulting mixture to 1000 mL with ultrapure water to obtain a buffer solution. Add 2.24 g of FaSSIF, FeSSIF, and FaSSGF powders to the buffer solution (500 mL), stir until completely dissolved, and then dilute to 1000 mL with the buffer solution. Allow the mixture to stand until slightly turbid to prepare a FaSSIF solution, which should be used within 48 hours at room temperature or within 24 hours at 37°C.

[0261] Dissolve 2.00 g of NaCl in 900 mL of ultrapure water. Adjust the pH of the solution to 1.6 with 1 N HCl aqueous solution, then dilute to 1000 mL with ultrapure water to obtain an HCl / NaCl solution. Add 0.06 g of FaSSIF, FeSSIF, and FaSSGF powders to 500 mL of the HCl / NaCl solution and stir until completely dissolved. Then dilute to 1000 mL with the HCl / NaCl solution. The resulting FaSSGF solution should be used within 48 hours at room temperature or within 24 hours at 37°C.

[0262] Preparation of standard solutions

[0263] Each test compound and positive control compound was diluted with DMSO to a concentration of 1 mg / mL, and then diluted with 50% acetonitrile containing an internal standard (IS, 100 ng / mL dexamethasone) to obtain a standard solution of each test compound and positive control compound (the dilution factor can be adjusted according to the LC-MS / MS response).

[0264] Preparation of test solutions and data analysis

[0265] Aliquots of each analyte (approximately 1 mg) into individual wells of a 96-well plate were prepared. Then, either FaSSIF or FaSSGF solution was added to each well to bring the concentration to 1 mg / mL. The 96-well plate was transferred to a thermostatic mixer and incubated at 37°C with shaking at 1200 rpm for 24 hours, followed by filtration. The filtrate (10 μL) was vortexed with a mixture of 50% acetonitrile (155°C, 100 ng / mL dexamethasone) (990 μL) for 5 minutes. The solution was then diluted with 50% acetonitrile containing the internal standard (155°C, 100 ng / mL dexamethasone) to obtain the test solution. The dilution factor could be adjusted based on the LC-MS / MS response. Wells containing the same percentage of diclofenac sodium served as positive controls. The solubility of the analyte was calculated using the following formula:

[0266] Sample solubility = Area Ratio sample *DF*[STD] / Area Ratio Std

[0267] Area Ratio sample This refers to the area ratio of the test solution (analyte peak area / internal standard peak area).

[0268] Area Ratio Std This refers to the area ratio of the standard solution (analyte peak area / internal standard peak area).

[0269] DF refers to the dilution factor.

[0270] [STD] refers to the concentration of the standard solution.

[0271] The experimental results of thermodynamic solubility are shown in Table 2 below:

[0272] Table 2

[0273]

[0274] As shown in Table 2, compound 1 has higher solubility. In FaSSIF solution, the solubility of compound 1 is 2.6 times that of compound HU6; in FaSSGF solution, the solubility of compound 1 is 3.4 times that of compound HU6.

[0275] 2. Pharmacokinetic studies in mice

[0276] The aim of this study was to evaluate the pharmacokinetic properties of the compounds in ICR mice (♂) after administration. A total of 54 mice were randomly divided into 18 groups (n=3 / group): 27 mice for compounds HU6 and 1, and 9 mice for DNP. For groups 1–18, mice were orally administered compounds HU6 and 1 at doses of 5 mg / kg, 10 mg / kg, 20 mg / kg, 30 mg / kg, 50 mg / kg, 100 mg / kg, 600 mg / kg, 1000 mg / kg, and 2000 mg / kg, respectively. Mice in groups 19–21 were orally administered the compounds at doses of 0.1 mg / kg, 0.5 mg / kg, and 10 mg / kg, respectively. Blood samples were collected from each mouse in all groups at 0.25, 0.5, 1, 2, 4, and 8 hours after administration. Blood samples were kept on ice until centrifuged to obtain plasma samples. Plasma samples were stored at -80°C until analysis. The concentrations of compounds in plasma samples were determined using LC-MS / MS.

[0277] The results are shown in Tables 3 and 4 below.

[0278] Table 3 PK Results

[0279]

[0280] Table 4. Cmax of plasma DNP after drug administration

[0281]

[0282] As can be seen from Tables 3 and 4, across all dosage ranges, the C of compound 1 compared to compound HU6 is... max The ratios ranged from 0.300 to 0.500. Representative compounds showed significantly lower exposure levels than compound HU6, and also lower direct oral DNP levels. Furthermore, C... max There was no significant increase in C of compound 1 at each dose. max All levels are lower than compound HU6, resulting in lower toxicity and clinical safety.

[0283] It is understood that if this document refers to any prior art publication, such reference does not constitute an admission that the publication constitutes part of the general knowledge of the art in any country.

[0284] All publications, patents, patent applications, and published patent applications cited in this article are incorporated herein by reference in their entirety.

[0285] Although the invention has been described in detail by way of embodiments and examples to provide clarity, it will be apparent to those skilled in the art that minor changes and modifications can be made. Therefore, the above description and embodiments should not be construed as limiting the scope of the invention.

Claims

1. A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative: in, Each occurrence of R1 is independently selected from -C 1-3 Alkyl and -C 2-3 Alkoxyalkyl; The R1 can be 1, 2, 3, 4, 5, 6 or 7 Rs. 11 replace; The R 11 Selected from deuterium, -C 2-3 Alkoxyalkyl and -O(C 1-3 Alkyl); when R 11 -C 2-3 alkoxyalkyl or -O(C) 1-3 When alkyl), the R 11 It can be replaced by one or more deuterium atoms; R4 is independently selected from -H, -D, halogen, and -C. 1-3 Alkyl, Halogenated C 1-3 Alkyl, -C 2-3 Alkoxyalkyl, -C 2-3 alkenyl, -C 2-3 Alkyne, -CN, -NH2, -C(=O)OH, -NH(C 1-3 alkyl), -N(C) 1-3 Alkyl group 2, -OH, -O(C) 1-3 Alkyl), -O (halogenated C) 1-3 Alkyl), -SH, -S(C 1-3 Alkyl), -C(=O)(C 1-3 Alkyl), -S(=O)(C 1-3 Alkyl) and -S(=O)2(C 1-3 Alkyl), wherein when R4 is not -H, -D, halogen, or -CN, said R4 may be substituted with one or more deuterium atoms; and R2 and R3 are each independently selected from -H, -D, halogen, and -C. 1-3 Alkyl and Halogenated C 1-3 Alkyl, wherein R2 or R3 is -C 1-3 Alkyl or -halogenated C 1-3 When alkyl, R2 or R3 may be substituted with one or more deuterium atoms.

2. The compound of formula (I) according to claim 1, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein, Each occurrence of R1 is independently selected from -C 1-3 Alkyl; R1 may be substituted with 1, 2, 3, 4, 5, 6 or 7 deuteriums; and when R1 is -CH3, the -CH3 is substituted with 1, 2 or 3 deuteriums.

3. The compound of formula (I) according to any one of claims 1 to 2, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein, Each occurrence of R1 is independently selected from -CD3, -CH2CH3, -CH2CH2CH3, -CH2CH2CD3, -CH2CD2CD3, -CD2CD2CD3, -CH(CH3)2, -CD(CH3)2, and -CD(CD3)2.

4. The compound of formula (I) according to any one of claims 1 to 3, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein, Each occurrence of R1 is independently selected from -CH3, and the -CH3 is replaced by 1, 2 or 3 deuterium.

5. The compound of formula (I) according to any one of claims 1 to 4, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein, Each occurrence of R1 is independently selected from -CD3.

6. The compound of formula (I) according to claim 1, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein, Each occurrence of R1 is independently selected from -C 1-3 Alkyl group, wherein R1 is R 11 Replace; the R 11 Selected from -C 2-3 Alkoxyalkyl, and the R 11 It can be replaced by one or more deuterium atoms.

7. The compound of formula (I) according to claim 1 or 6, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein, Each occurrence of R1 is independently selected from -CH3, -CH2CH3, -CH2CH2CH3, and -CH(CH3)2, wherein R1 is controlled by R 11 Replace; the R 11 Selected from -CH2-O-CH3, -CH2-O-CH2-CH3, -CH2-CH2-O-CH3 or -CH(CH3)-O-CH3; and the R 11 It can be replaced by 1, 2, 3, 4, 5, 6 or 7 deuteriums.

8. The compound of formula (I) according to claim 1, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein, Each occurrence of R1 is independently selected 9. The compound of formula (I) according to any one of claims 1 to 8, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein, R1 is selected independently each time it appears.

10. The compound of formula (I) according to any one of claims 1 to 9, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein, R4 is selected from -H, -D, and -C. 1-3 alkyl; Preferably, R4 is selected from -H, -D, -Cl, -F, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2F, -CHF2, -CF3, -CH2CH2F, -C H2CHF2, -CH2CF3, -CHFCH3, -CF2CH3, -CH2-O-CH3, -CH2-O-CH2-CH3, -CH2-CH2-O-CH3, -CH(CH3)-O-CH3, -CN, -C(=O)OH, -NH2, -NH(CH3), -N(CH3)2, -NH(CH2CH3), -OH, -O-CH3, -O-CH2-CH3, -O-CH2-CH2-C H3, -O-CH(CH3)2, -O-CF3, -SH, -S-CH3, -S-CH2CH3, -S-CH2CH2CH3, -S-CH(CH3)2, -C(=O)(CH3), -C =O)(CH2CH3), -C(=O)(CH(CH3)2), -S(=O)(CH3), -S(=O)(CH2CH3), -S(=O)(CH(CH3)2), -S(=O)2(CH3), -S(=O)2(CH2CH3) and -S(=O)2(CH(CH3)2), wherein when R4 is not -H, -D, -Cl, -F, -Br or -CN, R4 may be substituted with one or more deuteriums; More preferably, R4 is selected from -H, -D, -CD3, and -CH3; and More preferably, R4 is -H.

11. The compound of formula (I) according to any one of claims 1 to 10, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein, R4 is -H.

12. The compound of formula (I) according to any one of claims 1 to 11, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein, R2 and R3 are each independently selected from -H, -D, and -C. 1-3 alkyl; Preferably, R2 and R3 are each independently selected from -H, -D, -Cl, -F, -Br, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH3, and -CF2CH3, wherein when R2 or R3 is not -H, -D, -Cl, -F, or -Br, R2 or R3 may be substituted with one or more deuteriums; More preferably, R2 and R3 are each independently selected from -H, -D, -CD3, and -CH3; and More preferably, R2 and R3 are each independently selected from -H.

13. The compound of formula (I) according to any one of claims 1 to 12, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein, R2 is -H.

14. The compound of formula (I) according to any one of claims 1 to 13, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein, R3 is -H.

15. The compound of formula (I) according to any one of claims 1 to 14, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein, R2 is -H; and R3 is -H.

16. A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative: in, Each occurrence of R1 is independently selected from -C 1-3 Alkyl; the R1 may be 1, 2 or 3 R 11 replace; The R 11 Selected from deuterium, -C 2-3 Alkoxyalkyl and -O(C 1-3 Alkyl); wherein when R 11 -C 2-3 alkoxyalkyl or -O(C) 1-3 When alkyl), the R 11 It can be replaced by one or more deuterium atoms; R4 is independently selected from -H, -D, and -C. 1-3 Alkyl groups; and R2 and R3 are each independently selected from -H, -D, and -C. 1-3 alkyl.

17. A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative: in, Each occurrence of R1 is independently selected from -C 1-3 Alkyl group; R1 may be substituted with 1, 2, 3, 4, 5, 6 or 7 deuterium atoms; R4 is independently selected from -H, -D, and -C. 1-3 Alkyl groups; and R2 and R3 are each independently selected from -H, -D, and -C. 1-3 alkyl.

18. A compound of formula (I), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative: in, Each occurrence of R1 is independently selected from -C 1-3 Alkyl group, wherein R1 is R 11 Replace; the R 11 Selected from -C 2-3 alkoxyalkyl, the R 11 It can be replaced by one or more deuterium atoms; R4 is independently selected from -H, -D, and -C. 1-3 Alkyl groups; and R2 and R3 are each independently selected from -H, -D, and -C. 1-3 alkyl.

19. A compound of formula (I-1), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative: in, R4 is independently selected from -H, -D, and -C. 1-3 Alkyl groups; and R2 and R3 are each independently selected from -H, -D, and -C. 1-3 alkyl.

20. A compound of formula (I-2), its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative: in, R4 is independently selected from -H, -D, and -C. 1-3 Alkyl groups; and R2 and R3 are each independently selected from -H, -D, and -C. 1-3 alkyl.

21. The compound of formula (I) according to any one of claims 1 to 18, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein, The compound is any of the following formulas:

22. The compound of formula (I) according to any one of claims 1 to 18 and 21, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative; or the compound of formula (I-1) according to claim 19, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein, The compound is any of the following formulas:

23. The compound of formula (I) according to any one of claims 1 to 18 and 21, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative; or the compound of formula (I-2) according to claim 20, wherein its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, wherein, The compound is any of the following formulas:

24. A pharmaceutical composition comprising the compound of any one of claims 1 to 23, a deuterated derivative thereof, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the deuterated derivative thereof, and at least one pharmaceutically acceptable excipient.

25. A method for treating a subject with a mitochondrial-related disease or condition, the method comprising administering to the subject a therapeutically effective amount of the compound of any one of claims 1 to 23, a deuterated derivative thereof, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of a stereoisomer thereof, or a pharmaceutically acceptable salt of a deuterated derivative thereof; or the pharmaceutical composition of claim 24; wherein, The diseases or conditions mentioned are obesity, excessive body fat, diabetes, insulin resistance or intolerance, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hepatic steatosis, type 2 diabetes mellitus (T2DM), dyslipidemia, cardiovascular disease, heart disease, or atherosclerosis.

26. The use of the compound of any one of claims 1 to 23, its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of the stereoisomer, or pharmaceutically acceptable salt of the deuterated derivative, or the use of the pharmaceutical composition of claim 24 in the preparation of a medicament for treating mitochondrial-related diseases or conditions; wherein, The diseases or conditions mentioned are obesity, excessive body fat, diabetes, insulin resistance or intolerance, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hepatic steatosis, type 2 diabetes mellitus (T2DM), dyslipidemia, cardiovascular disease, heart disease, or atherosclerosis.

27. The compound of any one of claims 1 to 23, its deuterated derivative, stereoisomer, pharmaceutically acceptable salt thereof, pharmaceutically acceptable salt of its stereoisomer, or pharmaceutically acceptable salt of its deuterated derivative, or the pharmaceutical composition of claim 24, for treating mitochondrial-related diseases or conditions; wherein, The diseases or conditions mentioned are obesity, excessive body fat, diabetes, insulin resistance or intolerance, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hepatic steatosis, type 2 diabetes mellitus (T2DM), dyslipidemia, cardiovascular disease, heart disease, or atherosclerosis.

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