Indene compounds, their pharmaceutical compositions, and their therapeutic applications

Abstract

The present invention provides compounds for treating, preventing, or improving one or more symptoms of fibrous diseases. [Solution] An indene compound of formula (I) is provided. TIFF2026122957000177.tif18170

Description

[Technical Field]

[0001] (Cross-reference of related applications) This application primarily benefits from the priority of U.S. Provisional Application No. 63 / 038,737, filed on June 12, 2020. This is a matter of fact; its disclosure is incorporated in its entirety herein by reference.

[0002] (Reference to the sequence list) This specification is 1,427 bytes in size and was created on May 23, 2021, under the code 294A002W. Along with the sequence listing in computer-readable format (CRF) titled O01_SEQ_LIST_ST25.txt, it was released. It is requested; and its contents are incorporated in full herein by reference.

[0003] (Field) This specification provides indene compounds and their pharmaceutical compositions. The products provided are intended for the treatment, prevention, or improvement of one or more symptoms of fibrous disease. This is the method of use. [Background technology]

[0004] (background) Fibrosis is the accumulation of extracellular matrix components in organs or tissues, and their structure It alters the organs, leading to the destruction of normal function, and in many cases, ultimately resulting in organ failure and death. This brings about the following: Hernandez-Gea et al., Annu. Rev. Pathol. 2011, 6, 425-56; Makarev et al. Reference, Cell Cycle 2016, 15, 1667-73. Fibrosis can occur in almost any organ or tissue, and It is associated with a wide variety of diseases and contributes to up to 45% of deaths in developed countries. (Mehal et al., Nat) Med. 2011, 17, 552-3; Makarev et al., Cell Cycle 2016, 15, 1667-73.

[0005] NASH (non-alcoholic steatohepatitis) is a condition characterized by excessive fat in the liver, unrelated to alcohol use. It is a progressive disease caused by fat accumulation, which involves chronic inflammation and damage to liver cells. It induces hypertrophy, leading to cirrhosis, liver failure, and potentially fatal fibrosis. (Roenn's literature) Clin. Liver Dis.(Hoboken) 2018, 12, 35-6; Sheka et al., JAMA 2020, 323, 1175-83 The stage of liver fibrosis is a strong predictor of clinical outcome in patients with NASH. References: lo et al., Hepatology 1999, 30, 1356-62; Dulai et al., Hepatology 2017, 65, 15 57-65. The ongoing obesity associated with the increasing prevalence of diabetes will dramatically increase the incidence of NASH in the coming years. It is thought to increase the incidence of this disease, and it is predicted to become the leading cause of liver transplants in the United States. See Roenn's work, Clin. Liver Dis. (Hoboken) 2018, 12, 35-6; Sheka et al.'s work, JAMA. 2020, 323, 1175-83. Currently, there are no FDA-approved treatments for NASH. Ibid. Therefore, there is a need for effective treatments for fibrous diseases, particularly NASH. [Overview of the project]

[0006] (Summary of Disclosure) Provided herein are compounds of formula (I): [ka] or its enantiomer, mixture of enantiomers, diastereomer, mixture of two or more diastereomers, tautomer, mixture of two or more tautomers, or isotope variant; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; (wherein: R is (a) hydrogen, deuterium, cyano, halo, or nitro; or (b) C 2-6 , 3-10 , , 2-6 , 6-14 alkyl, C 1-6 alkenyl, C 2-6 alkynyl, C 2-6 cycloalkyl, C 3-10 aryl, C 6-14 aralkyl 7-15 heteroaryl, or heterocyclyl; R is -C(O)OR 2 , -C(O)NR 2a R 2b R 2c , -C(O)N(R 2b )OR 2c , or heteroaryl; wherein R 2a , R 2b , and R 2c are each independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C cycloalkyl, C 3-10 aryl, C 6-14 aralkyl, heteroaryl, 7-15 or heterocyclyl; R R 3 , R 4 , R 5 , and R 6 are each independently (a) hydrogen, deuterium, cyano, halo, or nitro; (b) C alkyl, C 1-6 alkenyl, C 2-6 alkynyl, C 2-6 cycloalkyl, C 3-10 aryl, C 6-14 aralkyl; Reel, C 7-15 Aralkyl, heteroaryl, or heterocyclyl; or (c)-C(O)R 1a , -C(O)OR 1a -C(O)NR 1b R 1c -C(NR 1a )NR 1b R 1c , -OR 1a ,-OC(O)R 1a -OC(O)OR 1a -OC(O) NR 1b R 1c -OC(NR 1a )NR 1b R 1c -OS(O)R 1a -OS(O)2R 1a -OS(O)NR 1b R 1c -OS(O)2NR 1b R 1c , -NR 1b R 1c , -NR 1a C(O)R 1d , -NR 1a C(O)OR 1d , -NR 1a C(O)NR 1b R 1c , -NR 1a C(NR 1d )NR 1b R 1c , -NR 1a S(O)R 1d , -NR 1a S(O)2R 1d , -NR 1a S(O)NR 1b R 1c , -NR 1a S(O)2NR 1b R 1c , -SR 1a ,-S(O)R 1 a -S(O)2R 1a -S(O)NR 1b R 1cor -S(O)2NR 1b R 1c and; R A is C 6-14 arylene or heteroarylene; R B and X are (i), (ii), or (iii): (i) X is -O-, -S-, -S(O)-, or -S(O)2-; and R B is C 6-14 aryl or heteroaryl; or (ii) X is -N(R X )-; R B is C 6-14 aryl or heteroaryl; and R X is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl , C 6-14 aryl, C 7-15 aralkyl, heteroaryl, or heterocyclyl; or ; or (iii) X is -N(R X )-; and R B and R X together with the N atom to which they are attached form heteroaryl or heterocy[[ID=6​​​​​​​​​​​​​​​​​​​​​​​​​​​​​3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralkil, Hete It is either a roaryl or heterocyclyl; or R 1a and R 1c They are combined Together with C and N atoms, they form a heterocycline; or R 1b and R 1c They combine Together with the N atom present, it forms a heterocycline; Here, each alkyl, alkylene, alkenyl, alkenylene, alkynyl, cyclo Roalkyl, cycloalkylene, aryl, arylene, aralkyl, heteroaryl, Heteroarylene, heterocyclyl, and heterocyclylene are one or more in one embodiment In this compound, one, two, three, or four substituents Q are arbitrarily substituted, where each Q is (a) Deuterium, cyano, halo, nitro, and oxo; (b) Each of them is one or more embodiments. In this, one, two, three, or four substituents Q a C is further arbitrarily substituted. 1-6 Al Kill, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralkyl, heteroaryl, and heterocyclyl; and (c)-C(O)R a , -C(O)OR a , -C(O) NR b R c -C(O)SR a -C(NR a )NR b R c ,-C(S)R a , -C(S)OR a -C(S)NR b R c , -ORa 、-OC(O)R a 、-O C(O)OR a 、-OC(O)NR b R c 、-OC(O)SR a 、-OC(NR a )NR b R c 、-OC(S)R a 、-OC(S)OR a 、-OC(S)NR b R c 、-OS(O)R a 、-OS(O)2R a 、-OS(O)NR b R c 、-OS(O)2NR b R c 、-NR b R c 、-NR a C(O)R d 、-NR a C(O)OR d 、-NR a C(O)NR b R c 、-NR a C(O)SR d 、-NR a C(NR d )NR b R c 、-NR a C(S)R d 、-NR a C(S)OR d 、-NR a C(S )NR b R c 、-NR a S(O)R d 、-NR a S(O)2R d 、-NR a S(O)NR b R c 、-NR a S(O)2NR b R c 、-SR a 、-S(O)R a 、- S(O)2R a -S(O)NR b R c , and -S(O)2NR b R c : are independently selected from, where each R a , R b , R c , and R d (i) hydrogen or deuterium; (ii) each of them in one or more embodiments In this, one, two, three, or four substituents Q a C is arbitrarily replaced by 1-6 Alkyl, C2 -6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralchi (iii)R b and R c Those Along with the bonded N atom, one or more, in one embodiment, one, two, three, or four substituted Q a It forms a heterocycline which is optionally substituted; Here, each Q a (a) Deuterium, cyano, halo, nitro, and oxo; (b) C 1-6 Alki Ru, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 a Larquil, heteroaryl, and heterocyclyl; and (c)-C(O)R e , -C(O)OR e -C(O)NR f R g -C(O)SR e -C(NR e )NR f Rg 、-C(S)R e 、-C(S)OR e 、-C(S)NR f R g 、-OR e 、-OC(O)R e 、-OC( O)OR e 、-OC(O)NR f R g 、-OC(O)SR e 、-OC(NR e )NR f R g 、-OC(S)R e 、-OC(S)OR e 、-OC(S)NR f R g 、 -OS(O)R e 、-OS(O)2R e 、-OS(O)NR f R g 、-OS(O)2NR f R g 、-NR f R g 、-NR e C(O)R h 、-NR e C(O)OR f 、-NR e C(O)NR f R g 、-NR e C(O)SR f 、-NR e C(NR h )NR f R g 、-NR e C(S)R h 、-NR e C(S)OR f 、-NR e C(S) NR f R g 、-NR e S(O)R h 、-NR e S(O)2R h 、-NR e S(O)NR f R g 、-NRe S(O)2NR f R g , -SR e ,-S(O)R e , -S (O)2R e -S(O)NR f R g , and -S(O)2NR f R g : independently selected from; here, each R e , R f , R g , and R h (i) hydrogen or deuterium; (ii) C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aalkyl, heteroaryl , or heterocyclyl; or (iii)R f and R g The N atoms to which they are bonded (Together, they form heterocyclines.)

[0007] Also provided herein are compounds of formula (I), or their enantiomers, enantiomers, etc. Omer mixtures, mixtures of two or more diastereomers, tautomers, two or more tautomers Mixtures or isotopic variants; or pharmaceutically acceptable salts, solvates, or hydrates thereof. A pharmaceutical composition comprising a substance or prodrug and a pharmaceutically acceptable excipient.

[0008] Furthermore, this specification provides for the treatment of one or more symptoms of fibrous disease in the subject. A method of prevention or improvement, wherein the compound of formula (I) or the target that needs it is used. The enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, Mutageners, mixtures of two or more tautomers, or isotopic variants; or as pharmaceuticals thereof This includes administering a therapeutically effective dose of an acceptable salt, solvate, hydrate, or prodrug. , that is the method.

[0009] Furthermore, this specification provides for the treatment of one or more symptoms of a proliferative disorder in the subject. A method of prevention or improvement, wherein the compound of formula (I) or the target that needs it is used. The enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, Mutageners, mixtures of two or more tautomers, or isotopic variants; or as pharmaceuticals thereof This includes administering a therapeutically effective dose of an acceptable salt, solvate, hydrate, or prodrug. , that is the method.

[0010] Provided herein is a method for inhibiting cell proliferation, wherein the cells are subjected to formula (I) Compounds, or their enantiomers, mixtures of enantiomers, two or more diastereomers A mixture of, tautomers, a mixture of two or more tautomers, or isotopic variants; or these Contact with an effective amount of a pharmaceutically acceptable salt, solvate, hydrate, or prodrug. This is a method that includes the following.

[0011] Provided herein are methods for treating, preventing, or treating one or more symptoms of fibrous disease in the subject. This is a method of improvement, and for the target that needs it, a compound of formula (IA): [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are therapeutically effective salts, solvates, hydrates, or prodrugs that are acceptable as pharmaceuticals. A method that involves administering a certain amount; (In the formula: R 1 (a) hydrogen, deuterium, cyano, halo, or nitro; or (b) C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralquil , heteroaryl, or heterocyclyl; R 2 -CN, -C(O)OR 2a -C(O)NR 2b R 2c ,-C(O)N(R 2b )OR 2c , -OR 2a , -NR 2b R 2c , or Hete It is a lower aryl; here, R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 Alkyl, C2 -6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralchi It is a heteroaryl or heterocyclyl; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of (a) hydrogen, deuterium, cyano, halo, or nitrate. (b)C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 a Reel, C 7-15Aralkyl, heteroaryl, or heterocyclyl; or (c)-C(O)R 1a , -C(O)OR 1a -C(O)NR 1b R 1c -C(NR 1a )NR 1b R 1c , -OR 1a ,-OC(O)R 1a -OC(O)OR 1a -OC(O) NR 1b R 1c -OC(NR 1a )NR 1b R 1c -OS(O)R 1a -OS(O)2R 1a -OS(O)NR 1b R 1c -OS(O)2NR 1b R 1c , -NR 1b R 1c , -NR 1a C(O)R 1d , -NR 1a C(O)OR 1d , -NR 1a C(O)NR 1b R 1c , -NR 1a C(NR 1d )NR 1b R 1c , -NR 1a S(O)R 1d , -NR 1a S(O)2R 1d , -NR 1a S(O)NR 1b R 1c , -NR 1a S(O)2NR 1b R 1c , -SR 1a ,-S(O)R 1 a -S(O)2R 1a -S(O)NR 1b R 1c , or -S(O)2NR 1bR 1c and; Each R 7 (a) Deuterium, cyano, halo, or nitro; (b) C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralchi (c)-C(O)R 1a , -C(O)OR 1a -C(O)NR 1b R 1c -C(NR 1a )NR 1b R 1c , -OR 1a ,-OC(O)R 1a -OC(O)OR 1a -OC(O)NR 1b R 1c -OC(NR 1a )NR 1b R 1c -OS(O)R 1a -OS(O)2R 1a -OS(O)NR 1b R 1c -OS(O)2NR 1b R 1c , -NR 1b R 1c , -NR 1a C(O)R 1 d , -NR 1a C(O)OR 1d , -NR 1a C(O)NR 1b R 1c , -NR 1a C(NR 1d )NR 1b R 1c , -NR 1a S(O)R 1d , -NR 1a S(O) 2R 1d , -NR1a S(O)NR 1b R 1c , -NR 1a S(O)2NR 1b R 1c , -SR 1a ,-S(O)R 1a -S(O)2R 1a -S(O)NR 1b R 1c , or -S(O)2NR 1b R 1c is; or two adjacent R 7 The f Together with the henyl group, it forms naphthyl or bicyclic heteroaryl groups; R C (a) hydrogen, deuterium, cyano, halo, or nitro; or (b) C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralquil , heteroaryl, or heterocyclyl; or (c)-OR 1a , -NR 1b R 1c , or -NR 1a C( O)R 1d and; L is C 1-6 Alkylene or C 2-6 It is an alkenylene; n is an integer of 0, 1, 2, 3, or 4; and Each R 1a , R 1b , R 1c , and R 1d These are, independently, hydrogen, deuterium, and C 1-6 Alkyl, C 2-6 Alke Nil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralkil, Hete It is either a roaryl or heterocyclyl; or R 1a and R 1c They are combined Together with C and N atoms, they form a heterocycline; or R 1b and R 1c They combine Together with the N atom present, it forms a heterocycline; Here, each alkyl, alkylene, alkenyl, alkenylene, alkynyl, cyclo Roalkyl, aryl, aralkyl, heteroaryl, and heterocyclyl are one or more In one embodiment, it is arbitrarily substituted with one, two, three, or four substituents Q, Here, each Q is (a) deuterium, cyano, halo, nitro, and oxo; (b) each of them is 1 or less In the above embodiment, one, two, three, or four substituents Q a And then it is arbitrarily replaced C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralkyl, heteroaryl, and heterocyclyl; and (c)-C(O)R a , -C(O)OR a -C(O)NR b R c -C(O)SR a -C(NR a )NR b R c ,-C(S)R a , -C(S)OR a -C(S)NR b R c , -OR a ,-OC(O)R a -OC(O)OR a -OC(O)NR b R c -OC(O)SRa -OC(NR a )NR b R c ,-OC(S)R a , -OC(S)O R a -OC(S)NR b R c -OS(O)R a -OS(O)2R a -OS(O)NR b R c -OS(O)2NR b R c , -NR b R c , -NR a C(O )R d , -NR a C(O)OR d , -NR a C(O)NR b R c , -NR a C(O)SR d , -NR a C(NR d )NR b R c , -NR a C(S)R d , -NR a C (S)OR d , -NR a C(S)NR b R c , -NR a S(O)R d , -NR a S(O)2R d , -NR a S(O)NR b R c , -NR a S(O)2NR b R c ,- SR a ,-S(O)R a -S(O)2R a -S(O)NR b R c , and -S(O)2NR b R c : Selected independently from, here, Each R a , R b , R c , and R d (i) hydrogen or deuterium; (ii) each of them is one or more In one embodiment, one, two, three, or four substituents Q a It is arbitrarily replaced by C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel , C 7-15 (iii)R b Reach biR c Together with the N atoms to which they are bonded, one or more, in one embodiment, one, two , three or four substituents Q a It forms a heterocycline which is optionally substituted; Here, each Q a (a) Deuterium, cyano, halo, nitro, and oxo; (b) C 1-6 Alki Ru, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 a Larquil, heteroaryl, and heterocyclyl; and (c)-C(O)R e , -C(O)OR e -C(O)NR f R g -C(O)SR e -C(NR e )NR f R g ,-C(S)R e , -C(S)OR e -C(S)NR f R g , -OR e ,-OC(O)Re 、-OC( O)OR e 、-OC(O)NR f R g 、-OC(O)SR e 、-OC(NR e )NR f R g 、-OC(S)R e 、-OC(S)OR e 、-OC(S)NR f R g 、 -OS(O)R e 、-OS(O)2R e 、-OS(O)NR f R g 、-OS(O)2NR f R g 、-NR f R g 、-NR e C(O)R h 、-NR e C(O)OR f 、-NR e C(O)NR f R g 、-NR e C(O)SR f 、-NR e C(NR h )NR f R g 、-NR e C(S)R h 、-NR e C(S)OR f 、-NR e C(S) NR f R g 、-NR e S(O)R h 、-NR e S(O)2R h 、-NR e S(O)NR f R g 、-NR e S(O)2NR f R g 、-SR e 、-S(O)R e 、-S (O)2Re -S(O)NR f R g , and -S(O)2NR f R g : independently selected from; here, each R e , R f , R g , and R h (i) hydrogen or deuterium; (ii) C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aalkyl, heteroaryl , or heterocyclyl; or (iii)R f and R g The N atoms to which they are bonded (Together, they form heterocyclines.) [Brief explanation of the drawing]

[0012] (Brief explanation of the drawing) [Figure 1] Figure 1 shows the effects of malotilate (Mal), as well as compounds A11 and B9, on body weight in C57 / BL6 mice.

[0013] [Figure 2] Figure 2 shows the effects of Mal, as well as compounds A11 and B9, on α-SMA mRNA levels in C57 / BL6 mice.

[0014] [Figure 3] Figure 3 shows the effects of Mal, as well as compounds A11 and B9, on the mRNA level of Col1a1 in C57 / BL6 mice.

[0015] [Figure 4]Figure 4 shows Sirius Red pathological staining images of liver samples from C57 / BL6 mice treated with Mal, or compound A11 or B9, demonstrating that each compound reverses CCl4-induced fibrosis.

[0016] [Figure 5] Figure 5 shows the effects of Mal and compound A23 on α-SMA mRNA levels in C57 / BL6 mice.

[0017] [Figure 6] Figure 6 shows the effects of Mal and compound A23 on Col1a1 mRNA levels in C57 / BL6 mice. [Modes for carrying out the invention]

[0018] (Detailed explanation) To facilitate understanding of the disclosures presented herein, several terms are defined below. .

[0019] Overall, the nomenclature used herein and the organic chemistry and pharmaceuticals described herein Experimental procedures in science, biochemistry, biology, and pharmacology are well known in the art and These are commonly used. Unless otherwise defined, all techniques used herein Technical and scientific terms, as a whole, are to be commonly understood by those skilled in the art to whom this disclosure belongs. It has the same meaning as [this].

[0020] The term "subject" is not limited to primates (e.g., humans), cattle, pigs, and sheep. This refers to animals including goats, horses, dogs, cats, rabbits, rats, or mice. The term “patient” is used, for example, in reference to mammals, for example, to humans, in this specification. It is used interchangeably. In one embodiment, the subject is a human.

[0021] The terms "treat," "treating," and "treatment" refer to a disorder. A disease, illness, or disorder, or one or more symptoms associated with a disease or illness. To alleviate or eliminate; or to alleviate or eradicate the cause of the disorder, disease, or disease itself. It is intended to include the following.

[0022] The terms "prevent," "preventing," and "prevention" are used to describe the prevention of disabilities. To delay and / or prevent the onset of harm, disease, or illness and / or associated symptoms thereof. A method to prevent the subject from suffering from a disability, disease, or illness; or a method to prevent the subject from suffering from a disability, disease It is intended to include methods to reduce the risk of contracting or developing a disease.

[0023] The terms "alleviate" and "alleviating" refer to a disability, disease, Alternatively, it refers to alleviating or reducing one or more symptoms of a disease (e.g., pain). These terms can also refer to reducing the adverse effects associated with the active ingredient. The beneficial effects obtained by the subject from the preventive or therapeutic agent result in the healing of a disorder, disease, or illness. Sometimes they don't.

[0024] The terms "contacting" or "contact" are used in such cases. A therapeutic agent and biomolecules (e.g.,) are brought into contact so that physiological and / or chemical effects result from the contact. This refers to the process of combining proteins, enzymes, RNA, or DNA, cells, or tissues. This is intended. Contact can occur in vitro, ex vivo, or in vivo. In one embodiment, in order to determine the effect of a therapeutic agent on biomolecules, the therapeutic agent is used in the biomolecules The child is brought into contact with the cells in vitro. In another embodiment, the effect of the therapeutic agent on the cells is determined. To achieve this, the therapeutic agent is brought into contact with the cells under cell culture conditions (in vitro). In another embodiment... In this regard, contact between the therapeutic agent and biomolecules, cells, or tissues is required for the biomolecules and cells that should be brought into contact. This includes administering a therapeutic agent to a subject having tissue, or other tissue.

[0025] The terms "therapeutic effective dose" or "effective dose" refer to the therapeutically effective dose at the time of administration, which is treating the disorder being treated. To prevent the occurrence of one or more symptoms of harm, disease, or illness, or to prevent them It is intended to contain an amount of the compound sufficient to alleviate the symptoms to a certain extent. “Therapeutic effective dose” or “ The term "effective dose" is also used by researchers, veterinarians, physicians, or clinicians to determine the appropriate dose. Biomolecules (e.g., proteins, enzymes, RNA, or DNA), cells, tissues, systems, animals, or This refers to the amount of a compound sufficient to induce a biological or medical response in a human.

[0026] "A carrier that is acceptable as a medicine," "An excipient that is acceptable as a medicine," "Physiologically acceptable" The terms "carrier obtained" or "physiologically acceptable excipient" refer to liquid or solid fillers. Pharmaceutically acceptable materials, compositions, or vehicles, such as diluents, solvents, or encapsulating materials. This refers to... In one embodiment, each component is compatible with other components of the pharmaceutical formulation and does not have excessive toxicity. Without irritation, allergic response, immunogenicity, or other problems or complications, the subject (e.g.) For example, it is suitable for use in contact with human tissue or organs, and provides reasonable benefits / risks. In the sense that it is commensurate with the ratio, it is "acceptable as a medicine." For example, Remint Remington: The Science and Practice of Pharmacy, 23rd edition; Adejare (ed.); Academic Press, 2020; Handbook of Pharmaceutical Excipients (Cal Excipients), 9th edition; edited by Sheskey et al.; Pharmaceutical Press, 2020; Handbook of Pharmaceutical Additives, 3rd edition; edited by Ash and Ash; Synapse Inf Pharmaceutical Preformulation and Prescription Resources, 2007; Pharmaceutical Preformulation and Prescription See Formulation, first edition; edited by Gibson; CRC Press, 2015.

[0027] The terms "about" or "approximately" are determined by those skilled in the art. This refers to the tolerance for a given value, which in part means how the value is measured or determined. It depends on whether it is "about" or "approximately". The term "approximately (ab)" means within 1, 2, or 3 standard deviations. In one embodiment, "approximately (ab)" means within 1, 2, or 3 standard deviations. The terms "out" or "approximately" refer to 25%, 20%, or 15% of a given value or range. This means within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, or 0.05%. do.

[0028] The term "alkyl" refers to a linear or branched saturated monovalent hydrocarbon radical, where The alkyl group is optionally substituted with one or more substituents Q as described herein. For example , C 1-6 Alkyls are linear saturated monovalent hydrocarbon radicals with 1 to 6 carbon atoms, or 3 to 6 carbon atoms. This refers to a branched saturated monovalent hydrocarbon radical of elementary atoms. In one embodiment, alkyl is 1~20 pieces (C 1-20 ), 1~15 pieces (C 1-15 ), 1~10 pieces (C 1-10 ), or 1 to 6 (C 1-6 ) the carbon atoms A linear saturated monovalent hydrocarbon radical, or 3 to 20 (C) 3-20 ), 3~15 pieces (C 3-15 ), 3~10(C3 -10 ) pieces, or 3 to 6 pieces (C 3-6 A branched saturated monovalent hydrocarbon radical having ) carbon atoms When used herein, linear C 1-6 and branched C 3-6 Alkyl is a "lower alkyl group." It is also called ''. Examples of alkyl groups include methyl, ethyl, and propyl (all isomers). Forms, for example, including n-propyl and isopropyl), butyl (all isomer forms, for example, (including n-butyl, isobutyl, sec-butyl, and t-butyl), pentyl (all isomer forms) For example, n-pentyl, isopentyl, sec-pentyl, neopentyl, and tert-pentyl (including n-hexyl), as well as hexyl (all isomer forms, e.g., n-hexyl, isohexyl, and Examples include, but are not limited to, sec-hexyl.

[0029] The terms "alkylene" and "alkanediyl" refer to linear or branched saturated divalent carbonized water. With respect to elementary radicals, they are used interchangeably in this specification, where the alkylene is this It is optionally substituted with one or more substituents Q as described in the specification. For example, C 1-6 Alkilen , linear saturated divalent hydrocarbon radicals of 1 to 6 carbon atoms, or branched saturated hydrocarbon radicals of 3 to 6 carbon atoms This refers to a divalent hydrocarbon radical. In one embodiment, alkylene has 1 to 30 (C) 1-30 ) , 1~20 pieces (C 1-20 ), 1~15 pieces (C 1-15 ), 1~10 pieces (C 1-10 ), or 1 to 6 (C 1-6 ) carbon atoms A linear saturated divalent hydrocarbon radical having 3 to 30 (C 3-30 ), 3~20 pieces (C 3-20 ), 3-15 pieces(C 3-15 ), 3~10 pieces (C 3-10 ), or 3-6 (C 3-6 ) Branched saturated divalent having carbon atoms It is a hydrocarbon radical. When used herein, linear C 1-6 and branched C 3-6 Alchile The alkylene group is also called a "lower alkylene." Examples of alkylene groups include methylene and ethyl acetate. Len (including all isomer forms, e.g., ethane-1,1-diyl and ethane-1,2-diyl), P Plylene (all isomer forms, e.g., propane-1,1-diyl, propane-1,2-diyl, and (including propane-1,3-diyl), butylene (all isomer forms, e.g., butane-1,1-diyl) (including butane-1,2-diyl, butane-1,3-diyl, and butane-1,4-diyl), pentylene n (all isomer forms, e.g., pentan-1,1-diyl, pentan-1,2-diyl, pentan- (including 1,3-diyl and pentane-1,5-diyl), and hexylene (all isomer forms, For example, hexane-1,1-diyl, hexane-1,2-diyl, hexane-1,3-diyl, and hexane Examples include, but are not limited to, san-1,6-zil.

[0030] The term "alkenyl" means one or more, in one embodiment, one, two, three, or four In another embodiment, a linear or branched monovalent nucleotide containing one carbon-carbon double bond. Refers to hydrocarbon radicals. Alkenyls are optionally substituted with one or more substituents Q as described herein. It is replaced. The term "alkenil" is understood by those skilled in the art as "cis". " or "trans" configuration or a mixture thereof, or "Z" or "E" configuration or so It includes radicals having a mixture of these. For example, C 2-6 Alkenyls are composed of 2 to 6 carbon atoms. These are linear unsaturated monovalent hydrocarbon radicals, or branched unsaturated monovalent hydrocarbon water with 3 to 6 carbon atoms. This refers to elementary radicals. In one embodiment, an alkenyl has 2 to 20 (C) 2-20 ), 2~15 pieces (C2 -15 ), 2~10 pieces (C 2-10 ), or 2-6 (C 2-6 Linear monovalent hydrocarbon radical of a carbon atom, Or 3 to 20 pieces (C 3-20 ), 3~15 pieces (C 3-15 ), 3~10 pieces (C 3-10 ), or 3-6 (C 3-6 ) carbon source This is a branched monovalent hydrocarbon radical. Examples of alkenyl groups include ethenyl and propene. Nyl (including all isomer forms, e.g., propen-1-yl, propen-2-yl, and allyl) (mu), and butenyl (all isomer forms, e.g., buten-1-yl, buten-2-yl, butenyl) Examples include, but are not limited to, ₁-3-yl and ₂-butene-1-yl.

[0031] The terms "alkenylene" and "alkenzyl" are used in one or more embodiments. And, in another embodiment, it contains one, two, three, or four carbon-carbon double bonds With respect to linear or branched divalent hydrocarbon radicals, the terms used herein are interchangeable. Alkenylene is optionally substituted with one or more substituents Q as described herein. The term "Kenilen" is understood by those skilled in the art to mean "cis" or "trans" Having a "Z" configuration or a mixture thereof, or a "Z" or "E" configuration or a mixture thereof It contains radicals. For example, C 2-6 Alkenylenes are linearly unsaturated divalent molecules with 2 to 6 carbon atoms. This refers to hydrocarbon radicals or branched unsaturated divalent hydrocarbon radicals consisting of 3 to 6 carbon atoms. In one embodiment, alkenylene is 2 to 30 (C 2-30 ), 2~20 pieces (C 2-20 ), 2~15 pieces (C 2-1 5), 2~10 pieces (C 2-10 ), or 2-6 (C 2-6 ) A linear divalent hydrocarbon radical of a carbon atom, 3 to 30 pieces (C 3-30 ), 3~20 pieces (C 3-20 ), 3~15 pieces (C 3-15 ), 3~10 pieces (C 3-10 ), or 3-6 pieces (C 3-6 It is a branched divalent hydrocarbon radical of a carbon atom. An example of an alkenylene group is: Ethenylene (including all isomer forms, e.g., ethene-1,1-diyl or ethene-1,2-diyl) (mu), propenylene (all isomer forms, e.g., 1-propene-1,1-diyl, 1-propene-1, (including 2-diyl and 1-propene-1,3-diyl), butenylene (all isomer forms, e.g.) (including 1-butene-1,1-diyl, 1-butene-1,2-diyl, and 1-butene-1,4-diyl), pen Tenylene (all isomer forms, e.g., 1-pentene-1,1-diyl, 1-pentene-1,2-diyl) , and including 1-pentene-1,5-diyl), and hexenylene (all isomer forms, e.g., (including 1-hexen-1,1-diyl, 1-hexen-1,2-diyl, and 1-hexen-1,6-diyl) These include, but are not limited to, the following:

[0032] The term "alkynyl" means one or more, in one embodiment, one, two, three, or four In another embodiment, a linear or branched monovalent nucleotide containing one carbon-carbon triple bond. Refers to hydrocarbon radicals. Alkynnyls are optionally substituted with one or more substituents Q as described herein. It has been replaced. For example, C 2-6 Alkynnyl is a linear unsaturated monovalent carbon dioxide with 2 to 6 carbon atoms. This refers to elementary radicals, or branched unsaturated monovalent hydrocarbon radicals consisting of 4 to 6 carbon atoms. In the embodiment, alkynyl is expressed in 2 to 20 (C) 2-20 ), 2~15 pieces (C 2-15 ), 2~10 pieces (C 2-10 ),too Or 2 to 6 (C 2-6 ) A linear monovalent hydrocarbon radical of carbon atoms, or 4 to 20 (C 4-20 ), 4~1 5 pieces (C 4-15 ), 4~10 pieces (C 4-10 ), or 4-6 pieces (C 4-6 ) branched monovalent hydrocarbons of carbon atoms It is dikal. Examples of alkynyl groups include ethynyl (-C≡CH) and propynyl (all isomers). Body morphology, for example, including 1-propynyl (-C≡CCH3) and propargyl (-CH2C≡CH), butyn Lu (including all isomer forms, e.g., 1-butyn-1-yl and 2-butyn-1-yl), pentinyl (including all isomer forms, e.g., 1-pentin-1-yl and 1-methyl-2-butyne-1-yl) ), as well as hexynyl (all isomer forms, e.g., 1-hexyn-1-yl and 2-hexyn-1- Examples include, but are not limited to, Ill.

[0033] The term "cycloalkyl" is optionally substituted with one or more substituents Q as described herein. This refers to a cyclic monovalent hydrocarbon radical. In one embodiment, cycloalkyl is , saturated or unsaturated but non-aromatic, and / or crosslinked or crosslinked It is not and / or a condensed bicyclic group. In one embodiment, the cycloalkyl is , 3~20 pieces (C 3-20 ), 3~15 pieces (C 3-15 , 3~10 pieces (C 3-10 ), or 3 to 7 pieces (C 3-7 ) has carbon atoms In one embodiment, the cycloalkyl group is monocyclic. In another embodiment, Cycloalkyls are bicyclic. In another embodiment, cycloalkyls are tricyclic. This is the formula. In another embodiment, the cycloalkyl is polycyclic. Examples of the cyclopropyl group include cyclopropyl, cyclobutyl, cyclopentyl, and cyclopentenyl. Cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cyclo Heptenyl, bicyclo[1.1.1]pentyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1] Examples include butyl, bicyclo[2.2.2]octyl, dekalinyl, and adamantyl, but These are not the only options.

[0034] The terms "cycloalkylene" and "cycloalkanediyl" are defined herein. With respect to cyclic divalent hydrocarbon radicals that can be optionally substituted with one or more substituents Q, this specification They are used interchangeably. In one embodiment, the cycloalkyl group is saturated or unsaturated. However, non-aromatic, and / or crosslinked, and / or uncrosslinked, and / or It may also be a condensed bicyclic group. In one embodiment, the cycloalkylene is 3 to 30 pieces(C 3-30 ), 3~20 pieces (C 3-20 ), 3~15 pieces (C 3-15 ), 3~10 pieces (C 3-10 ), or 3 to 7 pieces (C 3-10 ) charcoal It contains elementary atoms. An example of a cycloalkylene group is cyclopropylene (all isomers). (For example, including cyclopropa-1,1-diyl and cyclopropa-1,2-diyl), cyclo Thiene (all isomer forms, e.g., cyclobuta-1,1-diyl, cyclobuta-1,2-diyl) (and including cyclobuta-1,3-diyl), cyclopentylene (all isomer forms, e.g., cyclo Contains cyclopenta-1,1-diyl, cyclopenta-1,2-diyl, and cyclopenta-1,3-diyl (mu), cyclohexylene (all isomer forms, e.g., cyclohexa-1,1-diyl, cyclohex (including xa-1,2-diyl, cyclohexa-1,3-diyl, and cyclohexa-1,4-diyl), cyclo Loheptylene (all isomer forms, e.g., cyclohepta-1,1-diyl, cyclohepta-1,2) - Diyl, cyclohepta-1,3-diyl, and cyclohepta-1,4-diyl, decalyne n (all isomer forms, e.g., decalin-1,1-diyl, decalin-1,2-diyl, and decalin) (including phosphorus-1,8-diyl), and adamantylene (all isomer forms, e.g., adamantylene) Examples include ta-1,2-zyl, adamantha-1,3-zyl, and adamantha-1,8-zyl. However, it is not limited to these.

[0035] The term "aryl" refers to a monovalent monocyclic fragrance containing at least one aromatic carbocyclic ring. Refers to a group hydrocarbon radical and / or a monovalent polycyclic aromatic hydrocarbon radical. In one embodiment In this case, aryl has 6 to 20 (C 6-20 ), 6~15 pieces (C 6-15 ), or 6-10 pieces (C 6-10 ) ring carbon It contains atoms. Examples of aryl groups include phenyl, naphthyl, fluorenyl, and azulenyl. Examples include phenylyl, anthryl, phenanthryl, pyrenyl, biphenyl, and terphenyl. However, it is not limited to these. Aryls are those in which one of the rings is aromatic and the others are... A bicyclic or tricyclic carbon ring that may be saturated, partially unsaturated, or aromatic, for example, dihydrona This also refers to phthyl, indenyl, indanyl, or tetrahydronaphthyl (tetralinyl). In this embodiment, the aryl is monocyclic. In another embodiment, the aryl is bicyclic. It is ring-shaped. In another embodiment, the aryl is triring-shaped. In yet another embodiment In this embodiment, the aryl is polycyclic. In one embodiment, the aryl is as specified herein It is optionally substituted with one or more substituents Q as described.

[0036] The terms "arylene" and "arylenediyl" refer to at least one aromatic carbonized water. Divalent monocyclic aromatic hydrocarbon radicals or divalent polycyclic aromatic hydrocarbon radicals containing a primary ring With respect to the term, it is used interchangeably in this specification. In one embodiment, arylene is 6 ~20 pieces (C 6-20 ), 6~15 pieces (C 6-15), or 6-10 pieces (C 6-10 It has a ring atom of ) and an arylene group. Examples include phenylene (all isomer forms, e.g., phen-1,2-diyl, phen-1,3 -Diyl and phen-1,4-diyl), naphthylene (all isomer forms, e.g., naphthylene) (including ta-1,2-diyl, naphtha-1,3-diyl, and naphtha-1,8-diyl), fluorenylene ( All isomer forms, e.g., fluoren-1,2-diyl, fluoren-1,3-diyl, and fluoren-1,2-diyl. (including oren-1,8-diyl), azulenylene (all isomer forms, e.g., azulen-1,2-diyl) (including yl, azulene-1,3-diyl, and azulene-1,8-diyl), anthreene (all different Sexual forms, for example, anthra-1,2-diyl, anthra-1,3-diyl, and anthra-1,8-diyl (including yl), phenanthrylene (all isomer forms, e.g., phenanthrylene-1,2-diyl) (including phenantha-1,3-diyl and phenantha-1,8-diyl), pyrenylene (all Isomer forms, for example, pyrene-1,2-diyl, pyrene-1,3-diyl, and pyrene-1,8-diyl (including), biphenylene (all isomer forms, e.g., biphen-2,3-diyl, biphen-3, (including 4'-diyl and bifen-4,4'-diyl), and terphenylene (all isomers) For example, terphene-2,3-diyl, terphene-3,4'-diyl, and terphene-4,4'- Examples include, but are not limited to, diyl compounds. Arylenes are compounds in which one of the rings is aromatic. The others are bicyclic or tricyclic carbons, which may be saturated, partially unsaturated, or aromatic. Elementary rings, for example, dihydronaphthylene (all isomer forms, for example, dihydronaphtha-1,2-di (including yl or dihydronaphtha-1,8-diyl), indenylene (all isomer forms, e.g.) For example, including inden-1,2-zyle, inden-1,5-zyle, or inden-1,7-zyle. (mu), indanylene (all isomer forms, e.g., indan-1,2-diyl, indan-1,5-diyl) (containing yl or indan-1,7-diyl), or tetrahydronaphthylene (tetralini Len) (All isomer forms, e.g., tetrahydronaphtha-1,2-diyl, tetrahydronaph) This also refers to (including ta-1,5-diyl or tetrahydronaphtha-1,8-diyl). In one embodiment In this specification, arylene is optionally substituted with one or more substituents Q as described herein. .

[0037] The terms "aralkyl" or "arylalkyl" refer to a group substituted with one or more aryl groups. This refers to a monovalent alkyl group. In one embodiment, the aralkyl group consists of 7 to 30 (C) atoms. 7-30 ), 7 ~20 pieces (C 7-20 ), or 7-16 pieces (C 7-16 It has a carbon atom. An example of an aralkyl group is: Benzyl, phenylethyl (all isomer forms, e.g., 1-phenylethyl and 2-phenylethyl) (including ethyl phenylpropyl), and phenylpropyl (all isomer forms, e.g., 1-phenylpropyl Examples include phenylpropyl, 2-phenylpropyl, and 3-phenylpropyl, but these include Not limited to. In one embodiment, Aralkil is one or more of the positions described herein. It is arbitrarily substituted with substitution base Q.

[0038] The term "heteroaryl" refers to a monovalent monocyclic aromatic compound containing at least one aromatic ring. This refers to a group group or monovalent polycyclic aromatic group, where at least one aromatic ring is O, S, and N. Each ring contains one or more heteroatoms, independently selected from each group. Heteroaryls are aromatic compounds. It is bonded to the rest of the molecule via the heteroaryl ring. Each ring of the heteroaryl group is 1 if It may contain 2 oxygen atoms, 1 or 2 sulfur atoms, and / or 1 to 4 nitrogen atoms. However, the total number of heteroatoms in each ring is 4 or less, and each ring has at least one It contains carbon atoms. In one embodiment, the heteroaryl has 5 to 20, 5 to 15, Or it has 5 to 10 ring atoms. In one embodiment, the heteroaryl is monocyclic. Examples of monocyclic heteroaryl groups include furanyl, imidazolyl, isothiazolyl, and Soxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridadi Nyl, pyridyl, pyrimidinyl, pyrrolyl, thiadiazolyl, thiazolyl, thienyl, te Examples include, but are not limited to, torazolyl, triazinil, and triazolyl. In another embodiment, the heteroaryl group is bicyclic. Examples of bicyclic heteroaryl groups Examples include benzofuranil, benzimidazolyl, benzoisoxazolyl, and benzopyra. Nyl, benzothiadiazolyl, benzothiazolyl, benzothienyl, benzotriazolyl , benzoxazolyl, phlopyridyl, imidazopyridinyl, imidazothiazolyl, ing Doridinyl, indolyl, indazolyl, isobenzofuranyl, isobenzothienyl, i Soindolyl, Isoquinolinyl, Isothiazolyl, Naphthyridinyl, Oxazolopyridinyl Lu, Phthalazinil, Pteridinil, Purinyl, Pyridopyridyl, Pyrrolopyridyl, Quinoli Nyl, quinoxalinyl, quinazolinyl, thiadiazolopyrimidyl, and thienopyrimidyl These are some examples, but are not limited to them. In another embodiment, the heteroaryl is It is a tricyclic group. Examples of tricyclic heteroaryl groups include acridinyl and benzoindolyl. , carbazolyl, dibenzofuranil, perimidinil, phenanthrolinil, phenanthr Zinyl, phenalsadinyl, phenazinyl, phenothiazinyl, phenoxazinyl, and Examples include, but are not limited to, xanthenyl. In one embodiment, hetero The aryl is optionally substituted with one or more substituents Q as described herein.

[0039] The terms "heterearene" and "heterearenediyl" are defined as at least one With respect to divalent monocyclic aromatic groups or divalent polycyclic aromatic groups containing an aromatic ring, interchangeability is permitted in this specification. It is used in a manner in which at least one aromatic ring is derived from O, S, and N. It contains one or more independently selected heteroatoms in the ring. The heteroarylene group is It has at least one bond to the rest of the molecule via an aromatic ring. Heteroarylene Each ring of the group consists of 1 or 2 oxygen atoms, 1 or 2 sulfur atoms, and / or 1 to 4 nitrogen atoms. It may contain, provided that the total number of heteroatoms in each ring is 4 or less, and each The ring contains at least one carbon atom. In one embodiment, heteroalile The ring has 5 to 20, 5 to 15, or 5 to 10 ring atoms. Monocyclic heteroarylene group Examples include furanylene, imidazoylene, isothiazolylene, isoxazolylene, and Xadiazoylene, oxadiazoylene, oxazolylene, pyrazinylene, pyrazolylene Pyridazinylene, pyridylene, pyrimidinylene, pyrrolylene, thiadiazoylene, thia Examples include zolylene, thienylene, tetrazoylene, triazylene, and triazolylene. However, it is not limited to these. An example of a bicyclic heteroarylene group is benzofran. Len, benzimidazolylene, benzoisoxazolylene, benzopyranylene, benzoth Asiazoylene, benzothiazoylene, benzothienylene, benzotriazolilen, ben Zooxazolylene, phlopyridylene, imidazopyridinylene, imidazothiazoylene, i Indorylene, indazolylene, isobenzofuranylene, isobenzoth Enylene, Isoindrylene, Isoquinolinylene, Isothiazolylene, Naphthyridinylene oxazolopyridinylene, phthalazine, pteridine, prynylene, pyridopyridinylene Dilen, Pyrolopyridilene, Quinolinirene, Quinoxalinirene, Quinazolinirene, Thiad Examples include, but are not limited to, azolopyrimidylene and thienopyridylene. Examples of cyclic heteroarylene groups include acridinylene, benzoindrylene, and carbazo. Lylene, dibenzofuranylene, perimidinylene, phenanthrolinylene, phenanthridine Nirene, phenalsadinyrene, phenadinyrene, phenothiazinyrene, phenoxadinyrene Examples include, but are not limited to, , , and xantherine. In one embodiment The heteroarylene is optionally substituted with one or more substituents Q as described herein.

[0040] The terms "heterocyclyl" or "heterocycle" refer to a compound containing at least one non-aromatic ring. This refers to a monovalent monocyclic non-aromatic ring system or a monovalent polycyclic ring system, where one of the non-aromatic ring atoms or The plurality of are heteroatoms independently selected from O, S, and N; and the remaining ring atoms are It is a carbon atom. In one embodiment, there are 3 to 20 heterocyclyl or heterocyclic groups, 3 Heterocyclines have ~15, 3~10, 3~8, 4~7, or 5~6 ring atoms. It is bonded to the rest of the molecule via a non-aromatic ring. In one embodiment, heterocyclic A Lil is a mono-ring, bi-ring, tri-ring, or tetra-ring ring system, and the ring system may be condensed or cruciate. Bridged rings may also be present, and in the ring system, nitrogen or sulfur atoms may be optionally oxidized. The nitrogen atom may also be quaternized as desired, and some rings may be partially or They may be completely saturated or aromatic. Heterocyclines are stable compounds. The main structure may be bonded with any heteroatom or carbon atom that results in the formation. Examples of lyl and heterocyclic groups include azepinyl, benzodioxanil, and benzodioxol. Benzofuranonyl, benzopyranonyl, benzopyranyl, benzotetrahydrofuranyl Lu, benzotetraturbirthienyl, benzothiopyranil, benzooxazinyl, β-Cal Borinyl, Chromanil, Chromonil, Synnolinil, Coumarinil, Decahydroisoquinoli Nyl, dihydrobenzoisothiadinyl, dihydrobenzoisooxazinyl, dihydrofru Dihydroisoindolyl, Dihydropyranyl, Dihydropyrazolyl, Dihydropyradi Nyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dioxolanil , 1,4-Dithianyl, Furanolyl, Imidazolidinyl, Imidazolinyl, Indolinyl, I Sobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isochromanyl, i Socmalinyl, isoindolinyl, isothiazolidinyl, isoxazolidinyl, morpho Linyl, octahydroindolyl, octahydroisoindolyl, oxazolidinol, Oxazolidinil, oxyranil, piperazinil, piperidinil, 4-piperidonil, pyrazolidinil Zolidinyl, pyrazolinil, pyrrolidinyl, pyrrolidinyl, quinuclidinyl, tetrahydro Frill, tetrahydroisoquinolinyl, tetrahydropyranyl, tetrahydrothienyl, Thiamorpholinil, thiazolidinil, tetrahydroquinolinil, and 1,3,5-trithianil Examples include, but are not limited to, heterocyclils. It is optionally substituted with one or more substituents Q as described in the specification.

[0041] The term "heterocyclylene" refers to a divalent monocyclic compound containing at least one non-aromatic ring. This refers to a non-aromatic ring system or a divalent polycyclic ring system, where one or more of the non-aromatic ring atoms are O, S The heteroatoms are independently selected from N and the remaining ring atoms are carbon atoms. The telocyclylene group is bonded to the rest of the molecule via a non-aromatic ring. In one embodiment In this case, the heterocyclylene groups are 3-20, 3-15, 3-10, 3-8, 4-7, or 5 It has ~6 ring atoms. In one embodiment, heterocyclylene is monocyclic, bicyclic It is a tri-ring or tetra-ring ring system, and the ring system may be condensed or bridged. Furthermore, in the ring system, the nitrogen or sulfur atom may be optionally oxidized, and the nitrogen atom is optional They may be quaternized, and some rings may be partially or completely saturated. It may also be aromatic. Heterocyclylenes can lead to the formation of any stable compound. The main structure may be bonded to a tetraatom or carbon atom. Such heterocyclylene groups Examples include azepinyrene, benzodioxanilen, benzodioxorylene, and benzoflavin. Nonilene, benzopyranonelene, benzopyraninelene, benzotetrahydrofuranilene, benzo Nzotetrahydrothienylene, benzothiopyranylene, benzooxazinylene, β-Cal Borinylene, chromanilene, chromonirene, sinnorinirene, coumarinylen, decahydro Isoquinolinylene, dihydrobenzoisothiadinylene, dihydrobenzoisooxazinylene n, dihydroflurene, dihydroisoindolylene, dihydropyranylene, dihydropyranylene Zolylene, dihydropyridineylene, dihydropyridinylene, dihydropyrimidineylene, di Hydropyrrolylene, dioxolaniylene, 1,4-dithianylene, furanonirene, imidazolid Nirene, imidazolinyrene, indolinyrene, isobenzotetrahydrofuranylene, iso Benzotetrahydrothienylene, isochromaniylene, isocumarinylene, isoindolin Len, isothiazolidinylene, isoxazolidinylene, morpholinylene, octahydro Indrolylene, octahydroisoindrolylene, oxazolidinoneylene, oxazolidin Len, oxylanylene, piperadinylen, piperidinylene, 4-piperidylene, pyrazoli Dinylene, pyrazolinylene, pyrrolidinylene, pyrrolidinylene, quinucrine, tetra Hydroflylene, tetrahydroisoquinolinylene, tetrahydropyranylene, tetrahydro Rothienylene, thiamorpholinylene, thiazolidinylene, tetrahydroquinolinylene, and Examples include, but are not limited to, 1,3,5-trithianylene. The heterocyclylene is optionally substituted with one or more substituents Q as described herein.

[0042] The terms "halogen," "halide," or "halo" refer to fluoro, chloro, and brominated halogens. It refers to iodine, and / or other substances.

[0043] The term "arbitrarily substituted" refers to alkyl, alkylene, alkenyl, alkenile Alkynyl, cycloalkyl, cycloalkylene, aryl, arylene, aralkyl Groups such as heteroaryl, heteroarylene, heterocyclyl, or heterocyclylene groups. The group or substituent is one or more substituents Q, in one embodiment, one, two, three, or four substituents Q It is intended to mean that substitution is permitted, and each of the substituents Q may be, for example, (a) (b) Each of the following is present in a quantity of 1 or more: deuterium (-D), cyano (-CN), halo, nitro (-NO2), and oxo (=O); (b) each of these is present in a quantity of 1 or more. In one embodiment, one, two, three, or four substituents Q a It is further replaced by C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel , C 7-15 Aralkyl, heteroaryl, and heterocyclyl; and (c)-C(O)R a , -C(O)OR a -C(O)NR b R c -C(O)SR a -C(NR a )NR b R c ,-C(S)R a , -C(S)OR a -C(S)NR b R c , -OR a , -OC(O )R a -OC(O)ORa 、-OC(O)NR b R c 、-OC(O)SR a 、-OC(NR a )NR b R c 、-OC(S)R a 、-OC(S)OR a 、-OC( S)NR b R c 、-OS(O)R a 、-OS(O)2R a 、-OS(O)NR b R c 、-OS(O)2NR b R c 、-NR b R c 、-NR a C(O)R d 、-NR a C(O)OR d 、-NR a C(O)NR b R c 、-NR a C(O)SR d 、-NR a C(NR d )NR b R c 、-NR a C(S)R d 、-NR a C(S)OR d 、 -NR a C(S)NR b R c 、-NR a S(O)R d 、-NR a S(O)2R d 、-NR a S(O)NR b R c 、-NR a S(O)2NR b R c 、-SR a 、-S( O)R a 、-S(O)2R a 、-S(O)NR b Rc , and -S(O)2NR b R c Selected independently from, where each R a , R b , R c , and R d (i) hydrogen or deuterium; (ii) each of them contains one or more solid atoms. In this embodiment, one, two, three, or four substituents Q a C is arbitrarily replaced by 1-6 Al Kill, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 (iii)R b and R c teeth, Along with the N atoms to which they are bonded, there are one or more, in one embodiment, one, two, three, Or four substituents Q a It forms a heterocycline which is optionally substituted. When used, all bases that can be substituted are "arbitrarily substituted".

[0044] In one embodiment, each Q a (a) deuterium, cyano, halo, nitro, and oxo; (b )C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ally Ru, C 7-15 Aralkyl, heteroaryl, and heterocyclyl; and (c)-C(O)R e ,-C(O)O R e -C(O)NR f R g -C(O)SR e -C(NRe )NR f R g 、-C(S)R e 、-C(S)OR e 、-C(S)NR f R g 、-OR e 、-OC (O)R e 、-OC(O)OR e 、-OC(O)NR f R g 、-OC(O)SR e 、-OC(NR e )NR f R g 、-OC(S)R e 、-OC(S)OR e 、-O C(S)NR f R g ,-OS(O)R e 、-OS(O)2R e 、-OS(O)NR f R g 、-OS(O)2NR f R g 、-NR f R g 、-NR e C(O)R h 、-N R e C(O)OR f 、-NR e C(O)NR f R g 、-NR e C(O)SR f 、-NR e C(NR h )NR f R g 、-NR e C(S)R h 、-NR e C(S)OR f 、-NR e C(S)NR f R g 、-NR e S(O)R h 、-NR e S(O)2R h 、-NR e S(O)NRf R g 、 -NR e S(O)2NR f R g 、 -SR e 、 - S(O)R e ​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​ and contains other enantiomers at about 2% or less. In certain embodiments, the optically active compound is about 99% or more of one enantiomer and about 1% or less of other enantiomers, based on the total weight of the enantiomer mixture.

[0046] When describing an optically active compound, the prefixes R and S are used to indicate the absolute configuration of the compound with respect to its chiral center. (+) and (-) are used to indicate the direction of rotation of the plane of polarization of the compound, i.e., the direction in which the plane of polarization is rotated by the optically active compound. The prefix (-) indicates that the compound is levorotatory, i.e., <000553​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​O), oxygen-18( 18 O), fluorine -17( 17 F), Fluorine-18( 18 F), phosphorus-31( 31 P), phosphorus-32( 32 P), Lin-33( 33 P), sulfur-32( 32 S) , sulfur-33( 33 S), Sulfur-34( 34 S), Sulfur-35( 35 S), sulfur-36( 36 S), Chlorine-35( 35 Cl), Chlorine-36 ( 36 Cl), Chlorine-37( 37 Cl), bromine-79( 79 Br), Bromine-81( 81 Br), Iodine-123( 123 I) Iodine-12 5 125 I) Iodine-127( 127 I) Iodine-129( 129 I), and iodine-131( 131 I) including non-natural It contains one or more isotopes in a proportion of . In one embodiment, the isotope-enriched compound is stable It is in a non-radioactive form. In one embodiment, the isotope-enriched compound is limited However, hydrogen ( 1 H), deuterium ( 2 H), carbon-12 ( 12 C), carbon-13( 13 C), nitrogen-14( 14 N), nitrogen -15( 15 N), oxygen-16( 16 O), oxygen-17( 17 O), oxygen-18( 18 O), Fluorine-17( 17 F), phosphorus-31( 31 P) , sulfur-32( 32 S), sulfur-33( 33 S), Sulfur-34( 34S), sulfur-36( 36 S), chlorine-35( 35 Cl), chlorine-37 (<000095�>Cl), bromine-79( 79 Br), bromine-81( 81 Br), and iodine-127( 127 I) containing an unnatural proportion of one or more isotopes. In certain embodiments, the isotope-enriched compound is in an unstable form , i.e., radioactive. In certain embodiments, the isotope-enriched compound is not limited but includes tritium( 3 H), carbon-11( 11 C), carbon-14( 14 C), nitrogen-13( 13 N), oxygen-14( 14 O), oxygen-1 5( 15 O), fluorine-18( 18 F), phosphorus-32( 32 P), phosphorus-33( 33 P), sulfur-35( 35 S), chlorine-36( 36 Cl) , iodine-123( 123 I), iodine-125( 125 I), iodine-129( 129 I), and iodine-131( 131 I) and contains an unnatural proportion of one or more isotopes. Where feasible by the judgment of one skilled in the art , in the compounds provided herein, any hydrogen can, for example, be 2 H, or any carbon can, for example, be 13 C, or any nitrogen can, for example be 15 N, or any oxygen can, for example, 18 be understood to be <00 05564>

[0048] The term "isotope enrichment" refers to the enrichment of less common isotopes of an element (for example, deuterium). Or hydrogen-2 (D) is a more common isotope of that element (e.g., protium or hydrogen-1) 1 H) Instead, it refers to the proportion incorporated at a given position within the molecule. In some cases, an atom at a specific position in a molecule is designated as a particular, less common isotope. When it is present, the abundance of that isotope at that location is substantially greater than its natural abundance. It is understood that...

[0049] The term "isotope enrichment factor" refers to the ratio of the isotope enrichment compound to the natural abundance of a particular isotope. This refers to the ratio of isotopic abundances in a substance.

[0050] The term "hydrogen" or the symbol "H" is derived from protium. 1 H), deuterium ( 2 H or D), and Tritium ( 3 This refers to a composition of naturally occurring hydrogen isotopes, including H, in their natural abundances. Rotium is the most common hydrogen isotope, with a natural abundance exceeding 99.98%. Element is a relatively uncommon hydrogen isotope, with a natural abundance of approximately 0.0156%.

[0051] The term "deuterium enrichment" refers to the process where deuterium replaces hydrogen at a given position in the molecule. This refers to the proportion of deuterium present. For example, a 1% deuterium concentration at a given location is equivalent to a 1% deuterium concentration in a given sample. This means that 1% of the molecule contains deuterium at a specified position. The natural distribution of deuterium is Since the average is approximately 0.0156%, any position in the compound synthesized using unenriched starting materials The deuterium enrichment in isotopic enrichment is approximately 0.0156% on average. When a specific position in a compound is designated as having deuterium, that position in the compound It is understood that the abundance of deuterium in this location is substantially higher than its natural abundance (0.0156%). It can be done.

[0052] The term "carbon" or the symbol "C" refers to carbon-12. 12 C) and carbon-13 ( 13 C) This refers to the composition of naturally occurring carbon isotopes at their natural abundance. Carbon-12 is over 98.89%. It is the most common carbon isotope, with a naturally occurring abundance of approximately 1.11%. It is a relatively uncommon carbon isotope that exists in considerable quantities.

[0053] "Carbon-13 enrichment" or " 13 The term "C enrichment" refers to a situation where carbon-13 is present in the molecule instead of carbon. This refers to the proportion incorporated at a given position. For example, a 10% carbon-13 concentration at a given position. Shrinkage means that 10% of the molecules in a given sample contain carbon-13 at a specified position. Since the natural distribution of carbon-13 is approximately 1.11% on average, it is synthesized using unenriched starting materials. The carbon-13 enrichment at any position in the compound is approximately 1.11% on average. In such cases, the specific position in the isotope-enriched compound is designated as having carbon-13. When this happens, the amount of carbon-13 at that position in the compound is greater than its natural abundance (1.11%). It is understood that the actual number is large.

[0054] The terms “substantially pure” and “substantially homogeneous” are not limited to, but include thin-layer chloroforms. Mathematics (TLC), gel electrophoresis, high-performance liquid chromatography (HPLC), gas chromatography This includes tography (GC), nuclear magnetic resonance (NMR), and mass spectrometry (MS), as used by those skilled in the art. When determined by standard analytical methods, it is determined that the product does not contain easily detectable impurities. Being sufficiently homogeneous to be visible; or, by further purification, the physical, chemical, Biological and / or pharmacological properties, such as enzyme activity and biological activity, can be detected. It means that it is pure enough that it does not change into. In one embodiment, "substantially "Pure" and "substantially homogeneous" mean at least about 95% by weight of the molecule, and at least about 96% by weight. %, at least about 97% by weight, at least about 98% by weight, at least about 99% by weight, or less Approximately 99.5% by weight of each single enantiomer was determined by standard analytical methods. This refers to a group of molecules that are single compounds, including a racemic mixture or a mixture of enantiomers. When used herein, atoms at specific positions in isotope-enriched molecules are considered to be of a particular, less common nature. When an isotope is designated as not present, it contains other isotopes at a specific position. The molecule that does this is an impurity with respect to the isotopic enrichment compound. Therefore, it is designated as deuterium. For deuterated compounds having atoms at a specific position, protium is present at the same position. Compounds containing these substances are considered impurities.

[0055] The term "solvate" refers to one or more solutes present in stoichiometric or nonstoichiometric quantities. A molecule formed by, for example, the compound provided herein, and one or more solvent molecules. This refers to a complex or aggregate. Suitable solvents include water, methanol, ethanol, and n-propane. Examples include, but are not limited to, acetic acid, isopropanol, and acetic acid. In one embodiment, the solvent is pharmaceutically acceptable. The body or aggregate is in a crystalline form. In another embodiment, the composite or aggregate is non It is a crystalline form. When the solvent is water, the solvate is a hydrate. Examples of hydrates Examples include hemihydrate, monohydrate, dihydrate, trihydrate, tetrahydrate, and pentahydrate. , but not limited to these.

[0056] With respect to the divalent groups described herein, the orientation is indicated by the direction in which the divalent group is presented. It is not possible. For example, unless a specific orientation is specified, the formula -C(O)NH- is a combination of -C(O)NH- and -NHC(O)-. It represents both.

[0057] "The enantiomer, the mixture of enantiomers, the mixture of two or more diastereomers" tautomers, mixtures of two or more tautomers, or isotopic variants; or pharmaceuticals thereof The phrase "acceptable salts, solvates, hydrates, or prodrugs" is "(i) Honmei Enantiomers of the compounds mentioned in the document, mixtures of enantiomers, and two or more diastes. (ii) A mixture of Leomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; Pharmaceutically acceptable salts, solvates, hydrates, or plutons of the compounds referred to herein. (iii) Enantiomers of the compounds referred to herein, enantiomers of the compounds referred to herein Mixture, mixture of two or more diastereomers, tautomer, mixture of two or more tautomers, Alternatively, a salt, solvate, hydrate, or prodrug of an isotopic variant that is acceptable as a medicine. It has the same meaning as the word "gu".

[0058] (compound) In one embodiment, the compound of formula (I) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (In the formula: R 1 (a) hydrogen, deuterium, cyano, halo, or nitro; or (b) C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralquil , heteroaryl, or heterocyclyl; R 2 is -C(O)OR 2a -C(O)NR 2b R 2c ,-C(O)N(R 2b )OR 2c , or heteroaryl; here So, R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 a Lukinil, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aalkyl, heteroaryl, or heterocycline; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of (a) hydrogen, deuterium, cyano, halo, or nitrate. (b)C1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 a Reel, C 7-15 Aralkyl, heteroaryl, or heterocyclyl; or (c)-C(O)R 1a , -C(O)OR 1a -C(O)NR 1b R 1c -C(NR 1a )NR 1b R 1c , -OR 1a ,-OC(O)R 1a -OC(O)OR 1a -OC(O) NR 1b R 1c -OC(NR 1a )NR 1b R 1c -OS(O)R 1a -OS(O)2R 1a -OS(O)NR 1b R 1c -OS(O)2NR 1b R 1c , -NR 1b R 1c , -NR 1a C(O)R 1d , -NR 1a C(O)OR 1d , -NR 1a C(O)NR 1b R 1c , -NR 1a C(NR 1d )NR 1b R 1c , -NR 1a S(O)R 1d , -NR 1a S(O)2R 1d , -NR 1a S(O)NR 1b R 1c , -NR 1a S(O)2NR 1b R 1c , -SR 1a,-S(O)R 1 a -S(O)2R 1a -S(O)NR 1b R 1c , or -S(O)2NR 1b R 1c and; R A C 6-14 It is either allirene or heteroarirene; R B C 6-14 It is an aryl or heteroaryl; R B And X is (i), (ii), or (iii): (iv) X is -O-, -S-, -S(O)-, or -S(O)2-; and R B C 6-14 It is either an aryl or heteroaryl; (v)X is -N(R X )-and; R B C 6-14 It is aryl or heteroaryl; and R X is hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl , C 6-14 Ariel, C 7-15 Is it an aralkyl, heteroaryl, or heterocyclyl? ; or (vi)X is -N(R X )-and; and R B and R X These, along with the N atom to which they are bonded, form heteroaryl or heterosilicate compounds. Forming krill; L is C 1-6 Alkilen, C 2-6 Alkenylene, C 3-10 Cycloalkylene, or heterocycline It is a Len; and Each R 1a , R 1b , R 1c , and R 1d These are, independently, hydrogen, deuterium, and C 1-6 Alkyl, C 2-6 Alke Nil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralkil, Hete It is either a roaryl or heterocyclyl; or R 1a and R 1c They are combined Together with C and N atoms, they form a heterocycline; or R 1b and R 1c They combine Together with the N atom present, it forms a heterocycline; Here, each alkyl, alkylene, alkenyl, alkenylene, alkynyl, cyclo Roalkyl, cycloalkylene, aryl, arylene, aralkyl, heteroaryl, Heteroarylene, heterocyclyl, and heterocyclylene are one or more in one embodiment In this compound, one, two, three, or four substituents Q are arbitrarily substituted, where each Q is (a) Deuterium, cyano, halo, nitro, and oxo; (b) Each of them is one or more embodiments. In this, one, two, three, or four substituents Q a C is further arbitrarily substituted. 1-6 Al Kill, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralkyl, heteroaryl, and heterocyclyl; and (c)-C(O)R a , -C(O)OR a , -C(O) NR b Rc 、-C(O)SR a 、-C(NR a )NR b R c 、-C(S)R a 、-C(S)OR a 、-C(S)NR b R c 、-OR a 、-OC(O)R a 、-O C(O)OR a 、-OC(O)NR b R c 、-OC(O)SR a 、-OC(NR a )NR b R c 、-OC(S)R a 、-OC(S)OR a 、-OC(S)NR b R c 、-OS(O)R a 、-OS(O)2R a 、-OS(O)NR b R c 、-OS(O)2NR b R c 、-NR b R c 、-NR a C(O)R d 、-NR a C(O)OR d 、-NR a C(O)NR b R c 、-NR a C(O)SR d 、-NR a C(NR d )NR b R c 、-NR a C(S)R d 、-NR a C(S)OR d 、-NR a C(S )NR b R c 、-NR a S(O)R d 、-NR aS(O)2R d , -NR a S(O)NR b R c , -NR a S(O)2NR b R c , -SR a ,-S(O)R a ,- S(O)2R a -S(O)NR b R c , and -S(O)2NR b R c : are independently selected from, where each R a , R b , R c , and R d (i) hydrogen or deuterium; (ii) each of them in one or more embodiments In this, one, two, three, or four substituents Q a C is arbitrarily replaced by 1-6 Alkyl, C2 -6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralchi (iii)R b and R c Those Along with the bonded N atom, one or more, in one embodiment, one, two, three, or four substituted Q a It forms a heterocycline which is optionally substituted; Here, each Q a (a) Deuterium, cyano, halo, nitro, and oxo; (b) C 1-6 Alki Ru, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 a Larquil, heteroaryl, and heterocyclyl; and (c)-C(O)R e , -C(O)OR e -C(O)NR f R g -C(O)SR e -C(NR e )NR f R g ,-C(S)R e , -C(S)OR e -C(S)NR f R g , -OR e ,-OC(O)R e ,-OC( O)OR e -OC(O)NR f R g -OC(O)SR e -OC(NR e )NR f R g ,-OC(S)R e , -OC(S)OR e -OC(S)NR f R g , -OS(O)R e -OS(O)2R e -OS(O)NR f R g -OS(O)2NR f R g , -NR f R g , -NR e C(O)R h , -NR e C(O)OR f , -NR e C(O)NR f R g , -NR e C(O)SR f , -NR e C(NR h )NR f R g , -NR e C(S)R h , -NR e C(S)OR f , -NRe C(S) NR f R g , -NR e S(O)R h , -NR e S(O)2R h , -NR e S(O)NR f R g , -NR e S(O)2NR f R g , -SR e ,-S(O)R e , -S (O)2R e -S(O)NR f R g , and -S(O)2NR f R g : independently selected from; here, each R e , R f , R g , and R h (i) hydrogen or deuterium; (ii) C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aalkyl, heteroaryl , or heterocyclyl; or (iii)R f and R g The N atoms to which they are bonded (Together, they form heterocyclines.)

[0059] In another embodiment, a compound of formula (II) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R A , R B L and X are defined as follows in this specification, respectively. (It is.)

[0060] In one embodiment, in formula (I) or (II), R 1 is a halo or C 1-6 It is alkyl; R 2 is -C(O)OR 2a -C(O)NR 2b R 2c ,-C(O)N(R 2b )OR 2c , or heteroaryl, here So, each R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 Alkyl or heteroaryl can be; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R A C 6-14 It is either allirene or heteroarirene; R B And X is (i), (ii), or (iii): (i) X is -O-, -S-, -S(O)-, or -S(O)2-; and R B C 6-14 It is either an aryl or heteroaryl; (ii) X is -NR X -and; R BC 6-14 It is aryl or heteroaryl; and R X is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir; or (iii) X is -NR X -and; and R B and R X These, along with the N atom to which they are bonded, form heteroaryl or heterosilicate compounds. Forming krill; and L is C 1-6 Alkilen, C 2-6 Alkenylene, or C 3-10 It is a cycloalkylene; Here, each alkyl, alkylene, alkenylene, cycloalkylene, aryl, Arirenes, aralkyls, heteroaryls, heteroarirenes, and heterocyclyls are, It is arbitrarily substituted with one, two, or three substituents Q.

[0061] In another embodiment, in formula (I) or (II), R 1 is a halo or C 1-6 It is alkyl; R 2 is -C(O)OR 2a -C(O)NR 2b R 2c ,-C(O)N(R 2b )OR 2c or monocyclic heteroaryl Here, each R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 Alkyl or heteroalkyl It is; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6It is alkyl; R A C 6-14 It is an arylene or a monocyclic heteroarylene; R B And X is (i), (ii), or (iii): (i) X is -O-, -S-, -S(O)-, or -S(O)2-; and R B C 6-14 It is either an aryl or heteroaryl; (ii) X is -NR X -and; R B C 6-14 It is aryl or heteroaryl; and R X is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir; or (iii) X is -NR X -and; and R B and R X These, along with the N atom to which they are bonded, form heteroaryl or heterosilicate compounds. Forming krill; and L is C 1-6 Alkylene or C 2-6 It is an alkenylene; Here, each alkyl, alkylene, alkenylene, aryl, arylene, and aral are defined as follows: Kill, heteroaryl, heteroarylene, and heterocyclyl are one, two, or three It is arbitrarily substituted with substituent Q, and each substituent Q is (i) bromo, chloro, fluoro, and cyano; (ii) 1 or more substituents Q a C arbitrarily replaced by 1-6 Alkyl; and (iii)-C(O)R a , -OR a , and -NR b R c (Here, each R a , Rb , and R c As defined herein It is selected independently from (that which is).

[0062] In another embodiment, in formula (I) or (II), R 1 C 1-6 It is alkyl; R 2 -C(O)OH, -C(O)NR 2b R 2c ,-C(O)N(R 2b )OR 2c , or a 5-membered heteroaryl, Here, each R 2b and R 2c These are, independently, hydrogen and C 1-6 It is alkyl or heteroaryl; R 3 and R 4 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R A C 6-14 It is an allerene or a 6-membered heteroarirene; R B And X is (i), (ii), or (iii): (i) X is -O-, -S-, -S(O)-, or -S(O)2-; and R B This is a single-ring or double-ring C 6-14 Aryl, or monocyclic or bicyclic heteroaryl Is it a lu? (ii) X is -NR X -and; R B This is a single-ring or double-ring C 6-14 Aryl, or monocyclic or bicyclic heteroaryl It is; and R X is hydrogen, C 1-6 Alkyl, C6-14 Aryl, or C 7-15 Is it Aralkir? Or (iii) X is -NR X -and; and R B and R X These, along with the N atoms to which they are bonded, form monocyclic or bicyclic heterocyclic structures. Forming a ring, or a monocyclic or bicyclic heterocyclil; and L is C 1-6 Alkylene or C 2-6 It is an alkenylene; Here, each alkyl, alkylene, alkenylene, aryl, arylene, and aral are defined as follows: Kill, heteroaryl, heteroarylene, and heterocyclyl are one, two, or three It is optionally substituted with substituent Q, and each substituent Q is bromo, chloro, fluoro, or shea. No, methyl, trifluoromethyl, ethyl, propyl, formyl, hydroxyl, methyl It is independently selected from C and amino.

[0063] In another embodiment, in formula (I) or (II), R 1 It is methyl; R 2 -C(O)OH, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2CH2OH, -C(O)NHOH, -C(O)NH(tet) Lazolyl, tetrazolyl, or 1,2,4-oxadiazolyl; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R A These are phenylene, chlorophenylene, methoxyphenylene, pyridylene, or methylphenylene. It is lupyridylene; RB And X is (i), (ii), or (iii): (i) X is -O-, -S-, -S(O)-, or -S(O)2-; and R B These are phenyl, bromophenyl, fluorophenyl, cyanophenyl, and methylphenyl. L, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Lu, formylphenyl, bromo-fluorophenyl, difluorophenyl, trifluoro Phenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl, or quinoline Is it a lu? (ii) X is -NR X -and; R B These are phenyl, bromophenyl, fluorophenyl, cyanophenyl, and methylphenyl. L, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Lu, formylphenyl, bromo-fluorophenyl, difluorophenyl, trifluoro Phenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl, or quinoline It is; and R X These are hydrogen, methyl, ethyl, hydroxyethyl, propyl, phenyl, and fluoromethyl It is yl, formylphenyl, or benzyl; or (iii) X is -NR X -and; and R B and R X These, along with the N atom to which they are bonded, are pyrrolidinyl, piperidinyl, and mo Forming rufolinyl, pyrrolyl, aminoimidazolyl, or indolyl; and L is methylene, ethylene, or ethenylene.

[0064] In another embodiment, in formula (I) or (II), R 1 It is methyl; R 2 -C(O)OH, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2CH2OH, -C(O)NHOH, -C(O)NH(tet) It is rhazol-5-yl), tetrazol-5-yl, or 1,2,4-oxadiazole-5-yl; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R A These are fen-1,3-diyl, fen-1,4-diyl, 2-chlorophen-1,4-diyl, and 2-meth It is xi-phen-1,4-diyl, pyrido-2,5-diyl, or 3-methyl-pyrido-2,5-diyl; R B And X is (i), (ii), or (iii): (i) X is -O-, -S-, -S(O)-, or -S(O)2-; and R B These are phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, and 3-sheaphenyl. Nophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 4- Trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methoxy Phenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl, 2 ,4-difluorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoropyryl It is either do-5-yl, 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl; (ii) X is -NR X -and; R BThese are phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, and 3-sheaphenyl. Nophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 4- Trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methoxy Phenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl, 2 ,4-difluorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoropyryl It is do-5-yl, 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl; and R X These are hydrogen, methyl, ethyl, 2-hydroxyethyl, n-propyl, phenyl, 4-fluorine It is lophenyl, 4-formylphenyl, or benzyl; or (iii) X is -NR X -and; and R B and R X Together with the N atom to which they are bonded, pyrrole-1-yl, 2-amino-imi Dazole-1-yl, indole-1-yl, pyrrolidine-1-yl, piperidine-1-yl, or 4- Forms morpholin-4-yl; and L is methylene, ethane-1,2-diyl, or ethene-1 ,2-Jill.

[0065] In yet another embodiment, a compound of formula (III) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (In the formula: U 1 , V 1 , W 1 , and X 1 These are, independently of each other, (i) C or N; or (ii) -CR 7a =, -N=, -NR 7b -,- It is O- or -S-; Y 1 (i) C or N; or (ii) bond, -CR 7a =, -N=, -NR 7b -, -O-, or -S-; Z 1 is C or N; Each R 7a (a) hydrogen, deuterium, cyano, halo, or nitro; (b) C 1-6 Al Kill, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralkyl, heteroaryl, or heterocyclyl; or (c)-C(O)R 1a , -C(O)OR 1a ,- C(O)NR 1b R 1c -C(NR 1a )NR 1b R 1c , -OR 1a ,-OC(O)R 1a -OC(O)OR 1a -OC(O)NR 1b R 1c , -OC(N R 1a )NR 1b R 1c -OS(O)R 1a -OS(O)2R 1a -OS(O)NR 1b R 1c -OS(O)2NR 1b R1c , -NR 1b R 1c , -NR 1a C(O)R 1d , -NR 1a C(O)OR 1d , -NR 1a C(O)NR 1b R 1c , -NR 1a C(NR 1d )NR 1b R 1c , -NR 1a S(O)R 1d ,- NR 1a S(O)2R 1d , -NR 1a S(O)NR 1b R 1c , -NR 1a S(O)2NR 1b R 1c , -SR 1a ,-S(O)R 1a -S(O)2R 1a ,- S(O)NR 1b R 1c , or -S(O)2NR 1b R 1c and; Each R 7b These are, independently, hydrogen and C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralkyl, heteroaryl, or heterocycline It is; and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R B , R 1a , R 1b , R 1c , R 1d L and X are defined in this specification, respectively. As is justified; Here, each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and ara are defined as follows: Lukyl, heteroaryl, and heterocyclyl are one or more, in one embodiment, one It is arbitrarily substituted with two, three, or four substituents Q.

[0066] In yet another embodiment, a compound of formula (IV) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R B L, X, U 1 , V 1 , W 1 , X 1 , Y 1 , and Z 1 Each of these items is in this statement. (As defined in the book.)

[0067] In yet another embodiment, a compound of formula (V) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (In the formula: U 1 , V 1 , and X 1 Each of these is independently of -CR 7a =, -N=, -NR 7b -, -O-, or -S-; W 1 is C or N; Y 1 This is a combination, -CR 7a =, -N=, -NR 7b -, -O-, or -S-; and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R B , R 7a , R 7b , L, X, and Z 1 Each of these is defined herein. (As stated above.)

[0068] In yet another embodiment, a compound of formula (VI) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (In the formula: U 1 , V 1 , and X 1 Each of these is independently of -CR 7a =, -N=, -NR 7b -, -O-, or -S-; W 1 is C or N; Y 1 This is a combination, -CR 7a =, -N=, -NR 7b-, -O-, or -S-; and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R B , R 7a , R 7b , L, X, and Z 1 Each of these is defined herein. (As stated above.)

[0069] In yet another embodiment, a compound of formula (VII) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (In the formula: U 1 , W 1 , and X 1 Each of these is independently of -CR 7a =, -N=, -NR 7b -, -O-, or -S-; V 1 is C or N; Y 1 This is a combination, -CR 7a =, -N=, -NR 7b -, -O-, or -S-; and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R B , R 7a , R 7b , L, X, and Z 1 Each of these is defined herein. (As stated above.)

[0070] In yet another embodiment, a compound of formula (VIII) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (In the formula: U 1 , W 1 , and X 1 Each of these is independently of -CR 7a =, -N=, -NR 7b -, -O-, or -S-; V 1 is C or N; Y 1 This is a combination, -CR 7a =, -N=, -NR 7b -, -O-, or -S-; and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R B , R 7a , R 7b , L, X, and Z 1 Each of these is defined herein. (As stated above.)

[0071] In yet another embodiment, a compound of formula (IX) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (In the formula: Each R 7 (a) Deuterium, cyano, halo, or nitro; (b) C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralchi (c)-C(O)R 1a , -C(O)OR 1a -C(O)NR 1b R 1c -C(NR 1a )NR 1b R 1c , -OR 1a ,-OC(O)R 1a -OC(O)OR 1a -OC(O)NR 1b R 1c -OC(NR 1a )NR 1b R 1c -OS(O)R 1a -OS(O)2R 1a -OS(O)NR 1b R 1c -OS(O)2NR 1b R 1c , -NR 1b R 1c , -NR 1a C(O)R 1 d , -NR 1a C(O)OR 1d , -NR 1a C(O)NR 1b R 1c , -NR 1a C(NR 1d )NR 1b R 1c , -NR 1a S(O)R 1d , -NR 1a S(O) 2R 1d , -NR 1a S(O)NR 1b R 1c , -NR 1a S(O)2NR 1b R 1c , -SR 1a ,-S(O)R 1a -S(O)2R 1a -S(O)NR 1b R 1c , or -S(O)2NR 1b R 1c ; 1. n is an integer of 0, 1, 2, 3, or 4; and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R B , R 1a , R 1b , R 1c , R 1d L and X are defined in this specification, respectively. As is justified; Here, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and aralkyl The heteroaryl and heterocyclyl compounds are, in one embodiment, one or more, one or two. (Each of the substituents Q is arbitrarily substituted with three or four substituents Q).

[0072] In yet another embodiment, a compound of formula (X) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R2 , R 3 , R 4 , R 5 , R 6 , R 7 , R B L, X, and n are defined herein, respectively. (That is correct.)

[0073] In yet another embodiment, a compound of formula (XI) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R B L, X, and n are defined herein, respectively. (That is correct.)

[0074] In yet another embodiment, a compound of formula (XII) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 2 , R 3 , R 4 , R 5 , R6 , R 7a , R B L and X are defined herein, respectively. (That's right.)

[0075] In yet another embodiment, a compound of formula (XIII) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R B L, X, and n are defined herein, respectively. (That is correct.)

[0076] In one embodiment, in any one of formulas (IX) to (XI) and (XIII), R 1 is a halo or C 1-6 It is alkyl; R 2 is -C(O)OR 2a -C(O)NR 2b R 2c ,-C(O)N(R 2b )OR 2c , or heteroaryl, here So, each R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 Alkyl or heteroaryl can be; R 3 , R 4 , R5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7 is deuterium, halo, or -OC 1-6 It is alkyl; R B And X is (i), (ii), or (iii): (i) X is -O-, -S-, -S(O)-, or -S(O)2-; and R B C 6-14 It is either an aryl or heteroaryl; (ii) X is -NR X -and; R B C 6-14 It is aryl or heteroaryl; and R X is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir; or (iii) X is -NR X -and; and R B and R X These, along with the N atom to which they are bonded, form heteroaryl or heterosilicate compounds. Forming krill; L is C 1-6 Alkilen, C 2-6 Alkenylene, or C 3-10 It is a cycloalkylene; and n is an integer of 0, 1, 2, 3, or 4; Here, each alkyl, alkylene, alkenylene, cycloalkylene, aryl, Aralkyl, heteroaryl, and heterocyclyl compounds can be assigned one, two, or three substituents Q. It has been replaced with "meaning".

[0077] In another embodiment, in any one of formulas (IX) to (XI) and (XIII), R1 is a halo or C 1-6 It is alkyl; R 2 is -C(O)OR 2a -C(O)NR 2b R 2c ,-C(O)N(R 2b )OR 2c or monocyclic heteroaryl Here, each R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 Alkyl or heteroalkyl It is; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7 is deuterium, halo, or -OC 1-6 It is alkyl; R B And X is (i), (ii), or (iii): (i) X is -O-, -S-, -S(O)-, or -S(O)2-; and R B C 6-14 It is either an aryl or heteroaryl; (ii) X is -NR X -and; R B C 6-14 It is aryl or heteroaryl; and R X is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir; or (iii) X is -NR X -and; and R B and R X These, along with the N atom to which they are bonded, form heteroaryl or heterosilicate compounds. Forming krill; L is C 1-6 Alkylene or C 2-6 It is an alkenylene; and n is an integer of 0, 1, 2, 3, or 4; Here, each alkyl, alkylene, alkenylene, aryl, aralkyl, hetero Aryl and heterocyclyl compounds are optionally substituted with one, two, or three substituents Q. Each substituent Q is (i) bromo, chloro, fluoro, and cyano; (ii) one or more substituents Q a in Arbitrarily substituted C 1-6 Alkyl; and (iii)-C(O)R a , -OR a , and -NR b R c Select independently from And here, each R a , R b , and R c This is as defined herein.

[0078] In another embodiment, in any one of formulas (IX) to (XI) and (XIII), R 1 C 1-6 It is alkyl; R 2 -C(O)OH, -C(O)NR 2b R 2c ,-C(O)N(R 2b )OR 2c , or a 5-membered heteroaryl, Here, each R 2b and R 2c These are, independently, hydrogen and C 1-6 It is alkyl or heteroaryl; R 3 and R 4 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R7 is deuterium, halo, or -OC 1-6 It is alkyl; R B And X is (i), (ii), or (iii): (i) X is -O-, -S-, -S(O)-, or -S(O)2-; and R B This is a single-ring or double-ring C 6-14 Aryl, or monocyclic or bicyclic heteroaryl Is it a lu? (ii) X is -NR X -and; R B This is a single-ring or double-ring C 6-14 Aryl, or monocyclic or bicyclic heteroaryl It is; and R X is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir? Or (iii) X is -NR X -and; and R B and R X These, along with the N atoms to which they are bonded, form monocyclic or bicyclic heterocyclic structures. Forming a ring, or a monocyclic or bicyclic heterocycline; L is C 1-6 Alkylene or C 2-6 It is an alkenylene; and n is an integer of 0, 1, or 2; Here, each alkyl, alkylene, alkenylene, aryl, aralkyl, hetero Aryl and heterocyclyl compounds are optionally substituted with one, two, or three substituents Q. Each substituent Q is bromo, chloro, fluoro, cyano, methyl, or trifluoromethyl. , independently selected from ethyl, propyl, formyl, hydroxyl, methoxy, and amino It can be done.

[0079] In another embodiment, in any one of formulas (IX) to (XI) and (XIII), R 1 It is methyl; R 2 -C(O)OH, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2CH2OH, -C(O)NHOH, -C(O)NH(tet) Lazolyl, tetrazolyl, or 1,2,4-oxadiazolyl; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7 is chloro or methoxy; R B And X is (i), (ii), or (iii): (i) X is -O-, -S-, -S(O)-, or -S(O)2-; and R B These are phenyl, bromophenyl, fluorophenyl, cyanophenyl, and methylphenyl. L, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Lu, formylphenyl, bromo-fluorophenyl, difluorophenyl, trifluoro Phenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl, or quinoline Is it a lu? (ii) X is -NR X -and; R B These are phenyl, bromophenyl, fluorophenyl, cyanophenyl, and methylphenyl. L, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Lu, formylphenyl, bromo-fluorophenyl, difluorophenyl, trifluoro Phenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl, or quinoline It is; and R X These are hydrogen, methyl, ethyl, hydroxyethyl, propyl, phenyl, and fluoromethyl It is yl, formylphenyl, or benzyl; or (iii) X is -NR X -and; and R B and R X These, along with the N atom to which they are bonded, are pyrrolidinyl, piperidinyl, and mo Forming rufolinyl, pyrrolyl, aminoimidazolyl, or indolyl; L is methylene, ethylene, or ethenylene; and n is an integer, either 0 or 1.

[0080] In another embodiment, in any one of formulas (IX) to (XI) and (XIII), R 1 It is methyl; R 2 -C(O)OH, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2CH2OH, -C(O)NHOH, -C(O)NH(tet) It is rhazol-5-yl), tetrazol-5-yl, or 1,2,4-oxadiazole-5-yl; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7 is chloro or methoxy; R B And X is (i), (ii), or (iii): (i) X is -O-, -S-, -S(O)-, or -S(O)2-; and R BThese are phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, and 3-sheaphenyl. Nophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 4- Trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methoxy Phenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl, 2 ,4-difluorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoropyryl It is either do-5-yl, 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl; (ii) X is -NR X -and; R B These are phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, and 3-sheaphenyl. Nophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 4- Trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methoxy Phenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl, 2 ,4-difluorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoropyryl It is do-5-yl, 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl; and R X These are hydrogen, methyl, ethyl, 2-hydroxyethyl, n-propyl, phenyl, 4-fluorine It is lophenyl, 4-formylphenyl, or benzyl; or (iii) X is -NR X -and; and R B and R X Together with the N atom to which they are bonded, pyrrole-1-yl, 2-amino-imi Dazole-1-yl, indole-1-yl, pyrrolidine-1-yl, piperidine-1-yl, or It forms 4-morpholine-4-yl; L is methylene, ethane-1,2-diyl, or ethene-1,2-diyl; and n is an integer, either 0 or 1.

[0081] In one embodiment, in formula (XII), R 1 is a halo or C 1-6 It is alkyl; R 2 is -C(O)OR 2a -C(O)NR 2b R 2c ,-C(O)N(R 2b )OR 2c , or heteroaryl, here So, each R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 Alkyl or heteroaryl can be; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7a is hydrogen, deuterium, halo, or -OC 1-6 It is alkyl; R B And X is (i), (ii), or (iii): (i) X is -O-, -S-, -S(O)-, or -S(O)2-; and R B C 6-14 It is either an aryl or heteroaryl; (ii) X is -NR X -and; R B C 6-14 It is aryl or heteroaryl; and RX is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir; or (iii) X is -NR X -and; and R B and R X These, along with the N atom to which they are bonded, form heteroaryl or heterosilicate compounds. Forming krill; and L is C 1-6 Alkilen, C 2-6 Alkenylene, or C 3-10 It is a cycloalkylene; Here, each alkyl, alkylene, alkenylene, cycloalkylene, aryl, Aralkyl, heteroaryl, and heterocyclyl compounds can be assigned one, two, or three substituents Q. It has been replaced with "meaning".

[0082] In another embodiment, in formula (XII), R 1 is a halo or C 1-6 It is alkyl; R 2 is -C(O)OR 2a -C(O)NR 2b R 2c ,-C(O)N(R 2b )OR 2c or monocyclic heteroaryl Here, each R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 Alkyl or heteroalkyl It is; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7a is hydrogen, deuterium, halo, or -OC 1-6 It is alkyl; R B And X is (i), (ii), or (iii): (i) X is -O-, -S-, -S(O)-, or -S(O)2-; and R B C 6-14 It is either an aryl or heteroaryl; (ii) X is -NR X -and; R B C 6-14 It is aryl or heteroaryl; and R X is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir; or (iii) X is -NR X -and; and R B and R X These, along with the N atom to which they are bonded, form heteroaryl or heterosilicate compounds. Forming krill; and L is C 1-6 Alkylene or C 2-6 It is an alkenylene; Here, each alkyl, alkylene, alkenylene, aryl, aralkyl, hetero Aryl and heterocyclyl compounds are optionally substituted with one, two, or three substituents Q. Each substituent Q is (i) bromo, chloro, fluoro, and cyano; (ii) one or more substituents Q a in Arbitrarily substituted C 1-6 Alkyl; and (iii)-C(O)R a , -OR a , and -NR b R c Select independently from And here, each R a , R b , and R c This is as defined herein.

[0083] In another embodiment, in formula (XII), R 1 C 1-6 It is alkyl; R 2 -C(O)OH, -C(O)NR 2b R 2c ,-C(O)N(R 2b )OR 2c , or a 5-membered heteroaryl, Here, each R 2b and R 2c These are, independently, hydrogen and C 1-6 It is alkyl or heteroaryl; R 3 and R 4 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7a is hydrogen, deuterium, halo, or -OC 1-6 It is alkyl; R B And X is (i), (ii), or (iii): (i) X is -O-, -S-, -S(O)-, or -S(O)2-; and R B This is a single-ring or double-ring C 6-14 Aryl, or monocyclic or bicyclic heteroaryl Is it a lu? (ii) X is -NR X -and; R B This is a single-ring or double-ring C 6-14 Aryl, or monocyclic or bicyclic heteroaryl It is; and R X is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir? Or (iii) X is -NR X -and; and R B and R X These, along with the N atoms to which they are bonded, form monocyclic or bicyclic heterocyclic structures. Forming a ring, or a monocyclic or bicyclic heterocyclil; and L is C 1-6 Alkylene or C 2-6 It is an alkenylene; Here, each alkyl, alkylene, alkenylene, aryl, aralkyl, hetero Aryl and heterocyclyl compounds are optionally substituted with one, two, or three substituents Q. Each substituent Q is bromo, chloro, fluoro, cyano, methyl, or trifluoromethyl. , independently selected from ethyl, propyl, formyl, hydroxyl, methoxy, and amino It can be done.

[0084] In another embodiment, in formula (XII), R 1 It is methyl; R 2 -C(O)OH, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2CH2OH, -C(O)NHOH, -C(O)NH(tet) Lazolyl, tetrazolyl, or 1,2,4-oxadiazolyl; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7a is hydrogen, deuterium, chloro, or methoxy; R B And X is (i), (ii), or (iii): (i) X is -O-, -S-, -S(O)-, or -S(O)2-; and R B These are phenyl, bromophenyl, fluorophenyl, cyanophenyl, and methylphenyl. L, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Lu, formylphenyl, bromo-fluorophenyl, difluorophenyl, trifluoro Phenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl, or quinoline Is it a lu? (ii) X is -NR X -and; R B These are phenyl, bromophenyl, fluorophenyl, cyanophenyl, and methylphenyl. L, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Lu, formylphenyl, bromo-fluorophenyl, difluorophenyl, trifluoro Phenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl, or quinoline It is; and R X These are hydrogen, methyl, ethyl, hydroxyethyl, propyl, phenyl, and fluoromethyl It is yl, formylphenyl, or benzyl; or (iii) X is -NR X -and; and R B and R X These, along with the N atom to which they are bonded, are pyrrolidinyl, piperidinyl, and mo Forming rufolinyl, pyrrolyl, aminoimidazolyl, or indolyl; and L is methylene, ethylene, or ethenylene.

[0085] In another embodiment, in formula (XII), R 1 It is methyl; R 2 -C(O)OH, -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2CH2OH, -C(O)NHOH, -C(O)NH(tet) It is rhazol-5-yl), tetrazol-5-yl, or 1,2,4-oxadiazole-5-yl; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7a is hydrogen, deuterium, chloro, or methoxy; R B And X is (i), (ii), or (iii): (i) X is -O-, -S-, -S(O)-, or -S(O)2-; and R B These are phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, and 3-sheaphenyl. Nophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 4- Trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methoxy Phenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl, 2 ,4-difluorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoropyryl It is either do-5-yl, 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl; (ii) X is -NR X -and; R B These are phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, and 3-sheaphenyl. Nophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 4- Trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methoxy Phenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl, 2 ,4-difluorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoropyryl It is do-5-yl, 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl; and R X These are hydrogen, methyl, ethyl, 2-hydroxyethyl, n-propyl, phenyl, 4-fluorine It is lophenyl, 4-formylphenyl, or benzyl; or (iii) X is -NR X -and; and R B and R X Together with the N atom to which they are bonded, pyrrole-1-yl, 2-amino-imi Dazole-1-yl, indole-1-yl, pyrrolidine-1-yl, piperidine-1-yl, or It forms 4-morpholin-4-yl; and L is methylene, ethane-1,2-diyl, or ethene-1,2-diyl.

[0086] In yet another embodiment, a compound of formula (XIV) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (In the formula: R 2A is -OR 2a , -NR 2b R 2c , or -N(R 2b )OR 2c and; p is an integer of 1, 2, or 3; and R 1 , R 3 , R 4, R 5 , R 6 , R 7 , R B , R 2a , R 2b , R 2c n, and n are defined herein, respectively. (As is the case.)

[0087] In yet another embodiment, a compound of formula (XV) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R B , R 2A n and p are defined herein, respectively. (That's right.)

[0088] In yet another embodiment, a compound of formula (XVI) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 3 , R 4 , R 5 , R 6 , R7 , R B , R 2A n and p are defined herein, respectively. (That's right.)

[0089] In yet another embodiment, a compound of formula (XVII) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 3 , R 4 , R 5 , R 6 , R 7a , R B , R 2A , and p are as defined herein, respectively. (It is.)

[0090] In yet another embodiment, a compound of formula (XVIII) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R B , R 2An and p are defined herein, respectively. (That's right.)

[0091] In one embodiment, in any one of formulas (XIV) to (XVI) and (XVIII), R 1 is a halo or C 1-6 It is alkyl; R 2A is -OR 2a , -NR 2b R 2c , or -N(R 2b )OR 2c And here, each R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 It is alkyl or heteroaryl; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7 is deuterium, halo, or -OC 1-6 It is alkyl; R B C 6-14 It is an aryl or heteroaryl; n is an integer of 0, 1, 2, 3, or 4; and p is an integer of 1, 2, or 3; Here, each alkyl, aryl, and heteroaryl is one, two, or three in number. It is arbitrarily substituted with substitution base Q.

[0092] In another embodiment, in any one of formulas (XIV) to (XVI) and (XVIII), R 1 is a halo or C 1-6 It is alkyl; R 2A is -OR 2a , -NR 2b R 2c, or -N(R 2b )OR 2c And here, each R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 It is alkyl or heteroaryl; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7 is deuterium, halo, or -OC 1-6 It is alkyl; R B C 6-14 It is an aryl or heteroaryl; n is an integer of 0, 1, 2, 3, or 4; and p is an integer, either 1 or 2; Here, each alkyl, aryl, and heteroaryl is one, two, or three in number. It is arbitrarily substituted with substitution group Q, and each substituent Q is (i) bromo, chloro, fluoro, and cyano; (ii) 1 or more substituents Q a C arbitrarily replaced by 1-6 Alkyl; and (iii)-C(O)R a , -OR a , and -NR b R c Selected independently from, where each R a , R b , and R c This is defined in this specification. As stated above.

[0093] In another embodiment, in any one of formulas (XIV) to (XVI) and (XVIII), R 1 C 1-6 It is alkyl; R 2A -OH, -NR 2b R2c , or -N(R 2b )OR 2c And here, each R 2b and R 2c Independent In addition, hydrogen, C 1-6 It is alkyl or heteroaryl; R 3 and R 4 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7 is deuterium, halo, or -OC 1-6 It is alkyl; R B This is a single-ring or double-ring C 6-14 Aryl, or monocyclic or bicyclic heteroaryl It is; n is an integer of 0, 1, or 2; and p is an integer, either 1 or 2; Here, each alkyl, aryl, and heteroaryl is one, two, or three in number. It is arbitrarily substituted with substitution group Q, and each substituent Q is bromo, chloro, fluoro, cyano, Methyl, trifluoromethyl, ethyl, propyl, formyl, hydroxyl, methoxy, And are independently selected from amino acids.

[0094] In another embodiment, in any one of formulas (XIV) to (XVI) and (XVIII), R 1 It is methyl; R 2A These are -OH, -NH2, -NHCH3, -NHCH2CH2OH, -NHOH, or -NH(tetrazolyl); R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R6 Each is independently either hydrogen or deuterium; R 7 is chloro or methoxy; R B These are phenyl, bromophenyl, fluorophenyl, cyanophenyl, and methylphenyl. L, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Lu, formylphenyl, bromo-fluorophenyl, difluorophenyl, trifluoro Phenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl, or quinolinyl can be; n is an integer of 0 or 1; and p is an integer, either 1 or 2.

[0095] In another embodiment, in any one of formulas (XIV) to (XVI) and (XVIII), R 1 It is methyl; R 2A These are -OH, -NH2, -NHCH3, -NHCH2CH2OH, -NHOH, or -NH(tetrazolyl); R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7 is chloro or methoxy; R B These are phenyl, bromophenyl, fluorophenyl, cyanophenyl, and methylphenyl. L, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Bromo-fluorophenyl, difluorophenyl, trifluorophenyl, naphthyl , fluoropyridyl, fluoromethylpyridyl, or quinolinyl; n is an integer of 0 or 1; and p is an integer, either 1 or 2.

[0096] In another embodiment, in any one of formulas (XIV) to (XVI) and (XVIII), R 1 It is methyl; R 2A These are -OH, -NH2, -NHCH3, -NHCH2CH2OH, -NHOH, or -NH(tetrazole-5-yl). the law of nature; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7 is chloro or methoxy; R B These are phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, and 3-sheaphenyl. Nophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 4- Trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methoxy Phenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl, 2 ,4-difluorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoropyryl It is do-5-yl, 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl; n is an integer of 0 or 1; and p is an integer, either 1 or 2.

[0097] In another embodiment, in any one of formulas (XIV) to (XVI) and (XVIII), R 1 It is methyl; R 2AThese are -OH, -NH2, -NHCH3, -NHCH2CH2OH, -NHOH, or -NH(tetrazole-5-yl). the law of nature; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7 is chloro or methoxy; R B These are phenyl, 4-bromophenyl, 4-fluorophenyl, 3-cyanophenyl, and 3-methylphenyl. 4-methylphenyl, 3-trifluoromethylphenyl, 4-ethylphenyl, 4- Isopropylphenyl, 4-methoxyphenyl, 2-bromo-4-fluorophenyl, 2,4-diph Luorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoropyrido-5-yl It is either 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl; n is an integer of 0 or 1; and p is an integer, either 1 or 2.

[0098] In one embodiment, in formula (XVII), R 1 is a halo or C 1-6 It is alkyl; R 2A is -OR 2a , -NR 2b R 2c , or -N(R 2b )OR 2c And here, each R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 It is alkyl or heteroaryl; R 3 , R 4 , R 5 , and R6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7a is hydrogen, deuterium, halo, or -OC 1-6 It is alkyl; R B C 6-14 It is an aryl or heteroaryl; and p is an integer of 1, 2, or 3; Here, each alkyl, aryl, and heteroaryl is one, two, or three in number. It is arbitrarily substituted with substitution base Q.

[0099] In another embodiment, in formula (XVII), R 1 is a halo or C 1-6 It is alkyl; R 2A is -OR 2a , -NR 2b R 2c , or -N(R 2b )OR 2c And here, each R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 It is alkyl or heteroaryl; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7a is hydrogen, deuterium, halo, or -OC 1-6 It is alkyl; R B C 6-14 It is an aryl or heteroaryl; and p is an integer, either 1 or 2; Here, each alkyl, aryl, and heteroaryl is one, two, or three in number. It is arbitrarily substituted with substitution group Q, and each substituent Q is (i) bromo, chloro, fluoro, and cyano; (ii) 1 or more substituents Q a C arbitrarily replaced by 1-6 Alkyl; and (iii)-C(O)R a , -OR a , and -NR b R c Selected independently from, where each R a , R b , and R c This is defined in this specification. As stated above.

[0100] In another embodiment, in formula (XVII), R 1 C 1-6 It is alkyl; R 2A -OH, -NR 2b R 2c , or -N(R 2b )OR 2c And here, each R 2b and R 2c Independent In addition, hydrogen, C 1-6 It is alkyl or heteroaryl; R 3 and R 4 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7a is hydrogen, deuterium, halo, or -OC 1-6 It is alkyl; R B This is a single-ring or double-ring C 6-14 Aryl, or monocyclic or bicyclic heteroaryl It is; and p is an integer, either 1 or 2; Here, each alkyl, aryl, and heteroaryl is one, two, or three in number. It is arbitrarily substituted with substitution group Q, and each substituent Q is bromo, chloro, fluoro, cyano, Methyl, trifluoromethyl, ethyl, propyl, formyl, hydroxyl, methoxy, And are independently selected from amino acids.

[0101] In another embodiment, in formula (XVII), R 1 It is methyl; R 2A These are -OH, -NH2, -NHCH3, -NHCH2CH2OH, -NHOH, or -NH(tetrazolyl); R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7a is hydrogen, deuterium, chloro, or methoxy; R B These are phenyl, bromophenyl, fluorophenyl, cyanophenyl, and methylphenyl. L, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Lu, formylphenyl, bromo-fluorophenyl, difluorophenyl, trifluoro Phenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl, or quinolinyl Yes; and p is an integer, either 1 or 2.

[0102] In another embodiment, in formula (XVII), R 1 It is methyl; R 2A These are -OH, -NH2, -NHCH3, -NHCH2CH2OH, -NHOH, or -NH(tetrazolyl); R 3 and R 4These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7a is hydrogen, deuterium, chloro, or methoxy; R B These are phenyl, bromophenyl, fluorophenyl, cyanophenyl, and methylphenyl. L, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Bromo-fluorophenyl, difluorophenyl, trifluorophenyl, naphthyl , fluoropyridyl, fluoromethylpyridyl, or quinolinyl; and p is an integer, either 1 or 2.

[0103] In another embodiment, in formula (XVII), R 1 It is methyl; R 2A These are -OH, -NH2, -NHCH3, -NHCH2CH2OH, -NHOH, or -NH(tetrazole-5-yl). the law of nature; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7a is hydrogen, deuterium, chloro, or methoxy; R B These are phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, and 3-sheaphenyl. Nophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 4- Trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methoxy Phenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl, 2 ,4-difluorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoropyryl It is do-5-yl, 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl; and p is an integer, either 1 or 2.

[0104] In another embodiment, in formula (XVII), R 1 It is methyl; R 2A These are -OH, -NH2, -NHCH3, -NHCH2CH2OH, -NHOH, or -NH(tetrazole-5-yl). the law of nature; R 3 , R 5 , and R 6 Each is independently either hydrogen or deuterium; R 4 is hydrogen, deuterium, or fluorocarbon; R 7a is hydrogen, deuterium, chloro, or methoxy; R B These are phenyl, 4-bromophenyl, 4-fluorophenyl, 3-cyanophenyl, and 3-methylphenyl. 4-methylphenyl, 3-trifluoromethylphenyl, 4-ethylphenyl, 4- Isopropylphenyl, 4-methoxyphenyl, 2-bromo-4-fluorophenyl, 2,4-diph Luorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoropyrido-5-yl It is 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl; and p is an integer, either 1 or 2.

[0105] In yet another embodiment, a compound of formula (XIX) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R B , R X , R 2A n and p are defined herein, respectively. (As is the case.)

[0106] In yet another embodiment, a compound of formula (XX) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R B , R X , R 2A n and p are defined herein, respectively. (As is the case.)

[0107] In yet another embodiment, a compound of formula (XXI) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R B , R X , R 2A n and p are defined herein, respectively. (As is the case.)

[0108] In yet another embodiment, a compound of formula (XXII) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 3 , R 4 , R 5 , R 6 , R 7a , R B , R X , R 2A , and p are defined herein, respectively. (That is correct.)

[0109] In yet another embodiment, a compound of formula (XXIII) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R B , R X , R 2A n and p are defined herein, respectively. (As is the case.)

[0110] In one embodiment, in any one of formulas (XIX) to (XXI) and (XXIII), R 1 is a halo or C 1-6 It is alkyl; R 2A is -OR 2a , -NR 2b R 2c , or -N(R 2b )OR 2c And here, each R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 It is alkyl or heteroaryl; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7 is deuterium, halo, or -OC 1-6 It is alkyl; R B and R X is (i) or (ii): (i)R B C 6-14It is aryl or heteroaryl; and R X is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir; or (ii)R B and R X These, together with the N atom to which they are bonded, form heteroaryl or hetero Forming cyclils; n is an integer of 0, 1, 2, 3, or 4; and p is an integer of 1, 2, or 3; Each alkyl, aryl, aralkyl, heteroaryl, and heterocyclyl is 1 It is arbitrarily substituted with two or three substituents Q.

[0111] In another embodiment, in any one of formulas (XIX) to (XXI) and (XXIII), R 1 is a halo or C 1-6 It is alkyl; R 2A is -OR 2a , -NR 2b R 2c , or -N(R 2b )OR 2c And here, each R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 It is alkyl or heteroaryl; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7 is deuterium, halo, or -OC 1-6 It is alkyl; R B and R X is (i) or (ii): (i)RB C 6-14 It is aryl or heteroaryl; and R X is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir; or (ii)R B and R X These, together with the N atom to which they are bonded, form heteroaryl or hetero Forming cyclils; n is an integer of 0, 1, 2, 3, or 4; and p is an integer, either 1 or 2; Here, each of the alkyl, aryl, aralkyl, heteroaryl, and heterocycline compounds is represented. The molecule is optionally substituted with one, two, or three substituents Q, each substituent Q being (i) blot. (ii) one or more substituents Q a C arbitrarily replaced by 1-6 Alki Lu; and (iii)-C(O)R a , -OR a , and -NR b R c Selected independently from, where each R a , R b , and R c This is as defined herein.

[0112] In another embodiment, in any one of formulas (XIX) to (XXI) and (XXIII), R 1 C 1-6 It is alkyl; R 2A -OH, -NR 2b R 2c , or -N(R 2b )OR 2c And here, each R 2b and R 2c Independent In addition, hydrogen, C1-6 It is alkyl or heteroaryl; R 3 and R 4 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7 is deuterium, halo, or -OC 1-6 It is alkyl; R B and R X is (i) or (ii): (i)R B This is a single-ring or double-ring C 6-14 Aryl, or monocyclic or bicyclic heteroaryl It is; and R X is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir? Or (ii)R B and R X These, along with the N atoms to which they are bonded, form monocyclic or bicyclic heterocycles. Forming a reel, or a monocyclic or bicyclic heterocycline; n is an integer of 0, 1, or 2; and p is an integer, either 1 or 2; Here, each of the alkyl, aryl, aralkyl, heteroaryl, and heterocycline compounds is represented. The molecule is optionally substituted with one, two, or three substituents Q, each substituent Q being bromo chloromethyl A molecule is independently selected from hydroxyl, methoxyl, and amino.

[0113] In another embodiment, in any one of formulas (XIX) to (XXI) and (XXIII), R 1 It is methyl; R 2A These are -OH, -NH2, -NHCH3, -NHCH2CH2OH, -NHOH, or -NH(tetrazolyl); R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7 is chloro or methoxy; R B and R X is (i) or (ii): (i)R B These include phenyl, bromophenyl, fluorophenyl, cyanophenyl, and methylphenyl. Nyl, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Nyl, formylphenyl, bromo-fluorophenyl, difluorophenyl, trifluoro Lophenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl, or quinoli It is nil; and R X These are hydrogen, methyl, ethyl, hydroxyethyl, propyl, phenyl, and fluoromethyl It is yl, formylphenyl, or benzyl; or (ii)R B and R X Along with the N atom to which they are bonded, pyrrolidinyl, piperidinyl, Forming morpholinyl, pyrrolyl, aminoimidazolyl, or indolyl; n is an integer of 0 or 1; and p is an integer, either 1 or 2.

[0114] In another embodiment, in any one of formulas (XIX) to (XXI) and (XXIII), R 1 It is methyl; R 2AThese are -OH, -NH2, -NHCH3, -NHCH2CH2OH, -NHOH, or -NH(tetrazole-5-yl). the law of nature; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7 is chloro or methoxy; R B and R X is (i) or (ii): (i)R B These are phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, and 3-syl Anophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methoxymethylphenyl cyphenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl , 2,4-difluorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoro It is pyrido-5-yl, 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl; and R X These are hydrogen, methyl, ethyl, 2-hydroxyethyl, n-propyl, phenyl, 4-fluorine It is lophenyl, 4-formylphenyl, or benzyl; or (ii)R B and R X Along with the N atom to which they are bonded, pyrrole-1-yl, 2-amino-yl Midazole-1-yl, indole-1-yl, pyrrolizin-1-yl, piperizin-1-yl, if ku forms 4-morpholine-4-yl; n is an integer of 0 or 1; and p is an integer, either 1 or 2.

[0115] In one embodiment, in formula (XXII), R 1 is a halo or C 1-6 It is alkyl; R 2A is -OR 2a , -NR 2b R 2c , or -N(R 2b )OR 2c And here, each R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 It is alkyl or heteroaryl; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7a is hydrogen, deuterium, halo, or -OC 1-6 It is alkyl; R B and R X is (i) or (ii): (i)R B C 6-14 It is aryl or heteroaryl; and R X is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir; or (ii)R B and R X These, together with the N atom to which they are bonded, form heteroaryl or hetero Forming a cyclil; and p is an integer of 1, 2, or 3; Each alkyl, aryl, aralkyl, heteroaryl, and heterocyclyl is 1 It is arbitrarily substituted with two or three substituents Q.

[0116] In another embodiment, in formula (XXII), R 1 is a halo or C 1-6 It is alkyl; R 2A is -OR 2a , -NR 2b R 2c , or -N(R 2b )OR 2c And here, each R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 It is alkyl or heteroaryl; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7a is hydrogen, deuterium, halo, or -OC 1-6 It is alkyl; R B and R X is (i) or (ii): (i)R B C 6-14 It is aryl or heteroaryl; and R X is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir; or (ii)R B and R X These, together with the N atom to which they are bonded, form heteroaryl or hetero Forming a cyclil; and p is an integer, either 1 or 2; Here, each of the alkyl, aryl, aralkyl, heteroaryl, and heterocycline compounds is represented. The molecule is optionally substituted with one, two, or three substituents Q, each substituent Q being (i) blot. (ii) one or more substituents Q a C arbitrarily replaced by 1-6 Alki Lu; and (iii)-C(O)R a , -OR a , and -NR b R c Selected independently from, where each R a , R b , and R c This is as defined herein.

[0117] In another embodiment, in formula (XXII), R 1 C 1-6 It is alkyl; R 2A -OH, -NR 2b R 2c , or -N(R 2b )OR 2c And here, each R 2b and R 2c Independent In addition, hydrogen, C 1-6 It is alkyl or heteroaryl; R 3 and R 4 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7a is hydrogen, deuterium, halo, or -OC 1-6 It is alkyl; R B and R X is (i) or (ii): (i)R B This is a single-ring or double-ring C 6-14 Aryl, or monocyclic or bicyclic heteroaryl It is; and R X is hydrogen, C 1-6 Alkyl, C 6-14Aryl, or C 7-15 Is it Aralkir? Or (ii)R B and R X These, along with the N atoms to which they are bonded, form monocyclic or bicyclic heterocycles. Forming a reel, or a monocyclic or bicyclic heterocycline; and p is an integer, either 1 or 2; Here, each of the alkyl, aryl, aralkyl, heteroaryl, and heterocycline compounds is represented. The molecule is optionally substituted with one, two, or three substituents Q, each substituent Q being bromo chloromethyl A molecule is independently selected from hydroxyl, methoxyl, and amino.

[0118] In another embodiment, in formula (XXII), R 1 It is methyl; R 2A These are -OH, -NH2, -NHCH3, -NHCH2CH2OH, -NHOH, or -NH(tetrazolyl); R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7a is hydrogen, deuterium, chloro, or methoxy; R B and R X is (i) or (ii): (i)R B These include phenyl, bromophenyl, fluorophenyl, cyanophenyl, and methylphenyl. Nyl, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Nyl, formylphenyl, bromo-fluorophenyl, difluorophenyl, trifluoro Lophenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl, or quinoli It is nil; and R X These are hydrogen, methyl, ethyl, hydroxyethyl, propyl, phenyl, and fluoromethyl It is yl, formylphenyl, or benzyl; or (ii)R B and R X Along with the N atom to which they are bonded, pyrrolidinyl, piperidinyl, Forming morpholinyl, pyrrolyl, aminoimidazolyl, or indolyl; and p is an integer, either 1 or 2.

[0119] In another embodiment, in formula (XXII), R 1 It is methyl; R 2A These are -OH, -NH2, -NHCH3, -NHCH2CH2OH, -NHOH, or -NH(tetrazole-5-yl). the law of nature; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7a is hydrogen, deuterium, chloro, or methoxy; R B and R X is (i) or (ii): (i)R B These are phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, and 3-syl Anophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methoxymethylphenyl cyphenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl , 2,4-difluorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoro It is pyrido-5-yl, 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl; and R X These are hydrogen, methyl, ethyl, 2-hydroxyethyl, n-propyl, phenyl, 4-fluorine It is lophenyl, 4-formylphenyl, or benzyl; or (ii)R B and R X Along with the N atom to which they are bonded, pyrrole-1-yl, 2-amino-yl Midazole-1-yl, indole-1-yl, pyrrolizin-1-yl, piperizin-1-yl, if ku forms 4-morpholine-4-yl; and p is an integer, either 1 or 2.

[0120] In yet another embodiment, a compound of formula (XXIV) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (In the formula: U 2 is -N= or -O-; V 2 is -N= or -C(OH)= and R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , RB n and p are as defined herein, respectively. (ru).

[0121] In yet another embodiment, a compound of formula (XXV) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R B , U 2 , V 2 n and p are defined herein, respectively. (That is correct.)

[0122] In yet another embodiment, a compound of formula (XXVI) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R B , U 2 , V 2n and p are defined herein, respectively. (That is correct.)

[0123] In yet another embodiment, a compound of formula (XXVII) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 3 , R 4 , R 5 , R 6 , R 7a , R B , U 2 , V 2 , and p are defined in this specification, respectively. (That's right.)

[0124] In yet another embodiment, a compound of formula (XXVIII) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R B , U 2 , V 2 n and p are defined herein, respectively. (That is correct.)

[0125] In one embodiment, in any one of formulas (XXIV) to (XXVI) and (XXVIII), R 1 is a halo or C 1-6 It is alkyl; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7 is deuterium, halo, or -OC 1-6 It is alkyl; R B C 6-14 It is an aryl or heteroaryl; U 2 is -N= or -O-; V 2 is -N= or -C(OH)=; n is an integer of 0, 1, 2, 3, or 4; and p is an integer of 1, 2, or 3; Here, each alkyl, aryl, and heteroaryl is one, two, or three in number. It is arbitrarily substituted with substitution base Q.

[0126] In another embodiment, in any one of formulas (XXIV) to (XXVI) and (XXVIII), R 1 is a halo or C 1-6 It is alkyl; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7 is deuterium, halo, or -OC 1-6 It is alkyl; R B C 6-14It is an aryl or heteroaryl; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 -C(OH)=; n is an integer of 0, 1, 2, 3, or 4; and p is an integer, either 1 or 2; Here, each alkyl, aryl, and heteroaryl is one, two, or three in number. It is arbitrarily substituted with substitution group Q, and each substituent Q is (i) bromo, chloro, fluoro, and cyano; (ii) 1 or more substituents Q a C arbitrarily replaced by 1-6 Alkyl; and (iii)-C(O)R a , -OR a , and -NR b R c Selected independently from, where each R a , R b , and R c This is defined in this specification. As stated above.

[0127] In another embodiment, in any one of formulas (XXIV) to (XXVI) and (XXVIII), R 1 C 1-6 It is alkyl; R 3 and R 4 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7 is deuterium, halo, or -OC 1-6 It is alkyl; R B This is a single-ring or double-ring C 6-14 Aryl, or monocyclic or bicyclic heteroaryl It is; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 -C(OH)=; n is an integer of 0, 1, or 2; and p is an integer, either 1 or 2; Here, each alkyl, aryl, and heteroaryl is one, two, or three in number. It is arbitrarily substituted with substitution group Q, and each substituent Q is bromo, chloro, fluoro, cyano, Methyl, trifluoromethyl, ethyl, propyl, formyl, hydroxyl, methoxy, And are independently selected from amino acids.

[0128] In another embodiment, in any one of formulas (XXIV) to (XXVI) and (XXVIII), R 1 It is methyl; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7 is chloro or methoxy; R B These are phenyl, bromophenyl, fluorophenyl, cyanophenyl, and methylphenyl. L, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Lu, formylphenyl, bromo-fluorophenyl, difluorophenyl, trifluoro Phenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl, or quinolinyl can be; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2-C(OH)=; n is an integer of 0 or 1; and p is an integer, either 1 or 2.

[0129] In another embodiment, in any one of formulas (XXIV) to (XXVI) and (XXVIII), R 1 It is methyl; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7 is chloro or methoxy; R B These are phenyl, bromophenyl, fluorophenyl, cyanophenyl, and methylphenyl. L, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Bromo-fluorophenyl, difluorophenyl, trifluorophenyl, naphthyl , fluoropyridyl, fluoromethylpyridyl, or quinolinyl; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 -C(OH)=; n is an integer of 0 or 1; and p is an integer, either 1 or 2.

[0130] In another embodiment, in any one of formulas (XXIV) to (XXVI) and (XXVIII), R 1 It is methyl; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6Each is independently either hydrogen or deuterium; R 7 is chloro or methoxy; R B These are phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, and 3-sheaphenyl. Nophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 4- Trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methoxy Phenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl, 2 ,4-difluorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoropyryl It is do-5-yl, 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 -C(OH)=; n is an integer of 0 or 1; and p is an integer, either 1 or 2.

[0131] In another embodiment, in any one of formulas (XXIV) to (XXVI) and (XXVIII), R 1 It is methyl; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7 is chloro or methoxy; R B These are phenyl, 4-bromophenyl, 4-fluorophenyl, 3-cyanophenyl, and 3-methylphenyl. 4-methylphenyl, 3-trifluoromethylphenyl, 4-ethylphenyl, 4- Isopropylphenyl, 4-methoxyphenyl, 2-bromo-4-fluorophenyl, 2,4-diph Luorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoropyrido-5-yl It is either 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 -C(OH)=; n is an integer of 0 or 1; and p is an integer, either 1 or 2.

[0132] In one embodiment, in formula (XXVII), R 1 is a halo or C 1-6 It is alkyl; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7a is hydrogen, deuterium, halo, or -OC 1-6 It is alkyl; R B C 6-14 It is an aryl or heteroaryl; U 2 is -N= or -O-; V 2 is -N= or -C(OH)= and p is an integer of 1, 2, or 3; Here, each alkyl, aryl, and heteroaryl is one, two, or three in number. It is arbitrarily substituted with substitution base Q.

[0133] In another embodiment, in formula (XXVII), R 1 is a halo or C 1-6 It is alkyl; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7a is hydrogen, deuterium, halo, or -OC 1-6 It is alkyl; R B C 6-14 It is an aryl or heteroaryl; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 is -C(OH)=; or Tsu p is an integer, either 1 or 2; Here, each alkyl, aryl, and heteroaryl is one, two, or three in number. It is arbitrarily substituted with substitution group Q, and each substituent Q is (i) bromo, chloro, fluoro, and cyano; (ii) 1 or more substituents Q a C arbitrarily replaced by 1-6 Alkyl; and (iii)-C(O)R a , -OR a , and -NR b R c Selected independently from, where each R a , R b , and R c This is defined in this specification. As stated above.

[0134] In another embodiment, in formula (XXVII), R 1 C 1-6 It is alkyl; R 3 and R 4 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6It is alkyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7a is hydrogen, deuterium, halo, or -OC 1-6 It is alkyl; R B This is a single-ring or double-ring C 6-14 Aryl, or monocyclic or bicyclic heteroaryl It is; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 is -C(OH)=; or Tsu p is an integer, either 1 or 2; Here, each alkyl, aryl, and heteroaryl is one, two, or three in number. It is arbitrarily substituted with substitution group Q, and each substituent Q is bromo, chloro, fluoro, cyano, Methyl, trifluoromethyl, ethyl, propyl, formyl, hydroxyl, methoxy, And are independently selected from amino acids.

[0135] In another embodiment, in formula (XXVII), R 1 It is methyl; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7a is chloro or methoxy; R B These are phenyl, bromophenyl, fluorophenyl, cyanophenyl, and methylphenyl. L, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Lu, formylphenyl, bromo-fluorophenyl, difluorophenyl, trifluoro Phenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl, or quinolinyl can be; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 is -C(OH)=; or Tsu p is an integer, either 1 or 2.

[0136] In another embodiment, in formula (XXVII), R 1 It is methyl; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7a is chloro or methoxy; R B These are phenyl, bromophenyl, fluorophenyl, cyanophenyl, and methylphenyl. L, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Bromo-fluorophenyl, difluorophenyl, trifluorophenyl, naphthyl , fluoropyridyl, fluoromethylpyridyl, or quinolinyl; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 is -C(OH)=; or Tsu p is an integer, either 1 or 2.

[0137] In another embodiment, in formula (XXVII), R 1It is methyl; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7a is hydrogen, deuterium, chloro, or methoxy; R B These are phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, and 3-sheaphenyl. Nophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 4- Trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methoxy Phenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl, 2 ,4-difluorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoropyryl It is do-5-yl, 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 is -C(OH)=; or Tsu p is an integer, either 1 or 2.

[0138] In another embodiment, in formula (XXVII), R 1 It is methyl; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7a is hydrogen, deuterium, chloro, or methoxy; RB These are phenyl, 4-bromophenyl, 4-fluorophenyl, 3-cyanophenyl, and 3-methylphenyl. 4-methylphenyl, 3-trifluoromethylphenyl, 4-ethylphenyl, 4- Isopropylphenyl, 4-methoxyphenyl, 2-bromo-4-fluorophenyl, 2,4-diph Luorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoropyrido-5-yl It is either 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 is -C(OH)=; or Tsu p is an integer, either 1 or 2.

[0139] In yet another embodiment, a compound of formula (XXIX) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R B , R X , U 2 , V 2 n and p are defined herein, respectively. (As stated above.)

[0140] In another embodiment, a compound of formula (XXX) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R B , R X , U 2 , V 2 n and p are defined herein, respectively. (As stated above.)

[0141] In yet another embodiment, a compound of formula (XXXI) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R B , R X , U 2 , V 2 n and p are defined herein, respectively. (As stated above.)

[0142] In yet another embodiment, a compound of formula (XXXII) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 3 , R 4 , R 5 , R 6 , R 7a , R B , R X , U 2 , V 2 , and p are defined herein, respectively. (As is the case.)

[0143] In yet another embodiment, a compound of formula (XXXIII) is provided herein: [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (Formula Medium, R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R B , R X , U 2 , V 2 n and p are defined herein, respectively. (As stated above.)

[0144] In one embodiment, in any one of formulas (XXIX) to (XXXI) and (XXXIII), R 1 is a halo or C 1-6 It is alkyl; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7 is deuterium, halo, or -OC 1-6 It is alkyl; R B and R X is (i) or (ii): (i)R B C 6-14 It is aryl or heteroaryl; and R X is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir; or (ii)R B and R X These, together with the N atom to which they are bonded, form heteroaryl or hetero Forming cyclils; U 2 is -N= or -O-; V 2 is -N= or -C(OH)=; n is an integer of 0, 1, 2, 3, or 4; and p is an integer of 1, 2, or 3; Each alkyl, aryl, aralkyl, heteroaryl, and heterocyclyl is 1 It is arbitrarily substituted with two or three substituents Q.

[0145] In another embodiment, in any one of formulas (XXIX) to (XXXI) and (XXXIII), R 1 is a halo or C 1-6 It is alkyl; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7 is deuterium, halo, or -OC 1-6 It is alkyl; R B and R X is (i) or (ii): (i)R B C 6-14 It is aryl or heteroaryl; and R X is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir; or (ii)R B and R X These, together with the N atom to which they are bonded, form heteroaryl or hetero Forming cyclils; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 -C(OH)=; n is an integer of 0, 1, 2, 3, or 4; and p is an integer, either 1 or 2; Here, each of the alkyl, aryl, aralkyl, heteroaryl, and heterocycline compounds is represented. The molecule is optionally substituted with one, two, or three substituents Q, each substituent Q being (i) blot. (ii) one or more substituents Q a C arbitrarily replaced by 1-6 Alki Lu; and (iii)-C(O)R a , -OR a , and -NR b R c Selected independently from, where each R a , Rb , and R c This is as defined herein.

[0146] In another embodiment, in any one of formulas (XXIX) to (XXXI) and (XXXIII), R 1 C 1-6 It is alkyl; R 3 and R 4 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7 is deuterium, halo, or -OC 1-6 It is alkyl; R B and R X is (i) or (ii): (i)R B This is a single-ring or double-ring C 6-14 Aryl, or monocyclic or bicyclic heteroaryl It is; and R X is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir? Or (ii)R B and R X These, along with the N atoms to which they are bonded, form monocyclic or bicyclic heterocycles. Forming a reel, or a monocyclic or bicyclic heterocycline; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 -C(OH)=; n is an integer of 0, 1, or 2; and p is an integer, either 1 or 2; Here, each of the alkyl, aryl, aralkyl, heteroaryl, and heterocycline compounds is represented. The molecule is optionally substituted with one, two, or three substituents Q, each substituent Q being bromo chloromethyl A molecule is independently selected from hydroxyl, methoxyl, and amino.

[0147] In another embodiment, in any one of formulas (XXIX) to (XXXI) and (XXXIII), R 1 It is methyl; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7 is chloro or methoxy; R B and R X is (i) or (ii): (i)R B These include phenyl, bromophenyl, fluorophenyl, cyanophenyl, and methylphenyl. Nyl, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Nyl, formylphenyl, bromo-fluorophenyl, difluorophenyl, trifluoro Lophenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl, or quinoli It is nil; and R X These are hydrogen, methyl, ethyl, hydroxyethyl, propyl, phenyl, and fluoromethyl It is yl, formylphenyl, or benzyl; or (ii)R B and R X Along with the N atom to which they are bonded, pyrrolidinyl, piperidinyl, Forming morpholinyl, pyrrolyl, aminoimidazolyl, or indolyl; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 -C(OH)=; n is an integer of 0 or 1; and p is an integer, either 1 or 2.

[0148] In another embodiment, in any one of formulas (XXIX) to (XXXI) and (XXXIII), R 1 It is methyl; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7 is chloro or methoxy; R B and R X is (i) or (ii): (i)R B These are phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, and 3-syl Anophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methoxymethylphenyl cyphenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl , 2,4-difluorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoro It is pyrido-5-yl, 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl; and R XThese are hydrogen, methyl, ethyl, 2-hydroxyethyl, n-propyl, phenyl, 4-fluorine It is lophenyl, 4-formylphenyl, or benzyl; or (ii)R B and R X Along with the N atom to which they are bonded, pyrrole-1-yl, 2-amino-yl Midazole-1-yl, indole-1-yl, pyrrolizin-1-yl, piperizin-1-yl, if ku forms 4-morpholine-4-yl; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 -C(OH)=; n is an integer of 0 or 1; and p is an integer, either 1 or 2.

[0149] In one embodiment, in formula (XXX), R 1 is a halo or C 1-6 It is alkyl; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7a is hydrogen, deuterium, halo, or -OC 1-6 It is alkyl; R B and R X is (i) or (ii): (i)R B C 6-14 It is aryl or heteroaryl; and R X is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir; or (ii)R B and R XThese, together with the N atom to which they are bonded, form heteroaryl or hetero Forming cyclils; U 2 is -N= or -O-; V 2 is -N= or -C(OH)= and p is an integer of 1, 2, or 3; Each alkyl, aryl, aralkyl, heteroaryl, and heterocyclyl is 1 It is arbitrarily substituted with two or three substituents Q.

[0150] In another embodiment, in formula (XXX), R 1 is a halo or C 1-6 It is alkyl; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 7a is hydrogen, deuterium, halo, or -OC 1-6 It is alkyl; R B and R X is (i) or (ii): (i)R B C 6-14 It is aryl or heteroaryl; and R X is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir; or (ii)R B and R X These, together with the N atom to which they are bonded, form heteroaryl or hetero Forming cyclils; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 is -C(OH)=; or Tsu p is an integer, either 1 or 2; Here, each of the alkyl, aryl, aralkyl, heteroaryl, and heterocycline compounds is represented. The molecule is optionally substituted with one, two, or three substituents Q, each substituent Q being (i) blot. (ii) one or more substituents Q a C arbitrarily replaced by 1-6 Alki Lu; and (iii)-C(O)R a , -OR a , and -NR b R c Selected independently from, where each R a , R b , and R c This is as defined herein.

[0151] In another embodiment, in formula (XXX), R 1 C 1-6 It is alkyl; R 3 and R 4 Each of these independently consists of hydrogen, deuterium, halo, or C. 1-6 It is alkyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7a is hydrogen, deuterium, halo, or -OC 1-6 It is alkyl; R B and R X is (i) or (ii): (i)R B This is a single-ring or double-ring C 6-14 Aryl, or monocyclic or bicyclic heteroaryl It is; and R X is hydrogen, C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Is it Aralkir? Or (ii)R B and R X These, along with the N atoms to which they are bonded, form monocyclic or bicyclic heterocycles. Forming a reel, or a monocyclic or bicyclic heterocycline; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 is -C(OH)=; or Tsu p is an integer, either 1 or 2; Here, each of the alkyl, aryl, aralkyl, heteroaryl, and heterocycline compounds is represented. The molecule is optionally substituted with one, two, or three substituents Q, each substituent Q being bromo chloromethyl A molecule is independently selected from hydroxyl, methoxyl, and amino.

[0152] In another embodiment, in formula (XXX), R 1 It is methyl; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7a is hydrogen, deuterium, chloro, or methoxy; R B and R X is (i) or (ii): (i)R B These include phenyl, bromophenyl, fluorophenyl, cyanophenyl, and methylphenyl. Nyl, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Nyl, formylphenyl, bromo-fluorophenyl, difluorophenyl, trifluoro Lophenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl, or quinoli It is nil; and R X These are hydrogen, methyl, ethyl, hydroxyethyl, propyl, phenyl, and fluoromethyl It is yl, formylphenyl, or benzyl; or (ii)R B and R X Along with the N atom to which they are bonded, pyrrolidinyl, piperidinyl, Forming morpholinyl, pyrrolyl, aminoimidazolyl, or indolyl; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 is -C(OH)=; or Tsu p is an integer, either 1 or 2.

[0153] In another embodiment, in formula (XXX), R 1 It is methyl; R 3 and R 4 These are, independently, hydrogen, deuterium, fluoro, or methyl; R 5 and R 6 Each is independently either hydrogen or deuterium; R 7a is hydrogen, deuterium, chloro, or methoxy; R B and R X is (i) or (ii): (i)R B These are phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, and 3-syl Anophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methoxymethylphenyl cyphenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl , 2,4-difluorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoro It is pyrido-5-yl, 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl; and R X These are hydrogen, methyl, ethyl, 2-hydroxyethyl, n-propyl, phenyl, 4-fluorine It is lophenyl, 4-formylphenyl, or benzyl; or (ii)R B and R X Along with the N atom to which they are bonded, pyrrole-1-yl, 2-amino-yl Midazole-1-yl, indole-1-yl, pyrrolizin-1-yl, piperizin-1-yl, if ku forms 4-morpholine-4-yl; U 2 and V 2 Each of these is either -N= or U 2 is -O- and V 2 is -C(OH)=; or Tsu p is an integer, either 1 or 2.

[0154] Formulas (I) to (XXXIII), including the group R in the formulas described herein. 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 2A , R 7a , R A , R B , R X L, X, U 1 , V 1 , W 1 , X 1 , Y 1 , Z 1 , U 2 , V2 n and p are in this specification. Further definitions are provided in the embodiments described in this book. All combinations of embodiments provided are within the scope of this disclosure.

[0155] One reason, R 1 R is hydrogen. For one reason, 1 It is deuterium In one example, R 1 is cyano. In one example, R 1 , Yes, there is. One way of thinking about it is R 1 This is fluoro or chloro. In one embodiment, , R 1 is nitro. In one embodiment, R 1 is optionally substituted with one or more substituents Q Ta C 1-6 It is alkyl. In one example, R 1 is optionally substituted with one or more substituents Q It is methyl. In one example, R 1 It is methyl. In one example, R 1 C is a C which is optionally substituted with one or more substituents Q. 2-6 It is an alkenil. , R 1 C is a C which is optionally substituted with one or more substituents Q. 2-6 It is an alkynyl. In one embodiment, R 1 C is a C which is optionally substituted with one or more substituents Q. 3-10 It is a cycloalkyl. In Mr. R 1 C is a C which is optionally substituted with one or more substituents Q. 6-14 It is Ariel. A certain implementation In the following manner, R 1 C is a C which is optionally substituted with one or more substituents Q. 7-15 It is Aralkir. In this embodiment, R 1 This is a heteroaryl compound arbitrarily substituted with one or more substituents Q. By that means, R 1 This is a heterocycline arbitrarily substituted with one or more substituents Q.

[0156] One reason, R 2 is -C(O)OR 2a And here, R 2a This is defined herein As stated above, in one example, R 2 It is -C(O)OH. In one embodiment, R 2 is -C(O)OC 1-6 It is an alkyl group, where the alkyl group has one or more substituents Q. It is replaced with R 2 is -C(O)NR 2b R 2c And here, R 2b Reach biR 2c Each of these is as defined herein. In one embodiment, R 2 teeth,- C(O)NR 2b R 2c And here, R 2b and R 2c Each is independently (i) hydrogen; or (ii) each of them is 1 C is arbitrarily substituted with the above substituent Q. 1-6 It is alkyl or heteroaryl. By that means, R 2 is -C(O)NR 2b R 2c And here, R 2b and R 2c Each of them operates independently. (i) hydrogen; or (ii) methyl, ethyl, each of which is optionally substituted with one or more substituents Q. Or it is tetrazolyl. In one embodiment, R 2 is -C(O)NHR 2cAnd here , R 2c This is as defined herein. In one embodiment, R 2 is -C(O)NH R 2c And here, R 2c (i) hydrogen; or (ii) each of which is optionally substituted with one or more substituents Q C 1-6 It is alkyl or heteroaryl. In one embodiment, R 2 is -C (O)NHR 2c And here, R 2c (i) hydrogen; or (ii) each of them optionally has one or more substituents Q The substituted methyl, ethyl, or tetrazolyl is used. In one embodiment, R 2 These are -C(O)NH2, -C(O)NHCH3, -C(O)NHCH2CH2OH, or -C(O)NH (tetrazolyl). By that means, R 2 is -C(O)N(R 2b )OR 2c And here, R 2b and R 2c Each of these is a book. As defined in the specification. In one embodiment, R 2 is -C(O)N(R 2b )OR 2c in Yes, here, R 2b and R 2c Each is independently optionally substituted with hydrogen or one or more substituents Q. C 1-6 It is alkyl. In one example, R 2 is -C(O)NHOR 2c And here, R 2c teeth , as defined herein. In one embodiment, R 2 is -C(O)NHOR 2c in Yes, here, R 2cC is optionally substituted with hydrogen or one or more substituents Q. 1-6 It is alkyl In one embodiment, R 2 is -C(O)NHO-C 1-6 It is an alkyl, and here the alkyl is , optionally substituted with one or more substituents Q. In one embodiment, R 2 It is -C(O)NHOH Yes, there is. One way of thinking about it is R 2 This is a heteroaryl compound optionally substituted with one or more substituents Q. In one example, R 2 This is a monocyclic heterozygous compound optionally substituted with one or more substituents Q. It is aryl. In one example, R 2 This is a 6-member molecule optionally substituted with one or more substituents Q. It is a heteroaryl. In one embodiment, R 2 is optionally substituted with one or more substituents Q It is a 5-membered heteroaryl. In one embodiment, R 2 Each of them has one or more substituents Q It is a tetrazolyl or 1,2,4-oxadiazolyl that is optionally substituted with the above. In one embodiment In R 2 tetrazole-5-yl or 5-hydroxyl-1,2,4-oxadiazole-5- It is.

[0157] One reason, R 3 R is hydrogen. For one reason, 3 It is deuterium In one example, R 3 is cyano. In one example, R 3 , Yes, there is. One way of thinking about it is R 3 is fluoro. In one example, R 3 is, It is Rolo. In one embodiment, R 3is nitro. In one embodiment, R 3 teeth , C which is optionally substituted with one or more substituents Q 1-6 It is alkyl. In one example, R 3 teeth , is methyl. In one example, R 3 C is a C which is optionally substituted with one or more substituents Q. 2-6 It is an alkenil. 3 This is a C2 molecule optionally substituted with one or more substituents Q. -6 In one embodiment, R 3 is optionally substituted with one or more substituents Q C 3-10 It is a cycloalkyl. In one example, R 3 This can be any one substituent Q. Replaced C 6-14 It is aryl. In one example, R 3 is any one substituent Q Substituted C 7-15 It is an allatrical expression. 3 This is determined by one or more substituents Q. It is a heteroaryl compound that has been substituted with R. In one embodiment, R 3 is with one or more substituents Q These are heterocyclines with arbitrary substitutions.

[0158] One reason, R 3 is -C(O)R 1a And here, R 1a This is defined herein As stated above, in one example, R 3 is -C(O)OR 1a And here, R 1a This is As defined in the specification. In one embodiment, R 3 is -C(O)NR 1b R 1c and , here, R1b and R 1c Each of these is as defined herein. In one embodiment In R 3 -C(NR 1a )NR 1b R 1c And here, R 1a , R 1b , and R 1c Each of these is specified in this specification. As defined in R 3 is -OR 1a And here, R 1a This is as defined herein. In one embodiment, R 3 is methoxy In one example, R 3 is -OC(O)R 1a And here, R 1a This is defined herein. As stated above. In one embodiment, R 3 is -OC(O)OR 1a And here, R 1a teeth , as defined herein. In one embodiment, R 3 is -OC(O)NR 1b R 1c And here, R 1b and R 1c Each of these is as defined herein. In the following manner, R 3 -OC(NR 1a )NR 1b R 1c And here, R 1a , R 1b , and R 1c Each of them is, As defined herein. In one embodiment, R 3 -OS(O)R 1a and , here, R 1aThis is as defined herein. In one embodiment, R 3 teeth -OS(O)2R 1a And here, R 1a This is as defined herein. In the following manner, R 3 -OS(O)NR 1b R 1c And here, R 1b and R 1c Each of these is described herein. As defined. In one example, R 3 -OS(O)2NR 1b R 1c And here So, R 1b and R 1c These are as defined herein. In one embodiment , R 3 -NR 1b R 1c And here, R 1b and R 1c Each of these is defined herein as In one example, R 3 -NR 1a C(O)R 1d And here, R 1a and R 1d Each As defined herein. In one embodiment, R 3 -NR 1a C(O)OR 1 d And here, R 1a and R 1d These are as defined herein, respectively. In the manner of implementation, R 3 -NR 1a C(O)NR 1b R 1c And here, R 1a , R 1b , and R 1c Each , as defined herein. In one embodiment, R 3 -NR 1a C(NR 1d )NR 1b R 1c And here, R 1a , R 1b , R 1c , and R 1d Each of these is defined in this specification. That is the case. For one example, R 3 -NR 1a S(O)R 1d And here, R 1a and R 1d teeth, Each is as defined herein. In one embodiment, R 3 -NR 1a S(O)2 R 1d And here, R 1a and R 1d These are as defined herein. In this embodiment, R 3 -NR 1a S(O)NR 1b R 1c And here, R 1a , R 1b , and R 1c Each As defined herein. In one embodiment, R 3 -NR 1a S(O)2NR 1b R 1c And here, R 1a , R 1b , and R 1c Each of these is defined herein. In one example, R 3 -SR 1a And here, R 1a This is defined herein As is the case. In one embodiment, R 3 is -S(O)R 1aAnd here, R 1a is Honmyo As defined in the details. In one embodiment, R 3 is -S(O)2R 1a And this Here, R 1a This is as defined herein. In one embodiment, R 3 -S( O)NR 1b R 1c And here, R 1b and R 1c These are as defined herein. In one embodiment, R 3 is -S(O)2NR 1b R 1c And here, R 1b and R 1c Each of them is, As defined herein.

[0159] One reason, R 4 R is hydrogen. For one reason, 4 It is deuterium In one example, R 4 is cyano. In one example, R 4 , Yes, there is. One way of thinking about it is R 4 is fluoro. In one example, R 4 is, It is Rolo. In one embodiment, R 4 is nitro. In one embodiment, R 4 teeth , C which is optionally substituted with one or more substituents Q 1-6 It is alkyl. In one example, R 4 teeth , is methyl. In one example, R 4 C is a C which is optionally substituted with one or more substituents Q. 2-6 It is an alkenil. 4This is a C2 molecule optionally substituted with one or more substituents Q. -6 In one embodiment, R 4 is optionally substituted with one or more substituents Q C 3-10 It is a cycloalkyl. In one example, R 4 This can be any one substituent Q. Replaced C 6-14 It is aryl. In one example, R 4 is any one substituent Q Substituted C 7-15 It is an allatrical expression. 4 This is determined by one or more substituents Q. It is a heteroaryl compound that has been substituted with R. In one embodiment, R 4 is with one or more substituents Q These are heterocyclines with arbitrary substitutions.

[0160] One reason, R 4 is -C(O)R 1a And here, R 1a This is defined herein As stated above, in one example, R 4 is -C(O)OR 1a And here, R 1a This is As defined in the specification. In one embodiment, R 4 is -C(O)NR 1b R 1c and , here, R 1b and R 1c Each of these is as defined herein. In one embodiment In R 4 -C(NR 1a )NR 1b R 1c And here, R 1a , R 1b , and R 1c Each of these is specified in this specification. As defined in R4 is -OR 1a And here, R 1a This is as defined herein. In one embodiment, R 4 is methoxy In one example, R 4 is -OC(O)R 1a And here, R 1a This is defined herein. As stated above. In one embodiment, R 4 is -OC(O)OR 1a And here, R 1a teeth , as defined herein. In one embodiment, R 4 is -OC(O)NR 1b R 1c And here, R 1b and R 1c Each of these is as defined herein. In the following manner, R 4 -OC(NR 1a )NR 1b R 1c And here, R 1a , R 1b , and R 1c Each of them is, As defined herein. In one embodiment, R 4 -OS(O)R 1a and , here, R 1a This is as defined herein. In one embodiment, R 4 teeth -OS(O)2R 1a And here, R 1a This is as defined herein. In the following manner, R 4 -OS(O)NR 1b R 1c And here, R 1b and R 1c Each of these is described herein. As defined. In one example, R 4 -OS(O)2NR 1b R 1c And here So, R 1b and R 1c These are as defined herein. In one embodiment , R 4 -NR 1b R 1c And here, R 1b and R 1c Each of these is defined herein as In one example, R 4 -NR 1a C(O)R 1d And here, R 1a and R 1d Each As defined herein. In one embodiment, R 4 -NR 1a C(O)OR 1 d And here, R 1a and R 1d These are as defined herein, respectively. In the manner of implementation, R 4 -NR 1a C(O)NR 1b R 1c And here, R 1a , R 1b , and R 1c Each , as defined herein. In one embodiment, R 4 -NR 1a C(NR 1d )NR 1b R 1c And here, R 1a , R 1b , R 1c , and R 1d Each of these is defined in this specification. That is the case. For one example, R 4 -NR1a S(O)R 1d And here, R 1a and R 1d teeth, Each is as defined herein. In one embodiment, R 4 -NR 1a S(O)2 R 1d And here, R 1a and R 1d These are as defined herein. In this embodiment, R 4 -NR 1a S(O)NR 1b R 1c And here, R 1a , R 1b , and R 1c Each As defined herein. In one embodiment, R 4 -NR 1a S(O)2NR 1b R 1c And here, R 1a , R 1b , and R 1c Each of these is defined herein. In one example, R 4 -SR 1a And here, R 1a This is defined herein As is the case. In one embodiment, R 4 is -S(O)R 1a And here, R 1a is Honmyo As defined in the details. In one embodiment, R 4 is -S(O)2R 1a And this Here, R 1a This is as defined herein. In one embodiment, R 4 -S( O)NR 1b R 1c And here, R 1b and R1c These are as defined herein. In one embodiment, R 4 is -S(O)2NR 1b R 1c And here, R 1b and R 1c Each of them is, As defined herein.

[0161] One reason, R 5 R is hydrogen. For one reason, 5 It is deuterium In one example, R 5 is cyano. In one example, R 5 , Yes, there is. One way of thinking about it is R 5 is fluoro. In one example, R 5 is, It is Rolo. In one embodiment, R 5 is nitro. In one embodiment, R 5 teeth , C which is optionally substituted with one or more substituents Q 1-6 It is alkyl. In one example, R 5 teeth , is methyl. In one example, R 5 C is a C which is optionally substituted with one or more substituents Q. 2-6 It is an alkenil. 5 This is a C2 molecule optionally substituted with one or more substituents Q. -6 In one embodiment, R 5 is optionally substituted with one or more substituents Q C 3-10 It is a cycloalkyl. In one example, R 5 This can be any one substituent Q. Replaced C 6-14 It is aryl. In one example, R 5 is any one substituent Q Substituted C 7-15 It is an allatrical expression. 5 This is determined by one or more substituents Q. It is a heteroaryl compound that has been substituted with R. In one embodiment, R 5 is with one or more substituents Q These are heterocyclines with arbitrary substitutions.

[0162] One reason, R 5 is -C(O)R 1a And here, R 1a This is defined herein As stated above, in one example, R 5 is -C(O)OR 1a And here, R 1a This is As defined in the specification. In one embodiment, R 5 is -C(O)NR 1b R 1c and , here, R 1b and R 1c Each of these is as defined herein. In one embodiment In R 5 -C(NR 1a )NR 1b R 1c And here, R 1a , R 1b , and R 1c Each of these is specified in this specification. As defined in R 5 is -OR 1a And here, R 1a This is as defined herein. In one embodiment, R 5 is methoxy In one example, R 5 is -OC(O)R 1a And here, R 1a This is defined herein. As stated above. In one embodiment, R 5is -OC(O)OR 1a And here, R 1a teeth , as defined herein. In one embodiment, R 5 is -OC(O)NR 1b R 1c And here, R 1b and R 1c Each of these is as defined herein. In the following manner, R 5 -OC(NR 1a )NR 1b R 1c And here, R 1a , R 1b , and R 1c Each of them is, As defined herein. In one embodiment, R 5 -OS(O)R 1a and , here, R 1a This is as defined herein. In one embodiment, R 5 teeth -OS(O)2R 1a And here, R 1a This is as defined herein. In the following manner, R 5 -OS(O)NR 1b R 1c And here, R 1b and R 1c Each of these is described herein. As defined. In one example, R 5 -OS(O)2NR 1b R 1c And here So, R 1b and R 1c These are as defined herein. In one embodiment , R 5 -NR 1b R 1c And here, R 1b and R 1cEach of these is defined herein as In one example, R 5 -NR 1a C(O)R 1d And here, R 1a and R 1d Each As defined herein. In one embodiment, R 5 -NR 1a C(O)OR 1 d And here, R 1a and R 1d These are as defined herein, respectively. In the manner of implementation, R 5 -NR 1a C(O)NR 1b R 1c And here, R 1a , R 1b , and R 1c Each , as defined herein. In one embodiment, R 5 -NR 1a C(NR 1d )NR 1b R 1c And here, R 1a , R 1b , R 1c , and R 1d Each of these is defined in this specification. That is the case. For one example, R 5 -NR 1a S(O)R 1d And here, R 1a and R 1d teeth, Each is as defined herein. In one embodiment, R 5 -NR 1a S(O)2 R 1d And here, R 1a and R 1d These are as defined herein. In this embodiment, R 5 -NR 1a S(O)NR 1b R 1c And here, R 1a , R 1b , and R 1c Each As defined herein. In one embodiment, R 5 -NR 1a S(O)2NR 1b R 1c And here, R 1a , R 1b , and R 1c Each of these is defined herein. In one example, R 5 -SR 1a And here, R 1a This is defined herein As is the case. In one embodiment, R 5 is -S(O)R 1a And here, R 1a is Honmyo As defined in the details. In one embodiment, R 5 is -S(O)2R 1a And this Here, R 1a This is as defined herein. In one embodiment, R 5 -S( O)NR 1b R 1c And here, R 1b and R 1c These are as defined herein. In one embodiment, R 5 is -S(O)2NR 1b R 1c And here, R 1b and R 1c Each of them is, As defined herein.

[0163] One reason, R 6R is hydrogen. For one reason, 6 It is deuterium In one example, R 6 is cyano. In one example, R 6 , Yes, there is. One way of thinking about it is R 6 is fluoro. In one example, R 6 is, It is Rolo. In one embodiment, R 6 is nitro. In one embodiment, R 6 teeth , C which is optionally substituted with one or more substituents Q 1-6 It is alkyl. In one example, R 6 teeth , is methyl. In one example, R 6 C is a C which is optionally substituted with one or more substituents Q. 2-6 It is an alkenil. 6 This is a C2 molecule optionally substituted with one or more substituents Q. -6 In one embodiment, R 6 is optionally substituted with one or more substituents Q C 3-10 It is a cycloalkyl. In one example, R 6 This can be any one substituent Q. Replaced C 6-14 It is aryl. In one example, R 6 is any one substituent Q Substituted C 7-15 It is an allatrical expression. 6 This is determined by one or more substituents Q. It is a heteroaryl compound that has been substituted with R. In one embodiment, R 6 is with one or more substituents Q These are heterocyclines with arbitrary substitutions.

[0164] One reason, R 6 is -C(O)R 1aAnd here, R 1a This is defined herein As stated above, in one example, R 6 is -C(O)OR 1a And here, R 1a This is As defined in the specification. In one embodiment, R 6 is -C(O)NR 1b R 1c and , here, R 1b and R 1c Each of these is as defined herein. In one embodiment In R 6 -C(NR 1a )NR 1b R 1c And here, R 1a , R 1b , and R 1c Each of these is specified in this specification. As defined in R 6 is -OR 1a And here, R 1a This is as defined herein. In one embodiment, R 6 is methoxy In one example, R 6 is -OC(O)R 1a And here, R 1a This is defined herein. As stated above. In one embodiment, R 6 is -OC(O)OR 1a And here, R 1a teeth , as defined herein. In one embodiment, R 6 is -OC(O)NR 1b R 1c And here, R 1b and R 1c Each of these is as defined herein. In the following manner, R 6-OC(NR 1a )NR 1b R 1c And here, R 1a , R 1b , and R 1c Each of them is, As defined herein. In one embodiment, R 6 -OS(O)R 1a and , here, R 1a This is as defined herein. In one embodiment, R 6 teeth -OS(O)2R 1a And here, R 1a This is as defined herein. In the following manner, R 6 -OS(O)NR 1b R 1c And here, R 1b and R 1c Each of these is described herein. As defined. In one example, R 6 -OS(O)2NR 1b R 1c And here So, R 1b and R 1c These are as defined herein. In one embodiment , R 6 -NR 1b R 1c And here, R 1b and R 1c Each of these is defined herein as In one example, R 6 -NR 1a C(O)R 1d And here, R 1a and R 1d Each As defined herein. In one embodiment, R 6 -NR 1a C(O)OR 1 dAnd here, R 1a and R 1d These are as defined herein, respectively. In the manner of implementation, R 6 -NR 1a C(O)NR 1b R 1c And here, R 1a , R 1b , and R 1c Each , as defined herein. In one embodiment, R 6 -NR 1a C(NR 1d )NR 1b R 1c And here, R 1a , R 1b , R 1c , and R 1d Each of these is defined in this specification. That is the case. For one example, R 6 -NR 1a S(O)R 1d And here, R 1a and R 1d teeth, Each is as defined herein. In one embodiment, R 6 -NR 1a S(O)2 R 1d And here, R 1a and R 1d These are as defined herein. In this embodiment, R 6 -NR 1a S(O)NR 1b R 1c And here, R 1a , R 1b , and R 1c Each As defined herein. In one embodiment, R 6 -NR 1a S(O)2NR 1b R 1c And here, R1a , R 1b , and R 1c Each of these is defined herein. In one example, R 6 -SR 1a And here, R 1a This is defined herein As is the case. In one embodiment, R 6 is -S(O)R 1a And here, R 1a is Honmyo As defined in the details. In one embodiment, R 6 is -S(O)2R 1a And this Here, R 1a This is as defined herein. In one embodiment, R 6 -S( O)NR 1b R 1c And here, R 1b and R 1c These are as defined herein. In one embodiment, R 6 is -S(O)2NR 1b R 1c And here, R 1b and R 1c Each of them is, As defined herein.

[0165] One reason, R 7 It is deuterium. In one embodiment, R 7 is cyano Yes, there is. One way of thinking about it is R 7 This is a halo. In one embodiment, R 7 , Fluoro In one example, R 7 is chloroform. In one way, R 7 teeth, It is nitro. In one embodiment, R 7 C is a C which is optionally substituted with one or more substituents Q.1-6 a It is R. 7 is methyl. In one example, R 7 C is a C which is optionally substituted with one or more substituents Q. 2-6 It is an alkenil. In one example, R 7 C is a C which is optionally substituted with one or more substituents Q. 2-6 In one embodiment, it is alkinyl. , R 7 C is a C which is optionally substituted with one or more substituents Q. 3-10 It is a cycloalkyl group. In one embodiment In R 7 C is a C which is optionally substituted with one or more substituents Q. 6-14 It is an array. A certain implementation. In Mr. R 7 C is a C which is optionally substituted with one or more substituents Q. 7-15 It is Aralkil. In the manner of implementation, R 7 is a heteroaryl compound arbitrarily substituted with one or more substituents Q. In this embodiment, R 7 This is a heterocycline arbitrarily substituted with one or more substituents Q.

[0166] One reason, R 7 is -C(O)R 1a And here, R 1a This is defined herein As stated above, in one example, R 7 is -C(O)OR 1a And here, R 1a This is As defined in the specification. In one embodiment, R 7 is -C(O)NR 1b R 1c and , here, R 1b and R 1c Each of these is as defined herein. In one embodiment In R 7 -C(NR 1a )NR 1b R 1c And here, R 1a , R 1b , and R 1c Each of these is specified in this specification. As defined in R 7 is -OR 1a And here, R 1a This is as defined herein. In one embodiment, R 7 is methoxy In one example, R 7 is -OC(O)R 1a And here, R 1a This is defined herein. As stated above. In one embodiment, R 7 is -OC(O)OR 1a And here, R 1a teeth , as defined herein. In one embodiment, R 7 is -OC(O)NR 1b R 1c And here, R 1b and R 1c Each of these is as defined herein. In the following manner, R 7 -OC(NR 1a )NR 1b R 1c And here, R 1a , R 1b , and R 1c Each of them is, As defined herein. In one embodiment, R 7 -OS(O)R 1a and , here, R 1a This is as defined herein. In one embodiment, R 7 teeth -OS(O)2R 1a And here, R1a This is as defined herein. In the following manner, R 7 -OS(O)NR 1b R 1c And here, R 1b and R 1c Each of these is described herein. As defined. In one example, R 7 -OS(O)2NR 1b R 1c And here So, R 1b and R 1c These are as defined herein. In one embodiment , R 7 -NR 1b R 1c And here, R 1b and R 1c Each of these is defined herein as In one example, R 7 -NR 1a C(O)R 1d And here, R 1a and R 1d Each As defined herein. In one embodiment, R 7 -NR 1a C(O)OR 1 d And here, R 1a and R 1d These are as defined herein, respectively. In the manner of implementation, R 7 -NR 1a C(O)NR 1b R 1c And here, R 1a , R 1b , and R 1c Each , as defined herein. In one embodiment, R 7 -NR 1a C(NR 1d )NR 1b R 1c And here, R 1a , R 1b , R 1c , and R 1d Each of these is defined in this specification. That is the case. For one example, R 7 -NR 1a S(O)R 1d And here, R 1a and R 1d teeth, Each is as defined herein. In one embodiment, R 7 -NR 1a S(O)2 R 1d And here, R 1a and R 1d These are as defined herein. In this embodiment, R 7 -NR 1a S(O)NR 1b R 1c And here, R 1a , R 1b , and R 1c Each As defined herein. In one embodiment, R 7 -NR 1a S(O)2NR 1b R 1c And here, R 1a , R 1b , and R 1c Each of these is defined herein. In one example, R 7 -SR 1a And here, R 1a This is defined herein As is the case. In one embodiment, R 7 is -S(O)R 1a And here, R 1a is Honmyo As defined in the details. In one embodiment, R 7 is -S(O)2R1a And this Here, R 1a This is as defined herein. In one embodiment, R 7 -S( O)NR 1b R 1c And here, R 1b and R 1c These are as defined herein. In one embodiment, R 7 is -S(O)2NR 1b R 1c And here, R 1b and R 1c Each of them is, As defined herein.

[0167] One reason, R 2A is -OR 2a And here, R 2a This is defined herein As is the case. In one embodiment, R 2A is -OH. In one embodiment, R 2 A is, -OC 1-6 It is an alkyl group, where the alkyl group is optionally substituted with one or more substituents Q. In one way, R 2A -NR 2b R 2c And here, R 2b and R 2c Each , as defined herein. In one embodiment, R 2A -NR 2b R 2c dea Here, R 2b and R 2c Each is independently (i) hydrogen; or (ii) each of them has one or more substituents Q C is arbitrarily substituted. 1-6 It is alkyl or heteroaryl. In one embodiment R2A -NR 2b R 2c And here, R 2b and R 2c Each is independently (i) hydrogen; or (ii) so Each of these is optionally substituted with one or more substituents Q, such as methyl, ethyl, or tetrazoly In one embodiment, R 2A -NHR 2c And here, R 2c This is defined in this specification. As is stated. In one embodiment, R 2A -NHR 2c And here, R 2c teeth (i) hydrogen; or (ii) C, each of which is optionally substituted with one or more substituents Q. 1-6 Alkyl k is a heteroaryl. In one embodiment, R 2A -NHR 2c And here, R 2c (i) hydrogen; or (ii) each of which is optionally substituted with one or more substituents Q, methyl, eth It is either ru or tetrazolyl. In one embodiment, R 2A -NH2, -NHCH3, -NHCH It is 2CH2OH or -NH (tetrazolyl). In one embodiment, R 2A is -N(R 2b )OR 2c in Yes, here, R 2b and R 2c Each of these is defined herein. In Mr. R 2A is -N(R 2b )OR 2c And here, R 2b and R 2c Each of them independently uses hydrogen or C is optionally substituted with one or more substituents Q. 1-6 It is alkyl. In one example, R2A teeth , -NHOR 2c And here, R 2c This is as defined herein. In one embodiment In R 2A is -NHO-C 1-6 It is an alkyl group, where the alkyl group has one or more substituents Q. It is arbitrarily substituted. In one embodiment, R 2A It is -NHOH.

[0168] One reason, R 7a R is hydrogen. For one reason, 7a is deuterium Yes, there is. One way of thinking about it is R 7a is cyano. In one example, R 7a , In one example, R 7a is fluoro. In one example, R 7a is chloroform. In one way, R 7a It is nitro. In one embodiment, R 7a C is a C which is optionally substituted with one or more substituents Q. 1-6 It is alkyl. In one embodiment And, R 7a is methyl. In one example, R 7a This can be any one substituent Q. Replaced C 2-6 It is an alkenil. 7a Q is any one or more substituents Q C replaced 2-6 In one embodiment, R 7a is with one or more substituents Q Arbitrarily substituted C 3-10 It is a cycloalkyl. In one example, R 7a is 1 or more C arbitrarily substituted with substituent Q 6-14It is aryl. In one example, R 7a is 1 or more C arbitrarily substituted with substituent Q 7-15 It is an allatrical expression. 7a is, 1 The above is a heteroaryl compound optionally substituted with substituent Q. In one embodiment, R 7a teeth It is a heterocyclyl arbitrarily substituted with one or more substituents Q.

[0169] One reason, R 7a is -C(O)R 1a And here, R 1a This is defined herein As stated above, in one example, R 7a is -C(O)OR 1a And here, R 1a teeth, As defined herein. In one embodiment, R 7a is -C(O)NR 1b R 1c in Yes, here, R 1b and R 1c Each of these is defined herein. In Mr. R 7a -C(NR 1a )NR 1b R 1c And here, R 1a , R 1b , and R 1c Each of these is a book. As defined in the specification. In one embodiment, R 7a is -OR 1a And here So, R 1a This is as defined herein. In one embodiment, R 7a , Met It is Kishi. In one example, R 7a is -OC(O)R 1a And here, R 1a This is the details As defined in the book. In one embodiment, R 7a is -OC(O)OR 1a And this Here, R 1a This is as defined herein. In one embodiment, R 7a is, -O C(O)NR 1b R 1c And here, R 1b and R 1c Each of these is defined herein. In one example, R 7a -OC(NR 1a )NR 1b R 1c And here, R 1a , R 1b , and R 1c Each of these is as defined herein. In one embodiment, R 7a -OS (O)R 1a And here, R 1a This is as defined herein. In one embodiment, In R 7a is -OS(O)2R 1a And here, R 1a This is as defined herein. In one example, R 7a -OS(O)NR 1b R 1c And here, R 1b and R 1c Each , as defined herein. In one embodiment, R 7a -OS(O)2NR 1b R 1 c And here, R 1b and R 1c These are as defined herein, respectively. In the manner of implementation, R 7a -NR1b R 1c And here, R 1b and R 1c Each of these is defined in this specification. As is stated. In one embodiment, R 7a -NR 1a C(O)R 1d And here , R 1a and R 1d These are as defined herein. In one embodiment, R 7a -NR 1a C(O)OR 1d And here, R 1a and R 1d Each of these is defined herein. That's right. In one example, R 7a -NR 1a C(O)NR 1b R 1c And here, R 1a , R 1 b , and R 1c Each of these is as defined herein. In one embodiment, R 7 a -NR 1a C(NR 1d )NR 1b R 1c And here, R 1a , R 1b , R 1c , and R 1d Each of these is specified in this specification. As defined in R 7a -NR 1a S(O)R 1d And this Here, R 1a and R 1d These are as defined herein, respectively. In one embodiment, R 7a -NR 1a S(O)2R 1dAnd here, R 1a and R 1d Each of these is defined herein. As is the case. In one embodiment, R 7a -NR 1a S(O)NR 1b R 1c And here, R 1a , R 1b , and R 1c These are as defined herein. In one embodiment , R 7a -NR 1a S(O)2NR 1b R 1c And here, R 1a , R 1b , and R 1c Each of these is described herein. As defined. In one example, R 7a -SR 1a And here, R 1a This is as defined herein. In one embodiment, R 7a is -S(O)R 1a in Yes, here, R 1a This is as defined herein. In one embodiment, R 7a is -S(O)2R 1a And here, R 1a This is as defined herein. In the manner of implementation, R 7a is -S(O)NR 1b R 1c And here, R 1b and R 1c Each of these is specified in this specification. As defined in R 7a is -S(O)2NR 1b R 1c And this Here, R 1b and R 1cThese are as defined herein.

[0170] One reason, R A C is a C which is optionally substituted with one or more substituents Q. 6-14 At Ariren Yes, there is. One way of thinking about it is R A is a phenylene arbitrarily substituted with one or more substituents Q. In one example, R A This is a phen-1,2-diyx optionally substituted with one or more substituents Q. In one embodiment, R A This is phen-1,3, which is optionally substituted with one or more substituents Q. -It is Zill. In one embodiment, R A This is a phenotype that is optionally substituted with one or more substituents Q. It is n-1,4-diyl. In one embodiment, R A Each of them has one or more substituents Q, which is arbitrary. It is phen-1,3-diyl or phen-1,4-diyl that is substituted for it. In one embodiment, R A Each of them is either a halo or -OC 1-6 Phene-1,3-diys that are optionally substituted with alkyl groups It is either ru or fen-1,4-diyl. In one embodiment, R A Each of them is fluoro , phen-1,3-diyl or phen-1,4-diyl optionally substituted with chloro or methoxy In one embodiment, R A is Fen-1,3-Jiil, Fen-1,4-Jiil, 2-K These are lolofen-1,4-diyl and 2-methoxyphen-1,4-diyl. In one embodiment, , R A is a naphthylene optionally substituted with one or more substituents Q. In one embodiment, R A is a heteroarylene optionally substituted with one or more substituents Q. In one embodiment, R A This is a monocyclic heteroarylene arbitrarily substituted with one or more substituents Q. In one implementation In the following manner, R A This is a 5-membered heteroarylene that is arbitrarily substituted with one or more substituents Q. One reason, R A This is a 6-membered heteroarylene optionally substituted with one or more substituents Q. In one example, R A This is a pyridylene optionally substituted with one or more substituents Q. Yes, there is. One way of thinking about it is R A This is a pyrido-2,5-di compound optionally substituted with one or more substituents Q. It is. In one example, R A This is pyridylene or methylpyridylene. One reason, R A is pyrido-2,5-diyl or 3-methylpyrido-2,5-diyl In one example, R A This is a bicyclic heteroali which is optionally substituted with one or more substituents Q. It is -len.

[0171] One reason, R B C is a C which is optionally substituted with one or more substituents Q. 6-14 It's Ariel In one example, R B This is a monocyclic C atom optionally substituted with one or more substituents Q. 6-14 Ant It is. In one example, R B is a phenyl compound optionally substituted with one or more substituents Q. In one example, R B Each of them is (i) bromo, chloro, fluoro, and (ii) 1 or more substituents Q a C arbitrarily replaced by 1-6 Alkyl; and (iii)-OR a and -C (O)Ra (Here, each R a (as defined herein) are independently selected It is a phenyl molecule optionally substituted with one, two, or three substituents Q. In one embodiment, R B Each of these is bromo, fluoro, cyano, methyl, trifluoromethyl, ethinomethyl. One, two, or three substitutions independently selected from propyl, methoxy, and formyl It is a phenyl compound optionally substituted with group Q. In one embodiment, R B Each of them is, Romo, fluoro, cyano, methyl, trifluoromethyl, ethyl, propyl, and methoxymethyl It is optionally substituted with one, two, or three substituents Q independently selected from siphenyl. In one embodiment, R B These are phenyl, bromophenyl, fluorophenyl, and cyano Phenyl, methylphenyl, trifluoromethylphenyl, ethylphenyl, propylphenyl Phenyl, Methoxyphenyl, Formylphenyl, Bromo-Fluorophenyl, Difluoro It is phenyl or trifluorophenyl. In one embodiment, R B Phenyle, Bromophenyl, fluorophenyl, cyanophenyl, methylphenyl, trifluorophenyl Tylphenyl, ethylphenyl, propylphenyl, methoxyphenyl, bromo-fluorinated The compounds are fluorophenyl, difluorophenyl, or trifluorophenyl. In one embodiment, And, R B phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, 3- Cyanophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl , 4-trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-meth Xyphenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl The compounds are 2,4-difluorophenyl or 2,4,5-trifluorophenyl. In one embodiment, In R B These are phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, 3-Cyanophenyl, 3-Methylphenyl, 4-Methylphenyl, 3-Trifluoromethylphenyl L, 4-trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methylphenyl Toxyphenyl, 4-methoxyphenyl, 2-bromo-4-fluorophenyl, 2,4-difluoro It is phenyl or 2,4,5-trifluorophenyl.

[0172] One reason, R B This is a bicyclic C atom optionally substituted with one or more substituents Q. 6-14 Ally In one embodiment, R B This is a naphthyl molecule optionally substituted with one or more substituents Q. Yes, there is. One way of thinking about it is R B This is naphthal-1-yl, optionally substituted with one or more substituents Q. In one example, R B This is a naphtha-2-I that is optionally substituted with one or more substituents Q. It is.

[0173] One reason, R B is a heteroaryl compound that is arbitrarily substituted with one or more substituents Q. In one example, R B This is a monocyclic heteroali which is optionally substituted with one or more substituents Q. It is. In one example, R B This is a 5-membered heterozygous compound optionally substituted with one or more substituents Q. It is a lowaryl. In one embodiment, R B6 are optionally substituted with one or more substituents Q. It is a heteroaryl compound. In one embodiment, R B is arbitrarily substituted with one or more substituents Q It is a pyridyl. In one example, R B is fluoropyridyl or fluoro-meth It is chilpyridyl. In one embodiment, R B is 2-fluoropyrido-5-yl or 2-fluoro It is ruoro-3-methylpyrido-5-yl.

[0174] One reason, R B This is a bicyclic heteroary which is optionally substituted with one or more substituents Q. In one embodiment, R B This is a 5,6-condensed hematopoietic compound optionally substituted with one or more substituents Q. It is a terrorist aryl. In one example, R B is optionally substituted with one or more substituents Q It is a 6,6-condensed heteroaryl. In one embodiment, R B is any one substituent Q It is a substituted quinolinyl. In one embodiment, R B This can be any one substituent Q. It is the quinoline-5-yl that has been replaced.

[0175] One reason, R B These are phenyl, bromophenyl, fluorophenyl, and cyano Phenyl, methylphenyl, trifluoromethylphenyl, ethylphenyl, propylphenyl Phenyl, Methoxyphenyl, Formylphenyl, Bromo-Fluorophenyl, Difluoro Phenyl, trifluorophenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl It is zill or quinolinyl. In one embodiment, R B , is phenyl, 3-bromophenic Lu, 4-bromophenyl, 4-fluorophenyl, 3-cyanophenyl, 3-methylphenyl, 4- Methylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4- Isopropylphenyl, 4-Isopropylphenyl, 3-Methoxyphenyl, 4-Methoxyphenyl, 4- Formylphenyl, 2-bromo-4-fluorophenyl, 2,4-difluorophenyl, 2,4,5- Lifluorophenyl, naphthal-2-yl, 2-fluoropyrido-5-yl, 2-fluoro-3-methyl- It is pyrido-5-yl or quinoline-5-yl.

[0176] One reason, R X R is hydrogen. For one reason, X is 1 or more placements C arbitrarily substituted with substitution base Q 1-6 It is alkyl. In one example, R X is 1 or more placements These are methyl, ethyl, or propyl, each arbitrarily substituted with substitution group Q. In one embodiment, In R X These are methyl, ethyl, 2-hydroxyethyl, or n-propyl. In the following manner, R X C is a C which is optionally substituted with one or more substituents Q. 2-6 It is Alkenil. In the manner of implementation, R X C is a C which is optionally substituted with one or more substituents Q. 2-6 It is alkinyl. In this embodiment, R X C is a C which is optionally substituted with one or more substituents Q. 3-10 Cycloalkyl In one example, R X C is a C which is optionally substituted with one or more substituents Q. 6-14 In Arley Yes, there is. One way of thinking about it is R X is a phenyl compound optionally substituted with one or more substituents Q. . In certain embodiments, R X is phenyl, fluorophenyl, or formylphenyl . In certain embodiments, R X is phenyl, 4-fluorophenyl, or 4-formylp henyl. In certain embodiments, R X is C 7-15 aralkyl optionally substituted with one or more substituents Q X . In certain embodiments, R is benzyl optionally substituted with one or more substituents Q X . In certain embodiments, R is heteroaryl optionally substituted with one or more substituents Q<{ X . In certain embodiments, R is heterocyclyl optionally substituted with one or more substituents Q<{ <{

[0177] <{ . In certain embodiments, when X is -N(R X )-, R B and R X together with the N atom to which they are attached form a heteroaryl or he terocyclyl each optionally substituted with one or more substituents Q X . In certain embodiments, when X is -N(R B ) and R X are together with the N atom to which they are attached form a heteroaryl optionally substituted with one or more substituents Q X . In certain embodiments, when X is -N(R B and R X are, together with the N atom to which they are attached, a monocyclic heteroaryl optionally substituted with one or more substituents Q formed. In certain embodiments, when X is -N(R )-, R X and R B and R X are, together with the atom to which they are attached, Together with the N atom, it forms a 5-membered heteroaryl nucleotide optionally substituted with one or more substituents Q. In one embodiment, X is -N(R X )- When R B and R X N is the one that they are joined together Pyrrolyl or imidazo atoms, each optionally substituted with one or more substituents Q. Forms a rill. In one embodiment, X is -N(R X )- When R B and R X Those Together with the bonded N atom, it forms pyrrole-1-yl or 2-aminoimidazole-1-yl. In one embodiment, X is -N(R X )- When R B and R X They are combined Together with the N atom, it forms a 6-membered heteroaryl compound optionally substituted with one or more substituents Q. In this embodiment, X is -N(R X )- When R B and R X The N atoms to which they are bonded Together with it, it forms a bicyclic heteroaryl which is optionally substituted with one or more substituents Q. In the embodiment, X is -N(R X )- When R B and R X The N atom to which they are bonded and In addition, an indolyl is formed which is optionally substituted with one or more substituents Q. In one embodiment , X is -N(R X )- When R B and R X This involves one or more atoms, along with the N atom to which they are bonded. It forms a heterocycline arbitrarily substituted with substitution group Q. In one embodiment, X is -N(R X ) -When R Band R X These are any with one or more substituents Q together with the N atom to which they are bonded. It forms a monocyclic heterocycline that is substituted with -N(R X )-dea When R B and R X Each of them, along with the N atom to which they are bonded, has one or more substituent Q It forms a 5 or 6-membered heterocycline which is optionally substituted. In one embodiment, X ga-N(R X )- When R B and R X Each of them, along with the N atom to which they are bonded, is 1 Pyrrolidinyl, piperidinyl, or morpholinyl, which are optionally substituted with the above substituent Q. Forms a . In one embodiment, X is -N(R X )- When R B and R X They are connected Together with the bonded N atom, pyrrolidine-1-yl, piperidine-1-yl, or 4-morpholine 4-il is formed. In one embodiment, X is -N(R X )- When R B and R X Those A bicyclic heterocycline to which the N atom is bonded is optionally substituted with one or more substituents Q. Forms a circle.

[0178] In one embodiment, L is a C optionally substituted with one or more substituents Q. 1-6 Alkilen In one embodiment, each of L is optionally substituted with one or more substituents Q. It is methylene, ethylene, or propylene. In one embodiment, L is -(CH2) p -in Yes, where p is an integer of 1, 2, 3, or 4. In one embodiment, L is -(CH2) p -where p is an integer of 1, 2, or 3. In one embodiment, L is -(CH2 ) p -where p is an integer of 1 or 2. In one embodiment, L is -CH2CH2- In one embodiment, L is -CH2-. In one embodiment, L is 1 or greater. C arbitrarily substituted with substituent Q 2-6 It is an alkenylene. In one embodiment, L is 1 The ethenylene is optionally substituted with the substituent Q described above. In one embodiment, L is 1 or This is an ethene-1,2-diyl optionally substituted with the substituent Q shown above. In one embodiment, L is , is (E)-ethen-1,2-diyl. In one embodiment, L is (Z)-ethen-1,2-diyl In one embodiment, L is a C atom optionally substituted with one or more substituents Q. 3-10 Cycloa It is a lukilen. In one embodiment, L is a hete which is optionally substituted with one or more substituents Q. It is rosicrylene.

[0179] In one embodiment, X is -O-. In another embodiment, X is -NR X -and, Here, R X This is as defined herein. In one embodiment, X is -NH -is. In one embodiment, X is -S-. In one embodiment, X is -S(O)- In one embodiment, X is -S(O)2-.

[0180] In one statement, U 1 is C. In one example, U 1 It is N. In this embodiment, U 1 -CR 7a= and here, R 7a This is defined in this specification as This is the case. In one example, U 1 In one embodiment, U 1 -NR 7b -and here, R 7b This is as defined herein. In a certain embodiment, U 1 is -O-. In one embodiment, U 1 It is -S-.

[0181] For one reason, V 1 is C. For one reason, V 1 It is N. For this reason, V 1 -CR 7a = and here, R 7a This is defined in this specification as For one reason, V 1 In one embodiment, V 1 -NR 7b -and here, R 7b This is as defined herein. In a certain embodiment, V 1 is -O-. In one embodiment, V 1 It is -S-.

[0182] In one embodiment, W 1 is C. In one embodiment, W 1 It is N. In one embodiment, W 1 -CR 7a = and here, R 7a This is defined in this specification as In one example, W 1 In one embodiment, W 1 -NR 7b -and here, R 7b This is as defined herein. In a certain embodiment, W 1 is -O-. In one embodiment, W 1 It is -S-.

[0183] For one reason, X 1 In one example, X 1 It is N. In this embodiment, X 1 -CR 7a = and here, R 7a This is defined in this specification as In one example, X 1 In one embodiment, X 1 -NR 7b -and here, R 7b This is as defined herein. In a certain embodiment, X 1 is -O-. In one embodiment, X 1 It is -S-.

[0184] In one embodiment, Y 1 is C. For one reason, Y 1 It is N. In this embodiment, Y 1 Y is a combination. For one reason, 1 -CR 7a = and this Here, R 7a This is as defined herein. In one embodiment, Y 1 -N= In one embodiment, Y 1 -NR 7b -and here, R 7b This is defined in this specification. As stated above, in one embodiment, Y 1 It is -O-. In one embodiment So, Y 1 It is -S-.

[0185] A certain appeal, Z 1 In one presentation, Z 1 It is N.

[0186] In one statement, U 2 In one embodiment, U 2 It is -O-.

[0187] For one reason, V 2 In one embodiment, V 2 It is -O-. For one reason, V 2 The equation is -C(OH)=.

[0188] In one statement, U 2 and V 2 Each of these is -N=. In one embodiment, U 2 teeth , -O- and V 2 The equation is -C(OH)=.

[0189] In one embodiment, n is an integer of 0. In another embodiment, n is an integer of 1. Yes. In one embodiment, n is an integer of 2. In one embodiment, n is an integer of 3. It is a number. In one example, n is an integer equal to 4.

[0190] In one embodiment, p is an integer of 1. In another embodiment, p is an integer of 2. Yes. In one embodiment, p is an integer of 3. In one embodiment, p is an integer of 4. It is a number.

[0191] In one embodiment, the following compounds are provided herein: 2-[(1Z)-5-fluoro-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-indene-3- A1 yl acetate; 2-[(1Z)-5-fluoro-1-{[4-(4-methoxyphenoxy)phenyl]methylidene}-2-methyl-1H- Inden-3-yl acetate A2; 2-[(1Z)-1-({2-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}methylidene)-5- Fluoro-2-methyl-1H-inden-3-yl]acetic acid A3; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(4-methylphenoxy)phenyl]methylidene}-1H- [Lendene-3-yl]acetic acid A4; 2-[(1Z)-5-fluoro-2-methyl-1-({4-[4-(propan-2-yl)phenoxy]phenyl}methyl Den)-1H-Inden-3-yl]acetic acid A5; 2-[(1Z)-1-{[4-(4-bromophenoxy)phenyl]methylidene}-5-fluoro-2-methyl-1H- [Hendene-3-yl]acetic acid A6; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(3-methylphenoxy)phenyl]methylidene}-1H- [Denden-3-yl]acetic acid A7; 2-[(1Z)-1-{[4-(3-cyanophenoxy)phenyl]methylidene}-5-fluoro-2-methyl-1H- [Denden-3-yl]acetic acid A8; (Z)-2-(5-fluoro-2-methyl-1-(4-(3-(trifluoromethyl)phenoxy)benzylidene)- 1H-Inden-3-yl)acetic acid A9; 2-[(1Z)-1-{[4-(4-ethylphenoxy)phenyl]methylidene}-5-fluoro-2-methyl-1H- [Nden-3-yl]acetic acid A10; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H- Inden-3-yl acetate A11; 2-[(1Z)-1-{[2-chloro-4-(4-methoxyphenoxy)phenyl]methylidene}-5-fluoro-2- Methyl-1H-inden-3-yl]acetate A12; 2-[(1Z)-5-fluoro-1-({2-methoxy-4-[4-(propan-2-yl)phenoxy]phenyl}-methyl [Cylidene]-2-methyl-1H-inden-3-yl]acetic acid A13; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(naphthalene-2-yloxy)phenyl]methylidene}- 1H-Inden-3-yl]acetic acid A14; 2-[(1Z)-1-({2-chloro-4-[4-(propan-2-yl)phenoxy]phenyl}methylidene)-5-f Luoro-2-methyl-1H-inden-3-yl]acetate A15; 2-[(1Z)-1-{[4-(2,4-difluorophenoxy)phenyl]methylidene}-5-fluoro-2-methyl -1H-Inden-3-yl]acetic acid A16; 2-[(1Z)-1-{[4-(2-bromo-4-fluorophenoxy)phenyl]methylidene}-5-fluoro-2- Methyl-1H-inden-3-yl]acetic acid A17; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(2,4,5-trifluorophenoxy)phenyl]methyl Den-1H-Inden-3-yl]acetic acid A18; 3-[(1Z)-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H-indene-3- Il-propanoate A19; 2-[(1Z)-5-fluoro-1-({4-[(6-fluoropyridine-3-yl)oxy]phenyl}methylidene) -2-methyl-1H-inden-3-yl]acetic acid A20; 2-[(1Z)-5-fluoro-1-({4-[(6-fluoro-5-methylpyridine-3-yl)oxy]phenyl}- Methylidene)-2-methyl-1H-inden-3-yl]acetate A21; (Z)-2-(5-fluoro-2-methyl-1-(4-(quinoline-5-yloxy)benzylidene)-1H-indene A22-3-yl acetate; 2-[(1Z)-5-fluoro-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-indene-3- Il-N-hydroxyacetamide A23; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H- Inden-3-yl]-N-hydroxyacetamide A24; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H- Inden-3-yl]acetamide A25; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H- Inden-3-yl]-N-methylacetamide A26; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H- Inden-3-yl]-N-(2-hydroxyethyl)acetamide A27; (Z)-2-(5-fluoro-2-methyl-1-(4-phenoxybenzylidene)-1H-inden-3-yl)-N-(1 H-tetrazol-5-yl)acetamide A28; (2E)-3-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl Lu-1H-inden-3-yl]prop-2-enoic acid A61; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorobenzenesulfonyl)phenyl]methylidene}-2-methyl [Tyl-1H-inden-3-yl]acetate A62; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorobenzenesulfinyl)phenyl]methylidene}-2- Methyl-1H-inden-3-yl]acetic acid A63; 2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenyl)sulfanyl]phenyl}methylidene)- 2-methyl-1H-inden-3-yl]acetic acid A64; 2-[(1Z)-5-fluoro-1-{[6-(4-fluorophenoxy)pyridine-3-yl]methylidene}-2-methyl [Tyl-1H-inden-3-yl]acetic acid A65; 2-[(1Z)-5-fluoro-1-{[6-(4-fluorophenoxy)-5-methylpyridine-3-yl]methylide [N]-2-methyl-1H-inden-3-yl]acetic acid A66; (2E)-4-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl Lu-1H-inden-3-yl]buta-2-enoic acid A67; 2-[(1Z)-4,5-difluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl -1H-Inden-3-yl]acetic acid A68; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2,4-dimethyl -1H-Inden-3-yl]acetic acid A69; (2E)-3-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl Lu-1H-inden-3-yl]-N-hydroxypropane-2-enamide A76; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorobenzenesulfonyl)phenyl]methylidene}-2-methyl [Tyl-1H-inden-3-yl]-N-hydroxyacetamide A77; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorobenzenesulfinyl)phenyl]methylidene}-2- Methyl-1H-inden-3-yl]-N-hydroxyacetamide A78; 2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenyl)sulfanyl]phenyl}methylidene)- 2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A79; 2-[(1Z)-5-fluoro-1-{[6-(4-fluorophenoxy)pyridine-3-yl]methylidene}-2-methyl [Tyl-1H-inden-3-yl]-N-hydroxyacetamide A80; 2-[(1Z)-5-fluoro-1-{[6-(4-fluorophenoxy)-5-methylpyridine-3-yl]methylide [N-2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A81; (2E)-4-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl Lu-1H-inden-3-yl]-N-hydroxybuta-2-enamide A82; 2-[(1Z)-4,5-difluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl -1H-inden-3-yl]-N-hydroxyacetamide A83; or 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2,4-dimethyl -1H-Inden-3-yl]-N-hydroxyacetamide A84; or these tautomers, mixtures of two or more tautomers, or isotopic variants; or this These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

[0192] In another embodiment, the following compounds are provided herein: 2-[(1Z)-5-fluoro-2-methyl-1-({4-[methyl(phenyl)amino]phenyl}methylidene)-1 H-Inden-3-yl]acetate A29; 2-[(1Z)-1-({4-[benzyl(4-fluorophenyl)amino]phenyl}methylidene)-5-fluorine [L-2-methyl-1H-inden-3-yl]acetic acid A30; 2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenyl)(methyl)amino]phenyl}methylidene )-2-methyl-1H-inden-3-yl]acetic acid A31; 2-[(1Z)-1-({4-[ethyl(4-fluorophenyl)amino]phenyl}methylidene)-5-fluoro- 2-methyl-1H-inden-3-yl]acetate A32; 2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenyl)(propyl)amino]phenyl}methylide (n)-2-methyl-1H-inden-3-yl]acetic acid A33; 2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenyl)(2-hydroxyethyl)amino]phen [L-methylidene)-2-methyl-1H-inden-3-yl]acetic acid A34; 2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenyl)(4-formylphenyl)amino]phen [L-methylidene)-2-methyl-1H-inden-3-yl]acetic acid A35; 2-[(1Z)-5-fluoro-1-({4-[(4-formylphenyl)(phenyl)amino]phenyl}methyl (n)-2-methyl-1H-inden-3-yl]acetic acid A36; 2-[(1Z)-5-fluoro-2-methyl-1-({4-[methyl(phenyl)amino]phenyl}methylidene)-1 H-Inden-3-yl]-N-hydroxyacetamide A37; 2-[(1Z)-1-({4-[benzyl(4-fluorophenyl)amino]phenyl}methylidene)-5-fluorine [L-2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A38; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(morpholine-4-yl)phenyl]methylidene}-1H- [Nden-3-yl]acetic acid A55; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(piperidine-1-yl)phenyl]methylidene}-1H- [Denden-3-yl]acetic acid A56; 2-[(1Z)-5-fluoro-1-{[4-(1H-indole-1-yl)phenyl]methylidene}-2-methyl-1H- Inden-3-yl acetate A57; 2-[(1Z)-1-{[4-(2-amino-1H-imidazole-1-yl)phenyl]methylidene}-5-fluoro-2 -methyl-1H-inden-3-yl]acetic acid A58; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(pyrrolidine-1-yl)phenyl]methylidene}-1H- [Nden-3-yl]acetic acid A59; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(1H-pyrrole-1-yl)phenyl]methylidene}-1H- [(1Z)-5-fluoro-2-methyl-1-{[(morpholin-4-yl)acetic acid A60; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(morpholin-4-yl)acetic acid [nyl]methylidene}-1H-inden-3-yl]-N-hydroxyacetamide A70; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(piperidine-1-yl)phenyl]methylidene}-1H- [Nden-3-yl]-N-hydroxyacetamide A71; 2-[(1Z)-5-fluoro-1-{[4-(1H-indole-1-yl)phenyl]methylidene}-2-methyl-1H- Inden-3-yl]-N-hydroxyacetamide A72; 2-[(1Z)-1-{[4-(2-amino-1H-imidazole-1-yl)phenyl]methylidene}-5-fluoro-2 -methyl-1H-inden-3-yl]-N-hydroxyacetamide A73; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(pyrrolidine-1-yl)phenyl]methylidene}-1H- [Nden-3-yl]-N-hydroxyacetamide A74; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(1H-pyrrole-1-yl)phenyl]methylidene}-1H- [Nden-3-yl]-N-hydroxyacetamide A75; or 2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenyl)(2-hydroxyethyl)amino]phen (L)-methylidene)-2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A85; or these tautomers, mixtures of two or more tautomers, or isotopic variants; or this These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

[0193] In yet another embodiment, the following compounds are provided herein: 5-{[(1Z)-2-methyl-1-[(3-phenoxyphenyl)methylidene]-1H-inden-3-yl]methyl }-1H-1,2,3,4-tetrazole A39; 5-{[(1Z)-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-inden-3-yl]methyl }-1H-1,2,3,4-tetrazole A40; 5-{2-[(1Z)-2-methyl-1-{[4-(4-methylphenoxy)phenyl]methylidene}-1H-indene-3 -yl]ethyl}-1H-1,2,3,4-tetrazol A41; 5-{2-[(1Z)-1-{[4-(4-bromophenoxy)phenyl]methylidene}-2-methyl-1H-indene-3 -yl]ethyl}-1H-1,2,3,4-tetrazol A42; 5-{2-[(1Z)-2-methyl-1-({4-[4-(propan-2-yl)phenoxy]phenyl}methylidene)-1H [-Indene-3-yl]ethyl}-1H-1,2,3,4-tetrazol A43; 5-{2-[(1Z)-1-{[4-(4-methoxyphenoxy)phenyl]methylidene}-2-methyl-1H-indene [-3-yl]ethyl}-1H-1,2,3,4-tetrazol A44; 5-{2-[(1Z)-2-methyl-1-({4-[4-(trifluoromethyl)phenoxy]phenyl}methylidene) [-1H-Indene-3-yl]ethyl}-1H-1,2,3,4-tetrazol A45; 5-{2-[(1Z)-2-methyl-1-{[4-(3-methylphenoxy)phenyl]methylidene}-1H-indene-3 -yl]ethyl}-1H-1,2,3,4-tetrazol A46; 3-(4-{[(1Z)-2-methyl-3-[2-(1H-1,2,3,4-tetrazole-5-yl)ethyl]-1H-indene-1- Iridene methyl phenoxy benzonitrile A47; 5-{2-[(1Z)-1-{[4-(3-methoxyphenoxy)phenyl]methylidene}-2-methyl-1H-indene [-3-yl]ethyl}-1H-1,2,3,4-tetrazol A48; 5-{2-[(1Z)-1-{[4-(3-bromophenoxy)phenyl]methylidene}-2-methyl-1H-indene-3 -yl]ethyl}-1H-1,2,3,4-tetrazol A49; 5-{2-[(1Z)-2-methyl-1-({4-[3-(trifluoromethyl)phenoxy]phenyl}methylidene) [-1H-Indene-3-yl]ethyl}-1H-1,2,3,4-tetrazol A50; 5-{2-[(1Z)-2-methyl-1-{[4-(naphthalene-2-yloxy)phenyl]methylidene}-1H-yne Den-3-yl]ethyl}-1H-1,2,3,4-tetrazol A51; or (Z)-3-((2-methyl-1-(4-phenoxybenzylidene)-1H-inden-3-yl)methyl)-1,2,4- Oxadiazole-5(4H)-one A52; or these tautomers, mixtures of two or more tautomers, or isotopic variants; or this These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

[0194] In yet another embodiment, provided herein is 5-{[(1E)-1-[(4-phenoxy Phenyl)methylidene]-1H-inden-3-yl]methyl}-1H-1,2,3,4-tetrazole A53; if kuha 5-{[(1E)-1-[(3-phenoxyphenyl)methylidene]-1H-inden-3-yl]methyl}-1H- Compounds of 1,2,3,4-tetrazole A54; or tautomers thereof, or mixtures of two or more tautomers. Substances or isotopic variants thereof; or medicinally acceptable salts, solvates, or hydrates thereof. Alternatively, it is a prodrug.

[0195] In yet another embodiment, the following compounds are provided herein: 2-[(1Z)-5-fluoro-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-indene-3- Iyl-N-hydroxy-N-methylacetamide C1; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H- Inden-3-yl]-N-hydroxy-N-methylacetamide C2; ​​or (Z)-2-(5-fluoro-2-methyl-1-(3-phenoxybenzylidene)-1H-inden-3-yl)-N-H Droxy-N-methylacetamide C3; or these tautomers, mixtures of two or more tautomers, or isotopic variants; or this These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

[0196] In yet another embodiment, the following compounds are provided herein: 2-[(1Z)-5-fluoro-2-methyl-1-({4-[4-(propan-2-yl)phenoxy]phenyl}methyl Den)-1H-inden-3-yl]-N-hydroxyacetamide D1; 2-[(1Z)-5-fluoro-2-methyl-1-({4-[4-(tert-butyl)phenoxy]phenyl}methylidene )-1H-inden-3-yl]acetic acid D2; 2-[(1Z)-5-fluoro-2-methyl-1-({4-[3-(tert-butyl)phenoxy]phenyl}methylidene )-1H-inden-3-yl]acetic acid D3; 2-[(1Z)-5-fluoro-2-methyl-1-({4-[3-fluoro-4-methylphenoxy]phenyl}-methyl [Liden)-1H-Inden-3-yl]acetic acid D4; 2-[(1Z)-5-fluoro-2-methyl-1-({4-[3,4-difluorophenoxy]phenyl}methylidene) -1H-Inden-3-yl]acetic acid D5; 2-[(1Z)-5-fluoro-2-methyl-1-({4-[3-nitrophenoxy]phenyl}methylidene)-1H- D6 den-3-yl acetate; 2-[(1Z)-5-fluoro-2-methyl-1-({4-[4-(trifluoromethyl)phenoxy]phenyl}-methyl [Chilidene]-1H-Indene-3-yl]acetic acid D7; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-(2-methyl [Propyl)-1H-Inden-3-yl]acetic acid D8; 2-[(1Z)-5-fluoro-2-benzyl-1-({4-[4-fluorophenoxy]phenyl}methylidene)-1 H-Inden-3-yl]acetic acid D9; 2-[(1Z)-5-methoxy-2-methyl-1-({4-[4-fluorophenoxy]phenyl}methylidene)-1H- Inden-3-yl acetate D10; 2-[(1Z)-5-methoxy-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-indene-3- D11 yl acetate; 2-[(1Z)-1-{[2-trifluoromethyl-4-(4-fluorophenoxy)phenyl]methylidene}-5- Fluoro-2-methyl-1H-inden-3-yl]acetic acid D12; 2-[(1Z)-1-{[3-methyl-4-(4-fluorophenoxy)phenyl]methylidene}-5-fluoro-2- Methyl-1H-inden-3-yl]acetic acid D13; 2-[(1Z)-1-{[2-methyl-4-(4-fluorophenoxy)phenyl]methylidene}-5-fluoro-2- Methyl-1H-inden-3-yl]acetic acid D14; 2-[(1Z)-5,7-difluoro-2-methyl-1-({4-[4-fluorophenoxy]phenyl}methylidene) -1H-Inden-3-yl]acetic acid D15; 2-[(1Z)-4,6-difluoro-2-methyl-1-({4-[4-fluorophenoxy]phenyl}methylidene) -1H-Inden-3-yl]acetic acid D16; 2-[(1Z)-5-tert-butyl-2-methyl-1-({4-[4-fluorophenoxy]phenyl}methylidene)- 1H-Inden-3-yl]acetic acid D17; (Z)-2-(5-fluoro-2-methyl-1-(3-phenoxybenzylidene)-1H-inden-3-yl)acetic acid D 18; 2-[(1Z)-5-fluoro-1-(2-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]- Acetic acid D19; 2-[(1Z)-5,7-difluoro-1-(3-(phenoxy)benzylidene)-2-methyl-1H-indene-3-i [Lu]-acetic acid D2O; 2-[(1Z)-4,6-difluoro-1-(3-(phenoxy)benzylidene)-2-methyl-1H-indene-3-i [L]-acetic acid D21; 2-[(1Z)-5-fluoro-2-methyl-1-({3-[4-methoxyphenoxy]phenyl}methylidene)-1H- Inden-3-yl acetate D22; 2-[(1Z)-5-fluoro-1-(4-fluoro-3-(phenoxy)benzylidene)-2-methyl-1H-inde [-3-yl]-acetic acid D23; 2-[(1Z)-5-fluoro-2-methyl-1-({3-[4-cyanophenoxy]phenyl}methylidene)-1H- D24 den-3-yl acetate; 2-[(1Z)-5-fluoro-2-methyl-1-({3-[4-chlorophenoxy]phenyl}methylidene)-1H- D25 den-3-yl acetate; 2-[(1Z)-5-fluoro-2-methyl-1-({3-[4-trifluoromethylphenoxy]phenyl}-methyl [Lidene]-1H-Indene-3-yl]acetic acid D26; 2-[(1Z)-5-fluoro-2-methyl-1-({3-[3-trifluoromethylphenoxy]phenyl}-methyl [Lidene]-1H-Indene-3-yl]acetic acid D27; 2-[(1Z)-4-methoxy-1-(4-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]- Acetic acid D28; 2-[(1Z)-6-methoxy-1-(4-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]- Acetic acid D29; 2-[(1Z)-6-trifluoromethyl-2-methyl-1-({4-[4-fluorophenoxy]phenyl}-methyl [Lidene]-1H-Indene-3-yl]acetate D30; 2-[(1Z)-5-trifluoromethyl-2-methyl-1-({4-[4-fluorophenoxy]phenyl}-methyl [Lidene]-1H-Indene-3-yl]acetic acid D31; 2-[(1Z)-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-1H-inden-3-yl]acetic acid D32; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-1H-indene- 3-yl]acetic acid D33; 2-[(1Z)-5-trifluoromethyl-1-(3-(phenoxy)benzylidene)-2-methyl-1H-indene] -3-yl]-acetic acid D34; 2-[(1Z)-6-methoxy-1-(3-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]- Acetic acid D35; 2-[(1Z)-6-trifluoromethyl-1-(3-(phenoxy)benzylidene)-2-methyl-1H-indene] -3-yl]-acetic acid D36; 2-[(1Z)-5-fluoro-2-methyl-1-({3-[methyl(phenyl)amino]phenyl}methylidene)-1 H-Inden-3-yl]acetic acid D37; or 2-[(1Z)-5-fluoro-1-[(3-methoxy-5-phenoxyphenyl)methylidene]-2-methyl-1H- Inden-3-yl acetate D38; or these tautomers, mixtures of two or more tautomers, or isotopic variants; or this These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

[0197] In yet another embodiment, the following compounds are provided herein: 2-[(1E)-5-fluoro-2-methyl-1-({4-[3,4-difluorophenoxy]phenyl}methylidene) -1H-Inden-3-yl]acetic acid E1; 2-[(1E)-5-fluoro-2-methyl-1-({4-[4-fluorophenoxy]phenyl}methylidene)-1H- Inden-3-yl]acetate E2; 2-[(1E)-5-fluoro-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-indene-3- E3 yl acetate; 2-[(1E)-5,7-difluoro-2-methyl-1-({4-[4-fluorophenoxy]phenyl}methylidene) -1H-Inden-3-yl]acetic acid E4; 5-{2-[(1E)-1-[(4-phenoxyphenyl)methylidene]-1H-inden-3-yl]ethyl}-1H-1, 2,3,4-tetrazole E5; and 2-[(1E)-5,7-difluoro-1-(3-(phenoxy)benzylidene)-2-methyl-1H-indene-3-i [L]-acetic acid E6; or these tautomers, mixtures of two or more tautomers, or isotopic variants; or this These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

[0198] In one embodiment, the compounds provided herein are deuterium-enriched. In one embodiment, the compounds provided herein are carbon-13 enriched. In one embodiment, the compounds provided herein are carbon-14 enriched. In this specification, the compounds provided are, but are not limited to, those of nitrogen. 15 N; oxygen field Combined 17 O or 18 In the case of O and sulfur 34 S, 35 S, or 36 One or more remainder of other elements, including S It contains unusual isotopes.

[0199] In one embodiment, the compounds provided herein are approximately 5 or more, approximately 10 or more, approximately 20 or more Top, approximately 50 or more, approximately 100 or more, approximately 200 or more, approximately 500 or more, approximately 1,000 or more, approximately 2,000 or more, approximately 5,000 It has an isotope enrichment factor of the above, or approximately 10,000. However, in any case, specific The isotope enrichment factor for an isotope is the value obtained when a compound at a given position is 100% enriched with a specific isotope. The isotope enrichment factor in the case of isotope enrichment is less than or equal to the maximum isotope enrichment factor for a particular isotope. Therefore, the maximum isotope enrichment factor differs depending on the isotope. The maximum isotope enrichment factor is In the case of deuterium, the value is 6,410, and in the case of carbon-13, it is 90.

[0200] In one embodiment, the compounds provided herein are approximately 64 (approximately 1% deuterium concentration) Above, approximately 130 (approximately 2% deuterium concentration) or higher, approximately 320 (approximately 5% deuterium concentration) or higher, approximately 640 (approximately 10% deuterium concentration) Hydrogen concentration) or higher, approximately 1,300 (approximately 20% deuterium concentration) or higher, approximately 3,200 (approximately 50% deuterium concentration) or higher , approximately 4,800 (approximately 75% deuterium concentration) or more, approximately 5,130 (approximately 80% deuterium concentration) or more, approximately 5,450 (approximately 85 (Deuterium concentration of % or more), approximately 5,770 (approximately 90% deuterium concentration) or more, approximately 6,090 (approximately 95% deuterium concentration) ) or more, approximately 6,220 (approximately 97% deuterium concentration) or more, approximately 6,280 (approximately 98% deuterium concentration) or more, approximately 6,350 Deuterium concentration coefficient of approximately 99% or higher, or approximately 6,380 (approximately 99.5% deuterium concentration) or higher. It has. Deuterium enrichment is conventional, known to those skilled in the art, including mass spectrometry and nuclear magnetic resonance spectroscopy. This can be determined using analytical methods. In one embodiment, deuterium-enriched At least one of the atoms of the compounds provided herein designated as such is approximately 1 or more %, about 2 or more%, about 5 or more%, about 10 or more%, about 20 or more%, about 50 or more%, about 70 or more%, about 80 or more It has a deuterium concentration of over %, approximately 90% or more, or approximately 98% or more.

[0201] In one embodiment, the compounds provided herein are isolated or purified. In one embodiment, the compound provided herein is at least about 90% by weight, and at least Also approximately 95% by weight, at least approximately 98% by weight, at least approximately 99% by weight, or at least approximately 99.5% by weight It has a purity of % by quantity.

[0202] The compounds provided herein, unless otherwise specified, include all possible stereochemistry. It is intended to include stereoisomers. The compounds provided herein have an alkenyl group If present, the compound is one or a mixture of geometric cis / trans (or Z / E) isomers. They may exist as such. If structural isomers are interconvertible, the compound may exist as a single tautomer or It can exist as a mixture of tautomers. This could be, for example, imino, keto, or oxy. Proton tautomerism in compounds containing a sim group; or in compounds containing an aromatic moiety. It can take the form of so-called valence tautomerism in a single compound. An object can represent multiple types of the opposite sex.

[0203] The compounds provided herein are single enantiomers or single diastereomers. - Enantiomerically pure substances, or mixtures of enantiomers, for example For example, a racemic mixture of two enantiomers; or a mixture of two or more diastereomers. Any of these can be a mixture of stereoisomers. Therefore, those skilled in the art will know how to prepare its (R) form. If the compound administered is a compound that undergoes epimerization in vivo, then the administration of the (S) form of the compound They probably recognize that it is equivalent to the given. Conventional techniques for the preparation / isolation of individual enantiomers include suitable optically pure precursors. Synthesis from a compound, asymmetric synthesis from asymmetric starting materials, or separation of enantiomer mixtures, for example , chiral chromatography, recrystallization, resolution, diastereomer salt formation, or dias This includes derivatization to teleomer adducts and subsequent separation.

[0204] If a compound provided herein contains an acidic or basic portion, it is considered a pharmaceutical product. It can also be provided as an acceptable salt. (Berge et al., J. Pharm. Sci. 1977, 66) , 1-19; Handbook of Pharmaceutical Salts: Properties, Selection, and Use (Properties, Selection, and Use), 2nd edition; edited by Stahl and Wermuth; John Wiley & Sons See 2011. In one embodiment, the compounds provided herein are used as pharmaceuticals. The acceptable salts are solvates. In one embodiment, the compounds provided herein The only salts that are acceptable as medicine are hydrates.

[0205] For use in the preparation of pharmaceutically acceptable salts of the compounds provided herein Suitable acids include acetic acid, 2,2-dichloroacetic acid, acylated amino acids, adipic acid, and algin. Acids, ascorbic acid, L-aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamine Dibenzoic acid, boric acid, (+)-camphoric acid, camphor sulfonic acid, (+)-(1S)-camphor-10-sulfonic acid Capric acid, capric acid, caproic acid, caprylic acid, cinnamic acid, citric acid, cyclamic acid, cyanic acid, cyanic acid Crohexantholumic acid, dodecyl sulfate, ethane-1,2-disulfonic acid, ethane sulfonate Formic acid, 2-hydroxyethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid , glucoheptonic acid, D-gluconic acid, D-glucuronic acid, L-glutamic acid, α-oxogluc Taric acid, glycolic acid, hippuric acid, hydrobromic acid, hydrochloric acid, hydroiodic acid, (+)-L-lactic acid, (±)-D L-lactic acid, lactobionic acid, lauric acid, maleic acid, (-)-L-malic acid, malonic acid, (±)-D L-mandelic acid, methanesulfonic acid, naphthalene-2-sulfonic acid, naphthalene-1,5-disulfonic acid Nitric acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, nitrate, oleic acid, orotic acid, sulfate Perchloric acid, palmitic acid, pamoic acid, perchloric acid, phosphoric acid, L-pyroglutamic acid, saccharic acid Salicylic acid, 4-amino-salicylic acid, sebacic acid, stearic acid, succinic acid, sulfuric acid, ta Nic acid, (+)-L-tartaric acid, thiocyanic acid, p-toluenesulfonic acid, undecylenic acid, and Valeric acid is one example, but it is not limited to these.

[0206] For use in the preparation of pharmaceutically acceptable salts of the compounds provided herein Suitable bases include magnesium hydroxide, calcium hydroxide, potassium hydroxide, and hydroxide Inorganic bases such as zinc or sodium hydroxide; and, but not limited to, L-arginine, Netamine, benzathine, choline, deanol, diethanolamine, diethylamine, di Methylamine, dipropylamine, diisopropylamine, 2-(diethylamino)-ethano Ethylamine, ethanolamine, ethylamine, ethylenediamine, isopropylamine, N-methylamine Chil-glucamine, hydravamin, 1H-imidazole, L-lysine, morpholine, 4-(2-hydr Roxyethyl)-Morpholine, Methylamine, Piperidine, Piperazine, Propylamine, Pyrrolidine, 1-(2-hydroxyethyl)-pyrrolidine, pyridine, quinuclidine, quinoline Isoquinoline, triethanolamine, trimethylamine, triethylamine, N-meth Lu-D-glucamine, 2-amino-2-(hydroxymethyl)-1,3-propanediol, and tromethorrhea Organic bases including tamines, such as primary, secondary, tertiary, and quaternary aliphatic and aromatic amines. These include, but are not limited to, the following:

[0207] The compounds provided herein are functional derivatives of compounds and are in vivo parenthetical compounds. It can also be provided as a prodrug that can be easily converted into a substance. A prodrug is, In some situations, it may be easier to administer than the parent compound, and is therefore often useful. While prodrugs may be bioavailable, for example, through oral administration, The parent compound is not. Prodrugs also perform better than the parent compound in pharmaceutical compositions. It may have solubility. Prodrugs can undergo various processes, including enzymatic processes and metabolic hydrolysis. It can be converted to the parent drug through cannibalism.

[0208] (Pharmaceutical composition) In one embodiment, the foregoing provides a compound of formula (I), or its enantiolytic Omers, enantiomer mixtures, diastereomers, mixtures of two or more diastereomers Substances, tautomers, mixtures of two or more tautomers, or isotopic variants; or pharmaceuticals thereof. Salts, solvates, hydrates, or prodrugs that are acceptable as pharmaceuticals; and pharmaceutically acceptable It is a pharmaceutical composition containing excipients.

[0209] The pharmaceutical compositions provided herein are, but are not limited to, oral, parenteral, and topical administration. It can be formulated in various dosage forms, including those for delayed-release formulations. Extended-release formulation, long-term-release formulation, sustained-release formulation, pulse-release formulation, controlled-release formulation, accelerated-release formulation This includes dispensing formulations, fast-release formulations, targeted-release formulations, programmed-release formulations, and gastric-retention formulations. It can also be formulated as a modified-release dosage form. These dosage forms are conventional forms known to those skilled in the art. It can be prepared in accordance with laws and techniques. For example, Remington: The Science and Practice of Pharmaceutical Sciences (Re minton: The Science and Practice of Pharmacy), supra; Modified Release Drug Delivery Technology (Modifi) (ed-Release Drug Delivery Technology), 2nd edition; edited by Rathbone et al.; Drugs and the Pharmac See Eutical Sciences 184; CRC Press: Boca Raton, FL, 2008.

[0210] In one embodiment, the pharmaceutical composition provided herein is formulated in an oral dosage form. In another embodiment, the pharmaceutical composition provided herein is an agent for parenteral administration. It is formulated in a static form. In another embodiment, the pharmaceutical composition provided herein is static It is formulated in a dosage form for intravascular administration. In another embodiment, the medical The drug composition is formulated in a dosage form for intramuscular administration. In another embodiment, as specified herein The pharmaceutical composition provided is formulated in a dosage form for subcutaneous administration. In another embodiment, The pharmaceutical compositions provided herein are formulated in dosage forms for topical administration.

[0211] The pharmaceutical compositions provided herein may be provided in single dosage forms or multiple dosage forms. The unit dosage forms used herein are suitable for administration to the subject and are known in the art. This refers to individually packaged, physically separated units. Each unit dose is as needed. In relation to the pharmaceutical excipient, a predetermined amount of active ingredient sufficient to produce the desired therapeutic effect (for example) It contains the compounds provided herein. Examples of unit dosage forms include ampoules and syrups. Examples include, but are not limited to, individually packaged tablets and capsules. i. The unit dosage form may be administered in fractions or multiples thereof. Multiple dosage forms are separated unit forms Multiple dosage forms, packaged in a single container for administration in a single form. Examples include vials, bottles of tablets or capsules, or pints or gallons. Bottles are an example, but are not limited to them.

[0212] The pharmaceutical compositions provided herein can be administered in a single dose or in multiple doses at time intervals. This can be done. The exact dosage and duration of treatment depend on the age, weight, and condition of the person being treated. This may vary, and known test protocols may be used empirically, or in vivo. It is understood that this may be determined by estimation from in vitro tests or diagnostic data. For any particular individual, a specific medication regimen is developed based on the subject's needs and the pharmaceutical composition. The dosage should be adjusted over time based on the professional judgment of the person managing or supervising the administration. This will be further understood.

[0213] (A. Oral administration) The pharmaceutical compositions provided herein for oral administration are solids, semi-solids, or liquids for oral administration. It can be provided in a body dosage form. When used herein, oral administration refers to oral administration. This also includes oral administration and sublingual administration. Preferred oral dosage forms include tablets, fast melts, Chewable tablets, capsules, pills, strips, lozenges, troches, tablets, cachets, pellets Packs, medicinal chewing gum, bulk powder, effervescent or non-effervescent powder or granules, oral mist Solutions, emulsions, suspensions, wafers, sprinkles, elixirs, and syrups Examples include, but are not limited to, the active ingredients of the pharmaceutical composition. However, it does not contain binders, fillers, diluents, disintegrants, wetting agents, lubricants, flow promoters, colorants, or pigments. Transport inhibitors, sweeteners, flavoring agents, emulsifiers, suspending agents and dispersants, preservatives, solvents, non-aqueous liquids, Contains one or more pharmaceutically acceptable carriers or excipients, including organic acids and a carbon dioxide source. It is possible.

[0214] The binder or granulator imparts tackiness to the tablets so that they reliably retain their original shape after compression. Suitable binders or granulators include starch, such as corn starch, potato starch. Potato starch and pregelatinized starch (e.g., STARCH 1500®); gelatin; sugars For example, sucrose, glucose, dextrose, molasses, and lactose; natural and Synthetic rubber, such as gum arabic, alginate, alginate, and Irish moss extract. Material, Panval rubber, Gati rubber, Isagol exocoque mucus, Carboxymethylcellulose Methylcellulose, polyvinylpyrrolidone (PVP), VEEGUM®, Karamatsu Lab Galactan, powdered tragacanth, and guar gum; cellulose, e.g., ethyl cellulose Cellulose acetate, carboxymethylcellulose calcium, carboxymethylcellulose Sodium cellulose, methylcellulose, hydroxyethylcellulose (HEC), hydroxy Propylcellulose (HPC), hydroxypropyl methylcellulose (HPMC); and microcrystals cellulose, such as AVICEL (registered trademark) PH-101, AVICEL (registered trademark) PH-103, AVICEL ( Examples include, but are not limited to, the registered trademark PH-105 and AVICEL® RC-581. Suitable fillers include talc, calcium carbonate, microcrystalline cellulose, and powdered cellulose. Loin, dextrose, kaolin, mannitol, silicic acid, sorbitol, starch, Examples include, but are not limited to, pregelatinized starch. The amount of binder or filler in a pharmaceutical composition varies depending on the type of formulation and is easily understood by those skilled in the art. It is recognizable. The binder or filler is in the pharmaceutical composition provided herein. It can exist at a weight of approximately 50 to 99 percent.

[0215] Suitable diluents include dicalcium phosphate, calcium sulfate, lactose, and sorbitol. Cellulose, sucrose, inositol, cellulose, kaolin, mannitol, sodium chloride Examples include, but are not limited to, dried starch and powdered sugar. Certain diluents, For example, mannitol, lactose, sorbitol, sucrose, and inositol are When present in sufficient quantities, some compressed tablets disintegrate in the mouth when chewed. It is possible to impart properties that make it possible to do so. Such compressed tablets can be made into chewable tablets. It can be used as follows. The amount of diluent in the pharmaceutical composition provided herein is the amount of the formulation. This varies depending on the type and is easily recognizable to those skilled in the art.

[0216] Suitable disintegrants include agar; bentonite; cellulose, for example, methylcellulose and Carboxymethylcellulose; wood products; sponges; cation exchange resins; alginic acid; rubber, for example For example, guar rubber and VEEGUM® HV; citrus pulp; cross-linked cellulose, for example, Roscarmellose; cross-linked polymers, e.g., crospovidone; cross-linked starch; calcium carbonate Microcrystalline cellulose, e.g., sodium starch glycolate; polaritrin potassium Starch; for example, corn starch, potato starch, tapioca starch Examples include, but are not limited to, pregelatinized starch, clay, and algin. The amount of disintegrant in the pharmaceutical compositions provided herein varies depending on the type of formulation. This is easily recognizable to the business. The pharmaceutical compositions provided herein are about 0.5 to about 1 It may contain 5% by weight, or about 1 to about 5% by weight, of a disintegrant.

[0217] Suitable lubricants include calcium stearate; magnesium stearate; mineral oil; light Oil; glycerin; sorbitol; mannitol; glycol, e.g., glycerol behenate and polyethylene glycol (PEG); stearic acid; sodium lauryl sulfate; talc; hydrogen Chemical vegetable oils, such as peanut oil, cottonseed oil, sunflower oil, sesame oil, olive oil, corn oil Koshio oil and soybean oil; zinc stearate; ethyl oleate; ethyl laurate; agar; Lycopodium; lycopodium; and silica or silica gel, e.g., AEROSIL® 200 and CAB-O- Examples include, but are not limited to, SIL®, the pharmaceutical compositions provided herein. The amount of lubricant in a substance varies depending on the type of formulation and is easily recognizable to those skilled in the art. Yes. The pharmaceutical compositions provided herein may contain about 0.1 to about 5% by weight of a lubricant. ru.

[0218] Suitable flow promoters include colloidal silicon dioxide, CAB-O-SIL®, and stone Examples of suitable colorants include, but are not limited to, cotton-free talc. , guaranteed, water-soluble FD&C dyes, and water-insoluble FD&C dyes suspended in alumina white, and Lake pigments are, but are not limited to, any of the following: This is a combination that produces sexually shaped pigments through the adsorption of water-soluble dyes onto hydrated oxides of heavy metals. Suitable flavorings include natural flavors extracted from plants, such as fruits, and Compounds that produce pleasant tastes, such as peppermint and methyl salicylate, are used in the synthesis of these compounds. Examples of sweeteners include, but are not limited to, sucrose, raspberry. Cactose, mannitol, syrup, glycerin, and artificial sweeteners, such as saccharin. Examples of suitable emulsifiers include, but are not limited to, and aspartame. Gelatin, gum arabic, tragacanth, bentonite, and surfactants, for example, Polyoxyethylene sorbitan monooleate (TWEEN® 20), polyoxyethylene Sorbitan monooleate 80 (TWEEN® 80), and oleic acid triethanolamine. Examples include, but are not limited to, . Suitable suspending and dispersing agents include carbone. Sodium xymethylcellulose, pectin, tragacanth, VEEGUM®, Arabic Agomu, sodium carbomethylcellulose, hydroxypropylmethylcellulose, and Examples of suitable preservatives include, but are not limited to, polyvinylpyrrolidone. Glycerin, methylparaben and propylparaben, benzoic add, Examples include, but are not limited to, sodium benzoate and alcohol. Suitable wetting agents include propylene glycol monostearate and sorbitan monooleate. Diethylene glycol monolaurate and polyoxyethylene lauryl ether These are some examples, but are not limited to them. Preferred solvents include glycerin and sorbitol. Examples include, but are not limited to, ethyl alcohol and syrup. Suitable non-aqueous liquids to be used include, but are not limited to, mineral oil and cottonseed oil. Suitable organic acids include, but are not limited to, citric acid and tartaric acid. Suitable sources of carbon dioxide include sodium bicarbonate and sodium carbonate. However, it is not limited to these.

[0219] It is understood that many carriers and excipients can perform several functions within the same formulation. It should be done.

[0220] The pharmaceutical compositions provided herein for oral administration include compressed tablets, powder tablets, and chewable roses. Tablets, fast-dissolving tablets, multi-compressed tablets, or enteric-coated tablets, sugar-coated tablets, or film-coated tablets. It can be supplied as a tablet. Enteric-coated tablets are resistant to the action of stomach acid but not to the intestines. It dissolves or disintegrates, resulting in a coating of a substance that protects the active ingredient from the acidic environment of the stomach. It is a compressed tablet. The enteric coating consists of fatty acids, fats, and phenyl salicylate. Examples include waxes, shellac, ammonia-treated shellac, and cellulose phthalate acetate. However, it is not limited to these. Sugar-coated tablets are compressed tablets surrounded by a sugar coating. This may be useful in masking an unpleasant taste or odor and in protecting the tablet from oxidation. Film-coated tablets are compressed tablets that are covered with a thin layer or film of a water-soluble material. As for film coatings, hydroxyethylcellulose and carboxymethylcellulose are used. Examples include sodium phosphate, polyethylene glycol 4000, and cellulose acetate phthalate. However, it is not limited to these. Film coatings impart the same general characteristics as sugar coatings. A multi-layered compression tablet is a compression tablet made by multiple compression cycles, and this includes layered tablets. , and press-coated tablets or dry-coated tablets.

[0221] The tablet dosage form can be used alone or with a binder, disintegrant, controlled-release polymer, lubricant, diluent, and / or in combination with one or more carriers or excipients described herein, including a colorant. It can be prepared from the active ingredient in powder form, crystalline form, or granular form. The preparations and sweeteners are particularly useful in the formation of chewable tablets and lozenges.

[0222] The pharmaceutical compositions provided herein for oral administration are offered as soft capsules or hard capsules. The capsules can be made from gelatin, methylcellulose, starch, or argy It can be made from calcium phosphate. Hard gelatin capsules are dry-filled capsules (DFCs). It is also known as the process where one slides onto the other, and the active ingredient It consists of two parts that completely enclose the soft elastic capsule (SEC). Gel, for example, gelatin shell, which is glycerin, sorbitol, or similar It is plasticized by the addition of polyols. The soft gelatin shell prevents microbial growth. It may contain preservatives for the purpose of [details omitted]. Suitable preservatives are listed herein. This product contains methylparaben, propylparaben, and sorbic acid. The liquid, semi-solid, and solid dosage forms provided herein can be encapsulated in capsules. Yes, it is possible. Suitable liquid and semi-solid dosage forms include propylene carbonate, vegetable oil, or triglycerides. Examples include solutions and suspensions in lidone. Capsules containing such solutions have a U.S. rating of 4. It can be prepared as described in Nos. 328,245; Nos. 4,409,239; and Nos. 4,410,545. Capsules are used to modify or maintain the dissolution of the active ingredient, as is known to those skilled in the art. It can also be coated in that way.

[0223] The pharmaceutical compositions provided herein for oral administration are provided in liquid and semi-solid dosage forms. This can include emulsions, solutions, suspensions, elixirs, and syrups. An emulsion is a two-phase system in which one liquid is dispersed throughout the other liquid in the form of small spheres. It is a system, which can be oil-in-water or water-in-oil. Emulsions are used in pharmaceuticals and The suspension may contain permissible non-aqueous liquids or solvents, emulsifiers, and preservatives. It may contain pharmacopoeially acceptable suspending agents and preservatives. Aqueous alcohol solution This refers to acetals that are acceptable as pharmaceuticals, for example, di(lower alkylaldehydes). Kill(acetal), e.g., acetaldehyde diethyl acetal; and one or more hydroxyl groups Water-miscible solvents having the properties of, for example, propylene glycol and ethanol may be included. Elixir is a clear, sweet, water-alcoholic solution. Syrup is a sugar, for example. It is a concentrated aqueous solution of sucrose and may also contain preservatives. Regarding the liquid dosage form, For example, a solution in polyethylene glycol that is easily measured for administration. A liquid carrier of a quantity acceptable for pharmaceutical use, for example, one that can be diluted with water.

[0224] Other useful liquid and semi-solid dosage forms include the active ingredient and 1,2-dimethoxymethane, diglyceride. Polyethylene glycol-350-dimethyl ether, Poly Ethylene glycol-550-dimethyl ether, polyethylene glycol-750-dimethyl ether Tel (where 350, 550, and 750 refer to the approximate average molecular weight of polyethylene glycol) (including dialkylated monoalkylene glycol or polyalkylene glycol) Examples include, but are not limited to, those containing ru. These dosage forms include one or more acid-fastening agents. Reacting agents, for example, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA) Propyl gallate, vitamin E, hydroquinone, hydroxycoumarin, ethanolamine N, lecithin, kephalin, ascorbic acid, malic acid, sorbitol, phosphoric acid, sulfite Hydrogen salts, sodium metabisulfite, thiodipropionic acid and its esters, and dithio It can contain even more carbamates.

[0225] The pharmaceutical compositions provided herein for oral administration include liposomes, micelles, and microsulfates. It can also be supplied in the form of a micelle or nanosystem. The micelle formulation is U.S. 6.35 It can be prepared as described in No. 0.458.

[0226] Pharmaceutical compositions provided herein for oral administration, which are reconstituted into liquid dosage forms, are non-foaming. It can be provided as non-foaming or effervescent granules and powders. Acceptable carriers and excipients for use as pharmaceuticals include diluents, sweeteners, and humectants. Examples include: a carrier that is acceptable as a pharmaceutical when used in effervescent granules or powders. Examples of excipients include organic acids and sources of carbon dioxide.

[0227] Colorants and flavorings may be used in all dosage forms described herein. .

[0228] The pharmaceutical compositions provided herein for oral administration include delayed-release forms, sustained-release forms, and pulsed forms. Immediate-release agents, including release-type, controlled-release, targeted-release, and programmed-release forms. It can be formulated as a single-form or modified-release dosage form.

[0229] (B. Parenteral administration) The pharmaceutical compositions provided herein are for topical or systemic administration by injection, infusion, or embedding. It can be administered parenterally by mixing. Parenteral administration as used herein This includes intravenous, intraarterial, intraperitoneal, intrathecal, intraventricular, urethral, ​​intrasternal, intracranial, intramuscular, and synovial fluid. Intravesical, intravesical, and subcutaneous administration are also possible methods.

[0230] The pharmaceutical compositions provided herein for parenteral administration include, but are not limited to, solutions, suspensions, Emulsions, micelles, liposomes, microspheres, nanosystems, and pre-injection solutions It can be manufactured in any dosage form suitable for parenteral administration, including a solid form suitable for solutions or suspensions in the body. It can be formulated into a dosage form. Such dosage forms can be prepared according to conventional methods known to those skilled in the art of pharmaceutical science. It can be manufactured. For example, Remington: The Science of Pharmaceutical Sciences. (and Practice of Pharmacy), please refer to the above.

[0231] The pharmaceutical compositions provided herein for parenteral administration include one or more pharmaceutically acceptable compounds. It may contain bodies and excipients, including aqueous vehicles, water-miscible vehicles, and non-aqueous vehicles. Hickle, antimicrobial agents or preservatives against microbial growth, stabilizers, dissolution accelerators, isotonic agents, Buffers, antioxidants, local anesthetics, suspending agents and dispersants, wetting agents or emulsifiers, complexing agents, metals Ion sequestering agents or chelating agents, antifreeze agents, cryoprotection agents, thickeners, pH adjusters, and inactivators. This includes, but is not limited to, certain gases.

[0232] Suitable aqueous vehicles include water, saline solution, physiological saline solution, or phosphate-buffered saline (PBS). Sodium chloride injection, Ringer's injection, isotonic dextrose injection, sterile water injection Examples include, but are not limited to, dextrose and lactated Ringer's injection. Suitable non-aqueous vehicles include plant-derived fixed oils, castor oil, corn oil, and cottonseed oil. Olive oil, peanut oil, peppermint oil, safflower oil, sesame oil, soybean oil, hydrogenated Examples include vegetable oils, hydrogenated soybean oil, and medium-chain triglycerides from coconut oil and palm kernel oil. However, it is not limited to these. Suitable water-miscible vehicles include ethanol, 1,3- Butanediol, liquid polyethylene glycol (e.g., polyethylene glycol 300 and Polyethylene glycol 400), propylene glycol, glycerin, N-methyl-2-pyrrolic acid Examples include don, N,N-dimethylacetamide, and dimethyl sulfoxide, but these Not limited.

[0233] Suitable antimicrobial agents or preservatives include phenol, cresol, mercury compounds, and benzyl ammonium compounds. Alcohol, chlorobutanol, methyl p-hydroxybenzoate and p-hydroxybenzoate Ropil, thimerosal, benzalkonium chloride (e.g., benzethonium chloride), methyl phosphate Examples include, but are not limited to, lavens, propylparabens, and sorbic acid. Suitable isotonic agents include sodium chloride, glycerin, and dextrose. However, it is not limited to these. Suitable buffering agents include phosphates and citrates. However, it is not limited to these. Suitable antioxidants include those described herein. Examples include bisulfites and sodium metabisulfite. Suitable local anesthetics Examples include, but are not limited to, procaine hydrochloride. Suitable suspending agents and Examples of powders include those listed herein, for example, carboxymethylcellulose Examples include thorium, hydroxypropyl methylcellulose, and polyvinylpyrrolidone. Suitable emulsifiers include those described herein, for example, polyoxyethylene Sorbitan monolaurate, polyoxyethylene sorbitan monooleate 80, and Examples include triethanolamine leic acid. Suitable metal ion sequestering agents or chelating agents are EDTA is one example, but it is not limited to this. Suitable pH adjusters include sodium hydroxide. Examples include, but are not limited to, thorium, hydrochloric acid, citric acid, and lactic acid. The nitrifying agents include α-cyclodextrin, β-cyclodextrin, and hydroxypropyl- β-cyclodextrin, sulfobutyl ether-β-cyclodextrin, and sulfo Chil ether 7-β-cyclodextrin (containing CAPTISOL®, a registered trademark), cyclodextrin Examples include, but are not limited to, these.

[0234] When a pharmaceutical composition provided herein is formulated for multiple doses, Parenteral formulations must contain an antimicrobial agent at a bacteriostatic or fungiostatic concentration. All preparations must be sterilized as is known and practiced in the art. stomach.

[0235] In one embodiment, a pharmaceutical composition for parenteral administration is provided as a readily available sterile solution. Provided. In another embodiment, the pharmaceutical composition is reconstituted in a vehicle before use. It is provided as a sterile, dried, soluble product, including freeze-dried powder and tablets for subcutaneous injection. In another embodiment, the pharmaceutical composition is provided as a ready-to-use sterile suspension. In another embodiment, the pharmaceutical composition is sterile and dry, which is reconstituted in a vehicle before use. It is provided as a dry, insoluble product. In yet another embodiment, the pharmaceutical composition is immediately It is provided as a usable sterile emulsion.

[0236] The pharmaceutical compositions provided herein for parenteral administration include delayed-release forms, sustained-release forms, and Immediate release, including slus release mode, controlled release mode, targeted release mode, and programmed release mode. It can be formulated as a dosage form or a modified-release dosage form.

[0237] The pharmaceutical compositions provided herein for parenteral administration are administered as implantable depots. Therefore, it can be formulated as a suspension, solid, semi-solid, or thixotropic solution. In one embodiment, the pharmaceutical composition provided herein comprises a solid internal matrix. The matrix is ​​dispersed and does not dissolve in bodily fluids, but it expands the active ingredients in the pharmaceutical composition. It is surrounded by an external polymer film that can be dispersed.

[0238] Suitable internal matrices include polymethyl methacrylate and polybutyl methacrylate. Polyvinyl chloride, plasticized or non-plasticized polyvinyl chloride, plasticized nylon, plasticized polyethylene tere Phthalates, natural rubber, polyisoprene, polyisobutylene, polybutadiene, polyethylene Len, ethylene-vinyl acetate copolymer, silicone rubber, polydimethylsiloxane, cyanoacrylate Lycorn carbonate copolymer, hydrophilic polymer (e.g., acrylic acid and methacrylic acid) Acid ester hydrogel), collagen, cross-linked polyvinyl alcohol, and cross-linked portion Examples include, but are not limited to, hydrolyzed polyvinyl acetate.

[0239] Suitable external polymer membranes include polyethylene, polypropylene, and ethylene / propylene. Copolymer, ethylene / ethyl acrylate copolymer, ethylene / vinyl acetate copolymer, Silicone rubber, polydimethylsiloxane, neoprene rubber, chlorinated polyethylene, poly Vinyl chloride, vinyl chloride copolymer with vinyl acetate, vinylidene chloride, ethylene and pro Pyrene, ionomer polyethylene terephthalate, butyl rubber, epichlorohydrin rubber, Ethylene / vinyl alcohol copolymer, ethylene / vinyl acetate / vinyl alcohol tarpaulin Examples include rimers and ethylene / vinyloxyethanol copolymers, but these include Not limited.

[0240] (C. Local administration) The pharmaceutical compositions provided herein are intended for topical administration to the skin, orifices, or mucous membranes. This can be done. Topical administration as used in this specification includes intracutaneous, conjunctival, intracorneal, intraocular, Intraocular, ocular, transdermal, nasal, vaginal, urethral, ​​respiratory, and rectal administration are also possible methods.

[0241] The pharmaceutical compositions provided herein are suitable for topical or systemic administration. It can be formulated in any dosage form, including emulsion, solution, suspension, and cream. Gels, hydrogels, ointments, powders, bandages, elixirs, lotions, suspensions, tinctures, and more. Sters, foams, films, aerosols, irrigation solutions, sprays, suppositories, bandages, and skin This includes, but is not limited to, patches. Topical preparation of pharmaceutical compositions provided herein. The agent may also include liposomes, micelles, microspheres, and nanosystems.

[0242] Suitable carriers and excipients for use in topical formulations include aqueous vinyl Hicles, water-miscible vehicles, non-aqueous vehicles, antimicrobial agents or preservatives against microbial growth. Agents, stabilizers, dissolution accelerators, isotonic agents, buffers, antioxidants, local anesthetics, suspending agents, and dispersions. Agents, wetting agents or emulsifiers, complexing agents, metal ion sequestering agents or chelating agents, permeation enhancers, freeze-proofing agents. Examples include, but are not limited to, antifreezes, freeze-protectants, thickeners, and inert gases.

[0243] Pharmaceutical compositions are electroporated, iontophoresis, phonophoresis , sonophoresis, or microneedle injection or needle-free injection, for example, POWDERJECT (trademark) and It can also be administered topically using BIOJECT®.

[0244] The pharmaceutical compositions provided herein are provided in the form of ointments, creams, and gels. This can be done. Suitable ointment vehicles include lard, benzoin lard, olive oil, cottonseed oil, and Other oils, including white petrolatum, oily vehicles or hydrocarbon vehicles; emulsifiable vehicles or The absorbent vehicle is, for example, hydrophilic petrolatum, hydroxystearin sulfate, and no Water lanolin; water-removing vehicles, e.g., hydrophilic ointments; polyethylene glycosides of various molecular weights. Water-soluble ointment vehicle containing alcohol; cetyl alcohol, glyceryl monostearate, lano A water-in-oil (W / O) emulsion or an oil-in-water (O / W) emulsion containing phosphorus and stearic acid. Emulsion vehicles are one example. For instance, Remington: The Science and Practice of Pharmacy. See Science and Practice of Pharmacy (see above). These vehicles are suitable for use on the skin. Although it is a chemical additive, it usually requires the addition of antioxidants and preservatives.

[0245] A suitable cream base may be an oil-in-water or water-in-oil type. Hickle is washable and may contain an oil phase, an emulsifier, and an aqueous phase. Also known as the "internal" phase, it typically consists of petrolatum and fatty alcohols, such as cetyl alcohol. It consists of ethanol or stearyl alcohol. The aqueous phase is usually larger in volume than the oil phase. Generally, they contain moisturizers, but this is not always necessary. Emulsifiers in cream formulations The surfactant can be nonionic, anionic, cationic, or amphoteric.

[0246] A gel is a semi-solid suspension system. A single-phase gel is substantially distributed throughout the liquid carrier. It contains uniformly distributed organic polymers. Suitable gelling agents include crosslinked acrylic acid polymers. For example, carbomers, carboxypolyalkylenes, and CARBOPOL®; hydrophilic poly For example, polyethylene oxide, polyoxyethylene-polyoxypropylene copolymer Limers and polyvinyl alcohol; cellulose polymers, e.g., hydroxypropyl Cellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, lid Hydroxypropyl methylcellulose and methylcellulose; rubber, for example, tungsten. Examples include gacant and xanthan gum; sodium alginate; and gelatin, however These are not the only options. To prepare a uniform gel, a dispersant, such as an alcohol, may be used. Glycerin can be added, or a gelling agent can be added, by grinding, mechanical mixing, and / Alternatively, it can be dispersed by stirring.

[0247] The pharmaceutical compositions provided herein include suppositories, pessaries, bougies, patches, or poultices. Paste, powder, bandage, cream, ointment, contraceptive, ointment, solution, emulsion, suspension , in the form of tampons, gels, foams, sprays, or enemas, inserted into the rectum, urethra, vagina, These can be administered perianal. These dosage forms are from Remington: The Science and Practice of Pharmacy (Re (mington: The Science and Practice of Pharmacy), conventional methods as described above It can be manufactured using a process.

[0248] Suppositories for the rectum, urethra, and vagina are solid objects to be inserted into the orifices of the body, and these are It is solid at room temperature, but melts or softens at body temperature, releasing the active ingredient inside the opening. The carriers acceptable for use as pharmaceuticals in rectal and vaginal suppositories are the base or the vial. Hickle, for example, when formulated with an active ingredient, produces a hardness that results in a melting point close to body temperature. Reacting agents; and antimicrobial agents as described herein, including bisulfite and sodium metabisulfite. Oxidizing agents are mentioned. Suitable vehicles include cocoa butter (cocoa butter), glycerin- Gelatin, carbowax (polyoxyethylene glycol), whale wax, paraffin, white wax and Yellow wax, suitable mixtures of fatty acid monoglycerides, diglycerides and triglycerides, and to hydrogel, for example, polyvinyl alcohol, hydroxyethyl methacrylate, and Polyacrylic acid is one example, but it is not limited to this. Various vehicle combinations are used. It is also possible to prepare rectal and vaginal suppositories by compression or molding. The typical weight of rectal and vaginal suppositories is approximately 2 to 3 grams.

[0249] The pharmaceutical compositions provided herein include solutions, suspensions, ointments, emulsions, and gel-forming solutions. It is administered ophthalmologically in the form of a liquid, powder solution, gel, eye insert, and implant. It is possible.

[0250] The pharmaceutical compositions provided herein are administered by inhalation into the nasal cavity or into the airway. This can be done. The pharmaceutical composition can be used in pressurized containers, pumps, sprays, atomizers, etc. An atomizer or nebulizer that generates a fine mist using aerodynamics, can be used independently. Or a suitable propellant, for example, 1,1,1,2-tetrafluoroethane or 1,1,1,2,3,3,3-hep Provided in the form of an aerosol or solution for delivery in combination with fluoropropane. The pharmaceutical composition can be used alone or with an inert carrier, such as lactose. To be provided as a dry powder for blowing in combination with phospholipids, or as a nasal spray. It can also be used. For intranasal use, the powder contains a bio-enzyme containing chitosan or cyclodextrin. It may contain adhesive.

[0251] Solvent for use in pressurized containers, pumps, sprays, atomizers, or nebulizers The liquid or suspension contains ethanol, aqueous ethanol, or a substance that disperses or solubilizes the active ingredient. A suitable alternative agent for extending the release of the active ingredient; a propellant as a solvent; and / or surfactants, such as sorbitan trioleate, oleic acid, or oligosaccharides. It can be formulated to contain lactic acid.

[0252] The pharmaceutical compositions provided herein are of a size suitable for delivery by inhalation, for example, about 50 mg It can be miniaturized to less than 10 micrometers, or to approximately 10 micrometers or less. Particles of such size can be ground using grinding methods known to those skilled in the art, such as spiral jet milling. G, fluidized bed jet milling, supercritical fluid processing for forming nanoparticles, high It can be prepared using pressure homogenization or spray drying.

[0253] Capsules, blisters, and cartridges used in inhalers or blowers are specified herein. A powder mixture of pharmaceutical compositions provided; a suitable powder base, for example, lactose or starch n; and functional modifiers, for example, l-leucine, mannitol, or magnesium stearate It can be formulated to contain um. Lactose can be in the form of anhydrous or monohydrate. It may also be in a certain state. Other suitable excipients or carriers include dextran, glucose, and ma Fructose, sorbitol, xylitol, fructose, sucrose, and trehalose These include, but are not limited to, the following, provided herein for inhalation / intranasal administration. The pharmaceutical composition may have a suitable flavor, such as menthol and levomenthol; and / or It may further contain sweeteners, such as saccharin and sodium saccharin.

[0254] The pharmaceutical compositions provided herein for topical administration include delayed-release, sustained-release, pulsed-release, To enable immediate or modified release, including controlled release, targeted release, and programmed release. It can be formulated into a pharmaceutical product.

[0255] (D. modified release) The pharmaceutical compositions provided herein can be formulated as modified-release dosage forms. When used in the specification, the term "modified release" means that when administered via the same route, the active components This refers to a dosage form whose release rate or location differs from that of an immediate-release dosage form. Modified release dosage forms include Delayed-release formulation, extended-release formulation, long-term-release formulation, sustained-release formulation, pulsatile-release formulation, controlled-release formulation Dosage forms, accelerated and fast-release dosage forms, targeted-release dosage forms, programmed-release dosage forms, and gastric retention agents. Examples of modified release formulations of pharmaceutical compositions are known to those skilled in the art. It can be prepared using various modified emission devices and methods, including a matrix Osmotic pressure controlled release devices, osmotic pressure controlled release devices, multi-particle controlled release devices, ion exchange trees Lipids, enteric coatings, multilayer coatings, microspheres, liposomes, and this This includes, but is not limited to, the combinations of the active ingredient. The release rate of the active ingredient is the It can also be modified by changing the particle size and polymorphism.

[0256] (1. Matrix-controlled emission device) The pharmaceutical compositions provided herein in modified release formulations are matrix-controlled, as known to those skilled in the art. It can be manufactured using a release device. For example, see the literature by Takada et al., Controlled Drug Delivery Encyclopedia of Controlled Drug Delivery; edited by Mathiowitz; Wiley: 1999; Please refer to Volume 2.

[0257] In one embodiment, the pharmaceutical composition provided herein in a modified release form is erosive Formulated using a TRIX device, the device being, but not limited to, a synthetic polymer , as well as natural polymers and derivatives, such as polysaccharides and proteins, which are water-swellable and erosive. It is a soluble or non-soluble polymer.

[0258] Useful materials for forming an erosive matrix include chitin, chitosan, and dex. Tran and pullulan; agar gum, gum arabic, gum karaya, gum locust bean, Tragacanth gum, carrageenan, gua gum, guar gum, xanthan gum, and sucrose Leroglucan; starch, e.g., dextrin and maltodextrin; hydrophilic colloids For example, pectin; phosphatides; for example, lecithin; alginates; propyl alginate Lencolytes; gelatin; collagen; cellulose derivatives, e.g., ethylcellulose (EC ), methylethylcellulose (MEC), carboxymethylcellulose (CMC), CMEC, hydrox Cethylcellulose (HEC), hydroxypropylcellulose (HPC), cellulose acetate (CA), Cellulose propionate (CP), cellulose butyrate (CB), cellulose acetate butyrate (CAB), CAP, CA T, Hydroxypropyl methylcellulose (HPMC), HPMCP, HPMCAS, Trimellitate acetate hydride Roxypropyl methylcellulose (HPMCAT) and ethyl hydroxyethylcellulose (EHE C); polyvinylpyrrolidone; polyvinyl alcohol; polyvinyl acetate; glycerol fatty acid Polyacrylamide; polyacrylic acid; copolymer of ethacrylic acid or methacrylic acid - (EUDRAGIT(registered trademark); poly(2-hydroxyethyl methacrylate); polylactic acid; L-glutamic acid Copolymer of methyl acid and ethyl-L-glutamate; Degradable lactic acid-glycolic acid copolymer; Poly D-(-)-3-hydroxybutyrate; and other acrylic acid derivatives, such as butyl methacrylate. Methyl methacrylate, ethyl methacrylate, ethyl acrylate, (2-dimethyl methyl Homomethylaminoethyl methacrylate and (trimethylaminoethyl) methacrylate chloride Examples include, but are not limited to, polymers and copolymers.

[0259] In one embodiment, the pharmaceutical composition provided herein is a non-erosive matrix It is formulated using a vise. The active ingredient is dissolved or dispersed in an inactive matrix. Once administered, it is released primarily by diffusion through an inactive matrix. Suitable materials for use as non-erosive matrix devices include insoluble plastics. For example, polyethylene, polypropylene, polyisoprene, polyisobutylene, Libutadiene, polymethyl methacrylate, polybutyl methacrylate, chlorinated polyethylene Len, polyvinyl chloride, methyl acrylate-methyl methacrylate copolymer, ethylene- Vinyl acetate copolymer, ethylene / propylene copolymer, ethylene / ethyl acrylate Copolymers, vinyl chloride copolymers with vinyl acetate, vinylidene chloride, ethylene and pro Pyrene, ionomer polyethylene terephthalate, butyl rubber, epichlorohydrin rubber , ethylene / vinyl alcohol copolymer, ethylene / vinyl acetate / vinyl alcohol Polymer, ethylene / vinyl oxyethanol copolymer, polyvinyl chloride, plasticizer Polyethylene terephthalate, natural rubber, silicone rubber, polydimethylsilicone Roxane and silicone carbonate copolymers; hydrophilic polymers, e.g., ethyl acetate Lulurose, cellulose acetate, crospovidone, and crosslinked partially hydrolyzed polyvinyl acetate; Examples include aliphatic compounds, such as carnauba wax, microcrystalline wax, and triglycerides. However, it is not limited to these.

[0260] In a matrix-controlled release system, the desired release kinetics are controlled, for example, by the type of polymer used. The viscosity of the polymer, the particle size of the polymer and / or active ingredient, the ratio of active ingredient to polymer, Furthermore, it can be controlled by other excipients or carriers in the composition.

[0261] The pharmaceutical compositions provided herein in modified release formulations are derived from direct compression, dry or wet granulation and It is prepared by a method known to those skilled in the art, including compression after the initial granulation and melt granulation followed by compression. It is possible.

[0262] (2. Osmotic pressure controlled release device) The pharmaceutical compositions provided herein in modified release formulations are provided using an osmotic pressure-controlled release device. It can be manufactured, and the device includes a 1-chamber system, a 2-chamber system, This includes, but is not limited to, asymmetric membrane technology (AMT) and extrusion core systems (ECS). Generally, such devices have at least two components: (a) a core containing an active ingredient; and (b) having a semipermeable membrane having at least one delivery port that encloses the core. ...to cause drug release by extrusion from the delivery port, from the core in the water environment. Control the inflow of water to the source.

[0263] In addition to the active ingredient, the core of the osmotic device optionally contains an osmotic agent that creates a driving force to transport water from the environment of use to the core of the device. One class of osmotic agents is the water-swellable hydrophilic polymers, also called "osmopolymers" and "hydrogels". Suitable water-swellable hydrophilic polymers as osmotic agents include hydrophilic vinyl and acrylic polymers, polysaccharides such as calcium alginate, polyethylene oxide (PEO), polyethylene glycol (PEG), polypropylene glycol (PPG), poly(2-hydroxyethyl methacrylate ), poly(acrylic) acid, poly(methacrylic) acid, polyvinylpyrrolidone (PVP), crosslinked PVP, poly vinyl alcohol (PVA), PVA / PVP copolymers, hydrophobic monomers such as methyl methacrylate and PVA / PVP copolymers with vinyl acetate, hydrophilic polyurethanes containing large PEO blocks, croscarmellose sodium, carrageenan, hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPM C), carboxymethyl cellulose (CMC) and carboxyethyl cellulose (CEC), sodium alginate, polycarbophil, gelatin, xanthan gum, and sodium starch glycolate, but are not limited thereto. (HEC), hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPM C), carboxymethyl cellulose (CMC) and carboxyethyl cellulose (CEC), sodium alginate, polycarbophil, gelatin, xanthan gum, and sodium starch glycolate, but are not limited thereto. Another class of osmotic agents is the osmolytes, which can absorb water and affect the osmotic gradient across the surrounding coating barrier. Suitable osmolytes include inorganic salts such as magnesium sulfate, magnesium chloride, calcium chloride, sodium chloride,

[0264] lithium chloride, potassium chloride, potassium sulfate, potassium phosphate, sodium carbonate, sodium sulfite, but are not limited thereto. inorganic salts such as magnesium sulfate, magnesium chloride, calcium chloride, sodium chloride, lithium chloride, potassium chloride, potassium sulfate, potassium phosphate, sodium carbonate, sodium sulfite, Umm, lithium sulfate, potassium chloride, and sodium sulfate; sugars such as dextrose , fructose, glucose, inositol, lactose, maltose, mannitol, raffinose, sorbitol, sucrose, trehalose, and xylitol; organic acids, such as ascorbic acid, benzoic acid, fumaric acid, citric acid, maleic acid, sebacic acid, so luvinic acid, adipic acid, edetic acid, glutamic acid, p-toluenesulfonic acid, succinic acid, and tartaric acid; urea; and mixtures thereof are included, but not limited thereto.

[0265] By utilizing osmotic agents with different dissolution rates, it is possible to affect how quickly the active ingredient is initially delivered from the dosage form. For example, using amorphous sugars such as MANNOGEM (trademark) E Z results in faster delivery in the first few hours, rapidly producing the desired therapeutic effect and causing the release of the remaining amount to occur stepwise and continuously to maintain the desired level of therapeutic or preventive effect over a long period. In this case, the active ingredient is released at a rate that replaces the amount of active ingredient that is metabolized and excreted. The core can also contain a variety of other excipients and carriers described in the present specification for improving the performance of the dosage form or promoting stability or processing.

[0266] Materials useful for forming a semipermeable membrane include various grades of acrylic, vinyl, ether, polyamide, polyester, and cellulose derivatives that are water-permeable and water-insoluble at physiologically relevant pHs or are easily made water-insoluble by chemical changes such as crosslinking. Examples of suitable polymers useful for forming a coating include plasticized, non-plasticized

[0267] ​​​​​​ Plasticized and strengthened cellulose acetate (CA), cellulose diacetate, cellulose triacetate, pro Calcium ionate, cellulose nitrate, cellulose acetate butyrate (CAB), ethyl calcium carbamate, CAP, Methyl carbamate (CA), CA succinate (CA), cellulose trimellitic acetate (CAT), dimethylamine CA oxalate, ethyl carbonate, CA chloroacetate, ethyl oxalate, methyl sulfonate, sulfonate Butyl phosphate CA, p-toluene CA sulfonate, agar acetate, amylose triacetate, β-glucan acetate Trio of β-glucan triacetate, acetaldehyde dimethylacetic acid, and locust bean gum Ceteate, hydroxylated ethylene vinyl acetate, EC, PEG, PPG, PEG / PPG copolymer, PV P, HEC, HPC, CMC, CMEC, HPMC, HPMCP, HPMCAS, HPMCAT, poly(acrylic) acid and poly(acrylic) acid. Acrylic esters and poly(methacrylic) acids and poly(methacrylic) esters and these Copolymer, starch, dextran, dextrin, chitosan, collagen, gelatin Polyalkenes, polyethers, polysulfones, polyethersulfones, polystyrene polyhalogenated vinyl, polyvinyl esters and polyvinyl ethers, natural wax, Synthetic waxes are also mentioned.

[0268] The semipermeable membrane may also be a hydrophobic microporous membrane, in which case the pores are as specified in U.S. Patent No. 5,798,119. As disclosed, it is substantially filled with gas and not wetted by aqueous media. However, it is permeable to water vapor. Such hydrophobic but water vapor permeable membranes are usually, Hydrophobic polymers, such as polyalkenes, polyethylene, polypropylene, and polytetrafibers. Roroethylene, polyacrylic acid derivative, polyether, polysulfone, polyethersulfone Polysulfone, polystyrene, polyhalogenated vinyl, polyvinylidene fluoride, polyvinyl ester It is composed of tel and polyvinyl ether, natural wax, and synthetic wax.

[0269] The delivery port of the semipermeable membrane can be formed by mechanical perforation or laser perforation after coating. The delivery port can also be formed in situ by erosion of a plug of a water-soluble material or by rupture of a thinner portion of the membrane above the core indentation. It can also be formed in situ by erosion of a plug of a water-soluble material or by rupture of a thinner portion of the membrane above the core indentation. Furthermore, the delivery port can be formed during the coating process, as in the case of the asymmetric membrane coatings of the types disclosed in U.S. Patent Nos. 5,612,059 and 5,698,220. It can be formed during the coating process, as in the case of the asymmetric membrane coatings of the types disclosed in U.S. Patent Nos. 5,612,059 and 5,698,220. It can be done.

[0270] The total amount and release rate of the active ingredient released can be substantially adjusted by the thickness and porosity of the semipermeable membrane, the composition of the core, as well as the number, size, and position of the delivery ports.

[0271] The pharmaceutical composition in the osmotic pressure-controlled release dosage form can further contain additional conventional excipients or carriers described herein to facilitate the performance or processing of the formulation. It can further contain additional conventional excipients or carriers described herein to facilitate the performance or processing of the formulation.

[0272] The osmotic pressure-controlled release dosage form can be prepared according to conventional methods and techniques known to those skilled in the art. For example, Remington: The Science and Practice of Pharmacy, supra; Santus and Baker, J., Controlled Release, 1995, 35, 1-2 ; Santus and Baker, J., Controlled Release, 1995, 35, 1-2 1; Verma et al., Drug Dev. Ind. Pharm., 2000, 26, 695-708; Verma et al., J. Co. See the unreleased release, 2002, 79, 7-27.

[0273] In one embodiment, the pharmaceutical composition provided herein is an AMT controlled-release dosage form. Formulated, the dosage form comprises the active ingredient and other pharmaceutically acceptable excipients or carriers. Includes an asymmetric osmotic membrane coating A. For example, U.S. Patent No. 5,612,059 and WO 20 Please refer to issue 02 / 17918. AMT controlled release formulations are produced by direct compression, dry granulation, and wet granulation. , and prepared according to conventional methods and techniques known to those skilled in the art, including the dip coating method. It is possible.

[0274] In one embodiment, the pharmaceutical composition provided herein is an ESC-controlled release dosage form. Formulated, the dosage form contains the active ingredient, hydroxyethylcellulose, and other pharmaceutically permitted ingredients. The invention includes an osmotic membrane that coats a core containing an acceptable excipient or carrier.

[0275] (3. Multi-particle controlled emission devices) The pharmaceutical compositions provided herein in modified release formulations are manufactured as multi-particle controlled release devices. The device can be manufactured with a diameter of approximately 10 μm to approximately 3 mm, approximately 50 μm to approximately 2.5 mm, or approximately 10 Contains numerous particles, granules, or pellets ranging from 0 μm to approximately 1 mm. Such multiplicities are dry-processed. and wet granulation, extrusion / spheroidization, roller compression, melt-solidification, and spray coating. It can be manufactured by processes known to those skilled in the art, including those using seed cores. For example, Multiparticulate Oral Drug Delivery (Ghebre-Sellassi) e.; Drugs and the Pharmaceutical Sciences 65; CRC Press: 1994; and Pharmaceutical Peret Pharmaceutical Pelletization Technology; edited by Ghebre-Sellassie; Drugs and See Pharmaceutical Sciences 37; CRC Press: 1989.

[0276] Blending other excipients or carriers described herein with the pharmaceutical composition for the treatment of multiple particles and can aid in formation. The resulting particles themselves constitute a multi-particle device. It is possible to use various film-forming materials, such as enteric polymers, water-swellable polymers, and They can be coated with a water-soluble polymer. These particles can be used in capsules or It can be further processed into tablets.

[0277] (4. Targeted delivery) The pharmaceutical products provided herein include a delivery system based on liposomes, resealed red blood cells, and antibodies. The composition targets specific tissues, receptors, or other parts of the body to be treated. It can also be formulated in this way. Examples include U.S. Patent No. 6,316,652; No. 6,274,552; No. No. 6,271,359; No. 6,253,872; No. 6,139,865; No. 6,131,570; No. 6,120,751; No. 6,071,495 No. 6,060,082; No. 6,048,736; No. 6,039,975; No. 6,004,534; No. 5,985,307; No. 5,972 Disclosed in Nos. 366; Nos. 5,900,252; Nos. 5,840,674; Nos. 5,759,542; and Nos. 5,709,874 These are some examples, but are not limited to them.

[0278] (How to use) In one embodiment, this specification provides for one or more fibrous diseases in the subject. A method for treating, improving, or preventing symptoms, which is administered to a person in need of it, using formula (I) Compounds, or their enantiomers, mixtures of enantiomers, diastereomers, two or more A mixture of diastereomers, tautomers, a mixture of two or more tautomers, or isotopic Commodities; or pharmaceutically acceptable salts, solvates, hydrates, or prodrugs thereof The method involves administering a therapeutically effective dose.

[0279] In another embodiment, provided herein are one or more fibrous diseases in the subject. A method for treating, improving, or preventing the symptoms of, and for those who need it, Compounds of formula (IA): [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are therapeutically effective salts, solvates, hydrates, or prodrugs that are acceptable as pharmaceuticals. A method that involves administering a certain amount; (In the formula: R 1 (a) hydrogen, deuterium, cyano, halo, or nitro; or (b) C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10Cycloalkyl, C 6-14 Ariel, C 7-15 Aralquil , heteroaryl, or heterocyclyl; R 2 -CN, -C(O)OR 2a -C(O)NR 2b R 2c ,-C(O)N(R 2b )OR 2c , -OR 2a , -NR 2b R 2c , or Hete It is a lower aryl; here, R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 Alkyl, C2 -6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralchi It is a heteroaryl or heterocyclyl; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of (a) hydrogen, deuterium, cyano, halo, or nitrate. (b)C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 a Reel, C 7-15 Aralkyl, heteroaryl, or heterocyclyl; or (c)-C(O)R 1a , -C(O)OR 1a -C(O)NR 1b R 1c -C(NR 1a )NR 1b R 1c , -OR 1a ,-OC(O)R 1a -OC(O)OR 1a -OC(O) NR 1b R 1c -OC(NR 1a )NR 1b R 1c -OS(O)R 1a -OS(O)2R 1a -OS(O)NR 1b R 1c -OS(O)2NR 1b R 1c , -NR 1b R 1c , -NR 1a C(O)R 1d , -NR 1a C(O)OR 1d , -NR 1a C(O)NR 1b R 1c , -NR 1a C(NR 1d )NR 1b R 1c , -NR 1a S(O)R 1d , -NR 1a S(O)2R 1d , -NR 1a S(O)NR 1b R 1c , -NR 1a S(O)2NR 1b R 1c , -SR 1a ,-S(O)R 1 a -S(O)2R 1a -S(O)NR 1b R 1c , or -S(O)2NR 1b R 1c and; Each R 7 (a) Deuterium, cyano, halo, or nitro; (b) C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralchi (c)-C(O)R 1a , -C(O)OR 1a -C(O)NR 1b R 1c -C(NR 1a )NR 1b R 1c , -OR 1a ,-OC(O)R 1a -OC(O)OR 1a -OC(O)NR 1b R 1c -OC(NR 1a )NR 1b R 1c -OS(O)R 1a -OS(O)2R 1a -OS(O)NR 1b R 1c -OS(O)2NR 1b R 1c , -NR 1b R 1c , -NR 1a C(O)R 1 d , -NR 1a C(O)OR 1d , -NR 1a C(O)NR 1b R 1c , -NR 1a C(NR 1d )NR 1b R 1c , -NR 1a S(O)R 1d , -NR 1a S(O) 2R 1d , -NR 1a S(O)NR 1b R 1c , -NR 1a S(O)2NR 1b R 1c , -SR 1a ,-S(O)R 1a -S(O)2R 1a -S(O)NR 1b R 1c , or -S(O)2NR 1b R1c is; or two adjacent R 7 The f Together with the henyl group, it forms naphthyl or bicyclic heteroaryl groups; R C (a) hydrogen, deuterium, cyano, halo, or nitro; or (b) C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralquil , heteroaryl, or heterocyclyl; or (c)-OR 1a , -NR 1b R 1c , or -NR 1a C( O)R 1d and; L is C 1-6 Alkylene or C 2-6 It is an alkenylene; n is an integer of 0, 1, 2, 3, or 4; and Each R 1a , R 1b , R 1c , and R 1d These are, independently, hydrogen, deuterium, and C 1-6 Alkyl, C 2-6 Alke Nil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralkil, Hete It is either a roaryl or heterocyclyl; or R 1a and R 1c They are combined Together with C and N atoms, they form a heterocycline; or R 1b and R 1c They combine Together with the N atom present, it forms a heterocycline; Here, each alkyl, alkylene, alkenyl, alkenylene, alkynyl, cyclo Roalkyl, aryl, aralkyl, heteroaryl, and heterocyclyl are one or more In one embodiment, it is arbitrarily substituted with one, two, three, or four substituents Q, Here, each Q is (a) deuterium, cyano, halo, nitro, and oxo; (b) each of them is 1 or less In the above embodiment, one, two, three, or four substituents Q a And then it is arbitrarily replaced C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralkyl, heteroaryl, and heterocyclyl; and (c)-C(O)R a , -C(O)OR a -C(O)NR b R c -C(O)SR a -C(NR a )NR b R c ,-C(S)R a , -C(S)OR a -C(S)NR b R c , -OR a ,-OC(O)R a -OC(O)OR a -OC(O)NR b R c -OC(O)SR a -OC(NR a )NR b R c ,-OC(S)R a , -OC(S)O R a -OC(S)NR b R c -OS(O)R a -OS(O)2R a -OS(O)NR b R c -OS(O)2NRb R c , -NR b R c , -NR a C(O )R d , -NR a C(O)OR d , -NR a C(O)NR b R c , -NR a C(O)SR d , -NR a C(NR d )NR b R c , -NR a C(S)R d , -NR a C (S)OR d , -NR a C(S)NR b R c , -NR a S(O)R d , -NR a S(O)2R d , -NR a S(O)NR b R c , -NR a S(O)2NR b R c ,- SR a ,-S(O)R a -S(O)2R a -S(O)NR b R c , and -S(O)2NR b R c : Selected independently from, here, Each R a , R b , R c , and R d (i) hydrogen or deuterium; (ii) each of them is one or more In one embodiment, one, two, three, or four substituents Q a It is arbitrarily replaced by C 1-6 Alkyl, C 2-6 Alkenil, C 2-6Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel , C 7-15 (iii)R b Reach biR c Together with the N atoms to which they are bonded, one or more, in one embodiment, one, two , three or four substituents Q a It forms a heterocycline which is optionally substituted; Here, each Q a (a) Deuterium, cyano, halo, nitro, and oxo; (b) C 1-6 Alki Ru, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 a Larquil, heteroaryl, and heterocyclyl; and (c)-C(O)R e , -C(O)OR e -C(O)NR f R g -C(O)SR e -C(NR e )NR f R g ,-C(S)R e , -C(S)OR e -C(S)NR f R g , -OR e ,-OC(O)R e ,-OC( O)OR e -OC(O)NR f R g -OC(O)SR e -OC(NR e )NR f R g ,-OC(S)R e , -OC(S)OR e -OC(S)NR f R g , -OS(O)R e -OS(O)2R e -OS(O)NR f R g -OS(O)2NR f R g , -NR f R g , -NR e C(O)R h , -NR e C(O)OR f , -NR e C(O)NR f R g , -NR e C(O)SR f , -NR e C(NR h )NR f R g , -NR e C(S)R h , -NR e C(S)OR f , -NR e C(S) NR f R g , -NR e S(O)R h , -NR e S(O)2R h , -NR e S(O)NR f R g , -NR e S(O)2NR f R g , -SR e ,-S(O)R e , -S (O)2R e -S(O)NR f R g , and -S(O)2NR f R g : independently selected from; here, each R e , R f , R g , and R h (i) hydrogen or deuterium; (ii) C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aalkyl, heteroaryl , or heterocyclyl; or (iii)R f and R g The N atoms to which they are bonded (Together, they form heterocyclines.)

[0280] In one embodiment, the compound of formula (IA) has the structure of formula (II-A): [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or or have pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; ( In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R C L and n are defined herein, respectively. (That's right.)

[0281] In another embodiment, the compound of formula (IA) has the structure of formula (III-A): [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or or have pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; ( In the formula, R 1 , R 2, R 3 , R 4 , R 5 , R 6 , R 7 , R C L and n are defined herein, respectively. (That's right.)

[0282] In another embodiment, the compound of formula (IA) has the structure of formula (VI-A): [ka] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or or have pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; ( In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R C L and n are defined herein, respectively. (That's right.)

[0283] In one embodiment, in any one of the formulas (IA) to (IV-A), R 1 is hydrogen or C 1-6 It is alkyl; R 2 -CN, -C(O)OR 2a -C(O)NR 2b R 2c , -OR 2a , -NR 2b R 2c or heteroaryl Here, each R 2a , R 2b , and R 2c These are, independently, hydrogen or C 1-6 It is alkyl; R3 , R 4 , R 5 , and R 6 These are, independently, hydrogen, deuterium, halo, and C. 1-6 Alkyl, or -OC 1- It is a 6-alkyl group; R 7 And n is either (i) or (ii): (i)n is an integer of 0, 1, 2, 3, or 4; and Each R 7 These are independently deuterium, halo, and C. 1-6 Alkyl, or -OC 1-6 It is alkyl or (ii) n is an integer of 2, 3, or 4; and Two adjacent R 7 Together with the phenyl group to which they are bound, they form naphthyl molecules; R C is hydrogen, cyano, C 1-6 Alkyl, C 2-6 Alkenil, C 3-10 Cycloalkyl, hetero Aryl, heterocyclyl, -OC 1-6 Alkyl, -NHC(O)-C 1-6 Alkyl, or -N(C 1-6 Al Kill) 2; and L is C 1-6 Alkylene or C 2-6 It is an alkenylene; Here, each alkyl, alkylene, alkenyl, alkenylene, cycloalkyl, Heteroaryls and heterocyclyls are optionally substituted with one, two, or three substituents Q. It is.

[0284] In another embodiment, in any one of equations (IA) to (IV-A), R 1 is hydrogen or C 1-6 It is alkyl; R 2-CN, -C(O)OR 2a -C(O)NR 2b R 2c , -OR 2a , -NR 2b R 2c , or a 5-membered heteroaryl And here, each R 2a , R 2b , and R 2c These are, independently, hydrogen or C 1-6 It is alkyl; R 3 and R 5 Each is independently either hydrogen or deuterium; R 4 and R 6 These are, independently, hydrogen, deuterium, halo, and C. 1-6 Alkyl, or -OC 1-6 Alkyl and; R 7 And n is either (i) or (ii): (iii) n is an integer of 0, 1, or 2; and Each R 7 These are independently deuterium, halo, and C. 1-6 Alkyl, or -OC 1-6 It is alkyl or (iv) n is an integer of 2; and Two adjacent R 7 Along with the phenyl group to which they are bonded, naphthal-1-yl or It forms naphthal-2-yl; R C is hydrogen, cyano, C 1-6 Alkyl, C 2-6 Alkenil, C 3-10 Cycloalkyl, hetero Aryl, heterocyclyl, -OC 1-6 Alkyl, -NHC(O)-C 1-6 Alkyl, or -N(C 1-6 Al Kill) 2; and L is C 1-6 Alkylene or C 2-6 It is an alkenylene; Here, each alkyl, alkylene, alkenyl, alkenylene, cycloalkyl, Heteroaryls and heterocyclyls are optionally substituted with one, two, or three substituents Q. It is.

[0285] In another embodiment, in any one of equations (IA) to (IV-A), R 1 is hydrogen, methyl, ethyl, or butyl; R 2 is -CN, -C(O)OH, -C(O)NH2, -C(O)NHCH3, -OH, -NH2, or tetrazolyl; R 3 and R 5 Each is independently either hydrogen or deuterium; R 4 This includes hydrogen, fluoro, chloro, methyl, ethyl, isopropyl, methoxy, or ethyl It is Kishi; R 6 is hydrogen, deuterium, or fluorocarbon; R 7 And n is either (i) or (ii): (i) n is an integer of 0, 1, or 2; and Each R 7 is independently fluoro, chloro, or methoxy; or (ii) n is an integer of 2; and Two adjacent R 7 Along with the phenyl group to which they are bonded, naphthal-1-yl or It forms naphthal-2-yl; R C These are hydrogen, cyano, methyl, trifluoromethyl, ethyl, propyl, and fluoropropyl. Pill, difluoropropyl, hexafluoropropyl, butyl, propenyl, cyclopro Pyr, cyclopentyl, pyridyl, pyrrolidinyl, hydroxyl, methoxy, ethoxy, It is acetamide or dimethylamino; and L is methylene, ethylene, or ethenylene.

[0286] In another embodiment, in any one of equations (IA) to (IV-A), R 1 is hydrogen, methyl, ethyl, or (2-methyl)propyl; R 2 These are -CN, -C(O)OH, -C(O)NH2, -C(O)NHCH3, -OH, -NH2, or tetrazole-5-yl. can be; R 3 and R 5 Each is independently either hydrogen or deuterium; R 4 This includes hydrogen, fluoro, chloro, methyl, ethyl, isopropyl, methoxy, or ethyl It is Kishi; R 6 is hydrogen, deuterium, or fluorocarbon; R 7 And n is either (i) or (ii): (i) n is an integer of 0, 1, or 2; and Each R 7 is fluoro; or (ii) n is an integer of 2; and Two adjacent R 7 Along with the phenyl group to which they are bonded, naphthal-1-yl or It forms naphthal-2-yl; R C is hydrogen, cyano, methyl, trifluoromethyl, ethyl, 2-fluoropropane-2- Iyl, 1,3-difluoropropan-2-yl, di(trifluoromethyl)methyl, isopropyl t-butyl, prop-1-en-2-yl, cyclopropyl, cyclopentyl, pyrido-2-yl Pyrrolidine-1-yl, hydroxyl, methoxy, ethoxy, acetamide, or dimethyl It is a luamino; and L is methylene, ethane-1,2-diyl, or ethene-1,2-diyl.

[0287] In one embodiment, the compound of formula (IA) is (Z)-2-(2-methyl-1-(4-isopropylbenzylidene)-1H-inden-3-yl)acetic acid B1; (Z)-2-(5-fluoro-2-methyl-1-(benzylidene)-1H-inden-3-yl)acetic acid B2; (Z)-2-(5-fluoro-2-methyl-1-(3-cyanobenzylidene)-1H-inden-3-yl)acetic acid B3; (Z)-2-(5-fluoro-2-methyl-1-(4-cyanobenzylidene)-1H-inden-3-yl)acetic acid B4; (Z)-2-(5-fluoro-2-methyl-1-(4-methylbenzylidene)-1H-inden-3-yl)acetic acid B5; (Z)-2-(5-fluoro-2-methyl-1-(3-trifluoromethylbenzylidene)-1H-indene-3-i (Lu) Acetate B6; (Z)-2-(5-fluoro-2-methyl-1-(4-trifluoromethylbenzylidene)-1H-indene-3-i (Lu) Acetate B7; (Z)-2-(5-fluoro-2-methyl-1-(4-ethylbenzylidene)-1H-inden-3-yl)acetic acid B8; (Z)-2-(5-fluoro-2-methyl-1-(4-isopropylbenzylidene)-1H-inden-3-yl)vinegar Acid B9; (Z)-2-(5-fluoro-2-methyl-1-(4-t-butylbenzylidene)-1H-inden-3-yl)acetic acid B10 ; (Z)-2-(5-fluoro-2-ethyl-1-(4-isopropylbenzylidene)-1H-inden-3-yl)vinegar acid B11; (Z)-2-(5-fluoro-2-(2-methylpropyl)-1-(4-isopropylbenzylidene)-1H-inde B12 acetate (-3-yl) (Z)-2-(5-fluoro-2-methyl-1-(3-methoxybenzylidene)-1H-inden-3-yl)acetic acid B13 ; (Z)-2-(5-fluoro-2-methyl-1-(4-methoxybenzylidene)-1H-inden-3-yl)acetic acid B14 ; (Z)-2-(5-fluoro-2-methyl-1-(4-ethoxybenzylidene)-1H-inden-3-yl)acetic acid B15 ; (Z)-2-(5-fluoro-2-methyl-1-(4-(pyrrolidine-1-yl)benzylidene)-1H-indene-3- B16 yl acetate; (Z)-2-(5-fluoro-2-methyl-1-(4-(pyrido-2-yl)benzylidene)-1H-inden-3-yl) Acetate B17; (Z)-2-(5-chloro-2-methyl-1-(4-t-butylbenzylidene)-1H-inden-3-yl)acetic acid B18; (Z)-2-(5-methyl-2-methyl-1-(4-isopropylbenzylidene)-1H-inden-3-yl)acetic acid B 19; (Z)-2-(5-ethyl-2-methyl-1-(4-isopropylbenzylidene)-1H-inden-3-yl)acetic acid B 20; (Z)-2-(5-isopropyl-2-methyl-1-(4-isopropylbenzylidene)-1H-inden-3-yl ) Acetate B21; (Z)-2-(5-Methoxy-2-methyl-1-(4-isopropylbenzylidene)-1H-inden-3-yl)vinegar acid B22; (Z)-2-(5-ethoxy-2-methyl-1-(4-isopropylbenzylidene)-1H-inden-3-yl)vinegar Acid B23; (Z)-2-(5-fluoro-1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl) Cetoamide B24; (Z)-2-(5-fluoro-1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl)-N- Methylacetamide B25; (Z)-2-(5-fluoro-1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl)-N, N-dimethylacetamide B26; (Z)-2-(1-(4-acetamidobenzylidene)-5-fluoro-2-methyl-1H-inden-3-yl)vinegar Acid B27; (Z)-3-(5-fluoro-1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl) Ropanic acid B28; (Z)-5-(2-(5-fluoro-1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl) Ethyl)-1H-tetrazole B29; (Z)-5-(2-(1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl)ethyl)-1H- Tetrazole B30; (Z)-2-(4-fluoro-2-methyl-1-(benzylidene)-1H-inden-3-yl)acetic acid B31; (Z)-2-(5-fluoro-1-(4-dimethylaminobenzylidene)-2-methyl-1H-inden-3-yl) Propanic acid B32; 2-[(1Z)-5-fluoro-1-[(2-hydroxynaphthalene-1-yl)methylidene]-2-methyl-1H-yl [Denden-3-yl]acetic acid B33; 2-[(1Z)-5-fluoro-2-methyl-1-[(naphthalene-2-yl)methylidene]-1H-inden-3-yl Acetate B34; 2-[(1Z)-5-fluoro-2-methyl-1-[(4-methylnaphthalene-1-yl)methylidene]-1H-inde [N-3-yl]acetic acid B35; 2-[(1Z)-5-fluoro-1-[(2-methoxynaphthalene-1-yl)methylidene]-2-methyl-1H-yne Den-3-yl acetate B36; 2-[(1Z)-1-[(4-cyclopropylphenyl)methylidene]-5-fluoro-2-methyl-1H-indene B37-3-yl acetate; 2-[(1Z)-1-[(4-cyclopentylphenyl)methylidene]-5-fluoro-2-methyl-1H-indene B38-3-yl acetate; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(prop-1-en-2-yl)phenyl]methylidene}-1H- Inden-3-yl acetate B39; 2-[(1Z)-5-fluoro-1-{[4-(2-fluoropropan-2-yl)phenyl]methylidene}-2-methyl [Lu-1H-inden-3-yl]acetic acid B40; 2-[(1Z)-1-{[4-(dimethylamino)phenyl]methylidene}-5-fluoro-2-methyl-1H-inde [N-3-yl]acetic acid B41; 2-[(1Z)-5-fluoro-1-{[4-(1,1,1,3,3,3-hexafluoropropan-2-yl)phenyl]methyl [Chylidene]-2-methyl-1H-inden-3-yl]acetic acid B42; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(propan-2-yl)phenyl]methylidene}-1H-yne Den-3-yl]propanoate B43; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(trifluoromethyl)phenyl]methylidene}-1H- [Denden-3-yl]propanoate B44; 2-[(1Z)-7-fluoro-2-methyl-1-{[4-(propan-2-yl)phenyl]methylidene}-1H-yne Den-3-yl acetate B45; 2-[(1Z)-7-fluoro-2-methyl-1-{[4-(trifluoromethyl)phenyl]methylidene}-1H- [Denden-3-yl]acetic acid B46; 2-[(1Z)-1-{[4-(1,3-difluoropropan-2-yl)phenyl]methylidene}-5-fluoro-2- Methyl-1H-inden-3-yl]acetic acid B47; or 2-[(1Z)-5-fluoro-1-{[3-fluoro-4-(propan-2-yl)phenyl]methylidene}-2-methyl [Lu-1H-inden-3-yl]acetic acid B48; or these tautomers, mixtures of two or more tautomers, or isotopic variants; or this These are pharmaceutically acceptable salts, solvates, hydrates, or prodrugs:

[0288] In another embodiment, the compound of formula (IA) is (E)-2-(5-fluoro-2-methyl-1-(4-isopropylbenzylidene)-1H-inden-3-yl)vinegar acid B49; (E)-2-(5-fluoro-1-(4-isopropylbenzylidene...

Claims

1. Compound of formula (I): 【Chemistry 1】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or or the following pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (In the formula: R 1 (a) hydrogen, deuterium, cyano, halo, or nitro; or (b) C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralquil , heteroaryl, or heterocyclyl; R 2 is -C(O)OR 2a -C(O)NR 2b R 2c -C(O)N(R 2b )OR 2c or heteroaryl; where So, R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 a Lukinil, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aalkyl, heteroaryl, or heterocycline; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of (a) hydrogen, deuterium, cyano, halo, or nitrate. (b)C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 a Reel, C 7-15 Aralkyl, heteroaryl, or heterocyclyl; or (c)-C(O)R 1a 、-C(O)OR 1a 、-C(O)NR 1b R 1c 、-C(NR 1a )NR 1b R 1c 、-OR 1a 、-OC(O)R 1a 、-OC(O)OR 1a 、-OC(O) NR 1b R 1c ,-OC(NR 1a )NR 1b R 1c 、-OS(O)R 1a 、-OS(O) 2 R 1a 、-OS(O)NR 1b R 1c 、-OS(O) 2 NR 1b R 1c 、-NR 1b R 1c 、-NR 1a C(O)R 1d 、-NR 1a C(O)OR 1d 、-NR 1a C(O)NR 1b R 1c 、-NR 1a C(NR 1d )NR 1b R 1c 、 -NR 1a S(O)R 1d 、-NR 1a S(O) 2 R 1d 、-NR 1a S(O)NR 1b R 1c 、-NR 1a S(O) 2 NR 1b R 1c 、-SR 1a 、-S(O)R 1 a 、 -S(O) 2 R 1a 、 -S(O)NR 1b R 1c 、 or -S(O) 2 NR 1b R 1c ; and R A C 6-14 It is either allirene or heteroarirene; R B And X is (i), (ii), or (iii): (vii)X is -O-, -S-, -S(O)-, or -S(O) 2 -and; and R B C 6-14 It is either an aryl or heteroaryl; (viii) X is -N(R X )-; R B C 6-14 It is aryl or heteroaryl; and R X is hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl , C 6-14 Ariel, C 7-15 Is it an aralkyl, heteroaryl, or heterocyclyl? ; or (ix)X is -N(R X )-and; and R B and R X These, along with the N atom to which they are bonded, form heteroaryl or heterosilicate compounds. Forming krill; L is C 1-6 Alkylene, C 2-6 Alkenylene, C 3-10 Cycloalkylene, or heterocycline It is a Len; and Each R 1a , R 1b , R 1c , and R 1d These are, independently, hydrogen, deuterium, and C 1-6 Alkyl, C 2-6 Alke Nil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralkil, Hete It is either a roaryl or heterocyclyl; or R 1a and R 1c They are combined Together with C and N atoms, they form a heterocycline; or R 1b and R 1c They combine Together with the N atom present, it forms a heterocycline; Here, each alkyl, alkylene, alkenyl, alkenylene, alkynyl, cyclo Roalkyl, cycloalkylene, aryl, arylene, aralkyl, heteroaryl, Heteroarylene, heterocyclyl, and heterocyclylene are one or more in one embodiment In this compound, one, two, three, or four substituents Q are arbitrarily substituted, where each Q is (a) Deuterium, cyano, halo, nitro, and oxo; (b) Each of them is one or more embodiments. In this, one, two, three, or four substituents Q a C is further arbitrarily substituted. 1-6 Al Kill, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralkyl, heteroaryl, and heterocyclyl; and (c)-C(O)R a , -C(O)OR a , -C(O) NR b R c 、-C(O)SR a 、-C(NR a )NR b R c 、-C(S)R a 、-C(S)OR a 、-C(S)NR b R c 、-OR a 、-OC(O)R a 、-O C(O)OR a 、-OC(O)NR b R c 、-OC(O)SR a 、-OC(NR a )NR b R c 、-OC(S)R a 、-OC(S)OR a 、-OC(S)NR b R c 、-OS(O)R a 、-OS(O) 2 R a 、-OS(O)NR b R c 、-OS(O) 2 NR b R c 、-NR b R c 、-NR a C(O)R d 、-NR a C(O)OR d 、-NR a C(O)NR b R c 、-NR a C(O)SR d 、-NR a C(NR d )NR b R c 、-NR a C(S)R d 、-NR a C(S)OR d 、-NR a C(S )NR b R c 、-NR a S(O)R d 、-NR a S(O) 2 R d 、-NR a S(O)NR b R c 、-NR a S(O) 2 NR b R c 、-SR a 、-S(O)R a 、- S(O) 2 R a -S(O)NR b R c , and -S(O) 2 NR b R c : are independently selected from, where each R a , R b , R c , and R d (i) hydrogen or deuterium; (ii) each of them in one or more embodiments In this, one, two, three, or four substituents Q a C is arbitrarily replaced by 1-6 Alkyl, C 2 -6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralchi (iii)R b and R c Those Along with the bonded N atom, one or more, in one embodiment, one, two, three, or four substituted Q a It forms a heterocycline which is optionally substituted; Here, each Q a (a) Deuterium, cyano, halo, nitro, and oxo; (b) C 1-6 Alki Ru, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 a Larkyl, heteroaryl, and heterocyclyl; and (c)-C(O)R e , -C(O)OR e -C(O)NR f R g 、-C(O)SR e 、-C(NR e )NR f R g 、-C(S)R e 、-C(S)OR e 、-C(S)NR f R g 、-OR e 、-OC(O)R e 、-OC( O)OR e 、-OC(O)NR f R g 、-OC(O)SR e 、-OC(NR e )NR f R g 、-OC(S)R e 、-OC(S)OR e 、-OC(S)NR f R g 、 -OS(O)R e 、-OS(O) 2 R e 、-OS(O)NR f R g 、-OS(O) 2 NR f R g 、-NR f R g 、-NR e C(O)R h 、-NR e C(O)OR f 、-NR e C(O)NR f R g 、-NR e C(O)SR f 、-NR e C(NR h )NR f R g 、-NR e C(S)R h 、-NR e C(S)OR f 、-NR e C(S) NR f R g 、-NR e S(O)R h 、-NR e S(O) 2 R h 、-NR e S(O)NR f R g 、-NR e S(O) 2 NR f R g 、-SR e 、-S(O)R e 、-S (O) 2 R e -S(O)NR f R g , and -S(O) 2 NR f R g : independently selected from; here, each R e , R f , R g , and R h (i) hydrogen or deuterium; (ii) C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aalkyl, heteroaryl , or heterocyclyl; or (iii)R f and R g The N atoms to which they are bonded (Together, they form heterocyclines.)

2. R A C is optionally substituted with one or more substituents Q. 6-14 The compound according to claim 1, which is arylene. 。

3. R A The compound according to claim 1, wherein is a heteroarylene optionally substituted with one or more substituents Q. thing.

4. R A Claim 1 or 3, wherein is a monocyclic heteroarylene optionally substituted with one or more substituents Q. The compound described.

5. R A Claims 1, 3, and This is the compound described in section 4.

6. R A Any of claims 1 and 3 to 5, wherein is a pyridylene optionally substituted with one or more substituents Q. A compound as described in item 1.

7. A compound according to any one of claims 1 to 6, having the structure of formula (III): 【Chemistry 2】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or or the following pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (In the formula: U 1 , V 1 , W 1 , and X 1 These are, independently of each other, (i) C or N; or (ii) -CR 7a =, -N=, -NR 7b -,- It is O- or -S-; Y 1 (i) C or N; or (ii) bond, -CR 7a =, -N=, -NR 7b -, -O-, or -S-; Z 1 is C or N; Each R 7a (a) hydrogen, deuterium, cyano, halo, or nitro; (b) C 1-6 Al Kill, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralkyl, heteroaryl, or heterocyclyl; or (c)-C(O)R 1a , -C(O)OR 1a ,- C(O)NR 1b R 1c 、-C(NR 1a )NR 1b R 1c 、-OR 1a 、-OC(O)R 1a 、-OC(O)OR 1a 、-OC(O)NR 1b R 1c 、-OC(N R 1a )NR 1b R 1c 、-OS(O)R 1a 、-OS(O) 2 R 1a 、-OS(O)NR 1b R 1c 、-OS(O) 2 NR 1b R 1c 、-NR 1b R 1c 、-NR 1a C(O)R 1d 、-NR 1a C(O)OR 1d 、-NR 1a C(O)NR 1b R 1c 、-NR 1a C(NR 1d )NR 1b R 1c 、-NR 1a S(O)R 1d 、- NR 1a S(O) 2 R 1d 、-NR 1a S(O)NR 1b R 1c 、-NR 1a S(O) 2 NR 1b R 1c 、-SR 1a 、-S(O)R 1a 、-S(O) 2 R 1a 、- S(O)NR 1b R 1c , or -S(O) 2 NR 1b R 1c and Each R 7b These are, independently, hydrogen and C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralkyl, heteroaryl, or heterocycline It is; Here, each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and ara are defined as follows: Lukyl, heteroaryl, and heterocyclyl are optionally substituted with one or more substituents Q. (ru).

8. A compound according to any one of claims 1 to 7, having the structure of formula (IX): 【Transformation 3】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or or the following pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (In the formula: Each R 7 (a) Deuterium, cyano, halo, or nitro; (b) One or more of each. C is optionally substituted with substituent Q. 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralkyl, heteroaryl, or heteroaryl Rosicrill; or (c)-C(O)R 1a , -C(O)OR 1a -C(O)NR 1b R 1c -C(NR 1a )NR 1b R 1c , -OR 1a -OC (O)R 1a 、-OC(O)OR 1a 、-OC(O)NR 1b R 1c 、-OC(NR 1a )NR 1b R 1c 、-OS(O)R 1a 、-OS(O) 2 R 1a 、-OS( O)NR 1b R 1c 、-OS(O) 2 NR 1b R 1c 、-NR 1b R 1c 、-NR 1a C(O)R 1d 、-NR 1a C(O)OR 1d 、-NR 1a C(O)NR 1b R 1c 、-NR 1a C(NR 1d )NR 1b R 1c 、-NR 1a S(O)R 1d 、-NR 1a S(O) 2 R 1d 、-NR 1a S(O)NR 1b R 1c 、-NR 1a S(O ) 2 NR 1b R 1c , -SR 1a ,-S(O)R 1a , -S(O) 2 R 1a -S(O)NR 1b R 1c , or -S(O) 2 NR 1b R 1c and ;and n is an integer (0, 1, 2, 3, or 4).

9. C where L is arbitrarily substituted with one or more substituents Q 1-6 any one of claims 1 to 8, which is an alkylene. The compound described in item 1.

10. L is methylene, ethylene, or L, each of which is optionally substituted with one or more substituents Q. The compound according to any one of claims 1 to 9, wherein the compound is propylene.

11. C where L is arbitrarily substituted with one or more substituents Q 2-6 Alkenylene, any one of claims 1 to 8 A compound as described in item 1.

12. Any of claims 1 to 8 and 11, wherein L is ethenylene optionally substituted with one or more substituents Q. A compound as described in item 1.

13. X is -O- or -NR X -and here, R X (i) hydrogen; or (ii) each of them having one or more substituents Q C is arbitrarily substituted. 1-6 Alkyl, C 6-14 Aryl, or C 7-15 It is Aral Kil or the compound according to any one of claims 1 to 12.

14. The compound according to any one of claims 1 to 13, wherein X is -O-.

15. R 2 ga-C(O)OR 2a The compound according to any one of claims 1 to 14.

16. R 2 The compound according to claim 15, wherein is -C(O)OH.

17. R 2 -C(O)NR 2b R 2c The compound according to any one of claims 1 to 14.

18. R 2 ga-C(O)NHR 2c And R 2c However, each of them is arbitrarily substituted with one or more substituents Q. ru C 1-6 The compound according to claim 17, wherein it is alkyl or heteroaryl.

19. R 2 However, -C(O)NH 2 -C(O)NHCH 3 -C(O)NHCH 2 CH 2 It is either OH or -C(O)NH (tetrazolyl), The compound according to claim 17.

20. R 2 -C(O)N(R 2b )OR 2c The compound according to any one of claims 1 to 14.

21. R 2 -C(O)NHOR 2c The compound according to claim 20.

22. R 2 The compound according to claim 20, wherein is -C(O)NHOH.

23. A compound according to any one of claims 1 to 22, having the structure of formula (XIV): 【Chemistry 4】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug of these; (wherein R 2 A is -OR 2a , -NR 2b R 2c , or -N(R 2b )OR 2c (and p is an integer of 1, 2, or 3).

24. The compound according to claim 23, having the structure of formula (XV): 【Transformation 5】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These include pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

25. The compound according to claim 23, having the structure of formula (XVI): 【Transformation 6】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These include pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

26. The compound according to claim 23, having the structure of formula (XVIII): 【Transformation 7】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These include pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

27. R 7 However, deuterium, halo, or -OC may be optionally substituted with one or more substituents Q. 1-6 Alkyl a compound according to any one of claims 23 to 26.

28. R 7 The compound according to claim 27, wherein is chloro or methoxy.

29. The compound according to claim 23, having the structure of formula (XVII): 【Transformation 8】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These include pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

30. R 7a However, hydrogen, deuterium, halo, or -OC may be optionally substituted with one or more substituents Q. 1-6 Alki The compound according to claim 29.

31. R 7a The compound according to claim 29 or 30, wherein the compound is hydrogen, deuterium, chloro, or methoxy.

32. R B However, each of these is arbitrarily substituted with one or more substituents Q, resulting in a monocyclic or bicyclic C. 6-1 4 Any one of claims 1 to 31, which is an aryl, or a monocyclic or bicyclic heteroaryl. The compounds listed in the section.

33. R B However, each of these is arbitrarily substituted with one or more substituents Q, resulting in a monocyclic or bicyclic C. 6-1 4 It is an aryl, or a monocyclic or bicyclic heteroaryl, where each substituent Q is a bron. Mo, chloro, fluoro, cyano, methyl, trifluoromethyl, ethyl, propyl, hydroxy Any one of claims 1 to 32, independently selected from roxyl, methoxy, and formyl. The compound described.

34. R B However, each of these is arbitrarily substituted with one or more substituents Q, such as phenyl, naphthyl, and pyri compounds. The substituent Q is either zyl or quinolinyl, and each of the substituents Q is bromo, chloro, fluoro, or cyano German compounds derived from methyl, trifluoromethyl, ethyl, propyl, hydroxyl, and methoxy. A compound according to any one of claims 1 to 33, which is selected for standing.

35. R B However, phenyl, bromophenyl, fluorophenyl, cyanophenyl, methylphenyl L, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Lu, formylphenyl, bromo-fluorophenyl, difluorophenyl, trifluoro Phenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl, or quinolinyl A compound according to any one of claims 1 to 34.

36. R B However, phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, 3-shea Nophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 4- Trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methoxy Phenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl, 2 ,4-difluorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoropyryl Claim 1 is do-5-yl, 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl. Compounds described in any one of items ~35.

37. A compound according to any one of claims 1 to 22, having the structure of formula (XIX): 【Chemistry 9】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These include pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

38. A compound according to claim 37 having the structure of formula (XX): 【Chemistry 10】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These include pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

39. A compound according to claim 37 having the structure of formula (XXI): 【Chemistry 11】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These include pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

40. A compound according to claim 37 having the structure of formula (XXIII): 【Chemistry 12】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These include pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

41. R 7 However, deuterium, halo, or -OC may be optionally substituted with one or more substituents Q. 1-6 Alkyl a compound according to any one of claims 37 to 40.

42. R 7 The compound according to claim 41, wherein is chloro or methoxy.

43. A compound according to claim 37 having the structure of formula (XXII): 【Chemistry 13】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These include pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

44. R 7a However, hydrogen, deuterium, halo, or -OC may be optionally substituted with one or more substituents Q. 1-6 Alki The compound according to claim 43.

45. R 7a The compound according to claim 43 or 44, wherein the compound is hydrogen, deuterium, chloro, or methoxy.

46. R B However, each of these is arbitrarily substituted with one or more substituents Q, resulting in a monocyclic or bicyclic C. 6-1 4 Any of claims 37 to 45, which is an aryl, or a monocyclic or bicyclic heteroaryl. The compound described in item 1.

47. R B However, each of these is arbitrarily substituted with one or more substituents Q, resulting in a monocyclic or bicyclic C. 6-1 4 It is an aryl, or a monocyclic or bicyclic heteroaryl, where each substituent Q is a bron. Mo, chloro, fluoro, cyano, methyl, trifluoromethyl, ethyl, propyl, hydroxy Any one of claims 37 to 46, independently selected from roxyl, methoxy, and formyl. The compound described.

48. R B However, phenyl, bromophenyl, fluorophenyl, cyanophenyl, methylphenyl L, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Lu, formylphenyl, bromo-fluorophenyl, difluorophenyl, trifluoro Phenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl, or quinolinyl A compound according to any one of claims 37 to 47.

49. R B However, phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, 3-shea Nophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 4- Trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methoxy Phenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl, 2 ,4-difluorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoropyryl Claim 3, which is do-5-yl, 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl. A compound described in any one of items 7 to 48.

50. R X However, (i) hydrogen; or (ii) each of them is optionally substituted with one, two, or three substituents Q. C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 It is Aralkil, Claim 37- A compound as described in any one of item 49.

51. R X However, (i) hydrogen; or (ii) each of them is optionally substituted with one, two, or three substituents Q. C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 It is an aralkyl, and each substitution Group Q is bromo, chloro, fluoro, cyano, methyl, trifluoromethyl, ethyl, pr A compound independently selected from ropyl, hydroxyl, methoxy, and formyl, according to claims 37-50. Any compound listed in one of the items.

52. R X However, hydrogen, methyl, ethyl, hydroxyethyl, propyl, phenyl, fluoromethyl The compound according to any one of claims 37 to 51, which is nyl, formylphenyl, or benzyl thing.

53. R X However, hydrogen, methyl, ethyl, 2-hydroxyethyl, n-propyl, phenyl, 4-fluorine The following is a description of any one of claims 37 to 52, which is lophenyl, 4-formylphenyl, or benzyl. The compound listed.

54. R B and R X However, each of these atoms, along with the N atom to which they are bonded, can be arbitrarily substituted with one or more substituents Q. Forms a heteroaryl or heterocycline as described in any one of claims 37 to 45. A compound of [unclear].

55. R B and R X However, along with the N atom to which they are bonded, they can be optionally substituted with one or more substituents Q. The compound according to claim 54, which forms a heteroaryl compound.

56. R B and R X However, each of these atoms, along with the N atom to which they are bonded, can be arbitrarily substituted with one or more substituents Q. The compound according to claim 54 or 55, which forms a monocyclic or bicyclic heteroaryl.

57. R B and R X However, together with the N atom to which they are bonded, pyrrole-1-yl, 2-amino-imi The present invention relates to any one of claims 54 to 56, which forms dazole-1-yl or indole-1-yl. A compound of [unclear].

58. R B and R X However, along with the N atom to which they are bonded, they can be optionally substituted with one or more substituents Q. The compound according to claim 54, which forms a heterocycline.

59. R B and R X However, each of these atoms, along with the N atom to which they are bonded, can be arbitrarily substituted with one or more substituents Q. The compound according to claim 54 or 58, which forms a monocyclic or bicyclic heterocycline.

60. R B and R X However, together with the N atom to which they are bonded, pyrrolidine-1-yl, piperidine-1 The compound according to claim 54, 58, or 59, which forms -yl or 4-morpholine-4-yl.

61. R 2A ga-OR 2a The compound according to any one of claims 23 to 60.

62. R 2A The compound according to claim 61, wherein is -OH.

63. R 2A ga-NR 2b R 2c The compound according to any one of claims 23 to 60.

64. R 2A ga-NHR 2c And R 2c However, each of them is arbitrarily substituted with one or more substituents Q. 1 -6 The compound according to claim 63, wherein it is alkyl or heteroaryl.

65. R 2A However, -NH 2 , -NHCH 3 , -NHCH 2 CH 2 Claim 63 or 64, which is OH or -NH (tetrazolyl). The compound described.

66. R 2A ga-N(R 2b )OR 2c The compound according to any one of claims 23 to 60.

67. R 2A ga-NHOR 2c The compound according to claim 66.

68. R 2A The compound according to claim 66 or 67, wherein is -NHOH.

69. R 2 Any of claims 1 to 14, wherein is a heteroaryl which is optionally substituted with one or more substituents Q. A compound as described in item 1.

70. R 2 The compound is a monocyclic heteroaryl compound optionally substituted with one or more substituents Q, according to claims 1 to 14. is a compound as described in any one of item 69.

71. R 2 Claims 1 to 14, 69, wherein is a 5-membered heteroaryl optionally substituted with one or more substituents Q. Or a compound as described in any one of item 70.

72. A compound according to any one of claims 1 to 14 and 69 to 71, having the structure of formula (XXIV): 【Chemistry 14】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or or the following pharmaceutically acceptable salts, solvates, hydrates, or prodrugs; (In the formula, U 2 is -N= or -O-; and V 2 (is -N= or -C(OH)=).

73. The compound according to claim 72, wherein the compound is a compound of formula (XXV): 【Chemistry 15】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These include pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

74. The compound according to claim 72, wherein the compound is a compound of formula (XXVI): 【Chemistry 16】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These include pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

75. The compound according to claim 72, wherein the compound is a compound of formula (XXVIII): 【Chemistry 17】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These include pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

76. R 7 However, deuterium, halo, or -OC may be optionally substituted with one or more substituents Q. 1-6 Alkyl a compound according to any one of claims 72 to 75.

77. R 7 The compound according to claim 76, wherein is chloro or methoxy.

78. The compound according to claim 72, wherein the compound is a compound of formula (XXVII): [Chemistry 18] or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These include pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

79. R 7a However, hydrogen, deuterium, halo, or -OC may be optionally substituted with one or more substituents Q. 1-6 Alki The compound according to claim 78.

80. R 7a The compound according to claim 78 or 79, wherein the compound is hydrogen, deuterium, chloro, or methoxy.

81. R B However, each of these is arbitrarily substituted with one or more substituents Q, resulting in a monocyclic or bicyclic C. 6-1 4 Any of claims 72 to 80, which is an aryl, or a monocyclic or bicyclic heteroaryl. The compound described in item 1.

82. R B However, each of these is arbitrarily substituted with one or more substituents Q, resulting in a monocyclic or bicyclic C. 6-1 4 It is an aryl, or a monocyclic or bicyclic heteroaryl, where each substituent Q is a bron. Mo, chloro, fluoro, cyano, methyl, trifluoromethyl, ethyl, propyl, hydroxy Any one of claims 72 to 81, independently selected from roxyl, methoxy, and formyl. The compound described.

83. R B However, each of these is arbitrarily substituted with one or more substituents Q, such as phenyl, naphthyl, and pyri compounds. The substituent Q is either zyl or quinolinyl, and each of the substituents Q is bromo, chloro, fluoro, or cyano German compounds derived from methyl, trifluoromethyl, ethyl, propyl, hydroxyl, and methoxy. A compound according to any one of claims 72 to 82, which is selected for standing.

84. R B However, phenyl, bromophenyl, fluorophenyl, cyanophenyl, methylphenyl L, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Lu, formylphenyl, bromo-fluorophenyl, difluorophenyl, trifluoro Phenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl, or quinolinyl A compound according to any one of claims 72 to 83.

85. R B However, phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, 3-shea Nophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 4- Trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methoxy Phenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl, 2 ,4-difluorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoropyryl Claim 7, which is do-5-yl, 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl A compound described in any one of items 2 to 84.

86. A compound according to any one of claims 1 to 14 and 69 to 71, having the structure of formula (XXIX): 【Chemistry 19】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These include pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

87. A compound according to claim 86 having the structure of formula (XXX): 【Chemistry 20】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These include pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

88. A compound according to claim 86 having the structure of formula (XXXI): 【Chemistry 21】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These include pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

89. A compound according to claim 86 having the structure of formula (XXXIII): 【Chemistry 22】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These include pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

90. R 7 However, deuterium, halo, or -OC may be optionally substituted with one or more substituents Q. 1-6 Alkyl a compound according to any one of claims 86 to 89.

91. R 7 The compound according to claim 90, wherein is chloro or methoxy.

92. A compound according to claim 86 having the structure of formula (XXXII): 【Chemistry 23】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These include pharmaceutically acceptable salts, solvates, hydrates, or prodrugs.

93. R 7a However, hydrogen, deuterium, halo, or -OC may be optionally substituted with one or more substituents Q. 1-6 Alki The compound according to claim 92.

94. R 7a The compound according to claim 92 or 93, wherein the compound is hydrogen, deuterium, chloro, or methoxy.

95. R B However, each of these is arbitrarily substituted with one or more substituents Q, resulting in a monocyclic or bicyclic C. 6-1 4 Any of claims 86 to 94, which is an aryl, or a monocyclic or bicyclic heteroaryl. The compound described in item 1.

96. R B However, each of these is arbitrarily substituted with one or more substituents Q, resulting in a monocyclic or bicyclic C. 6-1 4 An aryl, or monocyclic or bicyclic heteroaryl, wherein each substituent is a bron. Mo, chloro, fluoro, cyano, methyl, trifluoromethyl, ethyl, propyl, hydroxy Any one of claims 86 to 95, independently selected from roxyl, methoxy, and formyl. The compound described.

97. R B However, phenyl, bromophenyl, fluorophenyl, cyanophenyl, methylphenyl L, trifluoromethylphenyl, ethylphenyl, propylphenyl, methoxyphenyl Lu, formylphenyl, bromo-fluorophenyl, difluorophenyl, trifluoro Phenyl, naphthyl, fluoropyridyl, fluoromethylpyridyl, or quinolinyl A compound according to any one of claims 86 to 96.

98. R B However, phenyl, 3-bromophenyl, 4-bromophenyl, 4-fluorophenyl, 3-shea Nophenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 4- Trifluoromethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-methoxy Phenyl, 4-methoxyphenyl, 4-formylphenyl, 2-bromo-4-fluorophenyl, 2 ,4-difluorophenyl, 2,4,5-trifluorophenyl, naphthal-2-yl, 2-fluoropyryl Claim 8, which is do-5-yl, 2-fluoro-3-methylpyrido-5-yl, or quinoline-5-yl. A compound described in any one of items 6 to 97.

99. R X However, (i) hydrogen; or (ii) each of them is optionally substituted with one, two, or three substituents Q. C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 Aralquil, claims 86- A compound as described in any one of item 98.

100. R X However, (i) hydrogen; or (ii) each of them is optionally substituted with one, two, or three substituents Q. C 1-6 Alkyl, C 6-14 Aryl, or C 7-15 It is an aralkyl, and each substitution Group Q is bromo, chloro, fluoro, cyano, methyl, trifluoromethyl, ethyl, pr A compound independently selected from ropyl, hydroxyl, methoxy, and formyl, according to claims 86-99. Any compound listed in one of the items.

101. R X However, hydrogen, methyl, ethyl, hydroxyethyl, propyl, phenyl, fluoromethyl The chemical according to any one of claims 86 to 100, which is nyl, formylphenyl, or benzyl. Compound.

102. R X However, hydrogen, methyl, ethyl, 2-hydroxyethyl, n-propyl, phenyl, 4-fluorine Any one of claims 86 to 101, which is lophenyl, 4-formylphenyl, or benzyl. The compound described.

103. R B and R X However, each of these atoms, along with the N atom to which they are bonded, can be arbitrarily substituted with one or more substituents Q. Forms a heteroaryl or heterocycline as described in any one of claims 86 to 94 A compound of [unclear].

104. R B and R X However, along with the N atom to which they are bonded, they can be optionally substituted with one or more substituents Q. The compound according to claim 103, which forms a heteroaryl compound.

105. R B and R X However, each of these atoms, along with the N atom to which they are bonded, can be arbitrarily substituted with one or more substituents Q. The compound according to claim 103 or 104, which forms a monocyclic or bicyclic heteroaryl.

106. R B and R X However, together with the N atom to which they are bonded, pyrrole-1-yl, 2-amino-imi A compound that forms dazole-1-yl or indole-1-yl, as described in any one of claims 103 to 105. The compound listed.

107. R B and R X However, along with the N atom to which they are bonded, they can be optionally substituted with one or more substituents Q. The compound according to claim 103, which forms a heterocycline.

108. R B and R X However, each of these atoms, along with the N atom to which they are bonded, can be arbitrarily substituted with one or more substituents Q. The compound according to claim 107, which forms a monocyclic or bicyclic heterocycline.

109. R B and R X However, together with the N atom to which they are bonded, pyrrolidine-1-yl, piperidine-1 The compound according to claim 107 or 108, which forms -yl or 4-morpholine-4-yl.

110. U 2 The compound according to any one of claims 86 to 109, wherein -N =

111. U 2 The compound according to any one of claims 86 to 109, wherein is -O-.

112. V 2 The compound according to any one of claims 86 to 111, wherein -N=.

113. V 2 The compound according to any one of claims 86 to 111, wherein is -C(OH)=.

114. U 2 and V 2 The compound according to any one of claims 86 to 109, wherein each of the following is -N=.

115. U 2 is -O- and V 2 The compound according to any one of claims 86 to 109, wherein is -C(OH)= 。

116. R 3 However, hydrogen, deuterium, halo, or C may be optionally substituted with one, two, or three substituents Q. 1 -6 A compound according to any one of claims 1 to 115, wherein it is alkyl.

117. R 3 The compound according to any one of claims 1 to 116, wherein the compound is hydrogen, deuterium, or methyl.

118. R 4 However, hydrogen, deuterium, halo, or C may be optionally substituted with one, two, or three substituents Q. 1 -6 A compound according to any one of claims 1 to 117, wherein it is alkyl.

119. R 4 The compound according to any one of claims 1 to 118, wherein is hydrogen or deuterium.

120. R 4 A compound according to any one of claims 1 to 118, wherein the compound is a halo.

121. R 4 A compound according to any one of claims 1 to 118 and 120, wherein is fluoro.

122. R 4 However, C is optionally substituted with one, two, or three substituents Q. 1-6 Claim 1 is alkyl Compounds described in any one of items ~118.

123. R 4 The compound according to any one of claims 1 to 118 and 122, wherein is methyl.

124. R 5 The compound according to any one of claims 1 to 123, wherein is hydrogen or deuterium.

125. R 6 The compound according to any one of claims 1 to 123, wherein is hydrogen or deuterium.

126. The aforementioned compound, 2-[(1Z)-5-fluoro-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-indene-3- A1 yl acetate; 2-[(1Z)-5-fluoro-1-{[4-(4-methoxyphenoxy)phenyl]methylidene}-2-methyl-1H- Inden-3-yl acetate A2; 2-[(1Z)-1-({2-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}methylidene)-5- Fluoro-2-methyl-1H-inden-3-yl]acetic acid A3; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(4-methylphenoxy)phenyl]methylidene}-1H- [Lendene-3-yl]acetic acid A4; 2-[(1Z)-5-fluoro-2-methyl-1-({4-[4-(propan-2-yl)phenoxy]phenyl}methyl Den)-1H-Inden-3-yl]acetic acid A5; 2-[(1Z)-1-{[4-(4-bromophenoxy)phenyl]methylidene}-5-fluoro-2-methyl-1H- [Hendene-3-yl]acetic acid A6; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(3-methylphenoxy)phenyl]methylidene}-1H- [Denden-3-yl]acetic acid A7; 2-[(1Z)-1-{[4-(3-cyanophenoxy)phenyl]methylidene}-5-fluoro-2-methyl-1H- [Denden-3-yl]acetic acid A8; (Z)-2-(5-fluoro-2-methyl-1-(4-(3-(trifluoromethyl)phenoxy)benzylidene)- 1H-Inden-3-yl)acetic acid A9; 2-[(1Z)-1-{[4-(4-ethylphenoxy)phenyl]methylidene}-5-fluoro-2-methyl-1H- [Nden-3-yl]acetic acid A10; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H- Inden-3-yl acetate A11; 2-[(1Z)-1-{[2-chloro-4-(4-methoxyphenoxy)phenyl]methylidene}-5-fluoro-2- Methyl-1H-inden-3-yl]acetate A12; 2-[(1Z)-5-fluoro-1-({2-methoxy-4-[4-(propan-2-yl)phenoxy]phenyl}-methyl [Cylidene]-2-methyl-1H-inden-3-yl]acetic acid A13; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(naphthalene-2-yloxy)phenyl]methylidene}- 1H-Inden-3-yl]acetic acid A14; 2-[(1Z)-1-({2-chloro-4-[4-(propan-2-yl)phenoxy]phenyl}methylidene)-5-f Luoro-2-methyl-1H-inden-3-yl]acetate A15; 2-[(1Z)-1-{[4-(2,4-difluorophenoxy)phenyl]methylidene}-5-fluoro-2-methyl -1H-Inden-3-yl]acetic acid A16; 2-[(1Z)-1-{[4-(2-bromo-4-fluorophenoxy)phenyl]methylidene}-5-fluoro-2- Methyl-1H-inden-3-yl]acetic acid A17; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(2,4,5-trifluorophenoxy)phenyl]methyl Den-1H-Inden-3-yl]acetic acid A18; 3-[(1Z)-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H-indene-3- Il-propanoate A19; 2-[(1Z)-5-fluoro-1-({4-[(6-fluoropyridine-3-yl)oxy]phenyl}methylidene) -2-methyl-1H-inden-3-yl]acetic acid A20; 2-[(1Z)-5-fluoro-1-({4-[(6-fluoro-5-methylpyridine-3-yl) oxyphenyl}- Methylidene)-2-methyl-1H-inden-3-yl]acetate A21; (Z)-2-(5-fluoro-2-methyl-1-(4-(quinoline-5-yloxy)benzylidene)-1H-indene A22-3-yl acetate; 2-[(1Z)-5-fluoro-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-indene-3- Il-N-hydroxyacetamide A23; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H- Inden-3-yl]-N-hydroxyacetamide A24; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H- Inden-3-yl]acetamide A25; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H- Inden-3-yl]-N-methylacetamide A26; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H- Inden-3-yl]-N-(2-hydroxyethyl)acetamide A27; (Z)-2-(5-fluoro-2-methyl-1-(4-phenoxybenzylidene)-1H-inden-3-yl)-N-(1 H-tetrazol-5-yl)acetamide A28; 2-[(1Z)-5-fluoro-2-methyl-1-({4-[methyl(phenyl)amino]phenyl}methylidene)-1 H-Inden-3-yl]acetate A29; 2-[(1Z)-1-({4-[benzyl(4-fluorophenyl)amino]phenyl}methylidene)-5-Fluoro [L-2-methyl-1H-inden-3-yl]acetic acid A30; 2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenyl)(methyl)amino]phenyl}methylidene )-2-methyl-1H-inden-3-yl]acetic acid A31; 2-[(1Z)-1-({4-[ethyl(4-fluorophenyl)amino]phenyl}methylidene)-5-fluoro- 2-methyl-1H-inden-3-yl]acetate A32; 2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenyl)(propyl)amino]phenyl}methylide (n)-2-methyl-1H-inden-3-yl]acetic acid A33; (Z)-2-(5-fluoro-1-(4-((4-fluorophenyl)(2-hydroxyethyl)amino)benzyli Den)-2-methyl-1H-inden-3-yl)acetic acid A34; 2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenyl)(4-formylphenyl)amino]phen [L-methylidene)-2-methyl-1H-inden-3-yl]acetic acid A35; 2-[(1Z)-5-fluoro-1-({4-[(4-formylphenyl)(phenyl)amino]phenyl}methyl (n)-2-methyl-1H-inden-3-yl]acetic acid A36; 2-[(1Z)-5-fluoro-2-methyl-1-({4-[methyl(phenyl)amino]phenyl}methylidene)-1 H-Inden-3-yl]-N-hydroxyacetamide A37; 2-[(1Z)-1-({4-[benzyl(4-fluorophenyl)amino]phenyl}methylidene)-5-Fluoro [L-2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A38; 5-{[(1Z)-2-methyl-1-[(3-phenoxyphenyl)methylidene]-1H-inden-3-yl]methyl }-1H-1,2,3,4-tetrazole A39; 5-{[(1Z)-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-inden-3-yl]methyl }-1H-1,2,3,4-tetrazole A40; 5-{2-[(1Z)-2-methyl-1-{[4-(4-methylphenoxy)phenyl]methylidene}-1H-indene-3 -yl]ethyl}-1H-1,2,3,4-tetrazol A41; 5-{2-[(1Z)-1-{[4-(4-bromophenoxy)phenyl]methylidene}-2-methyl-1H-indene-3 -yl]ethyl}-1H-1,2,3,4-tetrazol A42; 5-{2-[(1Z)-2-methyl-1-({4-[4-(propan-2-yl)phenoxy]phenyl}methylidene)-1H [-Indene-3-yl]ethyl}-1H-1,2,3,4-tetrazol A43; 5-{2-[(1Z)-1-{[4-(4-methoxyphenoxy)phenyl]methylidene}-2-methyl-1H-indene [-3-yl]ethyl}-1H-1,2,3,4-tetrazol A44; 5-{2-[(1Z)-2-methyl-1-({4-[4-(trifluoromethyl)phenoxy]phenyl}methylidene) [-1H-Indene-3-yl]ethyl}-1H-1,2,3,4-tetrazol A45; 5-{2-[(1Z)-2-methyl-1-{[4-(3-methylphenoxy)phenyl]methylidene}-1H-indene-3 -yl]ethyl}-1H-1,2,3,4-tetrazol A46; 3-(4-{[(1Z)-2-methyl-3-[2-(1H-1,2,3,4-tetrazole-5-yl)ethyl]-1H-indene-1- Iridene methyl phenoxy benzonitrile A47; 5-{2-[(1Z)-1-{[4-(3-methoxyphenoxy)phenyl]methylidene}-2-methyl-1H-indene [-3-yl]ethyl}-1H-1,2,3,4-tetrazol A48; 5-{2-[(1Z)-1-{[4-(3-bromophenoxy)phenyl]methylidene}-2-methyl-1H-indene-3 -yl]ethyl}-1H-1,2,3,4-tetrazol A49; 5-{2-[(1Z)-2-methyl-1-({4-[3-(trifluoromethyl)phenoxy]phenyl}methylidene) [-1H-Indene-3-yl]ethyl}-1H-1,2,3,4-tetrazol A50; 5-{2-[(1Z)-2-methyl-1-{[4-(naphthalene-2-yloxy)phenyl]methylidene}-1H-yne Den-3-yl]ethyl}-1H-1,2,3,4-tetrazol A51; (Z)-3-((2-methyl-1-(4-phenoxybenzylidene)-1H-inden-3-yl)methyl)-1,2,4- Oxadiazole-5(4H)-one A52; 5-{[(1E)-1-[(4-phenoxyphenyl)methylidene]-1H-inden-3-yl]methyl}-1H-1,2, 3,4-Tetrazole A53; 5-{[(1E)-1-[(3-phenoxyphenyl)methylidene]-1H-inden-3-yl]methyl}-1H-1,2, 3,4-Tetrazole A54; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(morpholine-4-yl)phenyl]methylidene}-1H- [Nden-3-yl]acetic acid A55; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(piperidine-1-yl)phenyl]methylidene}-1H- [Denden-3-yl]acetic acid A56; 2-[(1Z)-5-fluoro-1-{[4-(1H-indole-1-yl)phenyl]methylidene}-2-methyl-1H- Inden-3-yl acetate A57; 2-[(1Z)-1-{[4-(2-amino-1H-imidazole-1-yl)phenyl]methylidene}-5-fluoro-2 -methyl-1H-inden-3-yl]acetic acid A58; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(pyrrolidine-1-yl)phenyl]methylidene}-1H- [Nden-3-yl]acetic acid A59; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(1H-pyrrole-1-yl)phenyl]methylidene}-1H- [Denden-3-yl]acetic acid A60; (2E)-3-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl Lu-1H-inden-3-yl]prop-2-enoic acid A61; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorobenzenesulfonyl)phenyl]methylidene}-2-methyl [Tyl-1H-inden-3-yl]acetate A62; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorobenzenesulfinyl)phenyl]methylidene}-2- Methyl-1H-inden-3-yl]acetic acid A63; 2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenyl)sulfanyl]phenyl}methylidene)- 2-methyl-1H-inden-3-yl]acetic acid A64; 2-[(1Z)-5-fluoro-1-{[6-(4-fluorophenoxy)pyridine-3-yl]methylidene}-2-methyl [Tyl-1H-inden-3-yl]acetic acid A65; 2-[(1Z)-5-fluoro-1-{[6-(4-fluorophenoxy)-5-methylpyridine-3-yl]methylide [N]-2-methyl-1H-inden-3-yl]acetic acid A66; (2E)-4-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl Lu-1H-inden-3-yl]buta-2-enoic acid A67; 2-[(1Z)-4,5-difluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl -1H-Inden-3-yl]acetic acid A68; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2,4-dimethyl -1H-Inden-3-yl]acetic acid A69; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(morpholine-4-yl)phenyl]methylidene}-1H- [Nden-3-yl]-N-hydroxyacetamide A70; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(piperidine-1-yl)phenyl]methylidene}-1H- [Nden-3-yl]-N-hydroxyacetamide A71; 2-[(1Z)-5-fluoro-1-{[4-(1H-indole-1-yl)phenyl]methylidene}-2-methyl-1H- Inden-3-yl]-N-hydroxyacetamide A72; 2-[(1Z)-1-{[4-(2-amino-1H-imidazole-1-yl)phenyl]methylidene}-5-fluoro-2 -methyl-1H-inden-3-yl]-N-hydroxyacetamide A73; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(pyrrolidine-1-yl)phenyl]methylidene}-1H- [Nden-3-yl]-N-hydroxyacetamide A74; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(1H-pyrrole-1-yl)phenyl]methylidene}-1H- [Nden-3-yl]-N-hydroxyacetamide A75; (2E)-3-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl Lu-1H-inden-3-yl]-N-hydroxypropane-2-enamide A76; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorobenzenesulfonyl)phenyl]methylidene}-2-methyl [Tyl-1H-inden-3-yl]-N-hydroxyacetamide A77; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorobenzenesulfinyl)phenyl]methylidene}-2- Methyl-1H-inden-3-yl]-N-hydroxyacetamide A78; 2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenyl)sulfanyl]phenyl}methylidene)- 2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A79; 2-[(1Z)-5-fluoro-1-{[6-(4-fluorophenoxy)pyridine-3-yl]methylidene}-2-methyl [Tyl-1H-inden-3-yl]-N-hydroxyacetamide A80; 2-[(1Z)-5-fluoro-1-{[6-(4-fluorophenoxy)-5-methylpyridine-3-yl]methylide [N-2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A81; (2E)-4-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl Lu-1H-inden-3-yl]-N-hydroxybuta-2-enamide A82; 2-[(1Z)-4,5-difluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl -1H-Inden-3-yl]-N-hydroxyacetamide A83; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2,4-dimethyl -1H-inden-3-yl]-N-hydroxyacetamide A84; or 2-[(1Z)-5-fluoro-1-({4-[(4-fluorophenyl)(2-hydroxyethyl)amino]phen (L)-methylidene)-2-methyl-1H-inden-3-yl]-N-hydroxyacetamide A85; 2-[(1Z)-5-fluoro-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-indene-3- Iyl-N-hydroxy-N-methylacetamide C1; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-methyl-1H- Inden-3-yl]-N-hydroxy-N-methylacetamide C2; (Z)-2-(5-fluoro-2-methyl-1-(3-phenoxybenzylidene)-1H-inden-3-yl)-N-H Droxy-N-methylacetamide C3; 2-[(1Z)-5-fluoro-2-methyl-1-({4-[4-(propan-2-yl)phenoxy]phenyl}methyl Den)-1H-inden-3-yl]-N-hydroxyacetamide D1; 2-[(1Z)-5-fluoro-2-methyl-1-({4-[4-(tert-butyl)phenoxy]phenyl}methylidene )-1H-inden-3-yl]acetic acid D2; 2-[(1Z)-5-fluoro-2-methyl-1-({4-[3-(tert-butyl)phenoxy]phenyl}methylidene )-1H-inden-3-yl]acetic acid D3; 2-[(1Z)-5-fluoro-2-methyl-1-({4-[3-fluoro-4-methylphenoxy]phenyl}-methyl [Liden)-1H-Inden-3-yl]acetic acid D4; 2-[(1Z)-5-fluoro-2-methyl-1-({4-[3,4-difluorophenoxy]phenyl}methylidene) -1H-Inden-3-yl]acetic acid D5; 2-[(1Z)-5-fluoro-2-methyl-1-({4-[3-nitrophenoxy]phenyl}methylidene)-1H- D6 den-3-yl acetate; 2-[(1Z)-5-fluoro-2-methyl-1-({4-[4-(trifluoromethyl)phenoxy]phenyl}-methyl [Chilidene]-1H-Indene-3-yl]acetic acid D7; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-2-(2-methyl- [Propyl)-1H-Inden-3-yl]acetic acid D8; 2-[(1Z)-5-fluoro-2-benzyl-1-({4-[4-fluorophenoxy]phenyl}methylidene)-1 H-Inden-3-yl]acetic acid D9; 2-[(1Z)-5-methoxy-2-methyl-1-({4-[4-fluorophenoxy]phenyl}methylidene)-1H- Inden-3-yl acetate D10; 2-[(1Z)-5-methoxy-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-indene-3- D11 yl acetate; 2-[(1Z)-1-{[2-trifluoromethyl-4-(4-fluorophenoxy)phenyl]methylidene}-5- Fluoro-2-methyl-1H-inden-3-yl]acetic acid D12; 2-[(1Z)-1-{[3-methyl-4-(4-fluorophenoxy)phenyl]methylidene}-5-fluoro-2- Methyl-1H-inden-3-yl]acetic acid D13; 2-[(1Z)-1-{[2-methyl-4-(4-fluorophenoxy)phenyl]methylidene}-5-fluoro-2- Methyl-1H-inden-3-yl]acetic acid D14; 2-[(1Z)-5,7-difluoro-2-methyl-1-({4-[4-fluorophenoxy]phenyl}methylidene) -1H-Inden-3-yl]acetic acid D15; 2-[(1Z)-4,6-difluoro-2-methyl-1-({4-[4-fluorophenoxy]phenyl}methylidene) -1H-Inden-3-yl]acetic acid D16; 2-[(1Z)-5-tert-butyl-2-methyl-1-({4-[4-fluorophenoxy]phenyl}methylidene)- 1H-Inden-3-yl]acetic acid D17; (Z)-2-(5-fluoro-2-methyl-1-(3-phenoxybenzylidene)-1H-inden-3-yl)acetic acid D 18; 2-[(1Z)-5-fluoro-1-(2-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]- Acetic acid D19; 2-[(1Z)-5,7-difluoro-1-(3-(phenoxy)benzylidene)-2-methyl-1H-indene-3-i [Lu]-acetic acid D2O; 2-[(1Z)-4,6-difluoro-1-(3-(phenoxy)benzylidene)-2-methyl-1H-indene-3-i [L]-acetic acid D21; 2-[(1Z)-5-fluoro-2-methyl-1-({3-[4-methoxyphenoxy]phenyl}methylidene)-1H- Inden-3-yl acetate D22; 2-[(1Z)-5-fluoro-1-(4-fluoro-3-(phenoxy)benzylidene)-2-methyl-1H-inde [-3-yl]-acetic acid D23; 2-[(1Z)-5-fluoro-2-methyl-1-({3-[4-cyanophenoxy]phenyl}methylidene)-1H- D24 den-3-yl acetate; 2-[(1Z)-5-fluoro-2-methyl-1-({3-[4-chlorophenoxy]phenyl}methylidene)-1H- D25 den-3-yl acetate; 2-[(1Z)-5-fluoro-2-methyl-1-({3-[4-trifluoromethylphenoxy]phenyl}-methyl [Lidene]-1H-Indene-3-yl]acetic acid D26; 2-[(1Z)-5-fluoro-2-methyl-1-({3-[3-trifluoromethylphenoxy]phenyl}-methyl [Lidene]-1H-Indene-3-yl]acetic acid D27; 2-[(1Z)-4-methoxy-1-(4-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]- Acetic acid D28; 2-[(1Z)-6-methoxy-1-(4-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]- Acetic acid D29; 2-[(1Z)-6-trifluoromethyl-2-methyl-1-({4-[4-fluorophenoxy]phenyl}-methyl [Lidene]-1H-Indene-3-yl]acetate D30; 2-[(1Z)-5-trifluoromethyl-2-methyl-1-({4-[4-fluorophenoxy]phenyl}-methyl [Lidene]-1H-Indene-3-yl]acetic acid D31; 2-[(1Z)-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-1H-inden-3-yl]acetic acid D32; 2-[(1Z)-5-fluoro-1-{[4-(4-fluorophenoxy)phenyl]methylidene}-1H-indene- 3-yl]acetic acid D33; 2-[(1Z)-5-trifluoromethyl-1-(3-(phenoxy)benzylidene)-2-methyl-1H-indene] -3-yl]-acetic acid D34; 2-[(1Z)-6-methoxy-1-(3-(phenoxy)benzylidene)-2-methyl-1H-inden-3-yl]- Acetic acid D35; 2-[(1Z)-6-trifluoromethyl-1-(3-(phenoxy)benzylidene)-2-methyl-1H-indene] -3-yl]-acetic acid D36; 2-[(1Z)-5-fluoro-2-methyl-1-({3-[methyl(phenyl)amino]phenyl}methylidene)-1 H-Inden-3-yl]acetic acid D37; 2-[(1Z)-5-fluoro-1-[(3-methoxy-5-phenoxyphenyl)methylidene]-2-methyl-1H- Inden-3-yl acetate D38; 2-[(1E)-5-fluoro-2-methyl-1-({4-[3,4-difluorophenoxy]phenyl}methylidene) -1H-Inden-3-yl]acetic acid E1; 2-[(1E)-5-fluoro-2-methyl-1-({4-[4-fluorophenoxy]phenyl}methylidene)-1H- Inden-3-yl]acetate E2; 2-[(1E)-5-fluoro-2-methyl-1-[(4-phenoxyphenyl)methylidene]-1H-indene-3- E3 yl acetate; 2-[(1E)-5,7-difluoro-2-methyl-1-({4-[4-fluorophenoxy]phenyl}methylidene) -1H-Inden-3-yl]acetic acid E4; 5-{2-[(1E)-1-[(4-phenoxyphenyl)methylidene]-1H-inden-3-yl]ethyl}-1H-1, 2,3,4-tetrazole E5; and 2-[(1E)-5,7-difluoro-1-(3-(phenoxy)benzylidene)-2-methyl-1H-indene-3-i [L]-acetic acid E6; or these tautomers, mixtures of two or more tautomers, or isotopic variants; or this A pharmaceutically acceptable salt, solvate, hydrate, or prodrug of the following, as described in claim 1: The compound listed.

127. A compound according to any one of claims 1 to 126, or an enantiomer thereof. A mixture of, diastereomers, a mixture of two or more diastereomers, tautomers, two or more A mixture of tautomers or isotopic variants; or pharmaceutically acceptable salts or solutions thereof. A pharmaceutical composition comprising a mediator or hydrate; and a pharmaceutically acceptable excipient.

128. A method for treating, preventing, or improving one or more symptoms of fibrous disease in the subject, To the subject who requires this, a therapeutically effective amount of the compound according to any one of claims 1 to 126 The method, including administering.

129. The method according to claim 128, wherein the fibrous disease is a metabolic disease.

130. The method according to claim 128 or 129, wherein the fibrous disease is a liver disease.

131. The fibrous disease is non-alcoholic fatty liver disease (NAFLD), according to any of claims 128 to 130. The method described in one of the items.

132. Any of claims 128 to 131, wherein the fibrous disease is non-alcoholic steatohepatitis (NASH). The method described in item 1.

133. A method for treating, preventing, or improving one or more symptoms of a proliferative disorder in a subject, The treatment involves administering a therapeutically effective amount of the compound described in any one of claims 1 to 126 to the subject. The aforementioned method.

134. The method according to claim 133, wherein the proliferative disease is cancer.

135. The method according to any one of claims 128 to 134, wherein the subject is a human.

136. A method for inhibiting cell proliferation, wherein the cells are subjected to the chemical compound according to any one of claims 1 to 126. The method comprising bringing the substance into contact with an effective amount of the substance.

137. The method according to claim 136, wherein the cells are cancer cells.

138. A method for treating, preventing, or improving one or more symptoms of fibrous disease in the subject, For the subject requiring this, a compound of formula (IA): 【Chemistry 24】 or its enantiomer, mixture of enantiomers, diastereomer, two or more diastereomers A mixture of teleomers, tautomers, a mixture of two or more tautomers, or an isotopic variant; or These are therapeutically effective salts, solvates, hydrates, or prodrugs that are acceptable as pharmaceuticals. The method comprising administering a therapeutically effective amount; (In the formula: R 1 (a) hydrogen, deuterium, cyano, halo, or nitro; or (b) C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralquil , heteroaryl, or heterocyclyl; R 2 -CN, -C(O)OR 2a -C(O)NR 2b R 2c ,-C(O)N(R 2b )OR 2c , -OR 2a , -NR 2b R 2c , or Hete It is a lower aryl; here, R 2a , R 2b , and R 2c These are, independently, hydrogen and C 1-6 Alkyl, C 2 -6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralchi It is a heteroaryl or heterocyclyl; R 3 , R 4 , R 5 , and R 6 Each of these independently consists of (a) hydrogen, deuterium, cyano, halo, or nitrate. (b)C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 a Reel, C 7-15 Aralkyl, heteroaryl, or heterocyclyl; or (c)-C(O)R 1a 、-C(O)OR 1a 、-C(O)NR 1b R 1c 、-C(NR 1a )NR 1b R 1c 、-OR 1a 、-OC(O)R 1a 、-OC(O)OR 1a 、-OC(O) NR 1b R 1c ,-OC(NR 1a )NR 1b R 1c 、-OS(O)R 1a 、-OS(O) 2 R 1a 、-OS(O)NR 1b R 1c 、-OS(O) 2 NR 1b R 1c 、-NR 1b R 1c 、-NR 1a C(O)R 1d 、-NR 1a C(O)OR 1d 、-NR 1a C(O)NR 1b R 1c 、-NR 1a C(NR 1d )NR 1b R 1c 、 -NR 1a S(O)R 1d 、-NR 1a S(O) 2 R 1d 、-NR 1a S(O)NR 1b R 1c 、-NR 1a S(O) 2 NR 1b R 1c 、-SR 1a 、-S(O)R 1 a , -S(O) 2 R 1a -S(O)NR 1b R 1c , or -S(O) 2 NR 1b R 1c and; Each R 7 (a) Deuterium, cyano, halo, or nitro; (b) C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralchi (c)-C(O)R 1a , -C(O)OR 1a -C(O)NR 1b R 1c 、-C(NR 1a )NR 1b R 1c 、-OR 1a 、-OC(O)R 1a 、-OC(O)OR 1a 、-OC(O)NR 1b R 1c 、-OC(NR 1a )NR 1b R 1c 、-OS(O)R 1a 、-OS(O) 2 R 1a 、-OS(O)NR 1b R 1c 、-OS(O) 2 NR 1b R 1c 、-NR 1b R 1c 、-NR 1a C(O)R 1 d 、-NR 1a C(O)OR 1d 、-NR 1a C(O)NR 1b R 1c 、-NR 1a C(NR 1d )NR 1b R 1c 、-NR 1a S(O)R 1d 、-NR 1a S(O) 2 R 1d 、-NR 1a S(O)NR 1b R 1c 、-NR 1a S(O) 2 NR 1b R 1c 、-SR 1a 、-S(O)R 1a 、-S(O) 2 R 1a 、-S(O)NR 1b R 1c , or -S(O) 2 NR 1b R 1c is it; or two adjacent R 7 They are joined together Together with a phenyl group, it forms naphthyl or bicyclic heteroaryl groups; R C (a) hydrogen, deuterium, cyano, halo, or nitro; or (b) C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralquil , heteroaryl, or heterocyclyl; or (c)-OR 1a , -NR 1b R 1c , or -NR 1a C( O)R 1d and; L is C 1-6 Alkylene or C 2-6 It is an alkenylene; n is an integer of 0, 1, 2, 3, or 4; and Each R 1a , R 1b , R 1c , and R 1d These are, independently, hydrogen, deuterium, and C 1-6 Alkyl, C 2-6 Alke Nil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralkil, Hete It is either a roaryl or heterocyclyl; or R 1a and R 1c They are combined Together with C and N atoms, they form a heterocycline; or R 1b and R 1c They combine Together with the N atom present, it forms a heterocycline; Here, each alkyl, alkylene, alkenyl, alkenylene, alkynyl, cyclo Roalkyl, aryl, aralkyl, heteroaryl, and heterocyclyl are one or more In one embodiment, it is arbitrarily substituted with one, two, three, or four substituents Q, Here, each Q is (a) deuterium, cyano, halo, nitro, and oxo; (b) each of them is 1 or less In the above embodiment, one, two, three, or four substituents Q a And then it is arbitrarily replaced C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aralkyl, heteroaryl, and heterocyclyl; and (c)-C(O)R a , -C(O)OR a 、-C(O)NR b R c 、-C(O)SR a 、-C(NR a )NR b R c 、-C(S)R a 、-C(S)OR a 、-C(S)NR b R c 、-OR a 、-OC(O)R a 、-OC(O)OR a 、-OC(O)NR b R c 、-OC(O)SR a 、-OC(NR a )NR b R c 、-OC(S)R a 、-OC(S)O R a ,-OC(S)NR b R c 、-OS(O)R a 、-OS(O) 2 R a 、-OS(O)NR b R c 、-OS(O) 2 NR b R c 、-NR b R c 、-NR a C(O )R d 、-NR a C(O)OR d 、-NR a C(O)NR b R c 、-NR a C(O)SR d 、-NR a C(NR d )NR b R c 、-NR a C(S)R d 、-NR a C (S)OR d 、-NR a C(S)NR b R c 、-NR a S(O)R d 、-NR a S(O) 2 R d 、-NR a S(O)NR b R c 、-NR a S(O) 2 NR b R c 、- SR a ,-S(O)R a , -S(O) 2 R a -S(O)NR b R c , and -S(O) 2 NR b R c : Selected independently from, here, Each R a , R b , R c , and R d (i) hydrogen or deuterium; (ii) each of them is one or more In one embodiment, one, two, three, or four substituents Q a It is arbitrarily replaced by C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel , C 7-15 (iii)R b Reach biR c Together with the N atoms to which they are bonded, one or more, in one embodiment, one, two , three or four substituents Q a It forms a heterocycline which is optionally substituted; Here, each Q a (a) Deuterium, cyano, halo, nitro, and oxo; (b) C 1-6 Alki Ru, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 a Larkyl, heteroaryl, and heterocyclyl; and (c)-C(O)R e , -C(O)OR e -C(O)NR f R g 、-C(O)SR e 、-C(NR e )NR f R g 、-C(S)R e 、-C(S)OR e 、-C(S)NR f R g 、-OR e 、-OC(O)R e 、-OC( O)OR e 、-OC(O)NR f R g 、-OC(O)SR e 、-OC(NR e )NR f R g 、-OC(S)R e 、-OC(S)OR e 、-OC(S)NR f R g 、 -OS(O)R e 、-OS(O) 2 R e 、-OS(O)NR f R g 、-OS(O) 2 NR f R g 、-NR f R g 、-NR e C(O)R h 、-NR e C(O)OR f 、-NR e C(O)NR f R g 、-NR e C(O)SR f 、-NR e C(NR h )NR f R g 、-NR e C(S)R h 、-NR e C(S)OR f 、-NR e C(S) NR f R g 、-NR e S(O)R h 、-NR e S(O) 2 R h 、-NR e S(O)NR f R g 、-NR e S(O) 2 NR f R g 、-SR e 、-S(O)R e 、-S (O) 2 R e -S(O)NR f R g , and -S(O) 2 NR f R g : independently selected from; here, each R e , R f , R g , and R h (i) hydrogen or deuterium; (ii) C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Cycloalkyl, C 6-14 Ariel, C 7-15 Aalkyl, heteroaryl , or heterocyclyl; or (iii)R f and R g The N atoms to which they are bonded (Together, they form heterocyclines.)

139. The method according to claim 138, wherein the fibrous disease is a metabolic disease.

140. The method according to claim 138 or 139, wherein the fibrous disease is a liver disease.

141. The fibrous disease is non-alcoholic fatty liver disease (NAFLD), according to any of claims 138 to 140. The method described in one of the items.

142. Any of claims 138 to 141, wherein the fibrous disease is non-alcoholic steatohepatitis (NASH). The method described in item 1.

143. The method according to any one of claims 138 to 142, wherein the subject is a human.

144. The aforementioned compound, (Z)-2-(2-methyl-1-(4-isopropylbenzylidene)-1H-inden-3-yl)acetic acid B1; (Z)-2-(5-fluoro-2-methyl-1-(benzylidene)-1H-inden-3-yl)acetic acid B2; (Z)-2-(5-fluoro-2-methyl-1-(3-cyanobenzylidene)-1H-inden-3-yl)acetic acid B3; (Z)-2-(5-fluoro-2-methyl-1-(4-cyanobenzylidene)-1H-inden-3-yl)acetic acid B4; (Z)-2-(5-fluoro-2-methyl-1-(4-methylbenzylidene)-1H-inden-3-yl)acetic acid B5; (Z)-2-(5-fluoro-2-methyl-1-(3-trifluoromethylbenzylidene)-1H-indene-3-i (Lu) Acetate B6; (Z)-2-(5-fluoro-2-methyl-1-(4-trifluoromethylbenzylidene)-1H-indene-3-i (Lu) Acetate B7; (Z)-2-(5-fluoro-2-methyl-1-(4-ethylbenzylidene)-1H-inden-3-yl)acetic acid B8; (Z)-2-(5-fluoro-2-methyl-1-(4-isopropylbenzylidene)-1H-inden-3-yl)vinegar Acid B9; (Z)-2-(5-fluoro-2-methyl-1-(4-t-butylbenzylidene)-1H-inden-3-yl)acetic acid B10 ; (Z)-2-(5-fluoro-2-ethyl-1-(4-isopropylbenzylidene)-1H-inden-3-yl)vinegar acid B11; (Z)-2-(5-fluoro-2-(2-methylpropyl)-1-(4-isopropylbenzylidene)-1H-inde B12 acetate (-3-yl) (Z)-2-(5-fluoro-2-methyl-1-(3-methoxybenzylidene)-1H-inden-3-yl)acetic acid B13 ; (Z)-2-(5-fluoro-2-methyl-1-(4-methoxybenzylidene)-1H-inden-3-yl)acetic acid B14 ; (Z)-2-(5-fluoro-2-methyl-1-(4-ethoxybenzylidene)-1H-inden-3-yl)acetic acid B15 ; (Z)-2-(5-fluoro-2-methyl-1-(4-(pyrrolidine-1-yl)benzylidene)-1H-indene-3- B16 yl acetate; (Z)-2-(5-fluoro-2-methyl-1-(4-(pyrido-2-yl)benzylidene)-1H-inden-3-yl) Acetate B17; (Z)-2-(5-chloro-2-methyl-1-(4-t-butylbenzylidene)-1H-inden-3-yl)acetic acid B18; (Z)-2-(5-methyl-2-methyl-1-(4-isopropylbenzylidene)-1H-inden-3-yl)acetic acid B 19; (Z)-2-(5-ethyl-2-methyl-1-(4-isopropylbenzylidene)-1H-inden-3-yl)acetic acid B 20; (Z)-2-(5-isopropyl-2-methyl-1-(4-isopropylbenzylidene)-1H-inden-3-yl ) Acetate B21; (Z)-2-(5-Methoxy-2-methyl-1-(4-isopropylbenzylidene)-1H-inden-3-yl)vinegar acid B22; (Z)-2-(5-ethoxy-2-methyl-1-(4-isopropylbenzylidene)-1H-inden-3-yl)vinegar Acid B23; (Z)-2-(5-fluoro-1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl) Cetoamide B24; (Z)-2-(5-fluoro-1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl)-N- Methylacetamide B25; (Z)-2-(5-fluoro-1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl)-N, N-dimethylacetamide B26; (Z)-2-(1-(4-acetamidobenzylidene)-5-fluoro-2-methyl-1H-inden-3-yl)vinegar Acid B27; (Z)-3-(5-fluoro-1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl) Ropanic acid B28; (Z)-5-(2-(5-fluoro-1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl) Ethyl)-1H-tetrazole B29; (Z)-5-(2-(1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl)ethyl)-1H- Tetrazole B30; (Z)-2-(4-fluoro-2-methyl-1-(benzylidene)-1H-inden-3-yl)acetic acid B31; (Z)-2-(5-fluoro-1-(4-dimethylaminobenzylidene)-2-methyl-1H-inden-3-yl) Propanic acid B32; 2-[(1Z)-5-fluoro-1-[(2-hydroxynaphthalene-1-yl)methylidene]-2-methyl-1H-yl [Denden-3-yl]acetic acid B33; 2-[(1Z)-5-fluoro-2-methyl-1-[(naphthalene-2-yl)methylidene]-1H-inden-3-yl Acetate B34; 2-[(1Z)-5-fluoro-2-methyl-1-[(4-methylnaphthalene-1-yl)methylidene]-1H-inde [N-3-yl]acetic acid B35; 2-[(1Z)-5-fluoro-1-[(2-methoxynaphthalene-1-yl)methylidene]-2-methyl-1H-yne Den-3-yl acetate B36; 2-[(1Z)-1-[(4-cyclopropylphenyl)methylidene]-5-fluoro-2-methyl-1H-indene B37-3-yl acetate; 2-[(1Z)-1-[(4-cyclopentylphenyl)methylidene]-5-fluoro-2-methyl-1H-indene B38-3-yl acetate; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(prop-1-en-2-yl)phenyl]methylidene}-1H- Inden-3-yl acetate B39; 2-[(1Z)-5-fluoro-1-{[4-(2-fluoropropan-2-yl)phenyl]methylidene}-2-methyl [Lu-1H-inden-3-yl]acetic acid B40; 2-[(1Z)-1-{[4-(dimethylamino)phenyl]methylidene}-5-fluoro-2-methyl-1H-inde [N-3-yl]acetic acid B41; 2-[(1Z)-5-fluoro-1-{[4-(1,1,1,3,3,3-hexafluoropropan-2-yl)phenyl]methyl [Chylidene]-2-methyl-1H-inden-3-yl]acetic acid B42; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(propan-2-yl)phenyl]methylidene}-1H-yne Den-3-yl]propanoate B43; 2-[(1Z)-5-fluoro-2-methyl-1-{[4-(trifluoromethyl)phenyl]methylidene}-1H- [Denden-3-yl]propanoate B44; 2-[(1Z)-7-fluoro-2-methyl-1-{[4-(propan-2-yl)phenyl]methylidene}-1H-yne Den-3-yl acetate B45; 2-[(1Z)-7-fluoro-2-methyl-1-{[4-(trifluoromethyl)phenyl]methylidene}-1H- [Denden-3-yl]acetic acid B46; 2-[(1Z)-1-{[4-(1,3-difluoropropan-2-yl)phenyl]methylidene}-5-fluoro-2- Methyl-1H-inden-3-yl]acetic acid B47; 2-[(1Z)-5-fluoro-1-{[3-fluoro-4-(propan-2-yl)phenyl]methylidene}-2-methyl [Lu-1H-inden-3-yl]acetic acid B48; (E)-2-(5-fluoro-2-methyl-1-(4-isopropylbenzylidene)-1H-inden-3-yl)vinegar acid B49; (E)-2-(5-fluoro-1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl) Cetoamide B50; (E)-2-(5-fluoro-1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl)-N- Methylacetamide B51; (Z)-2-(5-fluoro-1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl) Tan-1-All B52; (Z)-2-(5-fluoro-1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl) Tan-1-amino B53; or (Z)-3-(5-fluoro-1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl) Ropannitrile B54; or these tautomers, mixtures of two or more tautomers, or isotopic variants; or this Claim 138: A pharmaceutically acceptable salt, solvate, hydrate, or prodrug: The method described in any one of items ~143.

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