Replacement Condensed Bicyclic Compounds and Related Therapeutic Methods

Abstract

The present invention provides a compound useful for treating narcolepsy or cataplexy in a subject in need of treatment for narcolepsy or cataplexy. Also provided are related pharmaceutical compositions and methods for treating narcolepsy or cataplexy in a subject in need of treatment for narcolepsy or cataplexy, which comprise administering to the subject a compound or a pharmaceutically acceptable salt thereof, or a composition.

Description

Technical Field

[0001] Related Applications This application claims the benefit of U.S. Provisional Patent Application No. 63 / 354,025, filed on June 21, 2022. The entire contents of the above application are incorporated herein by reference.

[0002] The present invention relates to substituted bicyclic compounds, particularly substituted fused bicyclic compounds having agonist activity.

Background Art

[0003] Orexin is a neuropeptide synthesized and released by a subpopulation of neurons in the lateral hypothalamus and surrounding regions. Orexin consists of two subtypes, namely orexin A and orexin B. Orexin A and orexin B bind to orexin receptors. Orexin receptors are G protein-coupled receptors that are preferentially expressed in the brain. There are two subtypes (type 1 and type 2) of orexin receptors (Cell, Vol. 92, 573-585, 1998). Activation of orexin receptors is known to be important for various central nervous system functions such as maintenance of the awake state, energy homeostasis, reward processing, and motivation (Saper et al., TRENDS in Neuroscience 2001; Yamanaka et al., Neuron 2003; Sakurai, Nature Reviews Neuroscience 2014).

[0004] Narcolepsy is a neurological disorder that causes excessive daytime sleepiness, sudden episodes of muscle paralysis (cataplexy), and disrupted sleep patterns (Mahoney et al., Nature Reviews Neuroscience, 2019). Narcolepsy is known to be caused by the degeneration of orexin neurons. Narcolepsy symptoms can be modeled in transgenic mice engineered to degenerate orexin neurons, and those symptoms can be reversed by intracerebroventricular administration of orexin peptides (Proc. Natl. Acad. Sci. USA, Vol. 101, 4649-4654, 2004). Studies of orexin 2 receptor knockout mice suggest that the orexin 2 receptor plays a preferential role in maintaining the waking state (Cell, Vol. 98, 437-451, 1999, Neuron, Vol. 38, 715-730, 2003). Therefore, orexin 2 receptor agonists may be therapeutic agents for narcolepsy or other disorders showing excessive daytime sleepiness, such as Parkinson's disease (CNS Drugs, Vol. 27, 83-90, 2013; Brain, Vol. 130, 2007, 1586-1595).

[0005] Compounds having agonist activity on orexin 2 receptor are considered to be useful as novel therapeutic agents for narcolepsy, idiopathic hypersomnia, hypersomnia, sleep apnea syndrome, disorders of consciousness such as coma, narcolepsy syndrome, hypersomnia syndrome characterized by hypersomnia (for example, in Parkinson's disease, Guillain-Barré syndrome or Kleine-Levin syndrome), Alzheimer's disease, obesity, insulin resistance syndrome, heart failure, diseases associated with bone loss, or sepsis, etc. (Cell Metabolism, Vol.9, 64-76, 2009; Neuroscience, Vol.121, 855-863, 2003; Respiration, Vol.71, 575-579, 2004; Peptides, Vol.23, 1683-1688, 2002; International Publication No. 2015 / 073707; Journal of the American College of Cardiology, Vol.66, 2015, pages 2522-2533; International Publication No. 2015 / 048091; International Publication No. 2015 / 147240).

[0006] Several compounds having orexin 2 receptor agonist activity have been reported (U.S. Patent No. 8,258,163; International Publication No. 2015 / 088000; International Publication No. 2014 / 198880; Journal of Medicinal Chemistry, Vol.58, pages 7931-7937; U.S. Patent Application Publication No. 20190040010; U.S. Patent Application Publication No. 20190031611; U.S. Patent Application Publication No. 20170226137). However, these compounds are considered not to be satisfactory in terms of activity, pharmacokinetics, permeability to the brain / central nervous system, safety, etc., and the development of improved compounds having orexin 2 receptor agonist activity is desired.

Summary of the Invention

[0007] An object of the present invention is to provide a condensed bicyclic compound having orexin 2 receptor agonist activity.

[0008] Accordingly, in a first aspect, the present invention provides a compound represented by formula I-A or a pharmaceutically acceptable salt thereof: [Chemical formula] (wherein, ring A is fused to ring B, ring A is selected from the group consisting of C3-C8 cycloalkyl, 4-7 membered heterocyclyl, C6-C 10 aryl and 5-7 membered heteroaryl, and C3-C8 cycloalkyl, 4-7 membered heterocyclyl, C6-C 10 aryl or 5-7 membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums, ring B is selected from the group consisting of C3-C8 cycloalkyl, 4-7 membered heterocyclyl, C6-C 10 aryl and 5-7 membered heteroaryl, and C3-C8 cycloalkyl, 4-7 membered heterocyclyl, C6-C 10 aryl or 5-7 membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums, X is N or CH, Y is S(=O)2, C(=O), or S(=O)(=NR e ), R e is selected from the group consisting of H, C1-C3 alkyl or C3-C5 cycloalkyl, E is NR a R b , C1-C3 alkylene-NR a R b, C1-C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C8 cycloalkyl, C1-C3 alkylene-(C3-C8 cycloalkyl), 4-10 membered heterocyclyl, C1-C3 alkylene-(4-10 membered heterocyclyl), C6-C 10 aryl, C1-C3 alkylene-(C6-C 10 aryl), 5-7 membered heteroaryl and C1-C3 alkylene-(5-7 membered heteroaryl) selected from the group consisting of, C1-C3 alkylene-NR a R b , C1-C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C8 cycloalkyl, C1-C3 alkylene-(C3-C8 cycloalkyl), 4-10 membered heterocyclyl, C1-C3 alkylene-(4-10 membered heterocyclyl), C6-C 10 aryl, C1-C3 alkylene-(C6-C 10 aryl), 5-7 membered heteroaryl or C1-C3 alkylene-(5-7 membered heteroaryl) is unsubstituted or substituted with one or more halogen, hydroxyl, NR c R d , CF3, CHF2, CH2F, C1-C3 alkyl or C1-C3 alkoxyl, R a and R b are each independently selected from the group consisting of H, C1-C3 alkyl, C3-C5 cycloalkyl, and 4-7 membered heterocyclyl, C1-C3 alkyl, C3-C5 cycloalkyl, or 4-7 membered heterocyclyl is unsubstituted or substituted with one or more halogen, hydroxyl, C1-C3 alkyl, or C1-C3 alkoxyl, or, R a and R b together with the N atom to which they are attached form a 4-7 membered heterocyclyl or 5-7 membered heteroaryl, 4-7 membered heterocyclyl or 5-7 membered heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, NR c R d、 substituted with C1-C3 alkyl, C1-C3 alkoxyl or C1-C3 alkyl substituted with 1-3 halogens, R1 is C(=O)-C1-C4 alkyl, C(=O)-C1-C4 alkoxyl, C(=O)-(CR c R d ) n -C3-C8 cycloalkyl, C(=O)-(CR c R d ) n -(4-7 membered heterocyclyl), C(=O)-(CR c R d ) n -(C6-C 10 aryl), C(=O)-(CR c R d ) n -(5-10 membered heteroaryl), C(=O)-O-(CR c R d ) n -C3-C8 cycloalkyl, C(=O)-O-(CR c R d ) n -(4-7 membered heterocyclyl), (CR c R d ) n -(C6-C 10 aryl) and (CR c R d ) n -(5-10 membered heteroaryl), selected from the group consisting of, C1-C4 alkyl, C1-C4 alkoxyl, C3-C8 cycloalkyl, 4-7 membered heterocyclyl, C6-C 10 aryl, or 5-10 membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums, R c and R d are each independently H, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums, n is 0, 1 or 2, Each of R2, R3, R4, R5, R6, R7, and R8 is independently H, halogen, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums, or alternatively, R3 and R6 together form unsubstituted C1-C3 alkylene or C1-C3 alkylene substituted with one or more halogens, alternatively, R4 and R5 together form unsubstituted C1-C3 alkylene or C1-C3 alkylene substituted with one or more halogens, m is 0 or 1, p is 0, 1, 2, 3, or 4, each R9 is independently selected from the group consisting of deuterium, halogen, hydroxyl, and cyano).

[0009] In one embodiment, provided herein is a compound of formula I-A having the structure of formula I or a pharmaceutically acceptable salt thereof: [Chemical formula] (wherein ring A is fused to ring B, ring A is selected from the group consisting of C3-C8 cycloalkyl, 4-7 membered heterocyclyl, C6-C 10 aryl and 5-7 membered heteroaryl, and C3-C8 cycloalkyl, 4-7 membered heterocyclyl, C6-C 10 aryl or 5-7 membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums, ring B is selected from the group consisting of C3-C8 cycloalkyl, 4-7 membered heterocyclyl, C6-C 10 aryl and 5-7 membered heteroaryl, and C3-C8 cycloalkyl, 4-7 membered heterocyclyl, C6-C 10Aryl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums, X is N or CH, Y is S(=O)2, C(=O), or S(=O)(=NR e ) R e is selected from the group consisting of H, C1-C3 alkyl, or C3-C5 cycloalkyl, E is NR a R b , C1-C3 alkylene-NR a R b , C1-C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C8 cycloalkyl, C1-C3 alkylene-(C3-C8 cycloalkyl), 4- to 10-membered heterocyclyl, C1-C3 alkylene-(4- to 10-membered heterocyclyl), C6-C 10 aryl, C1-C3 alkylene-(C6-C 10 aryl), 5- to 7-membered heteroaryl, and C1-C3 alkylene-(5- to 7-membered heteroaryl) is selected from the group consisting of C1-C3 alkylene-NR a R b , C1-C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C8 cycloalkyl, C1-C3 alkylene-(C3-C8 cycloalkyl), 4- to 10-membered heterocyclyl, C1-C3 alkylene-(4- to 10-membered heterocyclyl), C6-C 10 aryl, C1-C3 alkylene-(C6-C 10 aryl), 5- to 7-membered heteroaryl, or C1-C3 alkylene-(5- to 7-membered heteroaryl) is unsubstituted or substituted with one or more halogens, hydroxyls, NR c R d , CF3, CHF2, CH2F, C1-C3 alkyl, or C1-C3 alkoxyl, R a and R bis independently selected from the group consisting of H, C1-C3 alkyl, C3-C5 cycloalkyl, and 4-7 membered heterocyclyl, and C1-C3 alkyl, C3-C5 cycloalkyl, or 4-7 membered heterocyclyl is unsubstituted or substituted with one or more halogen, hydroxyl, C1-C3 alkyl, or C1-C3 alkoxyl, or R a and R b together with the N atom to which they are attached form a 4-7 membered heterocyclyl or 5-7 membered heteroaryl, and the 4-7 membered heterocyclyl or 5-7 membered heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, NR c R d , C1-C3 alkyl, C1-C3 alkoxyl or C1-C3 alkyl substituted with 1-3 halogen, R1 is C(=O)-C1-C4 alkyl, C(=O)-C1-C4 alkoxyl, C(=O)-(CR c R d ) n -C3-C8 cycloalkyl, C(=O)-(CR c R d ) n -(4-7 membered heterocyclyl), C(=O)-(CR c R d ) n -(C6-C 10 aryl), C(=O)-(CR c R d ) n -(5-10 membered heteroaryl), C(=O)-O-(CR c R d ) n -C3-C8 cycloalkyl, C(=O)-O-(CR c R d ) n -(4-7 membered heterocyclyl), (CR c R d ) n -(C6-C 10 aryl) and (CR c R d ) n- selected from the group consisting of (5- to 10-membered heteroaryl), C1-C4 alkyl, C1-C4 alkoxyl, C3-C8 cycloalkyl, 4- to 7-membered heterocyclyl, C6-C 10 aryl, or 5- to 10-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums, R c and R d are each, independently, H, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums, n is 0, 1, or 2, each of R2, R3, R4, R5, R6, R7, and R8 is independently H, halogen, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums, or alternatively, R3 and R6 together form unsubstituted C1-C3 alkylene or C1-C3 alkylene substituted with one or more halogens, alternatively, R4 and R5 together form unsubstituted C1-C3 alkylene or C1-C3 alkylene substituted with one or more halogens, m is 0 or 1, p is 0, 1, 2, 3, or 4, each R9 is independently selected from the group consisting of deuterium, halogen, hydroxyl, and cyano).

[0010] Also provided herein is a pharmaceutical composition comprising a compound of formula I-A or I or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

[0011] In another aspect, provided herein is a method of treating narcolepsy in a subject in need thereof, the method comprising administering to the subject a compound of formula I-A or I or a pharmaceutically acceptable salt thereof.

[0012] In another aspect, provided herein is a method of treating cataplexy in a subject in need thereof, the method comprising administering to the subject a compound of formula I-A or I or a pharmaceutically acceptable salt thereof.

Mode for Carrying Out the Invention

[0013] Provided herein are compounds useful for treating narcolepsy or cataplexy in a subject, such as a compound of formula I-A or I or a pharmaceutically acceptable salt thereof.

[0014] In a non-limiting aspect, these compounds may modulate the orexin 2 receptor. In certain embodiments, the compounds provided herein are considered orexin 2 agonists. Thus, in one aspect, the compounds provided herein are useful for treating narcolepsy in a subject by acting as an agonist of the orexin 2 receptor.

[0015] Definitions The following are definitions of various terms used to describe the present invention. These definitions apply to the terms used throughout this specification and the claims, individually or as part of a larger group, unless otherwise specifically limited in a particular instance.

[0016] Unless otherwise defined, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature used herein and the laboratory procedures in cell culture, molecular genetics, organic chemistry, and peptide chemistry are well known and commonly used in the art.

[0017] As used herein, the articles "a" and "an" refer to one or more than one (i.e., at least one) of the grammatical objects of the article. By way of example, "an element" means one element or more than one element. Further, the use of the term "including" and other forms such as "include", "includes", and "included" is not limiting.

[0018] As used herein, the term "about" is understood by those skilled in the art and varies to some extent depending on the context in which it is used. When used herein in reference to a measurable value such as an amount, duration, etc., the term "about" means an inclusion of a variation of ±20% or ±10% including ±5%, ±1%, and ±0.1% from the specified value, and such variations are suitable for carrying out the disclosed methods.

[0019] As used herein, "EC 50 " refers to the concentration of a compound required to achieve an effect that is 50% of the maximum observed effect of the compound.

[0020] As used herein, the term "agonist" refers to a compound that, when contacted with a target of interest (e.g., the orexin 2 receptor), causes an increase in the magnitude of a particular activity or function of the target as compared to the magnitude of the activity or function observed in the absence of the agonist.

[0021] The terms "treat", "treated", "treating" or "treatment" include a reduction or alleviation of at least one symptom associated with or caused by the condition, disorder or disease being treated. In certain embodiments, treatment includes contacting an orexin 2 receptor with an effective amount of a compound of the invention for a condition associated with narcolepsy or cataplexy.

[0022] As used herein, the terms "prevent" or "prevention" mean, when a disorder or disease has not occurred, the absence of the occurrence of the disorder or disease, or when a disorder or disease has already occurred, the absence of the occurrence of a further disorder or disease. The ability to prevent some or all of the symptoms associated with a disorder or disease is also contemplated.

[0023] As used herein, the terms "patient", "individual" or "subject" refer to a human or non-human mammal. Non-human mammals include, for example, domestic animals and pets such as sheep, cows, pigs, dogs, cats and mice. Preferably, the patient, subject or individual is human.

[0024] As used herein, the terms "effective amount", "pharmaceutically effective amount", and "therapeutically effective amount" refer to a non-toxic but sufficient amount of an agent to provide the desired biological result. The result can be a reduction or alleviation of the signs, symptoms, or causes of a disease, or any other desired change in a biological system. The appropriate therapeutic amount in any individual case can be determined by one of ordinary skill in the art using routine experimentation.

[0025] As used herein, the term "pharmaceutically acceptable" means that a material does not inactivate the biological activity or properties of a compound and is relatively non-toxic, i.e., the material can be administered to an individual without causing undesirable biological effects or interacting in a harmful manner with any of the components of the composition in which it is contained.

[0026] As used herein, the term "pharmaceutically acceptable salt" refers to derivatives of the disclosed compounds in which the parent compound is modified by converting an existing acidic or basic moiety into its salt form. Examples of pharmaceutically acceptable salts include, but are not limited to, inorganic or organic acid salts of basic residues such as amines, and alkali or organic salts of acidic residues such as carboxylic acids. Pharmaceutically acceptable salts of the present invention include, for example, conventional non-toxic salts of the parent compounds formed from non-toxic inorganic or organic acids. Pharmaceutically acceptable salts of the present invention can be synthesized from parent compounds containing basic or acidic moieties by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or free base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or an organic solvent, or in a mixture of the two, and generally, non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. The phrase "pharmaceutically acceptable salt" is not limited to mono-salts or 1:1 salts. For example, "pharmaceutically acceptable salts" include bis-salts such as bis-hydrochloride salts. Lists of suitable salts are found in Remington’s Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418 and Journal of Pharmaceutical Science, 66, 2 (1977), each of which is incorporated herein by reference in its entirety.

[0027] As used herein, the term "composition" or "pharmaceutical composition" refers to a mixture of at least one compound useful within the present invention and a pharmaceutically acceptable carrier. Pharmaceutical compositions facilitate the administration of the compounds to a patient or subject. A plurality of techniques for administering compounds exist in the art, including, but not limited to, intravenous, oral, aerosol, parenteral, ocular, pulmonary, and topical administration.

[0028] As used herein, the term "pharmaceutically acceptable carrier" means a pharmaceutically acceptable material, composition or carrier, such as a liquid or solid filler, stabilizer, dispersant, suspending agent, diluent, excipient, thickening agent, solvent or encapsulating material, involved in carrying or transporting a compound useful within the invention in or to a patient so as to perform the intended function. Typically, such constructs are carried or transported from one organ or part of the body to another organ or part of the body. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of a formulation containing a compound useful within the invention and not injurious to the patient. Some examples of substances which can function as pharmaceutically acceptable carriers include sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; tragacanth powder; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, soybean oil; glycols such as propylene glycol; polyols such as glycerin, sorbitol, mannitol and polyethylene glycol; esters such as ethyl oleate, ethyl laurate; agar; buffering agents such as magnesium hydroxide, aluminum hydroxide; surfactants; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; phosphate buffer solutions; and other non-toxic compatible substances used in pharmaceutical formulations.

[0029] As used herein, "pharmaceutically acceptable carrier" also includes any coating, antibacterial and antifungal agents, absorption delaying agents, etc. that are compatible with the activity of the compounds useful within the present invention and are physiologically acceptable to the patient. Additionally, auxiliary active compounds may be incorporated into the composition. "Pharmaceutically acceptable carrier" may further include pharmaceutically acceptable salts of the compounds useful within the present invention. Other additional components that may be included in the pharmaceutical compositions used in the practice of the present invention are known in the art and are described, for example, in Remington’s Pharmaceutical Sciences (Genaro, Ed., Mack Publishing Co., 1985, Easton, PA), which is incorporated herein by reference.

[0030] As used herein, the term "alkyl", by itself or as part of another substituent, unless otherwise specified, means a straight or branched chain hydrocarbon having the specified number of carbon atoms (i.e., C1-6 alkyl means an alkyl having 1 to 6 carbon atoms), including both straight and branched chains. Examples include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, neopentyl and hexyl. Other examples of C1-C6-alkyl include ethyl, methyl, isopropyl, isobutyl, n-pentyl and n-hexyl.

[0031] As used herein, the term "halo" or "halogen", by itself or as part of another substituent, unless otherwise specified, means a fluorine, chlorine, bromine or iodine atom, preferably fluorine, chlorine or bromine, more preferably fluorine or chlorine.

[0032] As used herein, the term "alkylene" refers to a divalent aliphatic hydrocarbyl group having 1 to 4 carbon atoms, which can be either straight-chain or branched. By way of example, this term includes methylene (-CH2-), ethylene (-CH2CH2-), n-propylene (-CH2CH2CH2-), isopropylene (-CH2CH(CH3)-), and the like.

[0033] As used herein, the term "alkenyl" means a monovalent group derived from a hydrocarbon moiety containing at least 2 carbon atoms and at least 1 carbon-carbon double bond. The double bond may or may not be a point of attachment to another group. Examples of alkenyl groups (e.g., C2-C8-alkenyl) include, but are not limited to, ethenyl, propenyl, prop-1-en-2-yl, butenyl, 1-methyl-2-buten-1-yl, heptenyl, octenyl, and the like.

[0034] As used herein, the term "alkynyl" means a monovalent group derived from a hydrocarbon moiety containing at least 2 carbon atoms and at least 1 carbon-carbon triple bond. The triple bond may or may not be a point of attachment to another group. Examples of alkynyl groups (e.g., C2-C8-alkynyl) include, but are not limited to, ethynyl, propynyl, prop-1-yn-2-yl, butynyl, 1-methyl-2-butyn-1-yl, heptynyl, octynyl, and the like.

[0035] As used herein, the term "alkoxy" refers to an -O-alkyl group where alkyl is as defined herein. Examples of alkoxy include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, t-butoxy, and the like.

[0036] As used herein, the term "cycloalkyl" means a partially or fully saturated non-aromatic carbocyclic system having 1, 2, or 3 rings, such rings may be fused. The term "fused" means that a second ring is present (i.e., attached or formed) by having two adjacent atoms in common (i.e., shared) with a first ring. Cycloalkyl also includes bicyclic structures that may be essentially bridged or spirocyclic, with each individual ring within the rings varying from 3 to 8 atoms. The term "cycloalkyl" includes, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo[3.1.0]hexyl, spiro[3.3]heptanyl, and bicyclo[1.1.1]pentyl.

[0037] As used herein, the term "heterocyclyl" means a non-aromatic carbocyclic system containing 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, having 1, 2, or 3 rings, such rings may be fused, and the fusion is defined above. Heterocyclyl also includes bicyclic structures that can be essentially bridged or spirocyclic, with each individual ring within the bicyclic varying from 3 to 8 atoms and containing 0, 1, or 2 N, O, or S atoms. The term "heterocyclyl" includes cyclic esters (i.e., lactones) and cyclic amides (i.e., lactams), and specifically includes, but is not limited to, epoxyidyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl (i.e., oxanyl), pyranyl, dioxanyl, aziridinyl, azetidinyl, pyrrolidinyl, 2,5-dihydro-1H-pyrrolyl, oxazolidinyl, thiazolidinyl, piperidinyl, morpholinyl, piperazinyl, thiomorpholinyl, 1,3-oxazinanyl, 1,3-thiazinanyl, etc. For example, the term "heterocyclyl" may include 4- to 10-membered heterocyclyl, 4- to 7-membered heterocyclyl, 5- to 10-membered heterocyclyl, 6- to 10-membered heterocyclyl, 4- to 6-membered heterocyclyl, 4-membered heterocyclyl, 5-membered heterocyclyl, 6-membered heterocyclyl, 7-membered heterocyclyl, 8-membered heterocyclyl, 9-membered heterocyclyl, or 10-membered heterocyclyl.

[0038] As used herein, the term "aromatic" refers to a carbocyclic or heterocyclic ring having one or more polyunsaturated rings and having aromaticity, i.e., having (4n + 2) delocalized π (pi) electrons, where n is an integer.

[0039] As used herein, the term "aryl" means an aromatic carbocyclic system containing 1, 2 or 3 rings, such rings may be fused, and the fusion is defined above. When the rings are fused, one of the rings must be completely unsaturated, and the fused ring(s) may be completely saturated, partially unsaturated or completely unsaturated. The term "aryl" includes, but is not limited to, phenyl, naphthyl, indanyl, and 1,2,3,4-tetrahydronaphthalenyl. For example, the term "aryl" may include C6-C 10 It may include aryl, C6-C8 aryl, or C6 aryl (i.e., phenyl).

[0040] As used herein, the term "heteroaryl" means an aromatic carbocyclic system having 1, 2 or 3 rings and containing 1, 2, 3 or 4 heteroatoms independently selected from N, O, and S, such rings may be fused, and the fusion is defined above. The term "heteroaryl" includes, but is not limited to, furanyl, thiophenyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, etc. For example, the term "heteroaryl" may include 5- to 10-membered heteroaryl, 5- to 8-membered heteroaryl, 5- to 6-membered heteroaryl, 6- to 10-membered heteroaryl, 6- to 8-membered heteroaryl, 5-membered heteroaryl, 6-membered heteroaryl, 7-membered heteroaryl, 8-membered heteroaryl, 9-membered heteroaryl, or 10-membered heteroaryl.

[0041] When an aryl, heteroaryl, cycloalkyl or heterocyclyl moiety can be attached or otherwise bonded to a designated moiety via different ring atoms (i.e., shown or described without indication of a specific point of attachment), it should be understood that all possible points, whether via a carbon atom or, for example, a trivalent nitrogen atom, are intended. For example, the term "pyridinyl" means 2-, 3- or 4-pyridinyl, the term "thiophenyl" means 2- or 3-thiophenyl, and the like.

[0042] As used herein, the term "substituted" means that an atom or group of atoms has replaced hydrogen as a substituent attached to another group.

[0043] The compounds of the present invention Accordingly, in a first aspect, the present invention provides a compound represented by formula I-A or a pharmaceutically acceptable salt thereof:

Chemical formula

[0044] In one embodiment, provided herein is a compound of formula I-A having the structure of formula I or a pharmaceutically acceptable salt thereof:

Chemical formula

[0045] In one embodiment of formula (I), ring A is selected from the group consisting of 4- to 7-membered heterocyclyl, C6-C 10 aryl and 5- to 7-membered heteroaryl, and the 4- to 7-membered heterocyclyl, C6-C 10 aryl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0046] In another embodiment of formula (I), ring A is selected from the group consisting of C3-C8 cycloalkyl, C6-C 10 aryl and 5- to 7-membered heteroaryl, and the C3-C8 cycloalkyl, C6-C 10 aryl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0047] In another embodiment of formula (I), ring A is selected from the group consisting of C3-C8 cycloalkyl, 4- to 7-membered heterocyclyl, and 5- to 7-membered heteroaryl, and the C3-C8 cycloalkyl, 4- to 7-membered heterocyclyl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0048] In another embodiment of formula (I), ring A is selected from the group consisting of C3-C8 cycloalkyl, 4- to 7-membered heterocyclyl, and C6-C 10 aryl, and the C3-C8 cycloalkyl, 4- to 7-membered heterocyclyl, C6-C 10Aryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0049] In another embodiment of formula (I), ring A is selected from the group consisting of C6-C 10 Aryl and 5-7 membered heteroaryl, and C6-C 10 Aryl or 5-7 membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0050] In another embodiment of formula (I), ring A is selected from the group consisting of C3-C8 cycloalkyl and 4-7 membered heterocyclyl, and C3-C8 cycloalkyl or 4-7 membered heterocyclyl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0051] In another embodiment of formula (I), ring A is selected from the group consisting of C3-C8 cycloalkyl and C6-C 10 Aryl, and C3-C8 cycloalkyl or C6-C 10 Aryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0052] In another embodiment of formula (I), ring A is selected from the group consisting of 4-7 membered heterocyclyl and C6-C 10 Aryl, and 4-7 membered heterocyclyl or C6-C 10Aryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0053] In another embodiment of formula (I), ring A is selected from the group consisting of 4- to 7-membered heterocyclyls and 5- to 7-membered heteroaryls, and the 4- to 7-membered heterocyclyl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0054] In another embodiment of formula (I), ring A is C3-C8 cycloalkyl, and the C3-C8 cycloalkyl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0055] In another embodiment of formula (I), ring A is 4- to 7-membered heterocyclyl, and the 4- to 7-membered heterocyclyl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0056] In another embodiment of formula (I), ring A is C6-C 10 aryl, and C6-C 10 aryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0057] In another embodiment of formula (I), ring A is a 5- to 7-membered heteroaryl, and the 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0058] In another embodiment of formula (I), ring B is selected from the group consisting of 4- to 7-membered heterocyclyl, C6-C 10 aryl and 5- to 7-membered heteroaryl, and the 4- to 7-membered heterocyclyl, C6-C 10 aryl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0059] In another embodiment of formula (I), ring B is selected from the group consisting of C3-C8 cycloalkyl, C6-C 10 aryl and 5- to 7-membered heteroaryl, and the C3-C8 cycloalkyl, C6-C 10 aryl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0060] In another embodiment of formula (I), ring B is selected from the group consisting of C3-C8 cycloalkyl, 4- to 7-membered heterocyclyl, and 5- to 7-membered heteroaryl, and the C3-C8 cycloalkyl, 4- to 7-membered heterocyclyl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0061] In another embodiment of formula (I), ring B is selected from the group consisting of C3-C8 cycloalkyl, 4- to 7-membered heterocyclyl, and C6-C10 Selected from the group consisting of aryl, C3-C8 cycloalkyl, 4-7 membered heterocyclyl, C6-C 10 The aryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0062] In another embodiment of formula (I), ring B is C6-C 10 Selected from the group consisting of aryl and 5-7 membered heteroaryl, C6-C 10 The aryl or 5-7 membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0063] In another embodiment of formula (I), ring B is selected from the group consisting of C3-C8 cycloalkyl and 4-7 membered heterocyclyl, and the C3-C8 cycloalkyl or 4-7 membered heterocyclyl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0064] In another embodiment of formula (I), ring B is selected from the group consisting of C3-C8 cycloalkyl and C6-C 10 Selected from the group consisting of aryl, and the C3-C8 cycloalkyl or C6-C 10 The aryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0065] In another embodiment of formula (I), ring B is selected from the group consisting of 4-7 membered heterocyclyl and C6-C 10 Selected from the group consisting of aryl, and the 4-7 membered heterocyclyl or C6-C 10Aryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0066] In another embodiment of formula (I), ring B is selected from the group consisting of 4- to 7-membered heterocyclyl and 5- to 7-membered heteroaryl, and the 4- to 7-membered heterocyclyl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0067] In another embodiment of formula (I), ring B is C3-C8 cycloalkyl, and the C3-C8 cycloalkyl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0068] In another embodiment of formula (I), ring B is 4- to 7-membered heterocyclyl, and the 4- to 7-membered heterocyclyl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0069] In another embodiment of formula (I), ring B is C6-C 10 aryl, and the C6-C 10 aryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0070] In another embodiment of formula (I), ring B is a 5- to 7-membered heteroaryl, and the 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0071] In another embodiment of formula (I), ring A and ring B are each independently selected from the group consisting of 4- to 7-membered heterocyclyl, C6-C 10 aryl and 5- to 7-membered heteroaryl, and the 4- to 7-membered heterocyclyl, C6-C 10 aryl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0072] In another embodiment of formula (I), ring A and ring B are each independently selected from the group consisting of C3-C8 cycloalkyl, C6-C 10 aryl and 5- to 7-membered heteroaryl, and the C3-C8 cycloalkyl, C6-C 10 aryl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0073] In another embodiment of formula (I), ring A and ring B are each independently selected from the group consisting of C3-C8 cycloalkyl, 4- to 7-membered heterocyclyl, and 5- to 7-membered heteroaryl, and the C3-C8 cycloalkyl, 4- to 7-membered heterocyclyl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0074] In another embodiment of formula (I), ring A and ring B are each independently selected from the group consisting of C3-C8 cycloalkyl, 4-7 membered heterocyclyl, and C6-C 10 aryl, and C3-C8 cycloalkyl, 4-7 membered heterocyclyl, C6-C 10 aryl is unsubstituted or substituted with one or more halogens, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums.

[0075] In another embodiment of formula (I), ring A and ring B are each independently selected from the group consisting of C6-C 10 aryl and 5-7 membered heteroaryl, and C6-C 10 aryl or 5-7 membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums.

[0076] In another embodiment of formula (I), ring A and ring B are each independently selected from the group consisting of C3-C8 cycloalkyl and 4-7 membered heterocyclyl, and C3-C8 cycloalkyl or 4-7 membered heterocyclyl is unsubstituted or substituted with one or more halogens, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums.

[0077] In another embodiment of formula (I), ring A and ring B are each independently selected from the group consisting of C3-C8 cycloalkyl and C6-C 10 aryl, and C3-C8 cycloalkyl or C6-C 10 aryl is unsubstituted or substituted with one or more halogens, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums.

[0078] In another embodiment of formula (I), ring A and ring B are each independently selected from the group consisting of 4- to 7-membered heterocyclyl and C6-C 10 aryl, and the 4- to 7-membered heterocyclyl or C6-C 10 aryl is unsubstituted or substituted with one or more halogens, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums.

[0079] In another embodiment of formula (I), ring A and ring B are each independently selected from the group consisting of 4- to 7-membered heterocyclyl and 5- to 7-membered heteroaryl, and the 4- to 7-membered heterocyclyl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums.

[0080] In another embodiment of formula (I), ring A is 5- to 7-membered heteroaryl and ring B is C6-C 10 aryl, and the 5- to 7-membered heteroaryl and C6-C 10 aryl are each independently unsubstituted or substituted with one or more halogens, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums.

[0081] In another embodiment of formula (I), ring A is 5- to 7-membered heteroaryl and ring B is 5- to 7-membered heteroaryl, and each 5- to 7-membered heteroaryl is independently unsubstituted or substituted with one or more halogens, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums.

[0082] In another embodiment of formula (I), ring A is 4- to 7-membered heterocyclyl and ring B is C6-C 10Aryl, 4- to 7-membered heterocyclyl, and C6-C 10 Each aryl is independently unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0083] In another embodiment of formula (I), ring A is a 4- to 7-membered heterocyclyl, ring B is a 5- to 7-membered heteroaryl, and each of the 4- to 7-membered heterocyclyl and the 5- to 7-membered heteroaryl is independently unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0084] In another embodiment of formula (I), ring A is C3-C8 cycloalkyl, ring B is C6-C 10 aryl, and each of the C3-C8 cycloalkyl and the C6-C 10 aryl is independently unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0085] In another embodiment of formula (I), ring A is C3-C8 cycloalkyl, ring B is a 5- to 7-membered heteroaryl, and each of the C3-C8 cycloalkyl and the 5- to 7-membered heteroaryl is independently unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0086] In another embodiment of formula (I),

Chemical formula

[0087] In another embodiment of formula (I),

Chemical formula

[0088] In another embodiment of formula (I),

Chemical formula

[0089] In another embodiment of formula (I),

Chemical formula

[0090] In another embodiment of formula (I),

Chemical formula

[0091] In another embodiment of formula (I),

Chemical formula

[0092] In another embodiment of formula (I), [Chemical formula] is indolinyl, and the indolinyl is unsubstituted or substituted with 1 to 3 substituents selected from halogen, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with 1 to 3 halogen atoms or deuterium atoms.

[0093] In another embodiment of formula (I), [Chemical formula] is indazolyl, and the indazolyl is unsubstituted or substituted with 1 to 3 substituents selected from halogen, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with 1 to 3 halogen atoms or deuterium atoms.

[0094] In another embodiment of formula (I), [Chemical formula] is isoindazolyl, and the isoindazolyl is unsubstituted or substituted with 1 to 3 substituents selected from halogen, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with 1 to 3 halogen atoms or deuterium atoms.

[0095] In another embodiment of formula (I), [Chemical formula] is benzothiazolyl, and benzothiazolyl is unsubstituted or substituted with 1 to 3 substituents selected from halogen, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with 1 to 3 halogen atoms or deuterium atoms.

[0096] In another embodiment of formula (I),

Chemical formula

[0097] In another embodiment of formula (I),

Chemical formula

[0098] In another embodiment of formula (I),

Chemical formula

[0099] In another embodiment of formula (I), [Chemical formula] is benzisothiazolyl, and the benzisothiazolyl is unsubstituted or substituted with 1 to 3 substituents selected from halogen, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with 1 to 3 halogen atoms or deuterium atoms.

[0100] In another embodiment of formula (I), [Chemical formula] is isobenzofuranyl, and the isobenzofuranyl is unsubstituted or substituted with 1 to 3 substituents selected from halogen, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with 1 to 3 halogen atoms or deuterium atoms.

[0101] In another embodiment of formula (I), [Chemical formula] is benzothiophenyl, and the benzothiophenyl is unsubstituted or substituted with 1 to 3 substituents selected from halogen, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with 1 to 3 halogen atoms or deuterium atoms.

[0102] In another embodiment of formula (I), [Chemical formula] is indoleninyl, and the indoleninyl is unsubstituted or substituted with 1 to 3 substituents selected from halogen, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with 1 to 3 halogen atoms or deuterium atoms.

[0103] In another embodiment of formula (I),

Chemical formula

[0104] In another embodiment of formula (I),

Chemical formula

[0105] In another embodiment of formula (I),

Chemical formula

[0106] In another embodiment of formula (I),

Chem.

[0107] In another embodiment of formula (I),

Chem.

[0108] In another embodiment of formula (I),

Chem.

Chem.

[0109] In another embodiment of formula (I),

Chem.

Chem.

[0110] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0111] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0112] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0113] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0114] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0115] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0116] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0117] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0118] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0119] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0120] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0121] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0122] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0123] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0124] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0125] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0126] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0127] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0128] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0129] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0130] In another embodiment of formula (I),

Chemical formula

Chemical formula

[0131] In another embodiment of formula (I), p is 0. In another embodiment of formula (I), p is 1. In another embodiment of formula (I), p is 2. In another embodiment of formula (I), p is 3. In another embodiment of formula (I), p is 4. In another embodiment of formula (I), p is 0, 1 or 2. In another embodiment of formula (I), p is 0 or 1.

[0132] In another embodiment of formula (I), p is 1 and R9 is deuterium. In another embodiment of formula (I), p is 1 and R9 is halogen. In another embodiment of formula (I), p is 1 and R9 is fluorine. In another embodiment of formula (I), p is 1 and R9 is hydroxyl. In another embodiment of formula (I), p is 1 and R9 is cyano. In another embodiment of formula (I), p is 2 and each R9 is hydroxyl. In another embodiment of formula (I), p is 2 and each R9 is halogen. In another embodiment of formula (I), p is 2 and each R9 is fluorine.

[0133] In another embodiment of formula (I), E is NR a R b In another embodiment of formula (I), E is C1-C3 alkylene-NR a R b In another embodiment of formula (I), E is unsubstituted C1-C3 alkyl, unsubstituted C2-C4 alkenyl or unsubstituted C 2~is C4 alkynyl. In another embodiment of formula (I), E is C1-C3 alkyl, C2-C4 alkenyl or C2-C4 alkynyl substituted with one or more halogen, hydroxyl, C1-C3 alkyl or C1-C3 alkoxyl. In another embodiment of formula (I), E is unsubstituted C1-C3 alkyl. In another embodiment of formula (I), E is c R d , CF3, CHF2, CH2F, C1-C3 alkyl substituted with C1-C3 alkyl or C1-C3 alkoxyl. In another embodiment of formula (I), E is unsubstituted C3-C8 cycloalkyl. In another embodiment of formula (I), E is c R d , CF3, CHF2, CH2F, C3-C8 cycloalkyl substituted with C1-C3 alkyl or C1-C3 alkoxyl. In another embodiment of formula (I), E is unsubstituted C1-C3 alkylene-(C3-C8 cycloalkyl). In another embodiment of formula (I), E is c R d , CF3, CHF2, CH2F, C1-C3 alkylene-(C3-C8 cycloalkyl) substituted with C1-C3 alkyl or C1-C3 alkoxyl. In another embodiment of formula (I), E is unsubstituted 4-10 membered heterocyclyl. In another embodiment of formula (I), E is c R d , CF3, CHF2, CH2F, 4-10 membered heterocyclyl substituted with C1-C3 alkyl or C1-C3 alkoxyl. In another embodiment of formula (I), E is unsubstituted C1-C3 alkylene-(4-10 membered heterocyclyl). In another embodiment of formula (I), E is c R d , CF3, CHF2, CH2F, C1-C3 alkylene-(4-10 membered heterocyclyl) substituted with C1-C3 alkyl or C1-C3 alkoxyl. In another embodiment of formula (I), E is unsubstituted C6-C 10It is aryl. In another embodiment of formula (I), E is one or more halogens, hydroxyl, NR c R d , CF3, CHF2, CH2F, C1-C3 alkyl or C1-C3 alkoxyl substituted C6-C 10 aryl. In another embodiment of formula (I), E is unsubstituted C1-C3 alkylene-(C6-C 10 aryl). In another embodiment of formula (I), E is one or more halogens, hydroxyl, NR c R d , CF3, CHF2, CH2F, C1-C3 alkyl or C1-C3 alkoxyl substituted C1-C3 alkylene-(C6-C 10 aryl). In another embodiment of formula (I), E is unsubstituted 5-7 membered heteroaryl. In another embodiment of formula (I), E is one or more halogens, hydroxyl, NR c R d , CF3, CHF2, CH2F, C1-C3 alkyl or C1-C3 alkoxyl substituted 5-7 membered heteroaryl. In another embodiment of formula (I), E is unsubstituted C1-C3 alkylene-(5-7 membered heteroaryl). In another embodiment of formula (I), E is one or more halogens, hydroxyl, NR c R d , CF3, CHF2, CH2F, C1-C3 alkyl or C1-C3 alkoxyl substituted C1-C3 alkylene-(5-7 membered heteroaryl).

[0134] In another embodiment of formula (I), E is C1-C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C8 cycloalkyl, C1-C3 alkylene-(C3-C8 cycloalkyl), 4-10 membered heterocyclyl, or C1-C3 alkylene-(4-10 membered heterocyclyl), and C1-C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C8 cycloalkyl, C1-C3 alkylene-(C3-C8 cycloalkyl), 4-10 membered heterocyclyl, or C1-C3 alkylene-(4-10 membered heterocyclyl) is unsubstituted or one or more halogens, hydroxyl, NRc R d , CF3, CHF2, CH2F, C1-C3 alkyl or C1-C3 alkoxyl.

[0135] In another embodiment of formula (I), E is C1-C3 alkyl, C3-C8 cycloalkyl, C1-C3 alkylene-(C3-C8 cycloalkyl), 4-10 membered heterocyclyl, or C1-C3 alkylene-(4-10 membered heterocyclyl), wherein the C1-C3 alkyl, C3-C8 cycloalkyl, C1-C3 alkylene-(C3-C8 cycloalkyl), 4-10 membered heterocyclyl, or C1-C3 alkylene-(4-10 membered heterocyclyl) is unsubstituted or is substituted with one or more of halogen, hydroxyl, NR c R d , CF3, CHF2, CH2F, C1-C3 alkyl or C1-C3 alkoxyl.

[0136] In another embodiment of formula (I), E is C1-C3 alkyl, C3-C8 cycloalkyl, or C1-C3 alkylene-(C3-C8 cycloalkyl), wherein C1-C3 alkyl, C3-C8 cycloalkyl, or C1-C3 alkylene-(C3-C8 cycloalkyl) is unsubstituted or substituted with one or more of halogen, hydroxyl, NR c R d , CF3, CHF2, CH2F, C1-C3 alkyl or C1-C3 alkoxyl.

[0137] In another embodiment of formula (I), E is methyl. In another embodiment of formula (I), E is one or more of halogen, hydroxyl, NR c R d , methyl substituted with CF3, CHF2, CH2F, C1-C3 alkyl, or C1-C3 alkoxyl. In another embodiment of Formula (I), E is CF3. In another embodiment of Formula (I), E is CHF2. In another embodiment of Formula (I), E is CH2F. In another embodiment of Formula (I), E is NH(CH3). In another embodiment of Formula (I), E is N(CH3)2.

[0138] In another embodiment of formula (I), E is C6-C 10 aryl, C1-C3 alkylene-(C6-C 10 aryl), 5-7 membered heteroaryl or C1-C3 alkylene-(5-7 membered heteroaryl). In another embodiment of formula (I), E is unsubstituted C6-C 10 aryl or C1-C3 alkylene-(C6-C 10 aryl). In another embodiment of formula (I), E is C6-C c aryl or C1-C3 alkylene-(C6-C d aryl) substituted with one or more halogens, hydroxyl, NR 10 R 10 , CF3, CHF2, CH2F, C1-C3 alkyl or C1-C3 alkoxyl.

[0139] In another embodiment of formula (I), E is 5-7 membered heteroaryl or C1-C3 alkylene-(5-7 membered heteroaryl). In another embodiment of formula (I), E is unsubstituted 5-7 membered heteroaryl or C1-C3 alkylene-(5-7 membered heteroaryl). In another embodiment of formula (I), E is 5-7 membered heteroaryl or C1-C3 alkylene-(5-7 membered heteroaryl) substituted with one or more halogens, hydroxyl, NR c R d , CF3, CHF2, CH2F, C1-C3 alkyl or C1-C3 alkoxyl.

[0140] In another embodiment of formula (I), Y is S(=O)2. In another embodiment of formula (I), Y is C(=O). In another embodiment of formula (I), Y is S(=O)(=NR e ).

[0141] In another embodiment of formula (I), X is N. In another embodiment of formula (I), X is CH.

[0142] In another embodiment of formula (I), R1 is C(=O)-C1-C4 alkyl, C(=O)-C1-C4 alkoxy, C(=O)-(CR c R d ) n -C3-C8 cycloalkyl, C(=O)-(CR c R d ) n -(4-7 membered heterocyclyl), C(=O)-(CR c R d ) n -(C6-C 10 aryl), and C(=O)-(CR c R d ) n -(5-10 membered heteroaryl), and is selected from the group consisting of; C1-C4 alkyl, C1-C4 alkoxyl, C3-C8 cycloalkyl, 4-7 membered heterocyclyl, C6-C 10 aryl, or 5-10 membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums.

[0143] In another embodiment of formula (I), R1 is C(=O)-C1-C4 alkyl, C(=O)-C1-C4 alkoxyl, and C(=O)-(CR c R d ) n -C3-C8 cycloalkyl, and is selected from the group consisting of; C1-C4 alkyl, C1-C4 alkoxyl, or C3-C8 cycloalkyl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums.

[0144] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(4-7 membered heterocyclyl), C(=O)-(CR c R d ) n -(C6-C 10(Aryl), and C(=O)-(CR c R d ) n -(a 5- to 10-membered heteroaryl) selected from the group consisting of, a 4- to 7-membered heterocyclyl, C6-C 10 aryl, or a 5- to 10-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0145] In another embodiment of formula (I), R1 is C(=O)-C1-C4 alkyl, and the C1-C4 alkyl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0146] In another embodiment of formula (I), R1 is C(=O)-C1-C4 alkoxy, and the C1-C4 alkoxy is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0147] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -C3-C8 cycloalkyl, and the C3-C8 cycloalkyl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0148] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n-(a 4- to 7-membered heterocyclyl), wherein the 4- to 7-membered heterocyclyl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0149] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(C 6~ C 10 aryl), wherein the C 6~ C 10 aryl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0150] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a 5- to 10-membered heteroaryl), wherein the 5- to 10-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0151] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a 5- to 7-membered heterocyclyl), wherein the 5- to 7-membered heterocyclyl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0152] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n-(a 5- or 6-membered heterocyclyl), wherein the 5- or 6-membered heterocyclyl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0153] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a 5-membered heterocyclyl), wherein the 5-membered heterocyclyl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0154] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a 6-membered heterocyclyl), wherein the 6-membered heterocyclyl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0155] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a C6 aryl), wherein the C6 aryl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0156] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a C8 aryl), wherein the C8 aryl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0157] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(C 10 aryl), and C 10 Aryl is unsubstituted or substituted with one or more halogen, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogen or deuterium.

[0158] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5-6 membered heteroaryl), wherein the 5-6 membered heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogen or deuterium.

[0159] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5-membered heteroaryl), wherein the 5-membered heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogen or deuterium.

[0160] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(6-membered heteroaryl), wherein the 6-membered heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogen or deuterium.

[0161] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n-(a 7-membered heteroaryl), where the 7-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0162] In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -C3-C8 cycloalkyl or C(=O)-O-(CR c R d ) n -(a 4-7-membered heterocyclyl), where the C3-C8 cycloalkyl or 4-7-membered heterocyclyl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -C3-C8 cycloalkyl, where the C3-C8 cycloalkyl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 4-7-membered heterocyclyl), where the 4-7-membered heterocyclyl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -C3-C5 cycloalkyl, where the C3-C5 cycloalkyl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums. In another embodiment of formula (I), R1 is C(=O)-O-(CRc R d ) n -(a 5- or 6-membered heterocyclyl), wherein the 5- or 6-membered heterocyclyl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 5-membered heterocyclyl), wherein the 5-membered heterocyclyl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 6-membered heterocyclyl), wherein the 6-membered heterocyclyl is unsubstituted or substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0163] In another embodiment of formula (I), R1 is (CR c R d ) n -(C6-C 10 aryl) or (CR c R d ) n -(a 5- to 10-membered heteroaryl), wherein the C6-C 10 aryl or 5- to 10-membered heteroaryl is unsubstituted. In another embodiment of formula (I), R1 is (CR c R d ) n -(C6-C 10 aryl) or (CR c R d ) n -(a 5- to 10-membered heteroaryl), wherein the C6-C 10Aryl or 5- to 10-membered heteroaryl is substituted with one or more halogens, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums.

[0164] In another embodiment of formula (I), R1 is (CR c R d ) n -(C6-C 10 aryl) or (CR c R d ) n -(5- to 10-membered heteroaryl), C6-C 10 aryl or 5- to 10-membered heteroaryl is unsubstituted, and further n is 0. In another embodiment of formula (I), R1 is (CR c R d ) n -(C6-C 10 aryl) or (CR c R d ) n -(5- to 10-membered heteroaryl), C6-C 10 aryl or 5- to 10-membered heteroaryl is substituted with one or more halogens, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums, and further n is 0.

[0165] In another embodiment of formula (I), R1 is (CR c R d ) n -(C6-C 10 aryl) or (CR c R d ) n -(5- to 10-membered heteroaryl), C6-C 10 aryl or 5- to 10-membered heteroaryl is unsubstituted, and further n is 1. In another embodiment of formula (I), R1 is (CR c R d ) n -(C6-C 10 aryl) or (CR c R d ) n-(5 to 10-membered heteroaryl), and C6-C 10 The aryl or 5 to 10-membered heteroaryl is substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums, and further n is 1.

[0166] In another embodiment of formula (I), R1 is (CR c R d ) n -(C6-C 10 aryl), and C6-C 10 aryl is unsubstituted. In another embodiment of formula (I), R1 is (CR c R d ) n -(C 6~ C 10 aryl), and C 6~ C 10 aryl is substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0167] In another embodiment of formula (I), R1 is (CR c R d ) n -(C6-C 10 aryl), and C6-C 10 aryl is unsubstituted, and further n is 0. In another embodiment of formula (I), R1 is (CR c R d ) n -(C 6~ C 10 aryl), and C 6~ C 10 aryl is substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums, and further n is 0.

[0168] In another embodiment of formula (I), R1 is (CR c R d ) n -(C6-C10 is (aryl), C6 - C 10 The aryl is unsubstituted, and further n is 1. In another embodiment of formula (I), R1 is (CR c R d ) n -(C 6~ C 10 is (aryl), C 6~ C 10 The aryl is substituted with one or more halogens, hydroxyls, unsubstituted C1 - C3 alkyls, or C1 - C3 alkyls substituted with one or more halogens or deuteriums, and further n is 1.

[0169] In another embodiment of formula (I), R1 is (CR c R d ) n -(5 - to 10 - membered heteroaryl), and the 5 - to 10 - membered heteroaryl is unsubstituted. In another embodiment of formula (I), R1 is (CR c R d ) n -(5 - to 10 - membered heteroaryl), and the 5 - to 10 - membered heteroaryl is substituted with one or more halogens, hydroxyls, unsubstituted C1 - C3 alkyls, or C1 - C3 alkyls substituted with one or more halogens or deuteriums.

[0170] In another embodiment of formula (I), R1 is (CR c R d ) n -(5 - to 10 - membered heteroaryl), and the 5 - to 10 - membered heteroaryl is unsubstituted, and further n is 0. In another embodiment of formula (I), R1 is (CR c R d ) n -(5 - to 10 - membered heteroaryl), and the 5 - to 10 - membered heteroaryl is substituted with one or more halogens, hydroxyls, unsubstituted C1 - C3 alkyls, or C1 - C3 alkyls substituted with one or more halogens or deuteriums, and further n is 0.

[0171] In another embodiment of formula (I), R1 is (CR c R d )n -(a 5- to 10-membered heteroaryl), the 5- to 10-membered heteroaryl is unsubstituted, and further n is 1. In another embodiment of formula (I), R1 is (CR c R d ) n -(a 5- to 10-membered heteroaryl), the 5- to 10-membered heteroaryl is substituted with one or more halogens, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuterium, and further n is 1.

[0172] In another embodiment of formula (I), R1 is (CR c R d ) n -(phenyl) or (CR c R d ) n -(a 5- to 7-membered heteroaryl), the phenyl or 5- to 7-membered heteroaryl is unsubstituted. In another embodiment of formula (I), R1 is (CR c R d ) n -(phenyl) or (CR c R d ) n -(a 5- to 7-membered heteroaryl), the phenyl or 5- to 7-membered heteroaryl is substituted with one or more halogens, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuterium.

[0173] In another embodiment of formula (I), R1 is (CR c R d ) n -(phenyl) or (CR c R d ) n -(a 5- to 7-membered heteroaryl), the phenyl or 5- to 7-membered heteroaryl is unsubstituted, and further n is 0. In another embodiment of formula (I), R1 is (CR c R d ) n -(phenyl) or (CR c R d ) n-(a 5- to 7-membered heteroaryl), wherein the phenyl or 5- to 7-membered heteroaryl is substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums, and further n is 0.

[0174] In another embodiment of formula (I), R1 is (CR c R d ) n -(phenyl) or (CR c R d ) n -(a 5- to 7-membered heteroaryl), wherein the phenyl or 5- to 7-membered heteroaryl is unsubstituted, and further n is 1. In another embodiment of formula (I), R1 is (CR c R d ) n -(phenyl) or (CR c R d ) n -(a 5- to 7-membered heteroaryl), wherein the phenyl or 5- to 7-membered heteroaryl is substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums, and further n is 1.

[0175] In another embodiment of formula (I), R1 is (CR c R d ) n -(phenyl) or (CR c R d ) n -(a 6-membered heteroaryl), wherein the phenyl or 6-membered heteroaryl is unsubstituted. In another embodiment of formula (I), R1 is (CR c R d ) n -(phenyl) or (CR c R d ) n -(a 6-membered heteroaryl), wherein the phenyl or 6-membered heteroaryl is substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuteriums.

[0176] In another embodiment of formula (I), R1 is (CR c R d ) n -(phenyl) or (CR c R d ) n -(6-membered heteroaryl), the phenyl or 6-membered heteroaryl is unsubstituted, and further n is 0. In another embodiment of formula (I), R1 is (CR c R d ) n -(phenyl) or (CR c R d ) n -(6-membered heteroaryl), the phenyl or 6-membered heteroaryl is substituted with one or more halogens, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuterium, and further n is 0.

[0177] In another embodiment of formula (I), R1 is (CR c R d ) n -(phenyl) or (CR c R d ) n -(6-membered heteroaryl), the phenyl or 6-membered heteroaryl is unsubstituted, and further n is 1. In another embodiment of formula (I), R1 is (CR c R d ) n -(phenyl) or (CR c R d ) n -(6-membered heteroaryl), the phenyl or 6-membered heteroaryl is substituted with one or more halogens, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuterium, and further n is 1.

[0178] In another embodiment of formula (I), R1 is (CR c R d ) n -(6-membered heteroaryl), the 6-membered heteroaryl is unsubstituted. In another embodiment of formula (I), R1 is (CRc R d ) n -(a 6-membered heteroaryl), where the 6-membered heteroaryl is substituted with one or more halogens, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums. In another embodiment of formula (I), R1 is pyridazinyl. In another embodiment of formula (I), R1 is 3-pyridazinyl.

[0179] In another embodiment of formula (I), R1 is (CR c R d ) n -(a 6-membered heteroaryl), where the 6-membered heteroaryl is unsubstituted and further n is 0. In another embodiment of formula (I), R1 is (CR c R d ) n -(a 6-membered heteroaryl), where the 6-membered heteroaryl is substituted with one or more halogens, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums, and further n is 0.

[0180] In another embodiment of formula (I), R1 is (CR c R d ) n -(a 6-membered heteroaryl), where the 6-membered heteroaryl is unsubstituted and further n is 1. In another embodiment of formula (I), R1 is (CR c R d ) n -(a 6-membered heteroaryl), where the 6-membered heteroaryl is substituted with one or more halogens, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums, and further n is 1.

[0181] In another embodiment of formula (I), R1 is (CR c R d ) n -(a 5-membered heteroaryl), where the 5-membered heteroaryl is unsubstituted. In another embodiment of formula (I), R1 is (CR c Rd ) n -(a 5-membered heteroaryl), wherein the 5-membered heteroaryl is substituted with one or more halogens, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums.

[0182] In another embodiment of formula (I), R1 is (CR c R d ) n -(a 5-membered heteroaryl), wherein the 5-membered heteroaryl is unsubstituted and further n is 0. In another embodiment of formula (I), R1 is (CR c R d ) n -(a 5-membered heteroaryl), wherein the 5-membered heteroaryl is substituted with one or more halogens, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums, and further n is 0.

[0183] In another embodiment of formula (I), R1 is (CR c R d ) n -(a 5-membered heteroaryl), wherein the 5-membered heteroaryl is unsubstituted and further n is 1. In another embodiment of formula (I), R1 is (CR c R d ) n -(a 5-membered heteroaryl), wherein the 5-membered heteroaryl is substituted with one or more halogens, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums, and further n is 1.

[0184] In another embodiment of formula (I), each of R2, R3, R4, R5, R6, R7, and R8 is independently H, halogen, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuteriums. In another embodiment of formula (I), each of R2, R3, R4, R5, R6, R7, and R8 is independently H, halogen, or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), each of R2, R3, R4, R5, R6, R7, and R8 is independently H, or halogen. In another embodiment of formula (I), each of R2, R3, R4, R5, R6, R7, and R8 is independently H, or fluorine. In another embodiment of formula (I), each of R2, R3, R4, R5, R6, R7, and R8 is independently H, or C1-C3 alkyl. In another embodiment of formula (I), each of R2, R3, R4, R5, R6, R7, and R8 is H.

[0185] In another embodiment of formula (I), R3 and R6 together form unsubstituted C1-C3 alkylene or C1-C3 alkylene substituted with one or more halogens. In another embodiment of formula (I), R3 and R6 together form unsubstituted C2 alkylene or C2 alkylene substituted with one or more halogens. In another embodiment of formula (I), R3 and R6 together form azabicyclo[3.2.1]octanyl-bridged bicyclic heterocyclyl.

[0186] In another embodiment of formula (I), R4 and R5 together form unsubstituted C1-C3 alkylene or C1-C3 alkylene substituted with one or more halogens. In another embodiment of formula (I), R4 and R5 together form unsubstituted C2 alkylene or C2 alkylene substituted with one or more halogens. In another embodiment of formula (I), R4 and R5 together form azabicyclo[3.2.1]octanyl-bridged bicyclic heterocyclyl.

[0187] In another embodiment of formula (I), R1 is C(=O)-C1-C4 alkyl, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-C1-C4 alkyl, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-C1-C4 alkyl, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-C1-C4 alkyl, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0188] In another embodiment of formula (I), R1 is C(=O)-C1-C4 alkoxy, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-C1-C4 alkoxy, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-C1-C4 alkoxy, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-C1-C4 alkoxy, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0189] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -C3-C8 cycloalkyl, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -C3-C8 cycloalkyl, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d) n -C3 to C8 cycloalkyl, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -C3 to C8 cycloalkyl, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0190] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -C3 to C8 cycloalkyl, n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -C3 to C8 cycloalkyl, n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1 to C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -C3 to C8 cycloalkyl, n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -C3 to C8 cycloalkyl, n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0191] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -C3 to C8 cycloalkyl, n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n-C3 to C8 cycloalkyl, n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1 to C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -C3 to C8 cycloalkyl, n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -C3 to C8 cycloalkyl, n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0192] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(4 to 7-membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(4 to 7-membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1 to C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(4 to 7-membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(4 to 7-membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0193] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n-(4 to 7-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(4 to 7-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(4 to 7-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(4 to 7-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0194] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(4 to 7-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(4 to 7-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(4 to 7-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n-(4 - 7 membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0195] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5 - membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5 - membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1 - C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5 - membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5 - membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0196] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5 - membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5 - membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1 - C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n-(a 5-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or a halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ). n -(a 5-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0197] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ). n -(a 5-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ). n -(a 5-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ). n -(a 5-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or a halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ). n -(a 5-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0198] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ). n -(a 6-membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ). n-(6-membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(6-membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(6-membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0199] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(6-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(6-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(6-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(6-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0200] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n-(a 6-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a 6-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a 6-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a 6-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0201] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a C6-C 10 aryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a C6-C 10 aryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a C6-C 10 aryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a C6-C10 is (aryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0202] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(C6-C 10 aryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(C6-C 10 aryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(C6-C 10 aryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(C6-C 10 aryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0203] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(C6-C 10 aryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(C6-C 10is aryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ). n -(C6-C 10 aryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ). n -(C6-C 10 aryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0204] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ). n -(C6 aryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ). n -(C6 aryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ). n -(C6 aryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ). n -(C6 aryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0205] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ). n-(C6 aryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(C6 aryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(C6 aryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(C6 aryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0206] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(C6 aryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(C6 aryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(C6 aryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n-(C6 aryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0207] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5- to 7-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5- to 7-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5- to 7-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5- to 7-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0208] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5- to 7-membered heteroaryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5- to 7-membered heteroaryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n-(5- to 7-membered heteroaryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5- to 7-membered heteroaryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0209] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5- to 7-membered heteroaryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5- to 7-membered heteroaryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5- to 7-membered heteroaryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5- to 7-membered heteroaryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0210] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d )n -(a 5-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a 5-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a 5-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0211] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a 5-membered heteroaryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a 5-membered heteroaryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a 5-membered heteroaryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(a 5-membered heteroaryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0212] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n-(5-membered heteroaryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5-membered heteroaryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5-membered heteroaryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(5-membered heteroaryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0213] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(6-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(6-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(6-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n-(6-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0214] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(6-membered heteroaryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(6-membered heteroaryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(6-membered heteroaryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(6-membered heteroaryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0215] In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(6-membered heteroaryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(6-membered heteroaryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n-(6-membered heteroaryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-(CR c R d ) n -(6-membered heteroaryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0216] In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -C3-C8 cycloalkyl, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -C3-C8 cycloalkyl, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -C3-C8 cycloalkyl, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -C3-C8 cycloalkyl, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0217] In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -C3-C8 cycloalkyl, n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n-C3 to C8 cycloalkyl, n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1 to C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -C3 to C8 cycloalkyl, n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -C3 to C8 cycloalkyl, n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0218] In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -C3 to C8 cycloalkyl, n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -C3 to C8 cycloalkyl, n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1 to C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -C3 to C8 cycloalkyl, n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -C3 to C8 cycloalkyl, n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0219] In another embodiment of formula (I), R1 is C(=O)-O-(CRc R d ) n -(4 - to 7 - membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(4 - to 7 - membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1 - C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(4 - to 7 - membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(4 - to 7 - membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0220] In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(4 - to 7 - membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(4 - to 7 - membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1 - C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(4 - to 7 - membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n-(4 to 7-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0221] In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(4 to 7-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(4 to 7-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(4 to 7-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(4 to 7-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0222] In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(5-membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(5-membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-O-(CR c Rd ) n -(a 5-membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 5-membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0223] In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 5-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 5-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 5-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 5-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0224] In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 5-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d) n -(a 5-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 5-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 5-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0225] In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 6-membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 6-membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 6-membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 6-membered heterocyclyl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0226] In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d )n -(a 6-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 6-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 6-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 6-membered heterocyclyl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0227] In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 6-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 6-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n -(a 6-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is C(=O)-O-(CR c R d ) n-(a 6-membered heterocyclyl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0228] In another embodiment of formula (I), R1 is (CR c R d ) n -(a 5- to 10-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is (CR c R d ) n -(a 5- to 10-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is (CR c R d ) n -(a 5- to 10-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is (CR c R d ) n -(a 5- to 10-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0229] In another embodiment of formula (I), R1 is (CR c R d ) n -(a 5- to 7-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is (CR c R d ) n -(a 5- to 7-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is (CR c R d ) n-(a 5- to 7-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or a halogen. In another embodiment of formula (I), R1 is (CR c R d ) n -(a 5- to 7-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0230] In another embodiment of formula (I), R1 is (CR c R d ) n -(a 6-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is (CR c R d ) n -(a 6-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is (CR c R d ) n -(a 6-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or a halogen. In another embodiment of formula (I), R1 is (CR c R d ) n -(a 6-membered heteroaryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0231] In another embodiment of formula (I), R1 is (CR c R d ) n -(a 6-membered heteroaryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is (CR c R d ) n -(a 6-membered heteroaryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is (CRc R d ) n -(6-membered heteroaryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is (CR c R d ) n -(6-membered heteroaryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0232] In another embodiment of formula (I), R1 is (CR c R d ) n -(6-membered heteroaryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is (CR c R d ) n -(6-membered heteroaryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is (CR c R d ) n -(6-membered heteroaryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is (CR c R d ) n -(6-membered heteroaryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0233] In another embodiment of formula (I), R1 is (CR c R d ) n -(C6-C 10 aryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is (CR c R d )n -(C6 to C 10 aryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1 - C3 alkyl. In another embodiment of formula (I), R1 is (CR c R d ) n -(C6 to C 10 aryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is (CR c R d ) n -(C6 to C 10 aryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0234] In another embodiment of formula (I), R1 is (CR c R d ) n -(C6 aryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is (CR c R d ) n -(C6 aryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1 - C3 alkyl. In another embodiment of formula (I), R1 is (CR c R d ) n -(C6 aryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is (CR c R d ) n -(C6 aryl), and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0235] In another embodiment of formula (I), R1 is (CR c R d ) n-(C6 aryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is (CR c R d ) n -(C6 aryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is (CR c R d ) n -(C6 aryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is (CR c R d ) n -(C6 aryl), n is 0, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0236] In another embodiment of formula (I), R1 is (CR c R d ) n -(C6 aryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H. In another embodiment of formula (I), R1 is (CR c R d ) n -(C6 aryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or unsubstituted C1-C3 alkyl. In another embodiment of formula (I), R1 is (CR c R d ) n -(C6 aryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or halogen. In another embodiment of formula (I), R1 is (CR c R d ) n -(C6 aryl), n is 1 or 2, and each of R2, R3, R4, R5, R6, R7, and R8 is H or fluorine.

[0237] Each of the embodiments described herein with respect to the compound of formula I also applies to the compound of formula I-A.

[0238] Certain embodiments of the compound of formula I-A or I, or a pharmaceutically acceptable salt thereof, are shown in Table 1 below. The compound of formula I-A or I, or a pharmaceutically acceptable salt thereof, and the compounds of Table 1, or a pharmaceutically acceptable salt thereof, may be referred to collectively or individually herein as "the compounds of the invention" or "the compounds provided herein".

Table 1-1

Table 1-2

Table 1-3

Table 1-4

Table 1-5

Table 1-6

Table 1-7

Table 1-8

Table 1-9

Table 1-10

Table 1-11

Table 1-12

Table 1-13

[0239] The disclosed compounds have one or more stereocenters, and each stereocenter can independently exist in either the R or S configuration. In one embodiment, the compounds described herein exist in an optically active form or a racemate. It should be understood that the compounds described herein include racemates, optically active forms, positional isomers, and stereoisomers, or combinations thereof, having the therapeutically useful properties described herein.

[0240] The preparation of optically active forms is accomplished by any suitable method including, by way of non-limiting example, resolution of a racemate by recrystallization techniques, synthesis from optically active starting materials, chiral synthesis, or chromatographic separation using a chiral stationary phase. In one embodiment, a mixture of two or more isomers is utilized as the disclosed compounds described herein. In another embodiment, pure isomers are utilized as the disclosed compounds described herein. In another embodiment, the compounds described herein contain one or more chiral centers. These compounds are prepared by any means including stereoselective synthesis, enantioselective synthesis, or separation of mixtures of enantiomers or diastereomers. Resolution of compounds and their isomers is accomplished by any means including, by way of non-limiting example, chemical processes, enzymatic processes, fractional crystallization, distillation, and chromatography.

[0241] In one embodiment, the disclosed compounds may exist as tautomers. All tautomers are included within the scope of the compounds presented herein.

[0242] The compounds described herein also include isotopically labeled compounds in which one or more atoms are replaced by atoms having the same atomic number but different atomic masses or mass numbers than those typically found in nature. Examples of isotopes suitable for inclusion in the compounds described herein include 2 H, 3 H, 11 C, 13 C, 14 C, 36 Cl, 18 F, 123 I, 125 I, 13 N, 15 N, 15 O, 17 O, 18 O, 32 P, and 35 S, among others, but are not limited thereto. In one embodiment, the isotopically labeled compound is useful for drug or substrate tissue distribution studies. In another embodiment, substitution with a heavier isotope such as deuterium provides greater metabolic stability (e.g., an increase in in vivo half-life or a decrease in required dosage). In another embodiment, the compounds described herein include 2 H (i.e., deuterium) isotopes.

[0243] In yet another embodiment, 11 C, 18 F, 15 O and 13 substitution with positron-emitting isotopes such as N is useful in positron emission tomography (PET) studies for examining substrate receptor occupancy. Isotopically labeled compounds are prepared by any suitable method or process using an appropriate isotopically labeled reagent in place of the unlabeled reagent used in other methods.

[0244] The specific compounds described herein, and other compounds embraced by one or more of the formulas described herein having different substituents, are described herein and are, for example, described in Fieser and Fieser’s Reagents for Organic Synthesis, Volumes 1-17 (John Wiley and Sons, 1991); Rodd’s Chemistry of Carbon Compounds, Volumes 1-5 and Supplementals (Elsevier Science Publishers, 1989); Organic Reactions, Volumes 1-40 (John Wiley and Sons, 1991), Larock’s Comprehensive Organic Transformations (VCH Publishers Inc., 1989), March, Advanced Organic Chemistry 4 th Ed., (Wiley 1992); Carey and Sundberg, Advanced Organic Chemistry 4th Ed., Vols. A and B (Plenum 2000, 2001), and Green and Wuts, Protective Groups in Organic Synthesis 3rd Ed., (Wiley 1999) (all of which are incorporated by reference for such disclosures). General methods for preparing compounds as described herein are varied by the use of appropriate reagents and conditions for introducing the various moieties found in the formulas as provided herein.

[0245] The compounds described herein are synthesized using any suitable procedure starting from compounds available from commercial sources or prepared using any of the procedures described herein.

[0246] Therapeutic methods The compounds of the present invention can be used in a method for treating a target disease or condition, the method comprising administering to a subject the compounds of the present invention or a pharmaceutical composition comprising the compounds of the present invention. In one embodiment of the methods described herein, the subject is a human. In one aspect, the compounds provided herein are useful for the treatment of a disease or condition by acting as an agonist of the orexin 2 receptor.

[0247] The compounds of the present invention can be used to treat a disease or condition selected from the group consisting of narcolepsy, cataplexy or hypersomnia in a subject in need of such treatment.

[0248] In one embodiment, the compounds of the present invention can be used to treat narcolepsy in a subject. In one embodiment, the compounds of the present invention can be used to treat cataplexy in a subject. In one embodiment, the compounds of the present invention can be used to treat hypersomnia in a subject.

[0249] The orexin 2 receptor is important in a wide range of biological functions. This suggests that the orexin 2 receptor plays a role in various disease processes in humans or other species. The compounds of the present invention are useful for treating, preventing or improving the following symptoms or one or more risks of diseases associated with changes in sleep / wake functions. That is, narcolepsy, narcolepsy with cataplexy, idiopathic hypersomnia, hypersomnia, sleep apnea syndrome, narcolepsy syndrome, hypersomnia syndrome characterized by hypersomnia (e.g., Kleine-Levin syndrome, major depressive disorder with hypersomnia, Lewy body dementia, Parkinson's disease, progressive supranuclear palsy, Prader-Willi syndrome, Moebius syndrome, hypoventilation syndrome, Niemann-Pick disease type C, brain contusion, cerebral infarction, brain tumor, muscular dystrophy, multiple sclerosis, multisystem atrophy, acute disseminated encephalomyelitis, Guillain-Barré syndrome, Rasmussen encephalitis, Wernicke encephalitis, limbic encephalitis, or Hashimoto's encephalopathy in a subject), lethargy, loss of consciousness, obesity (e.g., malignant obesity, exogenous obesity, hyperinsulinemic obesity, hyperplasmic obesity, pituitary obesity, hypoplasmic obesity, hypothyroid obesity, hypothalamic obesity, symptomatic obesity, infantile obesity, upper body obesity, diet-induced obesity, hypogonadal obesity, general obesity, simple obesity, or central obesity), insulin resistance syndrome, Alzheimer's disease, disorders of consciousness such as lethargy, side effects and complications of anesthesia, sleep disturbance, excessive daytime sleepiness, sleep problems, insomnia, intermittent sleep, nocturnal myoclonus, REM sleep disruption, jet lag, jet lag syndrome, shift work sleep disorder, sleep disorder, night terrors, depression, major depression, sleepwalking, nocturia, sleep disorder, Alzheimer's dusk, diseases related to the circadian rhythm, fibromyalgia, conditions resulting from a decrease in the quality of sleep, overeating, binge eating disorder, obesity-related diseases, hypertension, diabetes, increased plasma insulin concentration and insulin resistance, hyperlipidemia, hyperlipemia, endometrial cancer, breast cancer, prostate cancer, colorectal cancer, cancer, osteoarthritis, obstructive sleep apnea, cholelithiasis, gallstones, heart disease, abnormal heartbeat, arrhythmia, myocardial infarction,Congestive heart failure, heart failure, coronary heart disease, cardiovascular disorders, polycystic ovary disease, craniopharyngioma, Prader-Willi syndrome, Froehlich syndrome, growth hormone deficiency, normal variant short stature, Turner syndrome, children suffering from acute lymphoblastic leukemia, Syndrome X, reproductive hormone abnormalities, reduced fertility, infertility, male hypogonadism, female hirsutism and other sexual and reproductive dysfunctions, fetal defects related to obesity in pregnant women, obesity-related gastroesophageal reflux, gastrointestinal motility disorders such as obesity hypoventilation syndrome (Pickwick syndrome), respiratory diseases such as dyspnea, inflammation such as systemic inflammation of the vascular system, arteriosclerosis, hypercholesterolemia, hyperuricemia, low back pain, gallbladder disease, gout, renal cancer, risk of secondary consequences of obesity (e.g., reduction in the risk of left ventricular hypertrophy), migraine, headache, neuropathic pain, Parkinson's disease, psychosis, autoimmune encephalitis, cancer-related fatigue (such as excessive daytime sleepiness or fatigue related to cancer and / or chemotherapy), cancer-related nausea and vomiting, corticobasal degeneration, Huntington's disease, neuromyelitis optica, nociception, progressive supranuclear palsy, schizophrenia, systemic lupus erythematosus, traumatic brain injury, facial flushing, night sweats, genital / urinary system diseases, diseases related to sexual function or fertility, mood regulatory disorders, bipolar disorder, bipolar I disorder, bipolar II disorder, cyclothymic disorder, acute stress disorder, agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, panic attack, panic disorder, post-traumatic stress disorder (PTSD), separation anxiety disorder, social phobia, anxiety disorder, acute neurological and mental disorders such as brain dysfunction after cardiac bypass surgery and transplantation, stroke, ischemic stroke, cerebral ischemia, spinal cord injury, head injury, perinatal hypoxia, cardiac arrest, hypoglycemic nerve injury, Huntington's chorea, amyotrophic lateral sclerosis, eye injury, retinopathy, cognitive impairment, muscle contracture, tremor, epilepsy, disorders related to muscle spasm, delirium, amnestic disorder, age-related cognitive decline, schizoaffective disorder, delusional disorder, drug addiction, dyskinesia, chronic fatigue syndrome, fatigue, drug-induced parkinsonism syndrome, Gilles de la Tourette syndrome, chorea, myoclonus, tic, restless legs syndrome, dystonia, dyskinesia, attention deficit hyperactivity disorder (ADHD), behavioral disorders, urinary incontinence, withdrawal symptoms, trigeminal neuralgia, hearing loss, tinnitus, nerve injury, retinopathy, macular degeneration, vomiting, cerebral edema, pain, bone pain, joint pain, toothache, cataplexy and traumatic brain injury (TBI).

[0250] Particularly, it is useful as a therapeutic or prophylactic agent for narcolepsy, idiopathic hypersomnia, hypersomnia, sleep apnea syndrome, narcolepsy syndrome, hypersomnia syndrome characterized by hypersomnia (e.g., in Parkinson's disease, Guillain-Barré syndrome or Kleine-Levin syndrome), Alzheimer's disease, obesity, insulin resistance syndrome, heart failure, diseases associated with osteopenia, sepsis, disorders of consciousness such as coma, side effects and complications caused by anesthesia, etc.

[0251] In one embodiment, the compound of the present invention has orexin 2 receptor agonist activity and is useful as a prophylactic or therapeutic agent for narcolepsy.

[0252] In another embodiment, the compound of the present invention is useful as a prophylactic or therapeutic agent for type 1 narcolepsy. In another embodiment, the compound of the present invention is useful as a prophylactic or therapeutic agent for type 2 narcolepsy. In another embodiment, the compound of the present invention is useful as a prophylactic or therapeutic agent for narcolepsy and excessive daytime sleepiness. In another embodiment, the compound of the present invention is useful as a prophylactic or therapeutic agent for narcolepsy cataplexy and excessive daytime sleepiness. In another embodiment, the compound of the present invention is useful as a prophylactic or therapeutic agent for narcolepsy and cataplexy. In another embodiment, the compound of the present invention is useful as a prophylactic or therapeutic agent for excessive daytime sleepiness. In another embodiment, the compound of the present invention is useful as a prophylactic or therapeutic agent for idiopathic hypersomnia. In another embodiment, the compound of the present invention is useful as a prophylactic or therapeutic agent for obstructive sleep apnea.

[0253] In another embodiment, the compound of the present invention has orexin 2 receptor agonist activity and is useful as a prophylactic or therapeutic agent for hypersomnia in Parkinson's disease.

[0254] In another embodiment, the compound of the present invention has orexin 2 receptor agonist activity and is useful as a prophylactic or therapeutic agent for hypersomnia. In another embodiment, the compound of the present invention has orexin 2 receptor agonist activity and is useful as a prophylactic or therapeutic agent for excessive daytime sleepiness associated with Parkinson's disease.

[0255] In another embodiment, the compounds of the present invention have orexin 2 receptor agonist activity and are useful as prophylactic or therapeutic agents for cancer and / or daytime excessive somnolence or fatigue associated with chemotherapy.

[0256] In another embodiment, the present invention provides a method for treating narcolepsy in a subject in need thereof, comprising administering to the subject a compound of formula I-A or I or a pharmaceutically acceptable salt thereof.

[0257] In another embodiment, the present invention provides a method for treating type 1 narcolepsy in a subject in need thereof, comprising administering to the subject a compound of formula I-A or I or a pharmaceutically acceptable salt thereof.

[0258] In another embodiment, the present invention provides a method for treating type 2 narcolepsy in a subject in need thereof, comprising administering to the subject a compound of formula I-A or I or a pharmaceutically acceptable salt thereof.

[0259] In another embodiment, the present invention provides a method for treating narcolepsy and daytime excessive somnolence in a subject in need thereof, comprising administering to the subject a compound of formula I-A or I or a pharmaceutically acceptable salt thereof.

[0260] In another embodiment, the present invention provides a method for treating narcolepsy, cataplexy and daytime excessive somnolence in a subject in need thereof, comprising administering to the subject a compound of formula I-A or I or a pharmaceutically acceptable salt thereof.

[0261] In another embodiment, the present invention provides a method for treating narcolepsy and cataplexy in a subject in need of treatment of narcolepsy and cataplexy, the method comprising administering to the subject a compound of formula I-A or I or a pharmaceutically acceptable salt thereof.

[0262] In another embodiment, the present invention provides a method for treating excessive daytime sleepiness in a subject in need of treatment of excessive daytime sleepiness, the method comprising administering to the subject a compound of formula I-A or I or a pharmaceutically acceptable salt thereof.

[0263] In another embodiment, the present invention provides a method for treating idiopathic hypersomnia in a subject in need of treatment of idiopathic hypersomnia, the method comprising administering to the subject a compound of formula I-A or I or a pharmaceutically acceptable salt thereof.

[0264] In another embodiment, the present invention provides a method for treating excessive daytime sleepiness and idiopathic hypersomnia in a subject in need of treatment of excessive daytime sleepiness and idiopathic hypersomnia, the method comprising administering to the subject a compound of formula I-A or I or a pharmaceutically acceptable salt thereof.

[0265] In another embodiment, the present invention provides a method for treating obstructive sleep apnea in a subject in need of treatment of obstructive sleep apnea, the method comprising administering to the subject a compound of formula I-A or I or a pharmaceutically acceptable salt thereof.

[0266] In another embodiment, the present invention provides a method for treating excessive daytime sleepiness and obstructive sleep apnea in a subject in need of treatment of excessive daytime sleepiness and obstructive sleep apnea, the method comprising administering to the subject a compound of formula I-A or I or a pharmaceutically acceptable salt thereof.

[0267] In any of the methods as described herein, a compound of formula I is administered to the subject.

[0268] Each embodiment described herein regarding the use of the compound of formula I also applies to the compound of formula I-A.

[0269] In any of the compositions or methods described herein, the compound of formula I-A or I or a pharmaceutically acceptable salt thereof is present in and / or administered in a therapeutically effective amount.

[0270] Administration / Dosage / Formulation In another aspect, there is provided herein a pharmaceutical composition comprising at least one compound of the invention together with a pharmaceutically acceptable carrier.

[0271] The actual dosage level of the active ingredient in the pharmaceutical compositions of the invention may vary so as to obtain an amount of the active ingredient that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration without being toxic to the patient.

[0272] In particular, the selected dosage level will depend upon a variety of factors including the activity of the particular compound employed, the time of administration, the rate of excretion of the compound, the duration of the treatment, other drugs, compounds or materials used in combination with the compound, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts.

[0273] A physician or veterinarian, who is an artisan, can readily determine and prescribe the effective amount of the pharmaceutical composition required. For example, a physician or veterinarian can initiate the administration of the pharmaceutical composition at a level lower than the level required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved.

[0274] In certain embodiments, it is particularly advantageous to formulate the compounds in dosage unit form for ease of administration and uniformity of dosage. As used herein, a dosage unit form refers to physically discrete units suitable as unit dosages for the patients to be treated, each unit containing a predetermined quantity of the disclosed compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical vehicle. The dosage unit forms of the invention are determined by and directly depend on (a) the particular characteristics of the disclosed compound and the specific therapeutic effect to be achieved, and (b) the limitations inherent in the art of compounding / formulating such disclosed compounds for the treatment of narcolepsy or cataplexy in a patient.

[0275] In one embodiment, the compounds of the invention are formulated using one or more pharmaceutically acceptable excipients or carriers. In one embodiment, the pharmaceutical compositions of the invention comprise a therapeutically effective amount of the disclosed compound and a pharmaceutically acceptable carrier.

[0276] In some embodiments, the dosage of the disclosed compound is from about 1 mg to about 1,000 mg. In some embodiments, the dosage of the disclosed compound used in the compositions described herein is less than about 1,000 mg, or less than about 800 mg, or less than about 600 mg, or less than about 500 mg, or less than about 300 mg, or less than about 200 mg, or less than about 100 mg, or less than about 50 mg, or less than about 20 mg, or less than about 10 mg. For example, the dosage is about 10 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 120 mg, 140 mg, 160 mg, 180 mg, 200 mg, 220 mg, 240,260 mg, 280 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, or about 600 mg.

[0277] As any administration route of the composition of the present invention, oral, nasal, rectal, intravaginal, parenteral, buccal, sublingual or topical can be mentioned. The compounds for use in the present invention can be formulated for administration by any suitable route, such as oral or parenteral, for example, transdermal, transmucosal (e.g., sublingual, tongue, (trans)buccal, (trans)urethral, vaginal (e.g., intravaginal and perivaginal), nasal (in) and (trans)rectal), intravesical, intralung, intraduodenal, intragastric, intrathecal, subcutaneous, intramuscular, intradermal, intraarterial, intravenous, intratracheal, inhalation, and topical administration, etc. In one embodiment, the preferred administration route is oral.

[0278] Suitable compositions and dosage forms include, for example, tablets, capsules, caplets, pills, gel caps, troches, dispersions, suspensions, solutions, syrups, granules, beads, transdermal patches, gels, powders, pellets, magma, lozenges, creams, pastes, plasters, lotions, disks, suppositories, liquid sprays for nasal or oral administration, dry powders or aerosolized formulations for inhalation, compositions and formulations for intravesical administration, etc. It should be understood that the formulations and compositions that may be useful in the present invention are not limited to the specific formulations and compositions described herein.

[0279] For oral application, tablets, dragees, liquids, drops, suppositories, or capsules, caplets and gel caps are particularly suitable. Compositions intended for oral use can be prepared according to any method known in the art, and such compositions can contain one or more agents selected from the group consisting of inert and non-toxic pharmaceutical excipients suitable for the manufacture of tablets. Such excipients include, for example, inert diluents such as lactose; granulating agents and disintegrants such as corn starch; binders such as starch; and lubricants such as magnesium stearate. Tablets may or may not be coated, or they may be coated by known techniques to extend or delay the release of the active ingredient. Formulations for oral use can also be provided as hard gelatin capsules in which the active ingredient is mixed with an inert diluent.

[0280] For parenteral administration, the disclosed compounds can be formulated for injection or infusion, for example, intravenous, intramuscular or subcutaneous injection or infusion, or for administration as a bolus dose or by continuous infusion. Suspensions, solutions or emulsions in oily or aqueous vehicles, optionally containing other formulating agents such as suspending, stabilizing or dispersing agents, may be used.

[0281] One of ordinary skill in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific procedures, embodiments, claims, and examples described herein. Such equivalents are considered to be within the scope of this invention and are covered by the appended claims. For example, modifications to reaction times, reaction sizes / volumes, and experimental reagents such as solvents, catalysts, pressures, atmospheric conditions such as nitrogen atmosphere, and reducing / oxidizing agents, including but not limited to these, are within the scope of this application using recognized alternatives in the art and no more than routine experimentation.

[0282] Whenever values and ranges are provided herein, it is to be understood that all values and ranges subsumed by these values and ranges are meant to be embraced within the scope of this invention. Further, all values falling within these ranges, as well as the upper or lower limits of ranges of values, are also contemplated by this application.

[0283] The following examples further illustrate aspects of the invention. However, they are in no way intended to limit the teachings or disclosure of the invention described herein.

[0284] Examples The invention is further illustrated by the following examples, which should not be construed as further limitations. The practice of the invention, unless otherwise indicated, employs conventional techniques of organic synthesis, cell biology, cell culture, molecular biology, transgenic biology, microbiology, and immunology, which are within the skill of the art.

[0285] General Procedures Example 1: Synthetic Procedure The synthetic procedures for preparing the compounds of the present invention are readily available to those skilled in the art. Unless otherwise specified, starting materials were generally obtained from commercial sources. Synthetic procedures for other related compounds can be found, for example, in U.S. Patent Application No. 17 / 556,295 filed on December 20, 2021 and PCT Application No. PCT / US21 / 64484 filed on December 21, 2021, both of which are hereby expressly incorporated by reference herein.

[0286] Example 2: Human OX2R IP1 Assay In a T225 flask, T-Rex CHO cells that stably overexpress human orexin 2 receptor (OX2R) are induced overnight using 1 μg / mL doxycycline. Twenty-four hours after induction, the cells are lifted with Accutase and seeded at 30,000 cells / well in a 384-well ProxiPlate. The cells are then treated with different test compounds for 1 hour at 37 °C in 1× stimulation buffer containing 10 mM Hepes, 1 mM CaCl2, 0.5 mM MgCl2, 4.2 mM KCl, 146 mM NaCl, 5.5 mM glucose, and 50 mM LiCl, pH 7.4. After incubation, the reaction is stopped by adding a detection mixture composed of lysis buffer and IP1-d2 and anti-IP1 cryptate diluted in 1× stimulation buffer. The plate is incubated at room temperature for 1 hour and then read on an EnVision® multimode plate reader to measure inositol phosphate levels.

[0287] Cisbio IP1 is a cell-based functional assay that quantifies the accumulation of inositol monophosphate (IP), a metabolite released as a result of orexin 2 receptor activation via the phospholipase C-Gq signaling pathway. This is a competitive immunoassay in which IP1 produced by cells upon receptor activation competes with an IP1 analog coupled to a d2 fluorophore (acceptor) for binding to an anti-IP1 monoclonal antibody labeled with Eu cryptate (donor). The measured HTRF-FRET-based signal is inversely proportional to the concentration of IP1 produced.

[0288] Although the invention has been specifically shown and described with reference to its preferred embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the scope of the invention as encompassed by the appended claims.

Claims

1. Formula I-A: 【Chemistry 1】 (In the formula, Ring A is condensed with ring B, Ring A is C ３ to C ８ cycloalkyl, 4- to 7-membered heterocyclyl, C ６ to C １０ aryl and 5- to 7-membered heteroaryl, and is selected from the group consisting of, and said C ３ to C ８ cycloalkyl, 4- to 7-membered heterocyclyl, C ６ to C １０ aryl or 5- to 7-membered heteroaryl is unsubstituted or is substituted with one or more halogens, hydroxyl, C １ to C ３ alkoxyl, unsubstituted C １ to C ３ alkyl, or C substituted with one or more halogens or deuteriums １ to C ３ alkyl, and Ring B is C ３ ~C ８ Cycloalkyl, 4-7 membered heterocyclyl, C ６ ~C １０ Selected from the group consisting of aryls and 5- to 7-membered heteroaryls, the C ３ ~C ８ Cycloalkyl, 4-7 membered heterocyclyl, C ６ ~C １０ The aryl or 5- to 7-membered heteroaryl is either unsubstituted or contains one or more halogens, hydroxyl, or C １ ~C ３ Alkoxyl, unsubstituted C １ ~C ３ C substituted with alkyl or one or more halogens or deuterium １ ~C ３ It is substituted with alkyl, X is N or CH, Y is S (=O) ２ , C (=O), or S (=O) (=NR ｅ ) and R ｅ H, C １ ~C ３ Alkyl or C ３ ~C ５ Selected from the group consisting of cycloalkyl groups, E is NR ａ R ｂ , C １ ~C ３ Alkylene-NR ａ R ｂ , C １ ~C ３ Alkyl, C ２ ~C ４ Alkenil, C ２ ~C ４ Alkinyl, C ３ ~C ８ Cycloalkyl, C １ ~C ３ Alkylene-(C) ３ ~C ８ Cycloalkyl), 4-10 membered heterocyclyl, C １ ~C ３ Alkilen-(4-10 membered heterocyclyl), C ６ ~C １０ Ariel, C １ ~C ３ Alkylene-(C) ６ ~C １０ aryl), 5-7 member heteroaryl and C １ ~C ３ Selected from the group consisting of alkylene-(5-7 member heteroaryl), the C １ ~C ３ Alkylene-NR ａ R ｂ , C １ ~C ３ Alkyl, C ２ ~C ４ Alkenil, C ２ ~C ４ Alkinyl, C ３ ~C ８ Cycloalkyl, C １ ~C ３ Alkylene-(C) ３ ~C ８ Cycloalkyl), 4-10 membered heterocyclyl, C １ ~C ３ Alkilen-(4-10 membered heterocyclyl), C ６ ~C １０ Ariel, C １ ~C ３ Alkylene-(C) ６ ~C １０ Aryl), 5- to 7-membered heteroaryl or C １ -C ３ Alkylene-(5- to 7-membered heteroaryl) is unsubstituted or is substituted with one or more halogen, hydroxyl, NR ｃ R ｄ , CF ３ , CHF ２ , CH ２ F, C １ -C ３ Alkyl or C １ -C ３ Alkoxyl and is R ａ and R ｂ These are H and C, respectively, independently. １ ~C ３ Alkyl, C ３ ~C ５ Selected from the group consisting of cycloalkyl and 4- to 7-membered heterocyclyl, the C １ ~C ３ Alkyl, C ３ ~C ５ Cycloalkyls, or 4- to 7-membered heterocyclines, are either unsubstituted or contain one or more halogens, hydroxyls, or C １ ~C ３ Alkyl, or C １ ~C ３ Is it substituted with an alkoxyl? Alternatively, R ａ and R ｂ These, together with the N atoms to which they are bonded, form a 4-7 membered heterocycline or a 5-7 membered heteroaryl, and the 4-7 membered heterocycline or 5-7 membered heteroaryl is unsubstituted or contains one or more halogens, hydroxyls, NR ｃ R ｄ , C １ ~C ３ Alkyl, C １ ~C ３ C substituted with alkoxy or 1 to 3 halogens １ ~C ３ It is substituted with alkyl, R １ is C(=O)-C １ ~C ４ Alkyl, C(=O)-C １ ~C ４ Alkoxyl, C(=O)-(CR ｃ R ｄ ) ｎ -C ３ ~C ８ Cycloalkyl, C(=O)-(CR ｃ R ｄ ) ｎ - (4-7 member heterocyclyl), C(=O)-(CR ｃ R ｄ ) ｎ - (C ６ ~C １０ Ayl), C(=O)-(CR ｃ R ｄ ) ｎ - (5-10 member heteroaryl), C(=O)-O-(CR ｃ R ｄ ) ｎ -C ３ ~C ８ Cycloalkyl, C(=O)-O-(CR ｃ R ｄ ) ｎ - (4-7 member heterocyclyl), (CR ｃ R ｄ ) ｎ - (C ６ ~C １０ (Aryl) and (CR ｃ R ｄ ) ｎ - Selected from the group consisting of (5-10 member heteroaryls), C １ ~C ４ Alkyl, C １ ~C ４ Alkoxyl, C ３ ~C ８ Cycloalkyl, 4-7 membered heterocyclyl, C ６ ~C １０ The aryl or 5- to 10-membered heteroaryl is unsubstituted, or one or more halogens, hydroxyls, or unsubstituted C １ ~C ３ C substituted with alkyl or one or more halogens or deuterium １ ~C ３ It is substituted with alkyl, R ｃ and R ｄ These are H and unsubstituted C, respectively, independently. １ ~C ３ C substituted with alkyl or one or more halogens or deuterium １ ~C ３ It is alkyl, n is 0, 1, or 2. R ２ , R ３ , R ４ , R ５ , R ６ , R ７ , and R ８ Each of these is independently H, halogen, and unsubstituted C. １ ~C ３ C substituted with alkyl or one or more halogens or deuterium １ ~C ３ Is it alkyl? Alternatively, R ３ and R ６ They come together as non-substituted C １ ~C ３ C substituted with alkylene or one or more halogens １ ~C ３ Forming alkylenes, Alternatively, R ４ and R ５ They come together as non-substituted C １ ~C ３ C substituted with alkylene or one or more halogens １ ~C ３ Forming alkylenes, m is either 0 or 1. p is 0, 1, 2, 3, or 4. Each R ９ (These are independently selected from the group consisting of deuterium, halogens, hydroxyl, and cyano.) Compounds of or pharmaceutically acceptable salts thereof.

2. A compound of formula I-A or a pharmaceutically acceptable salt thereof, wherein formula I: 【Chemistry 2】 The compound according to claim 1, which is a compound or a pharmaceutically acceptable salt thereof.

3. Ring A is C ３ ~C ８ It is a cycloalkyl, and the C ３ ~C ８ The cycloalkyl group is unsubstituted, or contains one or more halogens, hydroxyls, or C １ ~C ３ Alkoxyl, unsubstituted C １ ~C ３ C substituted with alkyl or one or more halogens or deuterium １ ~C ３ Substituted with alkyl, or Ring A is a 4- to 7-membered heterocycline, and the 4- to 7-membered heterocycline is either unsubstituted or substituted with one or more halogens, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuterium. or Ring A is a C6-C10 aryl group, wherein the C6-C10 aryl group is either unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyl groups, or C1-C3 alkyl groups substituted with one or more halogens or deuterium. or The compound according to claim 1 or 2, wherein ring A is a 5- to 7-membered heteroaryl, and the 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogens, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuterium.

4. Ring B is C ３ ~C ８ It is a cycloalkyl, and the C ３ ~C ８ The cycloalkyl group is unsubstituted, or contains one or more halogens, hydroxyls, or C １ ~C ３ Alkoxyl, unsubstituted C １ ~C ３ C substituted with alkyl or one or more halogens or deuterium １ ~C ３ Substituted with alkyl, or Ring B is a 4- to 7-membered heterocycline, and the 4- to 7-membered heterocycline is either unsubstituted or substituted with one or more halogens, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuterium. or Ring B is a C6-C10 aryl group, wherein the C6-C10 aryl group is either unsubstituted or substituted with one or more halogens, hydroxyls, C1-C3 alkoxyls, unsubstituted C1-C3 alkyl groups, or C1-C3 alkyl groups substituted with one or more halogens or deuterium. or The compound according to claim 1 or 2, wherein ring B is a 5- to 7-membered heteroaryl, and the 5- to 7-membered heteroaryl is either unsubstituted or substituted with one or more halogens, hydroxyl, C1-C3 alkoxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuterium. 【Request Item 5】 【Chemistry 3】 However, the following is selected from the group consisting of benzimimidazolyl, 1H-pyrazolo[3,4-c]pyridinyl, imidazo[1,5-a]pyridinyl, indolyl, isoindolyl, indazolyl, isoindazolyl, benzothiazolyl, purinyl, benzofuranil, benzoisoxazolyl, benzoisothiazolyl, isobenzofuranil, benzothiofuranil, indoleninyl, pyrano[3,4-b]-pyrrolyl, indoxadinyl, benzoxazolyl, anthranillyl and indolidinyl, and the benzimi Dazolyl, 1H-pyrazolo[3,4-c]pyridinyl, imidazo[1,5-a]pyridinyl, indolyl, isoindolyl, indazolyl, isoindazolyl, benzothiazolyl, prinyl, benzofuranil, benzoisoxazolyl, benzoisothiazolyl, isobenzofuranil, benzothiofuranil, indoleninyl, pyrano[3,4-b]-pyrrolyl, indoxadinyl, benzoxazolyl, anthranillyl, and indolidinyl are either unsubstituted or have a halogen, hydroxyl, or C １ ~C ３ Alkoxyl, unsubstituted C １ ~C ３ C substituted with alkyl, or 1 to 3 halogen or deuterium atoms １ ~C ３ The compound according to claim 1 or 2, which is substituted with one to three substituents selected from alkyl groups. 【Request Item 6】 【Chemistry 4】 The benzimidazolyl is either unsubstituted or a halogen, hydroxyl, or C １ ~C ３ Alkoxyl, unsubstituted C １ ~C ３ C substituted with alkyl, or 1 to 3 halogen or deuterium atoms １ ~C ３ The compound according to claim 5, which is substituted with one to three substituents selected from alkyl groups. 【Request Item 7】 【Chemistry 5】 The compound is imidazo[1,5-a]pyridinyl, and the imidazo[1,5-a]pyridinyl is either unsubstituted or a halogen, hydroxyl, C １ ~C ３ Alkoxyl, unsubstituted C １ ~C ３ C substituted with alkyl, or 1 to 3 halogen or deuterium atoms １ ~C ３ The compound according to claim 5, which is substituted with one to three substituents selected from alkyl groups. 【Request Item 8】 【Transformation 6】 The indolyl is either unsubstituted or a halogen, hydroxyl, or C １ ~C ３ Alkoxyl, unsubstituted C １ ~C ３ C substituted with alkyl, or 1 to 3 halogen or deuterium atoms １ ~C ３ The compound according to claim 5, which is substituted with one to three substituents selected from alkyl groups. 【Request Item 9】 【Chemistry 7】 The indazolyl is either unsubstituted or a halogen, hydroxyl, or C １ ~C ３ Alkoxyl, unsubstituted C １ ~C ３ C substituted with alkyl, or 1 to 3 halogen or deuterium atoms １ ~C ３ The compound according to claim 5, which is substituted with one to three substituents selected from alkyl groups. 【Request Item 10】 【Chemistry 8】 The benzoxazolyl is either unsubstituted or a halogen, hydroxyl, or C １ ~C ３ Alkoxyl, unsubstituted C １ ~C ３ C substituted with alkyl, or 1 to 3 halogen or deuterium atoms １ ~C ３ The compound according to claim 5, which is substituted with one to three substituents selected from alkyl groups.

11. The compound according to claim 1 or 2, wherein p is 0 or 1.

12. E is NR ａ R ｂ The compound according to claim 1 or 2.

13. E is C １ ~C ３ Alkylene-NR ａ R ｂ The compound according to claim 1 or 2.

14. E is an unsubstituted C １ ~C ３ Alkyl, unsubstituted C ２ ~C ４ Alkenyl or unsubstituted C ２～ C ４ It is alkinyl, or The compound according to claim 1 or 2, wherein E is a C1-C3 alkyl, C2-C4 alkenyl or C2-C4 alkynyl substituted with one or more halogens, hydroxyl, C1-C3 alkyl or C1-C3 alkoxyl.

15. E is an unsubstituted C １ ~C ３ The compound according to claim 1 or 2, wherein E is alkyl, or a C1-C3 alkyl substituted with one or more halogens, hydroxyl, NR c R d, CF 3, CHF 2, CH 2 F, C1-C3 alkyl, or C1-C3 alkoxyl.

16. E is an unsubstituted C ３ ~C ８ The compound according to claim 1 or 2, wherein E is a cycloalkyl or a C3-C8 cycloalkyl substituted with one or more halogens, hydroxyl, NR c R d, CF 3, CHF 2, CH 2 F, C1-C3 alkyl or C1-C3 alkoxyl.

17. E is an unsubstituted C １ ~C ３ Alkylene-(C) ３ ~C ８ The compound according to claim 1 or 2, wherein E is a cycloalkyl or a C1-C3 alkylene-(C3-C8 cycloalkyl) substituted with one or more halogens, hydroxyl, NR c R d, CF 3, CHF 2, CH 2 F, C1-C3 alkyl or C1-C3 alkoxyl.

18. The compound according to claim 1 or 2, wherein E is an unsubstituted 4- to 10-membered heterocycline, or E is a 4- to 10-membered heterocycline substituted with one or more halogens, hydroxyl, NR c R d, CF 3, CHF 2, CH 2 F, C 1-C 3 alkyl, or C 1-C 3 alkoxyl.

19. E is an unsubstituted C １ ~C ３ The compound according to claim 1 or 2, wherein E is an alkylene-(4-10 membered heterocycline) or a C1-C3 alkylene (4-10 membered heterocycline) substituted with one or more halogens, hydroxyl, NR c R d, CF 3, CHF 2, CH 2 F, C1-C3 alkyl, or C1-C3 alkoxyl.

20. E is an unsubstituted C ６ ~C １０ The compound according to claim 1 or 2, wherein E is an aryl or a C6-C10-aryl substituted with one or more halogens, hydroxyl, NR c R d, CF 3, CHF 2, CH 2 F, C1-C3 alkyl or C1-C3 alkoxyl.

21. E is an unsubstituted C １ ~C ３ Alkylene-(C) ６ ~C １０ The compound according to claim 1 or 2, wherein E is an aryl or a C1-C3 alkylene-(C6-C10-aryl) substituted with one or more halogens, hydroxyl, NR c R d, CF 3, CHF 2, CH 2 F, C1-C3 alkyl or C1-C3 alkoxyl.

22. The compound according to claim 1 or 2, wherein E is an unsubstituted 5-7 membered heteroaryl, or E is a 5-7 membered heteroaryl substituted with one or more halogens, hydroxyl, NR c R d, CF 3, CHF 2, CH 2 F, C 1-C 3 alkyl, or C 1-C 3 alkoxyl.

23. E is an unsubstituted C １ ~C ３ The compound according to claim 1 or 2, wherein E is an alkylene-(5-7 member heteroaryl) or a C1-C3 alkylene-(5-7 member heteroaryl) substituted with one or more halogens, hydroxyl, NR c R d, CF 3, CHF 2, CH 2 F, C1-C3 alkyl, or C1-C3 alkoxyl.

24. The compound according to claim 1 or 2, wherein E is methyl, or E is methyl substituted with one or more halogens, hydroxyl, NR c R d, CF 3, CHF 2, CH 2 F, C1-C3 alkyl, or C1-C3 alkoxyl.

25. E is CF ３ The compound according to claim 1 or 2, which is CHF2 or CH2F.

26. E is NH(CH ３ The compound according to claim 1 or 2, wherein the compound is N(CH3)2.

27. Y is S (=O) ２ The compound according to claim 1 or 2.

28. The compound according to claim 1 or 2, wherein Y is C (=O).

29. The compound according to claim 1 or 2, wherein X is CH.

30. R １ However, C(=O)-C １ ~C ４ Alkyl, C(=O)-C １ ~C ４ Alkoxy, C(=O)-(CR ｃ R ｄ ) ｎ -C ３ ~C ８ Cycloalkyl, C(=O)-(CR ｃ R ｄ ) ｎ - (4-7 member heterocyclyl), C(=O)-(CR ｃ R ｄ ) ｎ - (C ６ ~C １０ aryl), and C(=O)-(CR ｃ R ｄ ) ｎ - Selected from the group consisting of (5-10 member heteroaryls), C １ ~C ４ Alkyl, C １ ~C ４ Alkoxyl, C ３ ~C ８ Cycloalkyl, 4-7 membered heterocyclyl, C ６ ~C １０ The aryl or 5- to 10-membered heteroaryl is unsubstituted, or one or more halogens, hydroxyls, or unsubstituted C １ ~C ３ C substituted with alkyl or one or more halogens or deuterium １ ~C ３ The compound according to claim 1 or 2, which is substituted with an alkyl group.

31. R １ However, C(=O)-C １ ~C ４ Alkyl, and the C １ ~C ４ The alkyl group is unsubstituted, or it contains one or more halogens, hydroxyls, and unsubstituted C atoms. １ ~C ３ C substituted with alkyl or one or more halogens or deuterium １ ~C ３ The compound according to claim 1 or 2, which is substituted with an alkyl group.

32. R １ However, C(=O)-C １ ~C ４ It is an alkoxy, and the C １ ~C ４ The alkoxy is unsubstituted, or one or more halogens, hydroxyls, and unsubstituted C. １ ~C ３ C substituted with alkyl or one or more halogens or deuterium １ ~C ３ The compound according to claim 1 or 2, which is substituted with an alkyl group.

33. R １ is C(=O)-(CR ｃ R ｄ ) ｎ -C ３ ~C ８ It is a cycloalkyl, and the C ３ ~C ８ The cycloalkyl group is unsubstituted, or contains one or more halogens, hydroxyls, or unsubstituted C. １ ~C ３ C substituted with alkyl or one or more halogens or deuterium １ ~C ３ The compound according to claim 1 or 2, which is substituted with an alkyl group.

34. R １ is C(=O)-(CR ｃ R ｄ ) ｎ - (4-7 member heterocycline), where the 4-7 member heterocycline is unsubstituted, or contains one or more halogens, hydroxyl groups, and unsubstituted C groups. １ ~C ３ C substituted with alkyl or one or more halogens or deuterium １ ~C ３ The compound according to claim 1 or 2, which is substituted with an alkyl group.

35. R １ is C(=O)-(CR ｃ R ｄ ) ｎ - (C ６ ~C １０ It is aryl, and the C ６ ~C １０ The aryl is unsubstituted, or one or more halogens, hydroxyls, and unsubstituted C. １ ~C ３ C substituted with alkyl or one or more halogens or deuterium １ ~C ３ The compound according to claim 1 or 2, which is substituted with an alkyl group.

36. R １ is C(=O)-(CR ｃ R ｄ ) ｎ - (5-10 member heteroaryl), where the 5-10 member heteroaryl is unsubstituted, or contains one or more halogens, hydroxyl, and unsubstituted C １ ~C ３ C substituted with alkyl or one or more halogens or deuterium １ ~C ３ The compound according to claim 1 or 2, which is substituted with an alkyl group.

37. R １ is C(=O)-O-(CR ｃ R ｄ ) ｎ -C ３ ~C ８ It is a cycloalkyl, and the C ３ ~C ８ The cycloalkyl group is unsubstituted, or contains one or more halogens, hydroxyls, or unsubstituted C. １ ~C ３ C substituted with alkyl or one or more halogens or deuterium １ ~C ３ Substituted with alkyl, or R1 is C(=O)-O-(CR c R d) n-(4-7 member heterocyclil), and the 4-7 member heterocyclil is either unsubstituted or substituted with one or more halogens, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuterium. or R1 is a C(=O)-O-(CR c R d)n-C3-C5 cycloalkyl group, where the C3-C5 cycloalkyl group is either unsubstituted or substituted with one or more halogens, hydroxyl groups, unsubstituted C1-C3 alkyl groups, or C1-C3 alkyl groups substituted with one or more halogens or deuterium groups. or R1 is C(=O)-O-(CR c R d) n-(5-6 member heterocyclyl), and the 5-6 member heterocyclyl is either unsubstituted or substituted with one or more halogens, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuterium. or R1 is C(=O)-O-(CR c R d) n-(5-membered heterocyclyl), and the 5-membered heterocyclyl is either unsubstituted or substituted with one or more halogens, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuterium. or The compound according to claim 1 or 2, wherein R1 is C(=O)-O-(CR c R d) n-(6-membered heterocyclyl), and the 6-membered heterocyclyl is either unsubstituted or substituted with one or more halogens, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuterium.

38. R １ However, (CR ｃ R ｄ ) ｎ - (C ６ ~C １０ (Aryl) or (CR ｃ R ｄ ) ｎ - (5-10 member heteroaryl), and the above C ６ ~C １０ The compound according to claim 1 or 2, wherein the aryl or 5-10 membered heteroaryl is unsubstituted, or the C6-C10 aryl or 5-10 membered heteroaryl is substituted with one or more halogens, hydroxyls, unsubstituted C1-C3 alkyls, or C1-C3 alkyls substituted with one or more halogens or deuterium.

39. R １ However, (CR ｃ R ｄ ) ｎ The compound according to claim 1 or 2, wherein the compound is a (six-membered heteroaryl), and the six-membered heteroaryl is unsubstituted, or the six-membered heteroaryl is substituted with one or more halogens, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogens or deuterium.

40. R ２ , R ３ , R ４ , R ５ , R ６ , R ７ , and R ８ Each of these independently consists of H, halogen, and unsubstituted C. １ ~C ３ C substituted with alkyl or one or more halogens or deuterium １ ~C ３ The compound according to claim 1 or 2, wherein it is alkyl.

41. R ２ , R ３ , R ４ , R ５ , R ６ , R ７ , and R ８ Each of these is independently H, halogen, or unsubstituted C. １ ~C ３ The compound according to claim 1 or 2, wherein it is alkyl.

42. R ２ , R ３ , R ４ , R ５ , R ６ , R ７ , and R ８ The compound according to claim 1 or 2, wherein each of them is H.

43. R １ However, C(=O)-C １ ~C ４ It is alkyl, R ２ , R ３ , R ４ , R ５ , R ６ , R ７ and R ８ Each of these is either H or unsubstituted C １ ~C ３ The compound according to claim 1 or 2, wherein it is alkyl.

44. R １ However, C(=O)-C １ ~C ４ It is an alkoxy, R ２ , R ３ , R ４ , R ５ , R ６ , R ７ and R ８ Each of these is either H or unsubstituted C １ ~C ３ The compound according to claim 1 or 2, wherein it is alkyl.

45. R １ is C(=O)-(CR ｃ R ｄ ) ｎ -C ３～ C ８ It is a cycloalkyl, R ２ , R ３ , R ４ , R ５ , R ６ , R ７ and R ８ Each of these is either H or unsubstituted C １ ~C ３ The compound according to claim 1 or 2, wherein it is alkyl.

46. R １ is C(=O)-(CR ｃ R ｄ ) ｎ - (4-7 member heterocyclyl), R ２ , R ３ , R ４ , R ５ , R ６ , R ７ and R ８ The compound according to claim 1 or 2, wherein each of them is H.

47. R １ is C(=O)-(CR ｃ R ｄ ) ｎ - (5-membered heterocycline), R ２ , R ３ , R ４ , R ５ , R ６ , R ７ and R ８ The compound according to claim 1 or 2, wherein each of them is H.

48. R １ is C(=O)-(CR ｃ R ｄ ) ｎ - (6-membered heterocyclyl), R ２ , R ３ , R ４ , R ５ , R ６ , R ７ and R ８ The compound according to claim 1 or 2, wherein each of them is H.

49. R １ is C(=O)-(CR ｃ R ｄ ) ｎ - (C ６ ~C １０ aryl) and R ２ , R ３ , R ４ , R ５ , R ６ , R ７ and R ８ The compound according to claim 1 or 2, wherein each of them is H.

50. R １ is C(=O)-(CR ｃ R ｄ ) ｎ - (C ６ aryl) and R ２ , R ３ , R ４ , R ５ , R ６ , R ７ and R ８ The compound according to claim 1 or 2, wherein each of them is H.

51. R １ is C(=O)-(CR ｃ R ｄ ) ｎ - (5-7 member heteroaryl), R ２ , R ３ , R ４ , R ５ , R ６ , R ７ and R ８ The compound according to claim 1 or 2, wherein each of them is H.

52. R １ is C(=O)-(CR ｃ R ｄ ) ｎ - (5-membered heteroaryl), R ２ , R ３ , R ４ , R ５ , R ６ , R ７ and R ８ The compound according to claim 1 or 2, wherein each of them is H.

53. R １ is C(=O)-(CR ｃ R ｄ ) ｎ - (6-membered heteroaryl), R ２ , R ３ , R ４ , R ５ , R ６ , R ７ and R ８ The compound according to claim 1 or 2, wherein each of them is H.

54. R １ is C(=O)-O-(CR ｃ R ｄ ) ｎ -C ３ ~C ８ It is a cycloalkyl, R ２ , R ３ , R ４ , R ５ , R ６ , R ７ and R ８ The compound according to claim 1 or 2, wherein each of them is H.

55. R １ is C(=O)-O-(CR ｃ R ｄ ) ｎ - (4-7 member heterocyclyl), R ２ , R ３ , R ４ , R ５ , R ６ , R ７ and R ８ The compound according to claim 1 or 2, wherein each of them is H.

56. R １ is C(=O)-O-(CR ｃ R ｄ ) ｎ - (5-membered heterocycline), R ２ , R ３ , R ４ , R ５ , R ６ , R ７ and R ８ The compound according to claim 1 or 2, wherein each of them is H.

57. R １ is C(=O)-O-(CR ｃ R ｄ ) ｎ - (6-membered heterocyclyl), R ２ , R ３ , R ４ , R ５ , R ６ , R ７ and R ８ The compound according to claim 1 or 2, wherein each of them is H.

58. R １ However, (CR ｃ R ｄ ) ｎ - (5-7 member heteroaryl), R ２ , R ３ , R ４ , R ５ , R ６ , R ７ and R ８ The compound according to claim 1 or 2, wherein each of them is H.

59. R １ However, (CR ｃ R ｄ ) ｎ - (C ６ ~C １０ aryl) and R ２ , R ３ , R ４ , R ５ , R ６ , R ７ and R ８ The compound according to claim 1 or 2, wherein each of them is H.

60. R １ The compound according to claim 1 or 2, wherein the compound is 3-pyridazinyl.

61. below: 【Chemistry 24-1】 【Chemistry 24-2】 【Chemistry 24-3】 【Chemistry 24-4】 【Chemistry 24-5】 【Chemistry 24-6】 and 【Chemistry 25】 A compound selected from the group consisting of the following, or a pharmaceutically acceptable salt thereof.

62. A pharmaceutical composition comprising a compound according to any one of claims 1 to 61 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

63. Use of a compound according to any one of claims 1 to 61, or a pharmaceutically acceptable salt thereof, or a composition thereof, for the manufacture of a medicine for narcolepsy.

64. Use of a compound according to any one of claims 1 to 61, or a pharmaceutically acceptable salt thereof, or a composition thereof, for the manufacture of a pharmacopoeia for cataplexy.

65. A compound according to any one of claims 1 to 61, or a pharmaceutically acceptable salt thereof, or a composition thereof, for use in a method of treating narcolepsy in a subject requiring treatment for narcolepsy.

66. A compound according to any one of claims 1 to 61, or a pharmaceutically acceptable salt thereof, or a composition thereof, for use in a method of treating cataplexy in a subject requiring treatment for cataplexy.

67. A pharmaceutical composition comprising the compound described in claim 61 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

68. Use of the compound according to claim 61 or a pharmaceutically acceptable salt thereof, or a composition thereof, for the manufacture of a medicine for narcolepsy.

69. Use of the compound according to claim 61 or a pharmaceutically acceptable salt thereof, or a composition thereof, for the manufacture of a pharmacopoeia for cataplexy.

70. The compound according to claim 61, or a pharmaceutically acceptable salt thereof, or a composition thereof, for use in a method of treating narcolepsy in a subject requiring treatment for narcolepsy.

71. The compound according to claim 61, or a pharmaceutically acceptable salt thereof, or a composition thereof, for use in a method of treating cataplexy in a subject requiring treatment for cataplexy.

Images