Dual MAGL and FAAH inhibitor

Abstract

The present invention provides compounds that have inhibitory activity against monoacylglycerol lipase (MAGL) and / or fatty acid amide hydrolase (FAAH), and are useful in the treatment of pain, neurological disorders, anxiety, inflammatory bowel disease, cancer, and the like. The present invention provides a spirocyclic compound represented by the following formula (III): TIFF2026035720000193.tif35170 [R 1 are each independently a halogen, C 1-6 Haloalkyl group, substituted phenoxy group, substituted heteroaryloxy group, etc.; R 3 is C 1-6 Haloalkyl groups, -C(O)NR 8 R 9 etc;R 3a are each independently a halogen, C 1-6 Alkyl group or C 1-6 Haloalkyl group; R 8 and R 9 are each independently H, etc.; m is an integer of 0 to 5; q is 0 or 1; w is 1 or 2; x is 0 or 1; y is 0 or 1; z is 0 or 1; when y and z are 0, x is 1 and w is 2; when y and z are 1, w is 1, y is 1 and z is 0, or y is 0; when z is 1, x is 1.

Description

[Technical Field]

[0001] cross reference This application is a continuation of U.S. Provisional Patent Application No. 62 / 470,830, filed March 13, 2017. This provisional application claims priority from US Provisional Patent Application No. 2004 / 0109994, filed on May 1, 2004, which application is incorporated herein by reference in its entirety. do. [Background technology]

[0002] Monoacylglycerol lipase (MAGL) is a lipase that converts 2-AG (2-aminoglycan) into 2-aminoglycan in the nervous system. Arachidonoylglycerol, an endocannabinoid-like lipid Fatty acid amide hydrolase (FAAH) is an enzyme responsible for the decomposition of water. It is another enzyme responsible for the hydrolysis of endocannabinoids such as acetylcholinesterase inhibitors (ACE inhibitors). Summary of the Invention

[0003] The present disclosure provides, for example, compounds that are modulators of MAGL and / or FAAH and The compositions, their use with medicinal agents, processes for their preparation, and the disclosed The present disclosure provides pharmaceutical compositions comprising, as at least one active ingredient, a compound selected from the group consisting of benzodiazepines, ... and / or in warm-blooded animals such as humans, Also provided is the use of the disclosed compounds in the manufacture of a medicament for inhibiting sexual activity. .

[0004] In some embodiments, a compound of formula (I): [ka] During the ceremony, [ka] but, [ka] and Each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C1 -6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -C(O)NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and and heteroaryl, wherein the aryl and heteroaryl are optionally independently selected from: and halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 from Substituted with one or two selected groups or two adjacent R 1 But, optional One or two R 11 forming a heterocycloalkyl ring substituted with R 2 But C 1-6 is alkyl, R 3 But halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -NR 8 R 9 , -C(O)NR 8 R 9 , -NR 8 C(O)R 9 and -NR 9 SO2R 8 Selected from And, R 3a But halogen, C 1-6Alkyl and C 1-6 haloalkyl , Each R 4 are independently H and C 1-6 alkyl, Each R 5 and R 6 are independent, H, C 1-6 Alkyl and C 3-8 Selected from cycloalkyl Selected or R 5 and R 6 However, together with the nitrogen bonded to them, One or two R's at will 10 forming a heterocycloalkyl substituted with Each R 7 are independent, H, C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and and heteroaryl, wherein the heterocycloalkyl, aryl and heteroaryl are selected from the group consisting of: aryl optionally independently selected from halogen, C 1-6 Alkyl and C 1-6 From haloalkyl substituted with one or two selected groups, Each R 8 and R 9 are independent, H, C 1-6 Alkyl, C 3-8 Cycloalkyl, aryl and selected from aryl and heteroaryl; Each R 10 independently, C 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Haloal Chloride, halogen, oxo, -CN, -C(O)OR 8 , -C(O)R 8 , -C(O)NR 8R 9 , -SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Selected from the law of nature, Each R 11 are independently halogen and C 1-6 alkyl, Each R 12 independently, C 1-6 Alkyl and C 3-8 cycloalkyl the law of nature, m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2 or 3; p is 0 or 1, a compound in which q is 0 or 1; or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

[0005] In some embodiments, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, a hydrate or stereoisomer of the formula R 4 is H.

[0006] In some embodiments, a compound of formula (II): [ka] During the ceremony, [ka] but, [ka] and Each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C1 -6 Alkyl-OR 7, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -C(O)NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and and heteroaryl, wherein the aryl and heteroaryl are optionally independently selected from: and halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 from Substituted with one or two selected groups or two adjacent R 1 But, optional One or two R 11 forming a heterocycloalkyl ring substituted with R 2 But C 1-6 is alkyl, R 3 But halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -NR 8 R 9 , -C(O)NR 8 R 9 , -NR 8 C(O)R 9 and -NR 9 SO2R 8 Selected from And, R 3a But halogen, C 1-6 Alkyl and C 1-6 haloalkyl , Each R 5 and R 6 are independent, H, C 1-6 Alkyl and C 3-8 Selected from cycloalkyl Selected or R 5 and R6 However, together with the nitrogen bonded to them, One or two R's at will 10 forming a heterocycloalkyl substituted with Each R 7 are independent, H, C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and and heteroaryl, wherein the heterocycloalkyl, aryl and heteroaryl are selected from the group consisting of: aryl optionally independently selected from halogen, C 1-6 Alkyl and C 1-6 From haloalkyl substituted with one or two selected groups, Each R 8 and R 9 are independent, H, C 1-6 Alkyl, C 3-8 Cycloalkyl, aryl and selected from aryl and heteroaryl; Each R 10 independently, C 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Haloal Chloride, halogen, oxo, -CN, -C(O)OR 8 , -C(O)R 8 , -C(O)NR 8 R 9 , -SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Selected from the law of nature, Each R 11 are independently halogen and C 1-6 alkyl, Each R 12 independently, C 1-6 Alkyl and C3-8 cycloalkyl the law of nature, m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2 or 3; p is 0 or 1, a compound in which q is 0 or 1; or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

[0007] In some embodiments, a compound of Formula (I) or (II), or a pharmaceutically acceptable salt thereof, Acceptable salts, solvates or stereoisomers are those wherein p is 0. In some embodiments, a compound of formula (I) or (II), or a pharmaceutically acceptable salt thereof, and acceptable salts, solvates or stereoisomers thereof, wherein p is 1. In some embodiments, a compound of Formula (I) or (II), or a pharmaceutically acceptable salt thereof, Possible salts, solvates or stereoisomers of the compound of formula R 2 C 1-6 is alkyl In some embodiments, a compound of formula (I) or (II) or A pharmaceutically acceptable salt, solvate or stereoisomer of 2 -CH3 In some embodiments, a compound of formula (I) or (II), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: [ka] but [ka] In some embodiments, a compound of formula (I) or (II), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: [ka] but [ka] In some embodiments, a compound of formula (I) or (II), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: [ka] but [ka] In some embodiments, a compound of formula (I) or (II), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and In some embodiments, a compound of formula (I) or (II), or A pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: [ka] but [ka] It is what it is.

[0008] In some embodiments, a compound of formula (III): [ka] During the ceremony, Each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C1 -6 Alkyl-OR7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -C(O)NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and and heteroaryl, wherein the aryl and heteroaryl are optionally independently selected from: and halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 from Substituted with one or two selected groups or two adjacent R 1 But, optional One or two R 11 forming a heterocycloalkyl ring substituted with R 3 But halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -NR 8 R 9 , -C(O)NR 8 R 9 , -NR 8 C(O)R 9 and -NR 9 SO2R 8 Selected from And, R 3a But halogen, C 1-6 Alkyl and C 1-6 haloalkyl , Each R 5 and R 6 are independent, H, C 1-6 Alkyl and C 3-8 Selected from cycloalkyl Selected or R 5 and R 6 However, together with the nitrogen bonded to them, One or two R's at will 10 forming a heterocycloalkyl substituted with Each R 7 are independent, H, C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and and heteroaryl, wherein the heterocycloalkyl, aryl and heteroaryl are selected from the group consisting of: aryl optionally independently selected from halogen, C 1-6 Alkyl and C 1-6 From haloalkyl substituted with one or two selected groups, Each R 8 and R 9 are independent, H, C 1-6 Alkyl, C 3-8 Cycloalkyl, aryl and selected from aryl and heteroaryl; Each R 10 independently, C 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Haloal Chloride, halogen, oxo, -CN, -C(O)OR 8 , -C(O)R 8 , -C(O)NR 8 R 9 , -SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Selected from the law of nature, Each R 11 are independently halogen and C 1-6 alkyl, Each R 12 independently, C 1-6 Alkyl and C 3-8 cycloalkyl the law of nature, m is 0, 1, 2, 3, 4 or 5; q is 0 or 1, w is 1 or 2; x is 0 or 1, y is 0 or 1, z is 0 or 1, when y and z are 0, x is 1 and w is 2; when y and z are 1, w is 1; When y is 1 and z is 0, or when y is 0 and z is 1, then x is 1. a compound which is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

[0009] In some embodiments, a compound of formula (III) having the structure of formula (IIIa): It is a thing. [ka]

[0010] In some embodiments, a compound of formula (III) having the structure of formula (IIIb): It is a thing. [ka]

[0011] In some embodiments, a compound of formula (IV): [ka] During the ceremony, Each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C1 -6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8Cycloalkyl, -NR 5 R 6 , -C(O)NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and and heteroaryl, wherein the aryl and heteroaryl are optionally independently selected from: and halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 from Substituted with one or two selected groups or two adjacent R 1 But, optional One or two R 11 forming a heterocycloalkyl ring substituted with R 3 But halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -NR 8 R 9 , -C(O)NR 8 R 9 , -NR 8 C(O)R 9 and -NR 9 SO2R 8 Selected from And, R 3a But halogen, C 1-6 Alkyl and C 1-6 haloalkyl , Each R 5 and R 6 are independent, H, C 1-6 Alkyl and C 3-8 Selected from cycloalkyl Selected or R 5 and R 6 However, together with the nitrogen bonded to them, One or two R's at will 10forming a heterocycloalkyl substituted with Each R 7 are independent, H, C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and and heteroaryl, wherein the heterocycloalkyl, aryl and heteroaryl are selected from the group consisting of: aryl optionally independently selected from halogen, C 1-6 Alkyl and C 1-6 From haloalkyl substituted with one or two selected groups, Each R 8 and R 9 are independent, H, C 1-6 Alkyl, C 3-8 Cycloalkyl, aryl and selected from aryl and heteroaryl; Each R 10 independently, C 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Haloal Chloride, halogen, oxo, -CN, -C(O)OR 8 , -C(O)R 8 , -C(O)NR 8 R 9 , -SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Selected from the law of nature, Each R 11 are independently halogen and C 1-6 alkyl, Each R 12 independently, C 1-6 Alkyl and C 3-8 cycloalkyl the law of nature, m is 0, 1, 2, 3, 4 or 5; a compound in which q is 0 or 1; or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

[0012] In some embodiments, the compound of formula (I), (II), (III), (IIIa), (III b) or (IV), or a pharmaceutically acceptable salt, solvate or In some embodiments, the compound of formula (I) is a stereoisomer wherein m is 1. ), (II), (III), (IIIa), (IIIb) or (IV), or or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 2 In some embodiments, the compound of formula (I), (II), (III), (II Ia), (IIIb) or (IV), or a pharmaceutically acceptable salt thereof; solvates or stereoisomers of the formula 3 C 1-6 haloalkyl In some embodiments, the compounds of formula (I), (II), (III), (IIIa), (I IIb) or (IV), or a pharmaceutically acceptable salt, solvate or or stereoisomers, wherein R 3 is -CF3. Then, formula (I), (II), (III), (IIIa), (IIIb) or (IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, In the formula, R 3 In some embodiments, the compound of formula (I), (II) , (III), (IIIa), (IIIb) or (IV), or a pharmaceutical preparation thereof a physiologically acceptable salt, solvate or stereoisomer of 3 -C(O)N In some embodiments, the compound of formula (I), (II), (III), ( IIIa), (IIIb) or (IV), or a pharmaceutically acceptable salt thereof A salt, solvate or stereoisomer of the formula R 3 is -CN. In some embodiments, formulas (I), (II), (III), (IIIa), and (IIIb) also include or a compound of formula (IV), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof In some embodiments, the compound of formula (I), ( II), (III), (IIIa), (IIIb) or (IV), or wherein q is 1. In some embodiments, the compound of formula (I), (II), (III), (IIIa) , (IIIb) or (IV), or a pharmaceutically acceptable salt or solvate thereof. a compound or stereoisomer of the formula 1 are independently halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -NR 5 R 6 , -OR 7 and heteroaryl In some embodiments, the compound of formula (I), (II), (III), ( IIIa), (IIIb) or (IV), or a pharmaceutically acceptable salt thereof A salt, solvate or stereoisomer of the formula 1 are independently halogen, C 1- 6 haloalkyl, -NR 5 R 6and-OR 7 It is selected from several In embodiments, a compound of formula (I), (II), (III), (IIIa), (IIIb) or (IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof In the formula, R 5 and R 6 However, together with the nitrogen bonded to them, one or two R's 10 These form heterocycloalkyl substituted with In some embodiments, formulas (I), (II), (III), (IIIa), and (IIIb) also include or a compound of formula (IV), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof isomer, wherein R 5 and R 6 However, together with the nitrogen bonded to them, C 1-6 Alkyl and -C(O)NR 8 R 9 One or two R selected from 10 In some embodiments, the heterocycloalkyl is substituted with , a compound of formula (I), (II), (III), (IIIa), (IIIb) or (IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein , R 5 and R 6 together with the nitrogen to which they are attached form an unsubstituted heterocycloalkane. In some embodiments, the compound of formula (I), (II), (II) I), (IIIa), (IIIb) or (IV), or a pharmaceutically acceptable salt thereof and an acceptable salt, solvate or stereoisomer thereof, wherein R 5 and R 6 But, Together with the nitrogen it is bonded to, [ka] In some embodiments, the heterocycloalkyl is selected from the group consisting of: , a compound of formula (I), (II), (III), (IIIa), (IIIb) or (IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein , each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and -OR 7 In some embodiments, the compound of formula (I), (II), (II I), (IIIa), (IIIb) or (IV), or a pharmaceutically acceptable salt thereof and an acceptable salt, solvate or stereoisomer thereof, wherein each R 7 independently, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, aryl and heteroaryl In some embodiments, the compound of formula (I), (II), (I II), (IIIa), (IIIb) or (IV), or a pharmaceutically acceptable salt thereof An acceptable salt, solvate or stereoisomer of 7 independently, C 1- 6 alkyl, C 1-6 haloalkyl and aryl. In some embodiments, the compound of formula (I), (II), (III), (IIIa), (IIIb) or or a pharmaceutically acceptable salt, solvate or stereoisomer thereof. wherein two adjacent R 1 but optionally one or two R 11replaced with In some embodiments, the heterocycloalkyl group of formula (I) , (II), (III), (IIIa), (IIIb) or (IV), or is a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein Contact R 1 but optionally one or two R 11 a heterocycloalkyl ring substituted with Each R 11 are independently selected from halogens.

[0013] In another embodiment, the compound of formula (I), (II), (III), (I IIa), (IIIb) or (IV), or a pharmaceutically acceptable salt thereof , solvates or stereoisomers thereof, and at least one pharmaceutically acceptable excipient. It is a pharmaceutical composition containing

[0014] In another embodiment, there is provided a method for treating pain in a patient in need thereof, comprising administering to the patient: Formula (I), (II), (III), (IIIa), (IIIb) or (IV), or a pharmaceutically acceptable salt, solvate or isoform thereof. The method comprises administering a therapeutically effective amount of a somatic isomer.

[0015] In another embodiment, a method for treating a neuropathy in a patient in need thereof, comprising: The patient is administered a compound of formula (I), (II), (III), (IIIa), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IIIg), (IIIh), (IIIj ... Compounds of formula IIIb) or (IV), or pharmaceutically acceptable salts or solvates thereof, or a method comprising administering a therapeutically effective amount of a stereoisomer. DETAILED DESCRIPTION OF THE INVENTION

[0016] The present disclosure is based, at least in part, on the discovery of modulators or inhibitors of MAGL and / or FAAH. For example, the present invention provides MAGL and / or inhibitors thereof. or a compound capable of inhibiting FAAH. The compound being studied is a dual inhibitor that can inhibit both MAGL and FAAH.

[0017] As used in this specification and the appended claims, the words "a," "an," and "the" Numeral forms include plural references unless the context clearly requires otherwise. For example, a reference to a "drug" includes multiple drugs, and a reference to a "cell" includes multiple drugs. When referring to a molecule, it includes one or more cells (or a plurality of cells) and their equivalents. Ranges are used for physical properties such as quantities or chemical properties such as chemical formulas. When used in conjunction with the present invention, all combinations and subcombinations of the scope and specific embodiments are included. The term "about" is intended to include combinations of "number" and "numbers." When referring to a range of values, it is understood that the number or range of values ​​being referred to is within experimental variation (or means that the value is an approximation (within statistical experimental error), i.e., the number or numerical range The value varies between 1% and 15% of the number or range of values ​​shown. The words (and "comprise," "comprises," "having" or related terms such as "include" or "includes" refer to other specific embodiments, e.g., those described herein. In embodiments of any of the compounds, compositions, methods, or processes described herein, It may "consist of" or "consist essentially of" the features described. It is not intended to exclude

[0018] definition As used in this specification and the appended claims, unless specified to the contrary, the following terms shall mean: It has the following meaning.

[0019] As used herein, C1-C x C1-C2, C1-C3...C1-C x but Included. C1-C x means the carbon atoms that make up the shown moiety (excluding any substituents). Refers to the number of children.

[0020] "Amino" refers to the group -NH2.

[0021] "Cyano" refers to the radical -CN.

[0022] "Nitro" refers to the -NO2 group.

[0023] "Oxa" refers to an --O-- group.

[0024] "Oxo" refers to the group =O.

[0025] "Thioxo" refers to the group ═S.

[0026] "Imino" refers to the group =NH.

[0027] "Oximo" refers to the =N-OH group.

[0028] "Alkyl" or "alkylene" means a straight or A branched hydrocarbon chain group containing no unsaturated bonds and having 1 to 15 carbon atoms. (For example, C1-C 15 In certain embodiments, alkyl refers to 1 to 13 alkyl groups. containing carbon atoms (e.g., C1-C13 In certain embodiments, alkyl is and 1 to 8 carbon atoms (e.g., C1-C8 alkyl). In another embodiment, alkyl contains 1 to 6 carbon atoms (e.g., C1-C6 alkyl). The alkyl contains 1 to 5 carbon atoms (e.g., C1-C5 alkyl). Alkyl contains 1 to 4 carbon atoms (e.g., C1-C4 alkyl). Alternatively, alkyl may contain 1 to 3 carbon atoms (e.g., C1-C3 alkyl). In some embodiments, alkyl contains 1 to 2 carbon atoms (e.g., C1-C2 alkyl). In embodiments, alkyl contains 1 carbon atom (e.g., C1 alkyl). In the formula, alkyl contains 5 to 15 carbon atoms (e.g., C5-C 15 alkyl). Another In embodiments, alkyl comprises 5 to 8 carbon atoms (eg, C5-C8 alkyl). In another embodiment, alkyl contains 2 to 5 carbon atoms (e.g., C2-C5 alkyl). In another embodiment, alkyl contains 3 to 5 carbon atoms (e.g., C3-C5 alkyl). In another embodiment, the alkyl group is methyl, ethyl, 1-propyl (n-propyl), or 2-methyl-2-propanol. 1-methylethyl (isopropyl), 1-butyl (n-butyl), 1-methylpropyl propyl (sec-butyl), 2-methylpropyl (isobutyl), 1,1-dimethylethyl (tert-butyl) and 1-pentyl (n-pentyl). is attached to the rest of the molecule by a single bond. The alkyl group may optionally be selected from the group consisting of halo, cyano, nitro, oxo, thioxo, imino, oximo , trimethylsilanyl, -OR a , -SR a, -OC(O)R a , -N(R a )2, -C (O)R a , -C(O)OR a , -C(O)N(R a )2, -N(R a )C(O)OR f , -OC(O)-NR a R f , -N(R a )C(O)R f , -N(R a )S(O) t R f (wherein t is 1 or 2), -S(O) t OR a (wherein t is 1 or 2) -S(O) t R f (wherein t is 1 or 2) and -S(O) t N(R a ) 2 (wherein t is 1 or 2) Each of these R a are independently hydrogen, alkyl, fluoroalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl or heteroarylar Kill, each R f are independently alkyl, fluoroalkyl, cycloalkyl, aryl aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl is.

[0029] "Alkoxy" refers to a group of the formula -O-alkyl attached through an oxygen atom. , where alkyl is an alkyl chain as defined above.

[0030] "Alkenyl" means a straight or branched hydrocarbon chain consisting solely of carbon and hydrogen atoms. R groups containing at least one carbon-carbon double bond and having 2 to 12 carbon atoms. In certain embodiments, alkenyl comprises 2 to 8 carbon atoms. In embodiments, the alkenyl contains 2 to 4 carbon atoms. The alkenyl is a single bond to the rest of the molecule. bond, e.g., ethenyl (i.e., vinyl), prop-1-enyl (i.e., allyl), but-1-enyl, pent-1-enyl, penta-1,4-dienyl Unless stated otherwise specifically in the specification, an alkenyl group can optionally be substituted with a halo. , cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR a , -SR a , -OC(O)-R f , -N(R a )2, -C(O)R a , -C(O)OR a , -C(O)N(R a )2, -N(R a )C(O)OR f , -OC(O)-NR a R f , -N(R a )C(O)R f , -N(R a )S(O) t R f (wherein t is 1 or 2) -S(O) t OR a (wherein t is 1 or 2), -S(O) t R f (formula wherein t is 1 or 2) and -S(O) t N(R a )2 (wherein t is 1 or 2 and each R a is independent , hydrogen, alkyl, fluoroalkyl, cycloalkyl, aryl, aralkyl, hetero cycloalkyl, heteroaryl, or heteroarylalkyl, and each R f is independent alkyl, fluoroalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl The alkyl group is aryl, heteroaryl, or heteroarylalkyl.

[0031] "Alkynyl" means a straight or branched hydrocarbon chain consisting solely of carbon and hydrogen atoms. R groups containing at least one carbon-carbon triple bond and having 2 to 12 carbon atoms. In certain embodiments, alkynyl comprises 2 to 8 carbon atoms. In embodiments, the alkynyl has 2 to 4 carbon atoms. The alkynyl is attached to the remainder of the molecule. It is bonded by a single bond, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, etc. Unless otherwise specifically stated in the specification, an alkynyl group is optionally Halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl , -OR a , -SR a , -OC(O)R a , -N(R a )2, -C(O)R a , -C(O ) OR a , -C(O)N(R a )2, -N(R a )C(O)OR f , -OC(O)-NR a R f , -N(R a )C(O)R f , -N(R a )S(O) t R f (where t is 1 or is 2), -S(O) t OR a(wherein t is 1 or 2), -S(O) t R f (wherein t is 1 or 2) and -S(O) t N(R a )2 (where t is 1 or or 2), each R a is German In particular, hydrogen, alkyl, fluoroalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl, and each R f teeth Independently, alkyl, fluoroalkyl, cycloalkyl, aryl, aralkyl, heptane The alkyl group is cycloalkyl, heteroaryl, or heteroarylalkyl.

[0032] "Aryl" means an aromatic monocyclic or cyclic ring formed by removing a hydrogen atom from a ring carbon atom. Aromatic monocyclic or polycyclic hydrocarbon ring systems are groups derived from aromatic monocyclic or polycyclic hydrocarbon ring systems. , containing only hydrogen and carbon (6-18 carbon atoms), and at least one ring in the ring system is , fully unsaturated, i.e., cyclically delocalized (4n+2 ) π electron systems. Ring systems from which aryl groups are derived include benzene, fluorene, and indane. groups such as, but not limited to, phenylene, indene, tetralin, and naphthalene. Unless otherwise specifically stated in this specification, the term "aryl" or "ar-" The prefixes "ar-" (as in "aralkyl") independently denote alkyl, aralkyl, and aryl. Alkenyl, alkynyl, halo, fluoroalkyl, cyano, nitro, aryl, aralkyl aryl, aralkenyl, aralkynyl, cycloalkyl, heterocycloalkyl, heteroaryl alkyl, heteroaryl, -Rb -OR a , -R b -OC(O)-R a , -R b - OC(O)-OR a , -R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a )2, -R b - OR c -C(O)N(R a )2, -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (wherein t is 1 or 2) ), -R b -S(O) t OR a (wherein t is 1 or 2), -R b -S(O) t R a (wherein t is 1 or 2) and -R b -S(O) t N(R a )2(where t is 1 or 2) Each R a are independently hydrogen, alkyl, fluoroalkyl, Cycloalkyl, cycloalkylalkyl, aryl (optionally substituted with one or more halo groups) (presumably a cycloalkyl group), aralkyl, heterocycloalkyl, heteroaryl or heteroaryl alkyl, and each R b are independently a direct bond or a straight or branched chain alkylene or an alkenylene chain, R c is a straight or branched chain alkylene or alkenyl It is a Ren chain.

[0033] "Aryloxy" refers to a group of the formula -O-aryl attached through an oxygen atom. refers to aryl, wherein aryl is as defined above.

[0034] "Aralkyl" is -R c -aryl, where R c is defined above The alkylene chain is, for example, methylene, ethylene, etc. The alkylene chain portion is optionally substituted as described above for an alkylene chain. The aryl portion of the ralkyl group may be optionally substituted as described above for an aryl group. do.

[0035] "Aralkyloxy" means an aryl group of the formula -O-aralkyl bonded through an oxygen atom. It refers to the group aralkyl, where aralkyl is as defined above.

[0036] "Aralkenyl" means -R d -aryl, where R d is defined above The aryl portion of the aralkenyl group is an alkenylene chain as defined above. The alkenylene chain portion of the aralkenyl group is optionally substituted as defined above. It is optionally substituted as defined above for an alkenylene group.

[0037] "Aralkynyl" means -R e -aryl, where R e is defined above The aryl portion of the aralkynyl group is an alkynylene chain as defined above. The alkynylene chain portion of the aralkynyl group is optionally substituted as defined above. The alkynylene chain may be optionally substituted as defined above.

[0038] "Cycloalkyl" means a stable non-aromatic monocyclic or cyclic ring consisting of only carbon and hydrogen atoms. is a polycyclic hydrocarbon group, containing fused or bridged ring systems, having 3 to 15 carbon atoms In certain embodiments, cycloalkyl contains 3 to 10 carbon atoms. In embodiments, cycloalkyl contains 5 to 7 carbon atoms. The cycloalkyl is saturated (i.e., C- C single bonds) or are partially unsaturated (i.e., contain one or more double or (The group containing a triple bond) Examples of monocyclic cycloalkyl include cyclopropyl, cyclopropyl, and cyclopropyl. Examples include cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. In certain embodiments, cycloalkyl contains 3 to 8 carbon atoms (e.g., C 3-C8 cycloalkyl). In another embodiment, cycloalkyl is a group having 3 to 7 carbon atoms. (e.g., C3-C7 cycloalkyl). In another embodiment, cycloalkyl is 3 In another embodiment, the cycloalkyl includes up to 6 carbon atoms (e.g., C3-C6 cycloalkyl). Cycloalkyl contains 3 to 5 carbon atoms (e.g., C3-C5 cycloalkyl). In embodiments, cycloalkyl contains 3 to 4 carbon atoms (e.g., C3-C4 cycloalkyl). Partially unsaturated cycloalkyls are also called "cycloalkenyls." Examples of alkenyl include cyclopentenyl, cyclohexenyl, and cycloheptenyl. Examples of polycyclic cycloalkyl groups include adamantyl and cyclooctenyl. norbornyl (i.e., bicyclo[2.2.1]heptanyl), norborneny Examples include cyclohexyl, decalinyl, and 7,7-dimethyl-bicyclo[2.2.1]heptanyl. Unless stated otherwise specifically in this specification, the term "cycloalkyl" includes alkyl, alkenyl, alkynyl, halo, fluoroalkyl, cyano, nitro, Aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, heterocycloa alkyl, heteroaryl, heteroarylalkyl, -R b -OR a , -R b -OC(O )-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a )2, -R b - N(R a )2, -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N( R a )2, -R b -OR c -C(O)N(R a )2, -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O)t R a (where t is , 1 or 2), -R b -S(O) t OR a (wherein t is 1 or 2), -R b -S(O) t R a (wherein t is 1 or 2) and -R b -S(O) t N( R a )2 (wherein t is 1 or 2), wherein each R a is independent and hydrogen, alkyl, fluoroalkyl, cycloalkyl, cycloalkylalkyl, and alkyl. aryl (optionally substituted with one or more halo groups), aralkyl, heterocycloalkyl aryl, heteroaryl, or heteroarylalkyl, and each R b are independently direct bonds or a linear or branched alkylene or alkenylene chain, R c is a linear chain Or it is a branched alkylene or alkenylene chain.

[0039] "Halo" or "halogen" refers to a bromo substituent, a chloro substituent, a fluoro substituent, or refers to the iodo substituent.

[0040] "Haloalkyl" means an alkyl group, as defined above, containing one or more aryl groups, as defined above. It refers to those substituted by the above halo groups.

[0041] "Fluoroalkyl" means an alkyl group, as defined above, having one or more fluoroalkyl groups, as defined above. or more fluoro groups, e.g., trifluoromethyl, Difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl The alkyl portion of the fluoroalkyl group is alkyl As defined above for the group, it is optionally substituted.

[0042] "Haloalkoxy" means an alkoxy group, as defined above, having one or more alkoxy groups, as defined above. It refers to a group substituted with one or more halo groups.

[0043] "Heterocycloalkyl" means a group of 2 to 12 carbon atoms and one or more of nitrogen, oxygen, and sulfur. The present invention refers to a stable non-aromatic ring group having 3 to 18 members and containing 1 to 6 heteroatoms selected from the following: Unless otherwise specifically stated in the specification, heterocycloalkyl groups include monocyclic, bicyclic, tricyclic, and cyclic rings. ring or tetracyclic ring systems, including fused, spiro or bridged ring systems. The heteroatoms of a heterocycloalkyl group are optionally oxidized. One or more nitrogen atoms If present, the atoms are optionally quaternized. is partially or fully saturated. In some embodiments, heterocycloalkyl The ring is attached to the rest of the molecule through any atom in the ring(s). Examples of heterocycloalkyl groups include dioxolanyl and thienyl[1,3]dithianyl. , decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, Isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoin Doryl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, Oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, Lazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianil, Tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpho Examples of thiomorpholinyl include, but are not limited to, 1,1-dioxo-thiomorpholinyl. Unless otherwise specifically stated in the specification, the term "heterocycloalkyl" includes any of the above. The heterocycloalkyl group as defined above is selected from the group consisting of alkyl, alkenyl, alkynyl, halo, , fluoroalkyl, oxo, thioxo, cyano, nitro, aryl, aralkyl, ara Alkenyl, aralkynyl, cycloalkyl, heterocycloalkyl, heteroaryl, Tetraarylalkyl, -R b -OR a , -R b -OC(O)-R a , -R b -OC(O )-OR a , -R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b -C( O)R a , -R b -C(O)OR a , -R b -C(O)N(R a )2, -R b -OR c -C(O)N(R a )2, -R b -N(R a )C(O)OR a , -R b -N(R a )C( O)R a , -R b -N(R a )S(O) t R a (wherein t is 1 or 2), -R b-S(O) t OR a (wherein t is 1 or 2), -R b -S(O) t R a (formula wherein t is 1 or 2) and -R b -S(O) t N(R a )2 (where t is 1 or or 2) optionally substituted with one or more substituents selected from In the formula, each R a are independently hydrogen, alkyl, fluoroalkyl, cycloalkyl, cycloalkyl, Cycloalkyl, alkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl or heteroarylalkyl, and each R b are independently a direct bond, or a linear or is a branched alkylene or alkenylene chain, and R c is a linear or branched chain Alkenylene or alkenylene chains are intended to be included.

[0044] "Heteroaryl" refers to a group derived from a 5- to 18-membered aromatic ring group, Contains 7 carbon atoms and 1 to 6 heteroatoms selected from nitrogen, oxygen, and sulfur As used herein, a heteroaryl group refers to a monocyclic, bicyclic, tricyclic or is a tetracyclic ring system in which at least one of the rings of the ring system is fully unsaturated, i.e., hydo According to the Suckel rule, they contain a cyclic delocalized (4n+2) π-electron system. The heteroatom(s) of the heteroaryl group include fused or bridged ring systems. If one or more nitrogen atoms are present, they may be optionally oxidized. Heteroaryl is an alkyl group that is attached to the rest of the molecule through any atom of the ring(s). Unless otherwise specifically stated in the specification, the term "heteroaryl" The term includes heteroaryl groups as defined above that are substituted with alkyl, alkenyl, alkynyl, aryl, halo, haloalkyl, oxo, thioxo, cyano, nitro, aryl, aralkyl, Aralkenyl, aralkynyl, cycloalkyl, heterocycloalkyl, heteroaryl , heteroarylalkyl, -R b -OR a , -R b -OC(O)-R a , -R b -OC (O)-OR a , -R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b - C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a )2, -R b -O- R c -C(O)N(R a )2, -R b -N(R a )C(O)OR a , -R b -N(R a ) C(O)R a , -R b -N(R a )S(O) t R a (wherein t is 1 or 2), -R b -S(O) t OR a (wherein t is 1 or 2), -R b -S(O) t R a (wherein t is 1 or 2) and -R b -S(O) tN(R a )2 (wherein t is 1 or 2) In the formula, each R a are independently hydrogen, alkyl, fluoroalkyl, cycloalkyl , cycloalkyl, alkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl aryl or heteroarylalkyl, and each R b Independently, direct bond or linear chain or a branched alkylene or alkenylene chain, R c is linear or branched It is intended to include those which are alkylene or alkenylene chains.

[0045] "N-heteroaryl" refers to a heteroaryl group as defined above, having at least one heteroaryl group. and the point of attachment of the heteroaryl group to the rest of the molecule is at the A heteroaryl group refers to a group that is substituted with a nitrogen atom. and optionally substituted as described above.

[0046] "C-heteroaryl" refers to a heteroaryl group, as defined above, in which the remainder of the molecule is The point of attachment of the heteroaryl group to the moiety is through a carbon atom of the heteroaryl group. C-heteroaryl groups are optionally substituted as described above for heteroaryl groups. It has been replaced.

[0047] "Heteroaryloxy" refers to an -O-heteroaryl bonded through an oxygen atom. wherein heteroaryl is as defined above.

[0048] "Heteroarylalkyl" refers to an -R c-heteroaryl, a group of the formula Medium, R c is an alkylene chain as defined above. When the heteroaryl is a heteroaryl containing an alkyl group at the nitrogen atom, the heteroaryl is The alkylene chain of a heteroarylalkyl group is optionally attached to an alkylene group. The heteroaryl group of a heteroarylalkyl group is optionally substituted as defined above for The heteroaryl moiety is optionally substituted as defined above for heteroaryl groups. do.

[0049] "Heteroarylalkoxy" refers to an -OR bonded through an oxygen atom. c -Hetero A group of the formula aryl, where R c is an alkylene chain as defined above When the heteroaryl is a nitrogen-containing heteroaryl, the heteroaryl The heteroaryl is optionally attached to the alkyl group at the nitrogen atom. The alkylene chain may be optionally substituted as defined above for an alkylene chain. The heteroaryl portion of the heteroarylalkoxy group is defined above for the heteroaryl group. As defined above, the aryl group is optionally substituted.

[0050] In some embodiments, the compounds disclosed herein have one or more asymmetric centers. In terms of absolute stereochemistry, the enantiomers are defined as (R)- or (S)-. This gives rise to asteromers, diastereomers and other stereoisomers. All stereoisomers of the compounds disclosed herein are contemplated by this disclosure. It is intended that the compounds described herein contain an alkene double bond. Unless otherwise specified, the disclosure includes both E and Z geometric isomers (e.g., , cis or trans isomers). isomers of the formula (I), as well as their racemic and optically pure forms, and all tautomeric forms thereof. The term "geometric isomer" refers to the geometric isomers of alkene double bonds. "Position" refers to either the E or Z geometric isomer (e.g., cis or trans). The term "isomers" refers to ortho, meta and para isomers around the benzene ring. It refers to structural isomers around a central ring, such as cyclobutenes.

[0051] "Tautomers" are compounds in which a proton moves from one atom of a molecule to another atom of the same molecule. In certain embodiments, the compounds presented herein are capable of undergoing tautomerization. In situations where tautomerization is possible, the chemical equilibrium of the tautomers is The exact ratio of tautomers will vary depending on the physical conditions, including temperature, solvent, and pH. The equilibrium state is governed by several factors, including: Examples include: [ka]

[0052] "Optional" or "optionally" means that the subsequently described event or circumstance occurs. The statement may or may not occur, and the event or circumstance may or may not occur. For example, "optionally substituted aryl" means that the aryl The aryl group may be substituted or unsubstituted, and the description may include substituted aryl. The term "aryl" is intended to include both aryl groups and unsubstituted aryl groups.

[0053] "Pharmaceutically acceptable salts" include both acid and base addition salts. A pharmaceutically acceptable salt of any one of the pyrazole compounds described in It is intended to include all pharmaceutically suitable salt forms. Preferred pharmaceutically acceptable salts of the compounds are pharmaceutically acceptable acid addition salts and pharmaceutically acceptable salts. are generally acceptable base addition salts.

[0054] "Pharmaceutically acceptable acid addition salts" means salts of compounds which retain the biological effectiveness and properties of the free base. and is not biologically or otherwise harmful, and contains hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, iodine, It refers to salts formed with inorganic acids such as hydrochloric acid, hydrofluoric acid, phosphonic acid, etc. Aliphatic monocarboxylic acids, aliphatic dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxyalkanoic acids such as carboxylic acids, alkanedioic acids, aromatic acids, aliphatic sulfonic acids and aromatic sulfonic acids. Also included are salts formed with organic acids, such as acetic acid, trifluoroacetic acid, propionic acid, Glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, alcohol Taric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid , p-toluenesulfonic acid, salicylic acid, etc. Therefore, exemplary salts include Sulfate, pyrosulfate, bisulfate, sulfite, bisulf phite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphos phosphate, pyrophosphate, chloride, bromide, iodide, acetate, Trifluoroacetate, Propionate, Caprylate, Isobutyrate, Oxalate ester, malonate, succinate, suberate, sebacate, fumarate, maleate, malate Benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate esters, phthalates, benzenesulfonates, toluenesulfonates, phenyl acetates Examples include citrate, citrate, lactate, malate, tartrate, and methanesulfonate. Salts of amino acids are also contemplated, such as alginates, gluconates, and galacturonates. (e.g., Berge SM et al., "Pharmaceuti cal Salts,”Journal of Pharmaceutical Sci. (See, for example, J. Chem. Soc., 66:1-19 (1997)). Acid addition salts of basic compounds include: The free base forms are prepared by contacting a sufficient amount of the desired acid to produce the salt.

[0055] "Pharmaceutically acceptable base addition salts" means salts that retain the biological effectiveness and properties of the free acids. These salts are salts of inorganic bases or organic bases that are not biologically or otherwise harmful. It is prepared from the addition of a base to a free acid. Suitable base addition salts include those derived from metals such as alkali metals and alkaline earth metals, or organic amines. or formed with amines. Salts derived from inorganic bases include sodium salts, potassium salts, Sodium salts, lithium salts, ammonium salts, calcium salts, magnesium salts, iron salts, zinc salts , copper salts, manganese salts, aluminum salts, etc., but are not limited to these. Salts derived from primary amines, secondary amines, tertiary amines, naturally occurring substituted amines, substituted amines, cyclic amines and base ion exchange resins, e.g., isopropylamine, trimethylsilyl amine, Trimethylamine, diethylamine, triethylamine, tripropylamine, ethanol Amine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol ol, dicyclohexylamine, lysine, arginine, histidine, caffeine, proline Caine, N,N-dibenzylethylenediamine, chloroprocaine, hydrabamine, coli betaine, ethylenediamine, ethylenedianiline, N-methylglucamine, glucoside glucamine, methylglucamine, theobromine, purine, piperazine, piperidine, N-ethyl Examples of the salts include, but are not limited to, salts of methylpiperidine, polyamine resins, etc. See rge et al.

[0056] For therapeutic use, salts of the compounds of the invention are salts whose counterions are pharmaceutically acceptable. However, for example, in the preparation or purification of a pharmaceutically acceptable compound, Salts of acids and bases that are not pharmaceutically acceptable may also be useful. All salts, whether or not possible, are included within the scope of the present invention.

[0057] The term "addition salt" or "salt" as used herein refers to the compounds of the present invention, and and the solvates which their (non-solvate) salts are able to form. Solvates such as, for example, hydrates, alcoholates, e.g., methanolates, ethanolates , propanolate, etc. Preferred are pharmaceutically acceptable solvates. Thus, the present invention includes pharmaceutically acceptable solutions of the compounds defined herein. Solvents are also included.

[0058] The compounds of the present invention may exist in N-oxide form. In compounds of which one or several nitrogen atoms are oxidized, the so-called N-oxy The compounds of formula (I) are intended to include compounds in which the trivalent nitrogen Among the procedures for converting to its N-oxide form, those known in the art include: Thus, it may be converted into the corresponding N-oxide form. The N-oxidation reaction generally comprises: by reacting the starting material of formula (I) with an appropriate organic or inorganic peroxide Suitable inorganic peroxides include, for example, hydrogen peroxide, alkali metal peroxides, oxides or alkaline earth metal peroxides, e.g. sodium peroxide, potassium Suitable organic peroxides include peroxides, such as benzeneperoxycarbonyl. Acid or halo-substituted benzeneperoxycarboxylic acids, e.g., 3-chlorobenzeneperoxy Carboxylic acids, peroxoalkanoic acids, e.g., peroxoacetic acid, alkyl hydroperoxy The peroxyacid may include, for example, a peroxy acid such as tert-butyl hydroperoxide. Suitable solvents include, for example, water, lower alcohols such as ethanol, hydrocarbons such as toluene, enes, ketones such as 2-butanone, halogenated hydrocarbons such as dichloromethane, and A mixture of such solvents.

[0059] The compounds of the present invention may exist as quaternary amines. The term "quaternary amine" refers to The basic nitrogen of the compounds of the present invention may be combined with, for example, an optionally substituted alkyl halide, aryl halides or arylalkyl halides, such as methyl iodide or benzyl The compounds of the present invention can be formed by reaction with a suitable quaternizing agent such as iodide. The definition of ammonium salts is as follows: alkyl trifluoromethanesulfonate, alkyl methyl Other compounds with suitable leaving groups, such as alkyl toluenesulfonates and alkyl p-toluenesulfonates, The following reaction substrates may be used. Quaternary amines have a positively charged nitrogen. Acceptable counterions include chloro, bromo, iodo, trifluoroacetate, and acetone. Counterions of choice can be introduced using ion exchange resins.

[0060] The compounds of the present invention may have metal binding, metal chelating, and metal complexing properties. It will be apparent that the compounds of the present invention may exist as metal complexes or metal chelates. Such metallated derivatives of the compounds are intended to be included within the scope of the present invention.

[0061] As used herein, "treatment," "treating," "alleviating," or "improving" "Improvement" and "improving" are used interchangeably herein. These terms refer to the process of achieving a beneficial or or an approach to achieving a desired result, which may include a therapeutic effect and / or "Therapeutic effect" refers to the reduction of the underlying disorder being treated. It means eradication or amelioration. Treatment is effective even if the patient remains affected by the underlying disorder. , eradicating or ameliorating one or more of the physiological symptoms associated with the underlying disorder, thereby improving the patient's condition. The preventive effect can be achieved even if no specific disease has been diagnosed. patients who are at risk of developing the disease or one of the physiological symptoms of the disease The composition is administered to patients for whom the above has been reported.

[0062] compound Formula (I), (II), (III), (IIIa), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IIIg), (IIIh), (IIIi), (IIIj ... Compounds of b) or (IV) are inhibitors of MAGL and / or FAAH. In some embodiments, the compound is an inhibitor of MAGL. In embodiments, the compound is an inhibitor of FAAH. This compound is an inhibitor of MAGL and FAAH. Compounds of formula (I), (II), (III), (IIIa), (IIIb) or (IV) and compositions containing these compounds are useful for treating pain or neurological disorders.

[0063] In some embodiments, a compound of formula (I): [ka] During the ceremony, [ka] but, [ka] and Each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C1 -6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -C(O)NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and and heteroaryl, wherein the aryl and heteroaryl are optionally independently selected from: and halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 from Substituted with one or two selected groups or two adjacent R 1 But, optional One or two R 11 forming a heterocycloalkyl ring substituted with R 2 But C 1-6 is alkyl, R 3 But halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -NR 8 R 9 , -C(O)NR 8 R 9 , -NR 8 C(O)R 9 and -NR 9 SO2R 8 Selected from And, R 3a But halogen, C 1-6 Alkyl and C 1-6 haloalkyl , Each R 4 are independently H and C 1-6 alkyl, Each R 5 and R 6 are independent, H, C 1-6 Alkyl and C 3-8 Selected from cycloalkyl Selected or R 5 and R 6 However, together with the nitrogen bonded to them, One or two R's at will 10 forming a heterocycloalkyl substituted with Each R 7 are independent, H, C1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and and heteroaryl, and is selected from heterocycloalkyl, aryl, and heteroaryl; The groups are optionally, independently, halogen, C 1-6 Alkyl and C 1-6 Select from haloalkyl and is substituted with one or two groups as follows: Each R 8 and R 9 are independent, H, C 1-6 Alkyl, C 3-8 Cycloalkyl, aryl and selected from aryl and heteroaryl; Each R 10 independently, C 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Haloal Chloride, halogen, oxo, -CN, -C(O)OR 8 , -C(O)R 8 , -C(O)NR 8 R 9 , -SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Selected from the law of nature, Each R 11 are independently halogen and C 1-6 alkyl, Each R 12 independently, C 1-6 Alkyl and C 3-8 cycloalkyl the law of nature, m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2 or 3; p is 0 or 1, a compound in which q is 0 or 1; or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

[0064] In some embodiments, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, a compound or stereoisomer, wherein each R 4 is H. In embodiments, a compound of formula (I) or a pharmaceutically acceptable salt, solvate or Stereoisomers, wherein one R 4 is H and one R 4 C 1-6 It is alkyl In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, Possible salts, solvates or stereoisomers of the formula 4 is H and one R 4 In some embodiments, the compound of formula (I) or A pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein one R 4 is H and one R 4 is -CH2CH3. In some embodiments, A compound of formula (I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof In the formula, one R 4 is H and one R 4 is -CH2CH2CH3 In some embodiments, a compound of formula (I), or a pharmaceutically acceptable salt thereof, , solvates or stereoisomers of the formula 4 is H and one R 4 but- In some embodiments, the compound of formula (I) is is a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein each R 4 but C 1-6 In some embodiments, the compounds of formula (I) and is a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein each R 4 but -CH3.

[0065] In some embodiments, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, A solvate or stereoisomer wherein p is 0. In one embodiment, a compound of formula (I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof In some embodiments, the isomer of formula (I) is a hydroxy group represented by the formula (I) where p is 1. A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula where p is 1 and R 2 In some embodiments, the compound of formula (I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, , where p is 1 and R 2 is -CH2CH3. is a compound of formula (I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein p is 1 and R 2 is -CH2CH2CH3. In some embodiments, a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, or a stereoisomer wherein p is 1 and R 2 Although it is -CH(CH3)2 That is why.

[0066] In some embodiments, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, a hydrate or stereoisomer of the formula R 3 are halogens. In this embodiment, a compound of formula (I), or a pharmaceutically acceptable salt, solvate or or stereoisomers, wherein R 3 is -CN. is a compound of formula (I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof is a compound in which R 3 C 1-6 In some embodiments, the aryl group is alkyl. , a compound of formula (I), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein R 3 In some embodiments, the compound of formula (I) is -CH3. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, In the formula, R 3 C 1-6 In some embodiments, the compound of formula (I) is a hydroxyalkyl group. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, , where R 3 In some embodiments, the compound of formula (I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein R 3 Ga-NR 8 R 9 In some embodiments, the compound of formula (I) is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein R 3 but- In some embodiments, the compound of formula (I), or a pharmaceutical thereof, is a physiologically acceptable salt, solvate or stereoisomer of 3 -C(O)N R 8 R 9 In some embodiments, the compound of formula (I), or a preparation thereof, A pharmaceutically acceptable salt, solvate or stereoisomer of 3 -C(O) In some embodiments, the compound of formula (I), or a pharmaceutical thereof, is a physiologically acceptable salt, solvate or stereoisomer of 3 Ga-NR 8 C( O)R 9 In some embodiments, the compound of formula (I), or a preparation thereof, A pharmaceutically acceptable salt, solvate or stereoisomer of 3 -NHC( In some embodiments, the compound of formula (I), or A pharmaceutically acceptable salt, solvate or stereoisomer of the formula wherein q is 0. In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, A suitable salt, solvate or stereoisomer of the formula: wherein q is 1. In embodiments, a compound of formula (I) or a pharmaceutically acceptable salt, solvate or A stereoisomer wherein q is 1 and R 3a are halogens. In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, or a stereoisomer, wherein q is 1 and R 3a C 1-6 Alkyl In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, A salt, solvate or stereoisomer of the formula wherein q is 1 and R 3a C 1-6 Halo It is an alkyl.

[0067] In some embodiments, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, a solvate or stereoisomer of the formula [ka] but [ka] In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, is Acceptable salts, solvates or stereoisomers are those in which m is 0. In some embodiments, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, a solvent solvates or stereoisomers, wherein m is 1. In the present invention, a compound of formula (I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof is wherein m is 1 and R 1 But halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cyclo Alkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and and heteroaryl. In some embodiments, the compound of formula (I) A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula where m is 1 and R 1 But halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C3 -8 Cycloalkyl, -NR 5 R 6 and-OR 7 The number of items selected is In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, or a stereoisomer, wherein m is 1 and R 1 But halogen, C 1-6 Alkyl , C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 Selected from In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, A salt, solvate or stereoisomer of the formula: 1 is a halogen In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, and a suitable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 Although F In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, a salt, solvate or stereoisomer of the formula: 1 Although Cl In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, a salt, solvate or stereoisomer of the formula: 1 is -CN In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, and a suitable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 C 1-6 a In some embodiments, the compound of formula (I), or a pharmaceutical thereof, is a physiologically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 In some embodiments, the compound of formula (I), or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein m is 1; R 1 In some embodiments, the compound of formula (I) is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and Yes, R 1 C 1-6 Alkyl-OR 7 In some embodiments, the formula (I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof where m is 1 and R 1 is -CH2-O-CH3. In an embodiment, a compound of formula (I) or a pharmaceutically acceptable salt, solvate or is a stereoisomer where m is 1 and R 1 C 1-6 haloalkyl In some embodiments, a compound of formula (I), or a pharmaceutically acceptable salt thereof, , solvates or stereoisomers, wherein m is 1 and R 1 Although it is -CF3 In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, a salt, solvate or stereoisomer of the formula: 1 C 3-8 Shik In some embodiments, the compound of formula (I), or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein m is 1; R 1 Ga-NR 5 R 6 In some embodiments, the compound of formula (I) or or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 However, they are bonded to nitrogen atoms. and then, optionally, one or two R 10 forming a heterocycloalkyl substituted with In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 together with the nitrogen to which they are bonded, form unsubstituted heteroatoms. In some embodiments, the compound of formula (I) forms a cycloalkyl. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 However, the nitrogen bonded to them Integrating with and independently C 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Hello Alkyl, halogen, oxo, -C(O)NR 8 R 9 , -SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Choose one or two R 10 Heterocyclic substituted with In some embodiments, the compound of formula (I) or or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 However, they are bonded to nitrogen atoms. And then, independently, C 1-6 Alkyl, C 3-8 Cycloalkyl and -C(O)NR 8 R 9 Choose one or two R 10 forming a heterocycloalkyl substituted with In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, and possible salts, solvates or stereoisomers thereof, wherein m is 1 and R 1 -OR 7 In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, is An acceptable salt, solvate or stereoisomer of 1 -O R 7 and R 7 But C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and heterocycloalkyl In some embodiments, the compound of formula (I) is selected from the group consisting of aryl, methyl ... or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: m is 1 and R 1 In some embodiments, the compound of formula (I) is -OCH3. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 In some embodiments, the formula (I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof where m is 1 and R 1 Ga-SO2R 12 Some embodiments are In one embodiment, a compound of formula (I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof isomers, wherein m is 1 and R 1 Some examples are -SF5. In embodiments, a compound of formula (I) or a pharmaceutically acceptable salt, solvate or stereoisomers, wherein m is 1 and R 1 Ga-SR 8 Some In this embodiment, a compound of formula (I), or a pharmaceutically acceptable salt, solvate or or a stereoisomer thereof, wherein m is 1 and R 1 are independently halogens, C 1-6 a Lukil, C 1-6 Haloalkyl and —C(O)NR 8 R 9 Choose one or two from In some embodiments, the compound of formula (I) is an aryl optionally substituted with a group. A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula where m is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Hello Aruki -C(O)NR 8 R9 a heterocyclic group optionally substituted with one or two groups selected from In some embodiments, the compound of formula (I), or a preparation thereof, is A pharmaceutically acceptable salt, solvate or stereoisomer of 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 Thiazole, pyrazine, pyridinium, and the like, optionally substituted with one or two groups selected from In some embodiments, the aryl group is selected from the group consisting of aryl, arylamine, and arylpyridine. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 2. In some embodiments, the compound of formula (I), or wherein m is 2 and , each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C1 -6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 aryl and heteroaryl In some embodiments, the compound of formula (I), or a pharmaceutical composition thereof, is a physiologically acceptable salt, solvate or stereoisomer thereof, wherein m is 2 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C3-8 Cycloa Lukil, -NR 5 R 6 and-OR 7 In some embodiments, In the present invention, a compound of formula (I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof is wherein m is 2 and each R 1 are independently halogen, -CN, C 1-6 a Lukil, C 1-6 Haloalkyl, -NR 5 R 6 , -OR 7 and heteroaryl In some embodiments, the compound of formula (I), or a pharmaceutical wherein m is 2 and each R 1 but Independently, halogen, C 1-6 Haloalkyl, -NR 5 R 6 , -OR 7 , thiazole, pi In some embodiments, the aryl group is selected from the group consisting of aryl, arylsulfonyl, arylpyrimidine, and arylpyrimidine. is a compound of formula (I) or a preparation thereof A pharmaceutically acceptable salt, solvate or stereoisomer of R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cyclo Alkyl and -OR 7 In some embodiments, the compound of formula (I) is selected from the group consisting of: or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, , where m is 2 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Halo Alkyl, C3-8 Cycloalkyl and -OR 7 are selected from, and each R 7 became independent , C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl , C 3-8 Selected from cycloalkyl, heterocycloalkyl, aryl and heteroaryl In some embodiments, the compound of formula (I), or a pharmaceutical composition thereof, is a physiologically acceptable salt, solvate or stereoisomer thereof, wherein m is 2 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloa Rukill and -OR 7 are selected from, and each R 7 independently, C 1-6 Alkyl, C 1- 6 haloalkyl, C 3-8 selected from cycloalkyl and heterocycloalkyl In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, and suitable salts, solvates or stereoisomers of the compound of formula (I) wherein m is 3. In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, or a stereoisomer wherein m is 3 and each R 1 are independently halogen, -CN , C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1-6 Hello Lukil, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR 7, -SO2R 12 , -SF5 , -SR 8 aryl and heteroaryl. In embodiments, a compound of formula (I) or a pharmaceutically acceptable salt, solvate or stereoisomers, wherein m is 3 and each R 1 are independently halogen, C 1-6 Al Kill, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 and-OR 7 from In some embodiments, the compound of formula (I), or a preparation thereof, A pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 3 and each R 1 but Independently, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkane -OR 7 In some embodiments, the compound of formula (I) is selected from: or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein , m is 3, and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Hello Aruki Lu, C 3-8 Cycloalkyl and -OR 7 are selected from, and each R 7 is independent, C1 -6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C3 -8 selected from cycloalkyl, heterocycloalkyl, aryl and heteroaryl In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, An acceptable salt, solvate or stereoisomer of 1 German Standing, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 cycloalkyl and-OR 7 are selected from, and each R 7 independently, C 1-6 Alkyl, C 1-6 Halo Alkyl, C 3-8 selected from cycloalkyl and heterocycloalkyl; be.

[0068] In some embodiments, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, a solvate or stereoisomer of the formula [ka] but [ka] In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, is An acceptable salt, solvate or stereoisomer of [ka] but [ka] In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, is An acceptable salt, solvate or stereoisomer of [ka] but [ka] In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, is Acceptable salts, solvates or stereoisomers are those in which n is 0. In some embodiments, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, a solvent solvates or stereoisomers where n is 1. In the present invention, a compound of formula (I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof is wherein n is 1 and R 1 But halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cyclo Alkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and and heteroaryl. In some embodiments, the compound of formula (I) A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula where n is 1 and R 1 But halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C3 -8 Cycloalkyl, -NR 5 R 6 and-OR 7 The number of items selected is In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, or a stereoisomer, wherein n is 1 and R 1 But halogen, C1-6 Alkyl , C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 Selected from In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, A salt, solvate or stereoisomer of the formula: 1 is a halogen In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, and a suitable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 Although F In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, a salt, solvate or stereoisomer of the formula: 1 Although Cl In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, a salt, solvate or stereoisomer of the formula: 1 is -CN In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, and a suitable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 C 1-6 a In some embodiments, the compound of formula (I), or a pharmaceutical thereof, is a physiologically acceptable salt, solvate or stereoisomer of 1 In some embodiments, the compound of formula (I), or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein n is 1; R 1 In some embodiments, the compound of formula (I) is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and Yes, R 1 C 1-6 Alkyl-OR 7 In some embodiments, the formula (I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof where n is 1 and R 1 is -CH2-O-CH3. In an embodiment, a compound of formula (I) or a pharmaceutically acceptable salt, solvate or is a stereoisomer where n is 1 and R 1 C 1-6 haloalkyl In some embodiments, a compound of formula (I), or a pharmaceutically acceptable salt thereof, , solvates or stereoisomers, wherein n is 1 and R 1 Although it is -CF3 In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, a salt, solvate or stereoisomer of the formula: 1 C 3-8 Shik In some embodiments, the compound of formula (I), or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein n is 1; R 1 Ga-NR 5 R 6 In some embodiments, the compound of formula (I) or or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 However, they are bonded to nitrogen atoms. and then, optionally, one or two R 10 forming a heterocycloalkyl substituted with In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 together with the nitrogen to which they are bonded, form unsubstituted heteroatoms. In some embodiments, the compound of formula (I) forms a cycloalkyl. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 However, the nitrogen bonded to them Integrating with and independently C 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Hello Alkyl, halogen, oxo, -C(O)NR 8 R 9 , -SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Choose one or two R 10 Heterocyclic substituted with In some embodiments, the compound of formula (I) or or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 However, they are bonded to nitrogen atoms. And then, independently, C 1-6 Alkyl, C 3-8 Cycloalkyl and -C(O)NR 8 R 9 Choose one or two R 10 forming a heterocycloalkyl substituted with In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, and possible salts, solvates or stereoisomers thereof, wherein n is 1 and R 1 -OR 7 In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, is An acceptable salt, solvate or stereoisomer of 1 -O R 7 and R 7 But C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and heterocycloalkyl In some embodiments, the compound of formula (I) is selected from the group consisting of aryl, methyl ... or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: n is 1 and R 1 In some embodiments, the compound of formula (I) is -OCH3. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 In some embodiments, the formula (I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof where n is 1 and R 1 Ga-SO2R 12Some embodiments are In one embodiment, a compound of formula (I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof isomers, wherein n is 1 and R 1 Some examples are -SF5. In embodiments, a compound of formula (I) or a pharmaceutically acceptable salt, solvate or A stereoisomer wherein n is 1 and R 1 Ga-SR 8 Some In this embodiment, a compound of formula (I), or a pharmaceutically acceptable salt, solvate or or a stereoisomer thereof, wherein n is 1 and R 1 are independently halogens, C 1-6 a Lukil, C 1-6 Haloalkyl and —C(O)NR 8 R 9 Choose one or two from In some embodiments, the compound of formula (I) is an aryl optionally substituted with a group. A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula where n is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Hello Aruki -C(O)NR 8 R 9 a heterocyclic group optionally substituted with one or two groups selected from In some embodiments, the compound of formula (I), or a preparation thereof, is A pharmaceutically acceptable salt, solvate or stereoisomer of 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9Thiazole, pyrazine, pyridinium, and the like, optionally substituted with one or two groups selected from In some embodiments, the aryl group is selected from the group consisting of aryl, arylamine, and arylpyridine. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 2. In some embodiments, the compound of formula (I), or A pharmaceutically acceptable salt, solvate or stereoisomer of the formula: , each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C1 -6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 aryl and heteroaryl In some embodiments, the compound of formula (I), or a pharmaceutical composition thereof, is a physiologically acceptable salt, solvate or stereoisomer of 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloa Lukil, -NR 5 R 6 and-OR 7 In some embodiments, In the present invention, a compound of formula (I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof is wherein n is 2 and each R 1 are independently halogen, -CN, C 1-6 a Lukil, C 1-6 Haloalkyl, -NR5 R 6 , -OR 7 and heteroaryl In some embodiments, the compound of formula (I), or a pharmaceutical wherein n is 2 and each R 1 but Independently, halogen, C 1-6 Haloalkyl, -NR 5 R 6 , -OR 7 , thiazole, pi In some embodiments, the aryl group is selected from the group consisting of aryl, arylsulfonyl, arylpyrimidine, and arylpyrimidine. is a compound of formula (I) or a preparation thereof A pharmaceutically acceptable salt, solvate or stereoisomer of the formula: R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cyclo Alkyl and -OR 7 In some embodiments, the compound of formula (I) is selected from the group consisting of: or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, , wherein n is 2 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Halo Alkyl, C 3-8 Cycloalkyl and -OR 7 are selected from, and each R 7 became independent , C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl , C 3-8 Selected from cycloalkyl, heterocycloalkyl, aryl and heteroaryl In some embodiments, the compound of formula (I), or a pharmaceutical composition thereof, is a physiologically acceptable salt, solvate or stereoisomer of 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloa Rukill and -OR 7 are selected from, and each R 7 independently, C 1-6 Alkyl, C 1- 6 haloalkyl, C 3-8 selected from cycloalkyl and heterocycloalkyl In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, and suitable salts, solvates or stereoisomers thereof, wherein n is 3.

[0069] In some embodiments, a compound of formula (II): [ka] During the ceremony, [ka] but [ka] and Each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C1 -6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -C(O)NR 5 R 6 , -OR7 , -SO2R 12 , -SF5, -SR 8 , aryl and and heteroaryl, wherein the aryl and heteroaryl are optionally independently selected from: and halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 from Substituted with one or two selected groups or two adjacent R 1 But, optional One or two R 11 forming a heterocycloalkyl ring substituted with R 2 But C 1-6 is alkyl, R 3 But halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -NR 8 R 9 , -C(O)NR 8 R 9 , -NR 8 C(O)R 9 and -NR 9 SO2R 8 Selected from And, R 3a But halogen, C 1-6 Alkyl and C 1-6 haloalkyl , Each R 5 and R 6 are independent, H, C 1-6 Alkyl and C 3-8 Selected from cycloalkyl Selected or R 5 and R 6 However, together with the nitrogen bonded to them, One or two R's at will 10 forming a heterocycloalkyl substituted with Each R 7are independent, H, C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and and heteroaryl, wherein the heterocycloalkyl, aryl and heteroaryl are selected from the group consisting of: aryl optionally independently selected from halogen, C 1-6 Alkyl and C 1-6 From haloalkyl substituted with one or two selected groups, Each R 8 and R 9 are independent, H, C 1-6 Alkyl, C 3-8 Cycloalkyl, aryl and selected from aryl and heteroaryl; Each R 10 independently, C 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Haloal Chloride, halogen, oxo, -CN, -C(O)OR 8 , -C(O)R 8 , -C(O)NR 8 R 9 , -SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Selected from the law of nature, Each R 11 are independently halogen and C 1-6 alkyl, Each R 12 independently, C 1-6 Alkyl and C 3-8 cycloalkyl the law of nature, m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2 or 3; p is 0 or 1, a compound in which q is 0 or 1; or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

[0070] In some embodiments, a compound of formula (II), or a pharmaceutically acceptable salt thereof: Solvates or stereoisomers where p is 0. In the form of a compound of formula (II), or a pharmaceutically acceptable salt, solvate or In some embodiments, the stereoisomer is a compound of formula (I) where p is 1. I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein p is 1 and R 2 is -CH3. In some embodiments, A compound of formula (II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein p is 1 and R 2 is -CH2CH3. In embodiments, a compound of formula (II) or a pharmaceutically acceptable salt, solvate or is a stereoisomer where p is 1 and R 2 is -CH2CH2CH3 In some embodiments, the compound of formula (II), or a pharmaceutically acceptable salt thereof, A salt, solvate or stereoisomer of the formula: 2 -CH(CH3 )2.

[0071] In some embodiments, a compound of formula (II), or a pharmaceutically acceptable salt thereof: solvates or stereoisomers of the formula 3 are halogens. In some embodiments, a compound of formula (II), or a pharmaceutically acceptable salt or solvate thereof, or a stereoisomer, wherein R 3 is -CN. In this embodiment, a compound of formula (II) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein R 3 C 1-6 Some embodiments are alkyl. In this embodiment, a compound of formula (II) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein R 3 is -CH3. In some embodiments, A compound of formula (II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein R 3 C 1-6 In some embodiments, the alkyl group is haloalkyl. is a compound of formula (II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof isomer, wherein R 3 In some embodiments, the formula ( II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof In the formula, R 3 Ga-NR 8 R 9 In some embodiments, the compound of formula (II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, , where R 3 In some embodiments, the compound of formula (II) is -NH2. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: R 3 -C(O)NR 8 R 9 In some embodiments, the compound of formula (II) A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula Medium, R 3 In some embodiments, the compound of formula (II) is -C(O)NH2. A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula Medium, R 3 Ga-NR 8 C(O)R 9 In some embodiments, the compound of formula (II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, , where R 3 In some embodiments, the formula ( II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein q is 0. In some embodiments, the compound of formula (II): or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein q is 1. In some embodiments, the compound of formula (II), or a pharmaceutical composition thereof, a commercially acceptable salt, solvate or stereoisomer of the compound of formula (I) wherein q is 1 and R 3a is halogen. In some embodiments, the compound of formula (II), or wherein q is 1 and , R 3a C 1-6 In some embodiments, the group of formula (II) is alkyl. A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula In this case, q is 1 and R 3a C 1-6 It is a haloalkyl.

[0072] In some embodiments, a compound of formula (II), or a pharmaceutically acceptable salt thereof: A solvate or stereoisomer of the formula: [ka] but [ka] In some embodiments, the compound of formula (II), or a pharmaceutical and an acceptable salt, solvate or stereoisomer of the formula: In some embodiments, a compound of formula (II), or a pharmaceutically acceptable salt thereof, solvates or stereoisomers, wherein m is 1. In the form of a compound of formula (II), or a pharmaceutically acceptable salt, solvate or stereoisomers, wherein m is 1 and R 1 But halogen, -CN, C 1-6 Archi Lu, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , Ant In some embodiments, the aryl is selected from aryl and heteroaryl. II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof where m is 1 and R 1 But halogen, C 1-6 Alkyl, C 1-6 Hello Aruki Lu, C 3-8 Cycloalkyl, -NR 5 R6 and-OR 7 is selected from In some embodiments, a compound of formula (II), or a pharmaceutically acceptable salt thereof, solvates or stereoisomers, wherein m is 1 and R 1 But halogen, C 1- 6 alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 Selected from In some embodiments, the compound of formula (II), or a pharmaceutical wherein m is 1 and R 1 Gaha In some embodiments, the compound of formula (II) or a preparation thereof is A pharmaceutically acceptable salt, solvate or stereoisomer of 1 is F. In some embodiments, the compound of formula (II), or a preparation thereof, A pharmaceutically acceptable salt, solvate or stereoisomer of 1 is Cl. In some embodiments, the compound of formula (II), or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein m is 1; R 1 In some embodiments, the compound of formula (II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1; R 1 C 1-6 In some embodiments, the group of formula (II) is alkyl. A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula where m is 1 and R 1In some embodiments, the compound of formula (I) I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 In some embodiments, , a compound of formula (II), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 C 1-6 Alkyl-OR 7 It is what it is. In some embodiments, a compound of formula (II), or a pharmaceutically acceptable salt thereof, a solvate or stereoisomer, wherein m is 1 and R 1 -CH2-O-CH3 In some embodiments, the compound of formula (II), or a pharmaceutical wherein m is 1 and R 1 C 1-6 In some embodiments, the compound of formula (II): or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein m is 1 and R 1 In some embodiments, the compound of formula (II) is -CF3. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein , m is 1, and R 1 C 3-8 In some embodiments, the alkyl group is cycloalkyl. In the present invention, a compound of formula (II) or a pharmaceutically acceptable salt, solvate or steric thereof is isomers, wherein m is 1 and R 1 Ga-NR 5 R 6 Some In this embodiment, the compound of formula (II), or a pharmaceutically acceptable salt or solvate thereof, or a stereoisomer, wherein m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 together with the nitrogen to which they are attached, optionally one or two R 10 Place In some embodiments, the formula (II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 But, together with the nitrogen to which it is attached form an unsubstituted heterocycloalkyl In some embodiments, a compound of formula (II), or a pharmaceutically acceptable salt thereof, solvates or stereoisomers, wherein m is 1 and R 1 Ga-NR 5 R 6 and , R 5 and R 6 However, together with the nitrogen bonded to them, they independently form C 1-6 Archi Lu, C 3-8 Cycloalkyl, C 1-6 Haloalkyl, halogen, oxo, -C(O)N R 8 R 9 , -SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Selected 1 from One or two R 10 This forms a heterocycloalkyl substituted with In some embodiments, a compound of Formula (II), or a pharmaceutically acceptable salt thereof, a solvent a solvate or stereoisomer thereof, wherein m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 However, together with the nitrogen bonded to them, they independently form C 1-6 Alkyl, C 3-8 Cycloalkyl and -C(O)NR 8 R 9 Choose one or two R 10 In some embodiments, the heterocycloalkyl is substituted with , a compound of formula (II), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 -OR 7 Some embodiments are In this embodiment, a compound of formula (II) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein m is 1 and R 1 -OR 7 and R 7 But C 1-6 Al Kill, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Shik and selected from the group consisting of cycloalkyl, heterocycloalkyl, aryl, and heteroaryl. In some embodiments, the compound of formula (II), or a pharmaceutically acceptable salt thereof, and a suitable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 -OCH3 In some embodiments, the compound of formula (II), or a pharmaceutical wherein m is 1 and R 1 but- OCF3. In some embodiments, the compound of formula (II), or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein m is 1; R 1 Ga-SO2R 12 In some embodiments, the compound of formula (II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 In some embodiments, the compound of formula (II) is -SF5. A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula where m is 1 and R 1 Ga-SR 8 In some embodiments, the compound of formula (I I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Halo Alkyl and -C(O)NR 8 R 9 optionally substituted with one or two groups selected from In some embodiments, the compound of formula (II) or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein m is 1; R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)N R 8 R 9 Heteroaryl optionally substituted with one or two groups selected from In some embodiments, the compound of formula (II), or a pharmaceutically acceptable salt thereof, a salt, solvate or stereoisomer of the formula: 1 But independently Rogen, C. 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 Choose from Thiazoles, pyrazines, pyrimidines and pyridines optionally substituted with one or two groups In some embodiments, the compound of formula (II) is selected from the group consisting of: or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 2 and In some embodiments, the compound of formula (II) or a pharmaceutically acceptable salt thereof is An acceptable salt, solvate or stereoisomer of 1 German In addition, halogens, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkyl -OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 aryl and heteroaryl In some embodiments, the compound of formula (II), or a pharmaceutically acceptable salt thereof, and a possible salt, solvate or stereoisomer thereof, wherein m is 2 and each R 1 became independent Halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, - NR 5 R 6and-OR 7 In some embodiments, the compound of formula ( II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 2 and each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -NR 5 R 6 , -OR 7 and heteroaryl In some embodiments, the compound of formula (II), or a pharmaceutically acceptable salt thereof, and a possible salt, solvate or stereoisomer thereof, wherein m is 2 and each R 1 became independent Halogens, C 1-6 Haloalkyl, -NR 5 R 6 , -OR 7 , thiazole, pyrazine , pyrimidine and pyridine In some embodiments, the compound of formula (II), or a pharmaceutical formulation thereof, a commercially acceptable salt, solvate or stereoisomer of 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloal Kill and -OR 7 In some embodiments, the compound of formula (II) is selected from the group consisting of: or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 2 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Hello Lukil, C 3-8 Cycloalkyl and -OR 7 are selected from, and each R7 became independent, C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 haloalkyl, C 3-8 Selected from cycloalkyl, heterocycloalkyl, aryl and heteroaryl In some embodiments, the compound of formula (II), or a pharmaceutical composition thereof, a physiologically acceptable salt, solvate or stereoisomer thereof, wherein m is 2 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloa Rukill and -OR 7 are selected from, and each R 7 independently, C 1-6 Alkyl, C 1- 6 haloalkyl, C 3-8 selected from cycloalkyl and heterocycloalkyl In some embodiments, the compound of formula (II), or a pharmaceutically acceptable salt thereof, Possible salts, solvates or stereoisomers of the formula wherein m is 3. In some embodiments, a compound of formula (II), or a pharmaceutically acceptable salt, solvate thereof, wherein m is 3 and each R 1 are independently halogen, - C.N., C. 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1-6 Ha Roalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -S F5, -SR8 aryl and heteroaryl. In this embodiment, the compound of formula (II), or a pharmaceutically acceptable salt or solvate thereof, or a stereoisomer wherein m is 3 and each R 1 are independently halogen, C 1- 6 alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 and-OR 7 In some embodiments, the compound of formula (II) is selected from: or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 3; Each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Shik -OR alkyl and -OR 7 In some embodiments, the compound of formula ( II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 3 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 are selected from, and each R 7 becomes independent Then, C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloal Kill, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and heteroaryl In some embodiments, the compound of formula (II) or wherein m is 3 and , each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 S Chloroalkyl and -OR 7 are selected from, and each R 7 independently, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 selected from cycloalkyl and heterocycloalkyl This is what is being done.

[0073] In some embodiments, a compound of formula (II), or a pharmaceutically acceptable salt thereof: A solvate or stereoisomer of the formula: [ka] but [ka] In some embodiments, the compound of formula (II), or a pharmaceutical an acceptable salt, solvate or stereoisomer of [ka] but [ka] In some embodiments, the compound of formula (II), or a pharmaceutical an acceptable salt, solvate or stereoisomer of [ka] but [ka] In some embodiments, the compound of formula (II), or a pharmaceutical and an acceptable salt, solvate or stereoisomer of the formula: In some embodiments, a compound of formula (II), or a pharmaceutically acceptable salt thereof, solvates or stereoisomers, wherein n is 1. In the form of a compound of formula (II), or a pharmaceutically acceptable salt, solvate or A stereoisomer wherein n is 1 and R 1 But halogen, -CN, C 1-6 Archi Lu, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , Ant In some embodiments, the aryl is selected from aryl and heteroaryl. II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof where n is 1 and R 1 But halogen, C 1-6 Alkyl, C 1-6 Hello Aruki Lu, C 3-8 Cycloalkyl, -NR 5 R 6 and-OR 7 is selected from In some embodiments, a compound of formula (II), or a pharmaceutically acceptable salt thereof, solvates or stereoisomers, wherein n is 1 and R 1 But halogen, C 1- 6 alkyl, C1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 Selected from In some embodiments, the compound of formula (II), or a pharmaceutical wherein n is 1 and R 1 Gaha In some embodiments, the compound of formula (II) or a preparation thereof is A pharmaceutically acceptable salt, solvate or stereoisomer of 1 is F. In some embodiments, the compound of formula (II), or a preparation thereof, A pharmaceutically acceptable salt, solvate or stereoisomer of 1 is Cl. In some embodiments, the compound of formula (II), or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein n is 1; R 1 In some embodiments, the compound of formula (II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1; R 1 C 1-6 In some embodiments, the group of formula (II) is alkyl. A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula where n is 1 and R 1 In some embodiments, the compound of formula (I) I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 In some embodiments, , a compound of formula (II), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 C 1-6 Alkyl-OR 7 It is what it is. In some embodiments, a compound of formula (II), or a pharmaceutically acceptable salt thereof, a solvate or stereoisomer, wherein n is 1 and R 1 -CH2-O-CH3 In some embodiments, the compound of formula (II), or a pharmaceutical wherein n is 1 and R 1 C 1-6 In some embodiments, the compound of formula (II): or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein n is 1 and R 1 In some embodiments, the compound of formula (II) is -CF3. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein , n is 1, and R 1 C 3-8 In some embodiments, the alkyl group is cycloalkyl. In the present invention, a compound of formula (II) or a pharmaceutically acceptable salt, solvate or steric thereof is isomers, wherein n is 1 and R 1 Ga-NR 5 R 6 Some In this embodiment, the compound of formula (II), or a pharmaceutically acceptable salt or solvate thereof, or a stereoisomer, wherein n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6together with the nitrogen to which they are attached, optionally one or two R 10 Place In some embodiments, the formula (II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 But, together with the nitrogen to which it is attached form an unsubstituted heterocycloalkyl In some embodiments, a compound of formula (II), or a pharmaceutically acceptable salt thereof, solvates or stereoisomers, wherein n is 1 and R 1 Ga-NR 5 R 6 and , R 5 and R 6 However, together with the nitrogen bonded to them, they independently form C 1-6 Archi Lu, C 3-8 Cycloalkyl, C 1-6 Haloalkyl, halogen, oxo, -C(O)N R 8 R 9 , -SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Selected 1 from One or two R 10 This forms a heterocycloalkyl substituted with In some embodiments, a compound of Formula (II), or a pharmaceutically acceptable salt thereof, a solvent a solvate or stereoisomer thereof, wherein n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R6 However, together with the nitrogen bonded to them, they independently form C 1-6 Alkyl, C 3-8 Cycloalkyl and -C(O)NR 8 R 9 Choose one or two R 10 In some embodiments, the heterocycloalkyl is substituted with , a compound of formula (II), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 -OR 7 Some embodiments are In this embodiment, a compound of formula (II) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein n is 1 and R 1 -OR 7 and R 7 But C 1-6 Al Kill, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Shik and selected from the group consisting of cycloalkyl, heterocycloalkyl, aryl, and heteroaryl. In some embodiments, the compound of formula (II), or a pharmaceutically acceptable salt thereof, and a suitable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 -OCH3 In some embodiments, the compound of formula (II), or a pharmaceutical wherein n is 1 and R 1 but- OCF3. In some embodiments, the compound of formula (II), or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein n is 1; R1 Ga-SO2R 12 In some embodiments, the compound of formula (II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 In some embodiments, the compound of formula (II) is -SF5. A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula where n is 1 and R 1 Ga-SR 8 In some embodiments, the compound of formula (I I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Halo Alkyl and -C(O)NR 8 R 9 optionally substituted with one or two groups selected from In some embodiments, the compound of formula (II) or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein n is 1; R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)N R 8 R 9 Heteroaryl optionally substituted with one or two groups selected from In some embodiments, the compound of formula (II), or a pharmaceutically acceptable salt thereof, a salt, solvate or stereoisomer of the formula: 1 But independently Rogen, C. 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9Choose from Thiazoles, pyrazines, pyrimidines and pyridines optionally substituted with one or two groups In some embodiments, the compound of formula (II) is selected from the group consisting of: or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 2 and In some embodiments, the compound of formula (II) or a pharmaceutically acceptable salt thereof is An acceptable salt, solvate or stereoisomer of 1 German In addition, halogens, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkyl -OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 aryl and heteroaryl In some embodiments, the compound of formula (II), or a pharmaceutically acceptable salt thereof, and a possible salt, solvate or stereoisomer thereof, wherein n is 2 and each R 1 became independent Halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, - NR 5 R 6 and-OR 7 In some embodiments, the compound of formula ( II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 2 and each R 1 are independently halogen, -CN, C 1-6 Alkyl, C1-6 Haloalkyl, -NR 5 R 6 , -OR 7 and heteroaryl In some embodiments, the compound of formula (II), or a pharmaceutically acceptable salt thereof, and a possible salt, solvate or stereoisomer thereof, wherein n is 2 and each R 1 became independent Halogens, C 1-6 Haloalkyl, -NR 5 R 6 , -OR 7 , thiazole, pyrazine , pyrimidine and pyridine In some embodiments, the compound of formula (II), or a pharmaceutical formulation thereof, a commercially acceptable salt, solvate or stereoisomer of 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloal Kill and -OR 7 In some embodiments, the compound of formula (II) is selected from the group consisting of: or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 2 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Hello Lukil, C 3-8 Cycloalkyl and -OR 7 are selected from, and each R 7 became independent, C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 haloalkyl, C 3-8 Selected from cycloalkyl, heterocycloalkyl, aryl and heteroaryl In some embodiments, the compound of formula (II), or a pharmaceutical composition thereof, a physiologically acceptable salt, solvate or stereoisomer of 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloa Rukill and -OR 7 are selected from, and each R 7 independently, C 1-6 Alkyl, C 1- 6 haloalkyl, C 3-8 selected from cycloalkyl and heterocycloalkyl In some embodiments, the compound of formula (II), or a pharmaceutically acceptable salt thereof, Possible salts, solvates or stereoisomers, where n is 3.

[0074] In some embodiments, a compound of formula (III): [ka] During the ceremony, Each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C1 -6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -C(O)NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and and heteroaryl, wherein the aryl and heteroaryl are optionally independently selected from: and halogens, C 1-6Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 from Substituted with one or two selected groups or two adjacent R 1 But, optional One or two R 11 forming a heterocycloalkyl ring substituted with R 3 But halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -NR 8 R 9 , -C(O)NR 8 R 9 , -NR 8 C(O)R 9 and -NR 9 SO2R 8 Selected from And, R 3a But halogen, C 1-6 Alkyl and C 1-6 haloalkyl , Each R 5 and R 6 are independent, H, C 1-6 Alkyl and C 3-8 Selected from cycloalkyl Selected or R 5 and R 6 However, together with the nitrogen bonded to them, One or two R's at will 10 forming a heterocycloalkyl substituted with Each R 7 are independent, H, C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and and heteroaryl, wherein the heterocycloalkyl, aryl and heteroaryl are selected from the group consisting of: aryl optionally independently selected from halogen, C 1-6 Alkyl and C 1-6 From haloalkyl substituted with one or two selected groups, Each R 8 and R 9 are independent, H, C 1-6 Alkyl, C 3-8 Cycloalkyl, aryl and selected from aryl and heteroaryl; Each R 10 independently, C 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Haloal Chloride, halogen, oxo, -CN, -C(O)OR 8 , -C(O)R 8 , -C(O)NR 8 R 9 , -SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Selected from the law of nature, Each R 11 are independently halogen and C 1-6 alkyl, Each R 12 independently, C 1-6 Alkyl and C 3-8 cycloalkyl the law of nature, m is 0, 1, 2, 3, 4 or 5; q is 0 or 1, w is 1 or 2; x is 0 or 1, y is 0 or 1, z is 0 or 1, when y and z are 0, x is 1 and w is 2; when y and z are 1, w is 1; When y is 1 and z is 0, or when y is 0 and z is 1, then x is 1. a compound which is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

[0075] In some embodiments, a compound of formula (III), or a pharmaceutically acceptable salt thereof: , solvates or stereoisomers, wherein y is 1, z is 1 and w is 1. and x is 0. In some embodiments, the compound of formula (III) is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein y is 1 and wherein z is 1, w is 1, and x is 1. In some embodiments , a compound of formula (III), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein y is 1, z is 0, w is 1, and x is 1. In some embodiments, the compound of formula (III), or a pharmaceutically acceptable salt thereof, a salt, solvate or stereoisomer of the formula: wherein y is 1, z is 0 and w is 2 and x is 1. In some embodiments, the compound of formula (III): or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein y is 0, z is 0, w is 2, and x is 1.

[0076] In some embodiments, a compound of formula (III), or a pharmaceutically acceptable salt thereof: , solvates or stereoisomers of the formula 3 are halogens. In some embodiments, a compound of Formula (III), or a pharmaceutically acceptable salt thereof, a solvent a solvate or stereoisomer of 3is -CN. In embodiments, a compound of formula (III), or a pharmaceutically acceptable salt, solvate or or stereoisomers, wherein R 3 C 1-6 Some are alkyl. In embodiments, the compound of formula (III), or a pharmaceutically acceptable salt or solvate thereof, or stereoisomers, wherein R 3 is -CH3. In one embodiment, a compound of formula (III) or a pharmaceutically acceptable salt, solvate or Stereoisomers, wherein R 3 C 1-6 Some are haloalkyl. In embodiments, the compound of formula (III), or a pharmaceutically acceptable salt or solvate thereof, or stereoisomers, wherein R 3 is -CF3. In one embodiment, a compound of formula (III) or a pharmaceutically acceptable salt, solvate or Stereoisomers, wherein R 3 Ga-NR 8 R 9 In some embodiments, In the present invention, a compound of formula (III) or a pharmaceutically acceptable salt, solvate or isoform thereof is isomers, wherein R 3 is -NH2. In some embodiments, A compound of formula (III) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof is a compound in which R 3 -C(O)NR 8 R 9 In some embodiments, In the present invention, a compound of formula (III) or a pharmaceutically acceptable salt, solvate or isoform thereof is isomers, wherein R3 is —C(O)NH2. In one embodiment, a compound of formula (III) or a pharmaceutically acceptable salt, solvate or Stereoisomers, wherein R 3 Ga-NR 8 C(O)R 9 Some In embodiments, the compound of formula (III), or a pharmaceutically acceptable salt or solvate thereof, or stereoisomers, wherein R 3 is -NHC(O)CH3. In some embodiments, a compound of Formula (III), or a pharmaceutically acceptable salt thereof, a solvent solvates or stereoisomers, wherein q is 0. In the present invention, a compound of formula (III) or a pharmaceutically acceptable salt, solvate or isoform thereof is In some embodiments, the compound of formula (II) is a diisomeric compound, wherein q is 1. I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein q is 1 and R 3a is a halogen. , a compound of formula (III), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein q is 1 and R 3a C 1-6 It is an alkyl group. In some embodiments, a compound of Formula (III), or a pharmaceutically acceptable salt thereof, a solvent a solvate or stereoisomer thereof, wherein q is 1 and R 3a C 1-6 Haloalkyl It is what it is.

[0077] In some embodiments, a compound of formula (III), or a pharmaceutically acceptable salt thereof: , solvates or stereoisomers in which m is 0. In embodiments, a compound of formula (III), or a pharmaceutically acceptable salt, solvate or In some embodiments, the formula is a stereoisomer wherein m is 1. (III) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 But halogen, -CN, C 1-6 Alkyl, C 2- 6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloal Kill, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and hexyl In some embodiments, the aryl group of formula (III) is selected from the group consisting of aryl, ... A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula where m is 1 and R 1 But halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C3 -8 Cycloalkyl, -NR 5 R 6 and-OR 7 The number of items selected is In some embodiments, a compound of formula (III), or a pharmaceutically acceptable salt, solvate thereof, a compound or stereoisomer of formula (I) wherein m is 1 and R 1 But halogen, C 1-6 Al Kill, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 Selected from In some embodiments, the compound of formula (III), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 Haloge In some embodiments, the compound of formula (III), or a pharmaceutical composition thereof, a physiologically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 is F. In some embodiments, the compound of formula (III), or a compound thereof, A pharmaceutically acceptable salt, solvate or stereoisomer of 1 In some embodiments, the compound of formula (III) or A pharmaceutically acceptable salt, solvate or stereoisomer of the formula: , R 1 In some embodiments, the compound of formula (III) or or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 C 1-6 In some embodiments, the aryl group of formula (II) is an alkyl group. I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 is -CH3. In some embodiments, A compound of formula (III) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 where -C≡CH. In the form of a compound of formula (III), or a pharmaceutically acceptable salt, solvate or is a stereoisomer where m is 1 and R 1 C 1-6Alkyl-OR 7 However In some embodiments, the compound of formula (III), or a pharmaceutically acceptable salt thereof, and possible salts, solvates or stereoisomers thereof, wherein m is 1 and R 1 -CH2 In some embodiments, the compound of formula (III) is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and Yes, R 1 C 1-6 In some embodiments, the compound of formula (I) is a hydroxyalkyl group. II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof where m is 1 and R 1 In some embodiments, , a compound of formula (III), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 C 3-8 It is a cycloalkyl. In some embodiments, a compound of formula (III), or a pharmaceutically acceptable salt thereof: solvates or stereoisomers, wherein m is 1 and R 1 Ga-NR 5 R 6 is In some embodiments, the compound of formula (III), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 However, together with the nitrogen atoms bound to them, one or The Two R's 10 These form an optionally substituted heterocycloalkyl. In some embodiments, a compound of Formula (III), or a pharmaceutically acceptable salt thereof, a solvent a solvate or stereoisomer thereof, wherein m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 together with the nitrogen to which they are attached form an unsubstituted heterocycloalkyl In some embodiments, the compound of formula (III) or A pharmaceutically acceptable salt, solvate or stereoisomer of the formula: , R 1 Ga-NR 5 R 6 and R 5 and R 6 However, they are combined with the nitrogen that is bound to them. And independently C 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Haloalkyl, halo Geno, oxo, -C(O)NR 8 R 9 , -SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Choose one or two R 10 heterocycloalkyl substituted with In some embodiments, a compound of formula (III), or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein m is 1; R 1 Ga-NR 5 R 6 and R 5 and R 6 together with the nitrogen bound to them , independently C 1-6 Alkyl, C 3-8Cycloalkyl and -C(O)NR 8 R 9 Choose from Select one or two R 10 forming a heterocycloalkyl substituted with In some embodiments, the compound of formula (III), or a pharmaceutically acceptable salt thereof, a salt, solvate or stereoisomer of the formula: 1 -OR 7 Yes In some embodiments, the compound of formula (III) or a pharmaceutically acceptable salt thereof is An acceptable salt, solvate or stereoisomer of 1 -O R 7 and R 7 But C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and heterocycloalkyl In some embodiments, the aryl group of formula (III) is selected from the group consisting of aryl, ... A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula where m is 1 and R 1 In some embodiments, the formula ( III) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 is -OCF3. In the present invention, a compound of formula (III) or a pharmaceutically acceptable salt, solvate or isoform thereof is isomers, wherein m is 1 and R 1 Ga-SO2R 12 It is what it is. In some embodiments, a compound of Formula (III), or a pharmaceutically acceptable salt thereof, a solvent a solvate or stereoisomer thereof, wherein m is 1 and R 1 is -SF5 In some embodiments, a compound of formula (III), or a pharmaceutically acceptable salt thereof, A salt, solvate or stereoisomer of the formula: 1 Ga-SR 8 is In some embodiments, the compound of formula (III), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 But independence and halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 from It is aryl optionally substituted with one or two selected groups. In some embodiments, a compound of formula (III), or a pharmaceutically acceptable salt, solvate thereof, a compound or stereoisomer of formula (I) wherein m is 1 and R 1 However, independently, halogen, C1 -6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 Select one from or In some embodiments, the aryl group is optionally substituted with two groups. , a compound of formula (III), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 Optionally, one or two groups selected from Selected from substituted thiazoles, pyrazines, pyrimidines and pyridines. In some embodiments, a compound of formula (III), or a pharmaceutically acceptable salt thereof, A salt, solvate or stereoisomer of the formula wherein m is 2. In embodiments, the compound of formula (III), or a pharmaceutically acceptable salt or solvate thereof, or a stereoisomer wherein m is 2 and each R 1 are independently halogen, -CN , C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1-6 Hello Lukil, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5 , -SR 8 aryl and heteroaryl. In embodiments, a compound of formula (III), or a pharmaceutically acceptable salt, solvate or or a stereoisomer thereof, wherein m is 2 and each R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 and-OR 7 In some embodiments, the compound of formula (III) is selected from or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 2 and Yes, each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl , -NR 5R 6 , -OR 7 and heteroaryl. In an embodiment, a compound of formula (III), or a pharmaceutically acceptable salt, solvate thereof or a stereoisomer wherein m is 2 and each R 1 However, independently, halogen, C1 -6 Haloalkyl, -NR 5 R 6 , -OR 7 , thiazole, pyrazine, pyrimidine and pyridine. In some embodiments, a compound of Formula (III), or a pharmaceutically acceptable salt thereof, a solvent a solvate or stereoisomer, wherein m is 2 and each R 1 However, independently, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 Choose from In some embodiments, a compound of formula (III) or A pharmaceutically acceptable salt, solvate or stereoisomer of: Each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Shik -OR alkyl and -OR 7 are selected from, and each R 7 independently, C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkane and wherein the alkyl is selected from the group consisting of alkyl, heterocycloalkyl, aryl, and heteroaryl. In some embodiments, a compound of formula (III), or a pharmaceutically acceptable salt thereof, , solvates or stereoisomers wherein m is 2 and each R 1 became independent and became Halo Gen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 are selected from, and each R 7 independently, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 It is selected from cycloalkyl and heterocycloalkyl. In some embodiments, a compound of formula (III), or a pharmaceutically acceptable salt, solvate thereof, In some embodiments, m is 3. is a compound of formula (III) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof isomers wherein m is 3 and each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl, and heteroaryl. , a compound of formula (III), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 3 and each R 1 are independently halogen, C 1-6 Alkyl, C1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 and-OR 7 Selected from In some embodiments, the compound of formula (III), or a pharmaceutical composition thereof, and a physiologically acceptable salt, solvate, or stereoisomer thereof, wherein m is 3 and each R 1 German Standing, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 cycloalkyl and-OR 7 In some embodiments, the compound of formula (III) is selected from the group consisting of: A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula In this case, m is 3 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloal Kill, C 3-8 Cycloalkyl and -OR 7 are selected from, and each R 7 independently, C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 selected from cycloalkyl, heterocycloalkyl, aryl and heteroaryl In some embodiments, the compound of formula (III), or a pharmaceutical composition thereof, a physiologically acceptable salt, solvate or stereoisomer thereof, wherein m is 3 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloa Rukill and -OR 7 are selected from, and each R 7independently, C 1-6 Alkyl, C 1- 6 haloalkyl, C 3-8 selected from cycloalkyl and heterocycloalkyl It is something.

[0078] In some embodiments, a compound of formula (III), or a pharmaceutically acceptable salt thereof: , solvates or stereoisomers where n is 0. In embodiments, a compound of formula (III), or a pharmaceutically acceptable salt, solvate or In some embodiments, the formula is a stereoisomer, wherein n is 1. (III) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 But halogen, -CN, C 1-6 Alkyl, C 2- 6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloal Kill, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and hexyl In some embodiments, the aryl group of formula (III) is selected from the group consisting of aryl, ... A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula where n is 1 and R 1 But halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C3 -8 Cycloalkyl, -NR 5 R 6 and-OR 7 The number of items selected is In some embodiments, a compound of formula (III), or a pharmaceutically acceptable salt, solvate thereof, a compound or stereoisomer of formula (I) wherein n is 1 and R 1 But halogen, C 1-6 Al Kill, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 Selected from In some embodiments, the compound of formula (III), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 Haloge In some embodiments, the compound of formula (III), or a pharmaceutical composition thereof, a physiologically acceptable salt, solvate or stereoisomer of 1 is F. In some embodiments, the compound of formula (III), or a compound thereof, A pharmaceutically acceptable salt, solvate or stereoisomer of 1 In some embodiments, the compound of formula (III) or A pharmaceutically acceptable salt, solvate or stereoisomer of the formula: , R 1 In some embodiments, the compound of formula (III) or or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 C 1-6 In some embodiments, the aryl group of formula (II) is an alkyl group. I) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 is -CH3. In some embodiments, A compound of formula (III) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 where -C≡CH. In the form of a compound of formula (III), or a pharmaceutically acceptable salt, solvate or is a stereoisomer where n is 1 and R 1 C 1-6 Alkyl-OR 7 However In some embodiments, the compound of formula (III), or a pharmaceutically acceptable salt thereof, and possible salts, solvates or stereoisomers thereof, wherein n is 1 and R 1 -CH2 In some embodiments, the compound of formula (III) is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and Yes, R 1 C 1-6 In some embodiments, the compound of formula (I) is a hydroxyalkyl group. II) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof where n is 1 and R 1 In some embodiments, , a compound of formula (III), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 C 3-8 It is a cycloalkyl. In some embodiments, a compound of formula (III), or a pharmaceutically acceptable salt thereof: solvates or stereoisomers, wherein n is 1 and R 1 Ga-NR 5 R 6 is In some embodiments, the compound of formula (III), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 However, together with the nitrogen bonded to them, one or two R's 10 These form heterocycloalkyl substituted with In some embodiments, a compound of Formula (III), or a pharmaceutically acceptable salt thereof, a solvent a solvate or stereoisomer thereof, wherein n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 together with the nitrogen to which they are attached form an unsubstituted heterocycloalkyl In some embodiments, the compound of formula (III) or A pharmaceutically acceptable salt, solvate or stereoisomer of the formula: , R 1 Ga-NR 5 R 6 and R 5 and R 6 However, they are combined with the nitrogen that is bound to them. And independently C 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Haloalkyl, halo Geno, oxo, -C(O)NR 8 R 9 , -SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Choose one or two R 10 heterocycloalkyl substituted with In some embodiments, a compound of formula (III), or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein n is 1; R 1 Ga-NR 5 R 6 and R 5 and R 6 together with the nitrogen bound to them , independently C 1-6 Alkyl, C 3-8 Cycloalkyl and -C(O)NR 8 R 9 Choose from Select one or two R 10 forming a heterocycloalkyl substituted with In some embodiments, the compound of formula (III), or a pharmaceutically acceptable salt thereof, a salt, solvate or stereoisomer of the formula: 1 -OR 7 Yes In some embodiments, the compound of formula (III) or a pharmaceutically acceptable salt thereof is An acceptable salt, solvate or stereoisomer of 1 -O R 7 and R 7 But C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and heterocycloalkyl In some embodiments, the aryl group of formula (III) is selected from the group consisting of aryl, ... A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula where n is 1 and R 1 In some embodiments, the formula ( III) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 is -OCF3. In the present invention, a compound of formula (III) or a pharmaceutically acceptable salt, solvate or isoform thereof is isomers, wherein n is 1 and R 1 Ga-SO2R 12 It is what it is. In some embodiments, a compound of Formula (III), or a pharmaceutically acceptable salt thereof, a solvent a solvate or stereoisomer thereof, wherein n is 1 and R 1 is -SF5 In some embodiments, a compound of formula (III), or a pharmaceutically acceptable salt thereof, A salt, solvate or stereoisomer of the formula: 1 Ga-SR 8 is In some embodiments, the compound of formula (III), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 But independence and halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 from aryl optionally substituted with one or two selected groups. In embodiments, the compound of formula (III), or a pharmaceutically acceptable salt or solvate thereof, or a stereoisomer, wherein n is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 Choose one or two from In some embodiments, the heteroaryl is optionally substituted with a group of formula (III) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1- 6 haloalkyl and -C(O)NR 8 R 9 Optionally substituted with one or two groups selected from The aryl group is selected from the group consisting of thiazole, pyrazine, pyrimidine and pyridine. In some embodiments, a compound of formula (III), or a pharmaceutically acceptable salt thereof: Solvates or stereoisomers, wherein n is 2. In the form of a compound of formula (III), or a pharmaceutically acceptable salt, solvate or is a stereoisomer where n is 2 and each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1-6 Hello Aruki Lu, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 ,-SF5,- SR 8 aryl and heteroaryl. In one embodiment, a compound of formula (III) or a pharmaceutically acceptable salt, solvate or stereoisomers, wherein n is 2 and each R 1 are independently halogen, C 1-6 Al Kill, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 and-OR 7 from In some embodiments, a compound of formula (III) or A pharmaceutically acceptable salt, solvate or stereoisomer of the formula: , each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, - NR 5 R 6 , -OR 7 and heteroaryl. In embodiments, a compound of formula (III), or a pharmaceutically acceptable salt, solvate or or a stereoisomer thereof, wherein n is 2 and each R 1 are independently halogen, C 1-6 Haloalkyl, -NR 5 R 6 , -OR 7 , thiazole, pyrazine, pyrimidine and pyridine. In some embodiments, a compound of Formula (III), or a pharmaceutically acceptable salt thereof, a solvent a solvate or stereoisomer, wherein n is 2 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 Choose from In some embodiments, a compound of formula (III) or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein n is 2; Each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Shik -OR alkyl and -OR 7 are selected from, and each R 7independently, C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkane and wherein the alkyl is selected from the group consisting of alkyl, heterocycloalkyl, aryl, and heteroaryl. In some embodiments, a compound of formula (III), or a pharmaceutically acceptable salt thereof, , solvate or stereoisomer, wherein n is 2 and each R 1 became independent and became Halo Gen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 are selected from, and each R 7 independently, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 It is selected from cycloalkyl and heterocycloalkyl. In some embodiments, a compound of formula (III), or a pharmaceutically acceptable salt, solvate thereof, A compound or stereoisomer of the formula wherein n is 3.

[0079] In some embodiments, a compound of formula (IIIa): [ka] During the ceremony, Each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C1 -6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -C(O)NR5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and and heteroaryl, wherein the aryl and heteroaryl are optionally independently selected from: and halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 from Substituted with one or two selected groups or two adjacent R 1 But, optional One or two R 11 forming a heterocycloalkyl ring substituted with R 3 But halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -NR 8 R 9 , -C(O)NR 8 R 9 , -NR 8 C(O)R 9 and -NR 9 SO2R 8 Selected from And, R 3a But halogen, C 1-6 Alkyl and C 1-6 haloalkyl , Each R 5 and R 6 are independent, H, C 1-6 Alkyl and C 3-8 Selected from cycloalkyl Selected or R 5 and R 6 However, together with the nitrogen bonded to them, One or two R's at will 10 forming a heterocycloalkyl substituted with Each R 7 are independent, H, C 1-6Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and and heteroaryl, wherein the heterocycloalkyl, aryl and heteroaryl are selected from the group consisting of: aryl optionally independently selected from halogen, C 1-6 Alkyl and C 1-6 From haloalkyl substituted with one or two selected groups, Each R 8 and R 9 are independent, H, C 1-6 Alkyl, C 3-8 Cycloalkyl, aryl and selected from aryl and heteroaryl; Each R 10 independently, C 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Haloal Chloride, halogen, oxo, -CN, -C(O)OR 8 , -C(O)R 8 , -C(O)NR 8 R 9 , -SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Selected from the law of nature, Each R 11 are independently halogen and C 1-6 alkyl, Each R 12 independently, C 1-6 Alkyl and C 3-8 cycloalkyl the law of nature, m is 0, 1, 2, 3, 4 or 5; a compound in which q is 0 or 1; or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

[0080] In some embodiments, a compound of Formula (IIIa), or a pharmaceutically acceptable salt thereof A salt, solvate or stereoisomer of the formula R 3 is a halogen. In some embodiments, a compound of formula (IIIa), or a pharmaceutically acceptable salt thereof: solvates or stereoisomers of the formula 3 is -CN. In an embodiment, the compound of formula (IIIa), or a pharmaceutically acceptable salt, solvate thereof, A compound or stereoisomer of formula R 3 C 1-6 It is an alkyl group. In some embodiments, the compound of Formula (IIIa), or a pharmaceutically acceptable salt thereof, a hydrate or stereoisomer of the formula R 3 is -CH3. In an embodiment, the compound of formula (IIIa), or a pharmaceutically acceptable salt, solvate thereof, A compound or stereoisomer of formula R 3 C 1-6 It is a haloalkyl. In some embodiments, a compound of Formula (IIIa), or a pharmaceutically acceptable salt thereof: , solvates or stereoisomers of the formula 3 is -CF3. In some embodiments, the compound of Formula (IIIa), or a pharmaceutically acceptable salt thereof, a hydrate or stereoisomer of the formula R 3 Ga-NR 8 R 9 It is what it is. In some embodiments, the compound of Formula (IIIa), or a pharmaceutically acceptable salt thereof, a hydrate or stereoisomer of the formula R 3 is -NH2. In an embodiment, the compound of formula (IIIa), or a pharmaceutically acceptable salt, solvate thereof, A compound or stereoisomer of formula R 3 -C(O)NR 8 R 9 It is what it is. In some embodiments, a compound of Formula (IIIa), or a pharmaceutically acceptable salt thereof: , solvates or stereoisomers of the formula 3 is -C(O)NH2 In some embodiments, the compound of formula (IIIa), or a pharmaceutically acceptable salt thereof, a salt, solvate or stereoisomer of the formula 3 Ga-NR 8 C(O)R 9 is In some embodiments, the compound of formula (IIIa), or a pharmaceutically acceptable salt thereof, An acceptable salt, solvate or stereoisomer of 3 -NHC(O)CH 3. In some embodiments, the compound of formula (IIIa), or a preparation thereof, A pharmaceutically acceptable salt, solvate or stereoisomer of the formula: In some embodiments, the compound of formula (IIIa), or a pharmaceutically acceptable salt thereof, Possible salts, solvates or stereoisomers of the formula: wherein q is 1. In some embodiments, the compound of Formula (IIIa), or a pharmaceutically acceptable salt thereof, a compound or stereoisomer of formula (I) wherein q is 1 and R 3a is a halogen In some embodiments, the compound of formula (IIIa), or a pharmaceutically acceptable salt thereof, and possible salts, solvates or stereoisomers thereof, wherein q is 1 and R3a C 1- In some embodiments, the compound of formula (IIIa) is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein q is 1 and Yes, R 3a C 1-6 It is a haloalkyl.

[0081] In some embodiments, a compound of Formula (IIIa), or a pharmaceutically acceptable salt thereof A salt, solvate or stereoisomer of the formula wherein m is 0. In an embodiment, a compound of formula (IIIa), or a pharmaceutically acceptable salt, solvate thereof or a stereoisomer wherein m is 1. In some embodiments, , a compound of formula (IIIa), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof isomers, wherein m is 1 and R 1 But halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Shik alkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and heteroaryl. In some embodiments, the compound of formula (II) Ia) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof where m is 1 and R 1 But halogen, C 1-6 Alkyl, C 1-6 Hello Aruki Lu, C 3-8Cycloalkyl, -NR 5 R 6 and-OR 7 is selected from In some embodiments, the compound of formula (IIIa), or a pharmaceutically acceptable salt thereof, A salt, solvate or stereoisomer of the formula: 1 But halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 Choose from In some embodiments, the compound of formula (IIIa), or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein m is 1; R 1 is a halogen. In some embodiments, the compound of formula (IIIa): or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein m is 1 and R 1 is F. In some embodiments, the compound of formula (IIIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: m is 1 and R 1 In some embodiments, the compound of formula (IIIa) is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 In some embodiments, the compound of formula (I) IIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 C 1-6 Some examples are alkyl groups. In embodiments, the compound of formula (IIIa), or a pharmaceutically acceptable salt or solvate thereof, is or a stereoisomer, wherein m is 1 and R 1 is -CH3. In some embodiments, a compound of formula (IIIa), or a pharmaceutically acceptable salt thereof: solvates or stereoisomers, wherein m is 1 and R 1 Although -C≡CH In some embodiments, the compound of formula (IIIa), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 C 1- 6 alkyl-OR 7 In some embodiments, the compound of formula (IIIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: m is 1 and R 1 is —CH—O—CH. In some embodiments, , a compound of formula (IIIa), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof isomers, wherein m is 1 and R 1 C 1-6 It is a haloalkyl. In some embodiments, a compound of Formula (IIIa), or a pharmaceutically acceptable salt thereof: , solvates or stereoisomers, wherein m is 1 and R 1 Although it is -CF3 In some embodiments, the compound of formula (IIIa), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 C 3- 8 cycloalkyl. In some embodiments, the compound of formula (IIIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 Ga-NR5 R 6 In some embodiments, the compound of formula (II) Ia) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof where m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 But combined with them Optionally, one or two R 10 Heterocyclo substituted with In some embodiments, the compound of formula (IIIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 But the nitrogen bonded to them together form an unsubstituted heterocycloalkyl. In the form of a compound of formula (IIIa), or a pharmaceutically acceptable salt, solvate or or a stereoisomer thereof, wherein m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 However, together with the nitrogen bonded to them, they independently form C 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Haloalkyl, halogen, oxo, -C(O)NR 8 R 9 ,- SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Choose one or two from R 10 In some embodiments, the heterocycloalkyl group is substituted with . In the form of a compound of formula (IIIa), or a pharmaceutically acceptable salt, solvate or or a stereoisomer thereof, wherein m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 However, together with the nitrogen bonded to them, they independently form C 1-6 Alkyl, C 3-8 Cycloalkyl and -C(O)NR 8 R 9 Choose one or two R 10 Replaced with In some embodiments, the heterocycloalkyl of formula (I) IIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 -OR 7 In some embodiments, is a compound of formula (IIIa) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein m is 1 and R 1 -OR 7 and R 7 But C 1-6 Al Kill, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Shik and selected from the group consisting of cycloalkyl, heterocycloalkyl, aryl, and heteroaryl. In some embodiments, the compound of formula (IIIa), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 Ga-OC H3. In some embodiments, the compound of formula (IIIa), or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein m is 1; R 1 In some embodiments, the compound of formula (IIIa) is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 Ga-SO2R 12 In some embodiments, the compound of formula (I IIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 In some embodiments, is a compound of formula (IIIa) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein m is 1 and R 1 Ga-SR 8 Some In an embodiment, a compound of formula (IIIa), or a pharmaceutically acceptable salt, solvate thereof or a stereoisomer wherein m is 1 and R 1 are independently halogens, C 1- 6 alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 Choose one or two from In some embodiments, the aryl group is an aryl group optionally substituted with one or more groups of formula (I). IIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9optionally substituted with one or two groups selected from In some embodiments, the compound of formula (IIIa) is a heteroaryl. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: m is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)NR 8 R 9 a thiazole optionally substituted with one or two groups selected from , pyrazine, pyrimidine, and pyridine. In one embodiment, a compound of formula (IIIa) or a pharmaceutically acceptable salt, solvate or is a stereoisomer where m is 2. In some embodiments, IIIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 2 and each R 1 are independently halogen, -CN, C 1-6 Archi Lu, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , Ant In some embodiments, the aryl is selected from aryl and heteroaryl. IIIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 2 and each R 1 are independently halogen, C 1-6 Alkyl, C1 -6Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 and-OR 7 Selected from In some embodiments, a compound of formula (IIIa), or a pharmaceutical composition thereof, a commercially acceptable salt, solvate or stereoisomer of 1 are independently halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -NR 5 R 6 , -OR 7 and heteroaryl. is a compound of formula (IIIa) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein m is 2 and each R 1 are independently halogen, C 1-6 Haloalkyl, -NR 5 R 6 , -OR 7 , thiazole, pyrazine, pyrimidine and pyridinium In some embodiments, the compound is selected from the group consisting of: or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein m is 2, and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 In some embodiments, In the present invention, a compound of formula (IIIa) or a pharmaceutically acceptable salt, solvate or stereoisomers, wherein m is 2 and each R 1 are independently halogen, C 1-6 Al Kill, C 1-6Haloalkyl, C 3-8 Cycloalkyl and -OR 7 It is selected from , each R 7 independently, C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and heterocycloalkyl In some embodiments, the aryl group is selected from the group consisting of aryl, ... or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 2 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Hello Lukil, C 3-8 Cycloalkyl and -OR 7 are selected from, and each R 7 became independent, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and heterocycloalkyl In some embodiments, the compound of formula (IIIa) is selected from the group consisting of alkyl, aryl, methyl ... or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: In some embodiments, the compound of formula (IIIa) or wherein m is 3 and , each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C1 -6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 aryl and heteroaryl In some embodiments, the compound of formula (IIIa) or wherein m is 3 and , each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 S Chloroalkyl, -NR 5 R 6 and-OR 7 The following are selected from several In embodiments, the compound of formula (IIIa), or a pharmaceutically acceptable salt or solvate thereof, is or a stereoisomer in which m is 3 and each R 1 are independently halogen, C 1-6 Al Kill, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 Selected from In some embodiments, the compound of formula (IIIa), or a pharmaceutically acceptable salt thereof, An acceptable salt, solvate or stereoisomer of 1 German Standing, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 cycloalkyl and-OR 7 are selected from, and each R 7 independently, C 1-6 Alkyl, C 1-6 Al Kill-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, hetero It is selected from cycloalkyl, aryl and heteroaryl. In an embodiment, the compound of formula (IIIa), or a pharmaceutically acceptable salt, solvate thereof, wherein m is 3 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 Choose from Each R 7 independently, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 S It is selected from cycloalkyl and heterocycloalkyl.

[0082] In some embodiments, a compound of Formula (IIIa), or a pharmaceutically acceptable salt thereof A salt, solvate or stereoisomer of the formula wherein n is 0. In an embodiment, a compound of formula (IIIa), or a pharmaceutically acceptable salt, solvate thereof or a stereoisomer wherein n is 1. In some embodiments, , a compound of formula (IIIa), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof isomers, wherein n is 1 and R 1 But halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Shik alkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and heteroaryl. In some embodiments, the compound of formula (II) Ia) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof where n is 1 and R 1 But halogen, C 1-6 Alkyl, C 1-6 Hello Aruki Lu, C 3-8 Cycloalkyl, -NR 5 R 6 and-OR 7 is selected from In some embodiments, the compound of formula (IIIa), or a pharmaceutically acceptable salt thereof, A salt, solvate or stereoisomer of the formula: 1 But halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 Choose from In some embodiments, the compound of formula (IIIa), or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein n is 1; R 1 is a halogen. In some embodiments, the compound of formula (IIIa): or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein n is 1 and R 1 is F. In some embodiments, the compound of formula (IIIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: n is 1 and R 1 In some embodiments, the compound of formula (IIIa) is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1In some embodiments, the compound of formula (I) IIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 C 1-6 Some examples are alkyl groups. In embodiments, the compound of formula (IIIa), or a pharmaceutically acceptable salt or solvate thereof, is or a stereoisomer, wherein n is 1 and R 1 is -CH3. In some embodiments, a compound of formula (IIIa), or a pharmaceutically acceptable salt thereof: solvates or stereoisomers, wherein n is 1 and R 1 Although -C≡CH In some embodiments, the compound of formula (IIIa), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 C 1- 6 alkyl-OR 7 In some embodiments, the compound of formula (IIIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: n is 1 and R 1 is —CH—O—CH. In some embodiments, , a compound of formula (IIIa), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof isomers, wherein n is 1 and R 1 C 1-6 It is a haloalkyl. In some embodiments, a compound of Formula (IIIa), or a pharmaceutically acceptable salt thereof: , solvates or stereoisomers, wherein n is 1 and R 1 Although it is -CF3 In some embodiments, the compound of formula (IIIa), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 C 3- 8 cycloalkyl. In some embodiments, the compound of formula (IIIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 Ga-NR 5 R 6 In some embodiments, the compound of formula (II) Ia) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof where n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 But combined with them Optionally, one or two R 10 Heterocyclo substituted with In some embodiments, the compound of formula (IIIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 But the nitrogen bonded to them together form an unsubstituted heterocycloalkyl. In the form of a compound of formula (IIIa), or a pharmaceutically acceptable salt, solvate or or a stereoisomer thereof, wherein n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6However, together with the nitrogen bonded to them, they independently form C 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Haloalkyl, halogen, oxo, -C(O)NR 8 R 9 ,- SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Choose one or two from R 10 In some embodiments, the heterocycloalkyl group is substituted with . In the form of a compound of formula (IIIa), or a pharmaceutically acceptable salt, solvate or or a stereoisomer thereof, wherein n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 However, together with the nitrogen bonded to them, they independently form C 1-6 Alkyl, C 3-8 Cycloalkyl and -C(O)NR 8 R 9 Choose one or two R 10 Replaced with In some embodiments, the heterocycloalkyl of formula (I) IIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 -OR 7 In some embodiments, is a compound of formula (IIIa) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein n is 1 and R 1 -OR 7 and R 7 But C 1-6 Al Kill, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Shik and selected from the group consisting of cycloalkyl, heterocycloalkyl, aryl, and heteroaryl. In some embodiments, the compound of formula (IIIa), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 Ga-OC H3. In some embodiments, the compound of formula (IIIa), or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein n is 1; R 1 In some embodiments, the compound of formula (IIIa) is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 Ga-SO2R 12 In some embodiments, the compound of formula (I IIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 In some embodiments, is a compound of formula (IIIa) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein n is 1 and R 1 Ga-SR 8 Some In an embodiment, a compound of formula (IIIa), or a pharmaceutically acceptable salt, solvate thereof or a stereoisomer wherein n is 1 and R 1 are independently halogens, C 1- 6 alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9Choose one or two from In some embodiments, the aryl group is an aryl group optionally substituted with one or more groups of formula (I). IIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 optionally substituted with one or two groups selected from In some embodiments, the compound of formula (IIIa) is a heteroaryl. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: n is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)NR 8 R 9 a thiazole optionally substituted with one or two groups selected from , pyrazine, pyrimidine, and pyridine. In one embodiment, a compound of formula (IIIa) or a pharmaceutically acceptable salt, solvate or is a stereoisomer where n is 2. In some embodiments, IIIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 2 and each R 1 are independently halogen, -CN, C 1-6 Archi Lu, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR7 , -SO2R 12 , -SF5, -SR 8 , Ant In some embodiments, the aryl is selected from aryl and heteroaryl. IIIa) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 2 and each R 1 are independently halogen, C 1-6 Alkyl, C1 -6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 and-OR 7 Selected from In some embodiments, a compound of formula (IIIa), or a pharmaceutical composition thereof, a commercially acceptable salt, solvate or stereoisomer of 1 are independently halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -NR 5 R 6 , -OR 7 and heteroaryl. is a compound of formula (IIIa) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein n is 2 and each R 1 are independently halogen, C 1-6 Haloalkyl, -NR 5 R 6 , -OR 7 , thiazole, pyrazine, pyrimidine and pyridinium In some embodiments, the compound is selected from the group consisting of: or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein n is 2, and each R 1 are independently halogen, C1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 In some embodiments, In the present invention, a compound of formula (IIIa) or a pharmaceutically acceptable salt, solvate or stereoisomers, wherein n is 2 and each R 1 are independently halogen, C 1-6 Al Kill, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 It is selected from , each R 7 independently, C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and heterocycloalkyl In some embodiments, the aryl group is selected from the group consisting of aryl, ... or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 2 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Hello Lukil, C 3-8 Cycloalkyl and -OR 7 are selected from, and each R 7 became independent, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and heterocycloalkyl In some embodiments, the compound of formula (IIIa) is selected from the group consisting of alkyl, aryl, methyl ... or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: n is 3.

[0083] In some embodiments, a compound of formula (IIIb): [ka] During the ceremony, Each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C1 -6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -C(O)NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and and heteroaryl, wherein the aryl and heteroaryl are optionally independently selected from: and halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 from Substituted with one or two selected groups or two adjacent R 1 But, optional One or two R 11 forming a heterocycloalkyl ring substituted with R 3 But halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -NR 8 R 9 , -C(O)NR 8 R 9 , -NR 8 C(O)R 9 and -NR 9 SO2R 8 Selected from And, R 3aBut halogen, C 1-6 Alkyl and C 1-6 haloalkyl , Each R 5 and R 6 are independent, H, C 1-6 Alkyl and C 3-8 Selected from cycloalkyl Selected or R 5 and R 6 However, together with the nitrogen bonded to them, One or two R's at will 10 forming a heterocycloalkyl substituted with Each R 7 are independent, H, C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and and heteroaryl, wherein the heterocycloalkyl, aryl and heteroaryl are selected from the group consisting of: aryl optionally independently selected from halogen, C 1-6 Alkyl and C 1-6 From haloalkyl substituted with one or two selected groups, Each R 8 and R 9 are independent, H, C 1-6 Alkyl, C 3-8 Cycloalkyl, aryl and selected from aryl and heteroaryl; Each R 10 independently, C 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Haloal Chloride, halogen, oxo, -CN, -C(O)OR 8 , -C(O)R 8 , -C(O)NR 8 R 9 , -SO2R 8 , -NR9 C(O)R 8 and -NR 9 SO2R 8 Selected from the law of nature, Each R 11 are independently halogen and C 1-6 alkyl, Each R 12 independently, C 1-6 Alkyl and C 3-8 cycloalkyl the law of nature, m is 0, 1, 2, 3, 4 or 5; a compound in which q is 0 or 1; or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

[0084] In some embodiments, a compound of Formula (IIIb), or a pharmaceutically acceptable salt thereof, A salt, solvate or stereoisomer of the formula R 3 is a halogen. In some embodiments, a compound of formula (IIIb), or a pharmaceutically acceptable salt thereof: solvates or stereoisomers of the formula 3 is -CN. In an embodiment, the compound of formula (IIIb), or a pharmaceutically acceptable salt, solvate thereof, A compound or stereoisomer of formula R 3 C 1-6 It is an alkyl group. In some embodiments, the compound of Formula (IIIb), or a pharmaceutically acceptable salt thereof, a hydrate or stereoisomer of the formula R 3 is -CH3. In an embodiment, the compound of formula (IIIb), or a pharmaceutically acceptable salt, solvate thereof, A compound or stereoisomer of formula R 3 C 1-6 It is a haloalkyl. In some embodiments, a compound of Formula (IIIb), or a pharmaceutically acceptable salt thereof: , solvates or stereoisomers of the formula 3 is -CF3. In some embodiments, the compound of Formula (IIIb), or a pharmaceutically acceptable salt thereof, a hydrate or stereoisomer of the formula R 3 Ga-NR 8 R 9 It is what it is. In some embodiments, the compound of Formula (IIIb), or a pharmaceutically acceptable salt thereof, a hydrate or stereoisomer of the formula R 3 is -NH2. In an embodiment, the compound of formula (IIIb), or a pharmaceutically acceptable salt, solvate thereof, A compound or stereoisomer of formula R 3 -C(O)NR 8 R 9 It is what it is. In some embodiments, a compound of Formula (IIIb), or a pharmaceutically acceptable salt thereof: , solvates or stereoisomers of the formula 3 is -C(O)NH2 In some embodiments, the compound of formula (IIIb), or a pharmaceutically acceptable salt thereof, a salt, solvate or stereoisomer of the formula 3 Ga-NR 8 C(O)R 9 is In some embodiments, the compound of formula (IIIb), or a pharmaceutically acceptable salt thereof, An acceptable salt, solvate or stereoisomer of 3 -NHC(O)CH 3. In some embodiments, the compound of formula (IIIb) or a compound thereof A pharmaceutically acceptable salt, solvate or stereoisomer of the formula: In some embodiments, the compound of formula (IIIb), or a pharmaceutically acceptable salt thereof, is Possible salts, solvates or stereoisomers of the formula: wherein q is 1. In some embodiments, the compound of Formula (IIIb), or a pharmaceutically acceptable salt thereof, a compound or stereoisomer of formula (I) wherein q is 1 and R 3a is a halogen In some embodiments, the compound of formula (IIIb), or a pharmaceutically acceptable salt thereof, is and possible salts, solvates or stereoisomers thereof, wherein q is 1 and R 3a C 1- In some embodiments, the compound of formula (IIIb) is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein q is 1 and Yes, R 3a C 1-6 It is a haloalkyl.

[0085] In some embodiments, a compound of Formula (IIIb), or a pharmaceutically acceptable salt thereof, A salt, solvate or stereoisomer of the formula wherein m is 0. In an embodiment, a compound of formula (IIIb), or a pharmaceutically acceptable salt, solvate thereof or a stereoisomer wherein m is 1. In some embodiments, , a compound of formula (IIIb), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof isomers, wherein m is 1 and R 1 But halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C1-6 Haloalkyl, C 3-8 Shik alkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and heteroaryl. In some embodiments, the compound of formula (II) Ib) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof where m is 1 and R 1 But halogen, C 1-6 Alkyl, C 1-6 Hello Aruki Lu, C 3-8 Cycloalkyl, -NR 5 R 6 and-OR 7 is selected from In some embodiments, the compound of formula (IIIb), or a pharmaceutically acceptable salt thereof, A salt, solvate or stereoisomer of the formula: 1 But halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 Choose from In some embodiments, the compound of formula (IIIb) or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein m is 1; R 1 is a halogen. In some embodiments, the compound is of formula (IIIb): or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein m is 1 and R 1 is F. In some embodiments, the compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: m is 1 and R 1 In some embodiments, the compound of formula (IIIb) is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 In some embodiments, the compound of formula (I) IIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 C 1-6 Some examples are alkyl groups. In embodiments, the compound of formula (IIIb), or a pharmaceutically acceptable salt or solvate thereof, is or a stereoisomer, wherein m is 1 and R 1 is -CH3. In some embodiments, a compound of formula (IIIb), or a pharmaceutically acceptable salt thereof: solvates or stereoisomers, wherein m is 1 and R 1 Although -C≡CH In some embodiments, the compound of formula (IIIb), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 C 1- 6 alkyl-OR 7 In some embodiments, the compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: m is 1 and R 1 is —CH—O—CH. In some embodiments, , a compound of formula (IIIb), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof isomers, wherein m is 1 and R 1 C 1-6 It is a haloalkyl. In some embodiments, a compound of Formula (IIIb), or a pharmaceutically acceptable salt thereof: , solvates or stereoisomers, wherein m is 1 and R 1 Although it is -CF3 In some embodiments, the compound of formula (IIIb), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 C 3- 8 cycloalkyl. In some embodiments, the compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 Ga-NR 5 R 6 In some embodiments, the compound of formula (II) Ib) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof where m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 But combined with them Optionally, one or two R 10 Heterocyclo substituted with In some embodiments, the compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 But the nitrogen bonded to them together form an unsubstituted heterocycloalkyl. In the form of a compound of formula (IIIb), or a pharmaceutically acceptable salt, solvate or or a stereoisomer thereof, wherein m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 However, together with the nitrogen bonded to them, they independently form C 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Haloalkyl, halogen, oxo, -C(O)NR 8 R 9 ,- SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Choose one or two from R 10 In some embodiments, the heterocycloalkyl group is substituted with . In the form of a compound of formula (IIIb), or a pharmaceutically acceptable salt, solvate or or a stereoisomer thereof, wherein m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 However, together with the nitrogen bonded to them, they independently form C 1-6 Alkyl, C 3-8 Cycloalkyl and -C(O)NR 8 R 9 Choose one or two R 10 Replaced with In some embodiments, the heterocycloalkyl of formula (I) IIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 -OR 7 In some embodiments, is a compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein m is 1 and R 1 -OR 7 and R 7 But C 1-6 Al Kill, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Shik and selected from the group consisting of cycloalkyl, heterocycloalkyl, aryl, and heteroaryl. In some embodiments, the compound of formula (IIIb), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 Ga-OC H3. In some embodiments, the compound of formula (IIIb), or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein m is 1; R 1 In some embodiments, the compound of formula (IIIb) is -OCF3. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 Ga-SO2R 12 In some embodiments, the compound of formula (I IIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 In some embodiments, is a compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein m is 1 and R 1 Ga-SR 8 Some In an embodiment, a compound of formula (IIIb), or a pharmaceutically acceptable salt, solvate thereof or a stereoisomer wherein m is 1 and R1 are independently halogens, C 1- 6 alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 Choose one or two from In some embodiments, the aryl group is an aryl group optionally substituted with one or more groups of formula (I). IIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 optionally substituted with one or two groups selected from In some embodiments, the compound of formula (IIIb) is a heteroaryl. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: m is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)NR 8 R 9 a thiazole optionally substituted with one or two groups selected from , pyrazine, pyrimidine, and pyridine. In one embodiment, a compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or is a stereoisomer where m is 2. In some embodiments, IIIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 2 and each R 1 are independently halogen, -CN, C 1-6 Archi Lu, C 2-6 Alkynyl, C 1-6Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , Ant In some embodiments, the aryl is selected from aryl and heteroaryl. IIIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 2 and each R 1 are independently halogen, C 1-6 Alkyl, C1 -6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 and-OR 7 Selected from In some embodiments, a compound of formula (IIIb), or a pharmaceutical composition thereof, a commercially acceptable salt, solvate or stereoisomer of 1 are independently halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -NR 5 R 6 , -OR 7 and heteroaryl. is a compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein m is 2 and each R 1 are independently halogen, C 1-6 Haloalkyl, -NR 5 R 6 , -OR 7 , thiazole, pyrazine, pyrimidine and pyridinium In some embodiments, the compound is selected from the group consisting of: or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein m is 2, and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 In some embodiments, In the present invention, a compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or stereoisomers, wherein m is 2 and each R 1 are independently halogen, C 1-6 Al Kill, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 It is selected from , each R 7 independently, C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and heterocycloalkyl In some embodiments, the aryl group is selected from the group consisting of aryl, ... or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 2 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Hello Lukil, C 3-8 Cycloalkyl and -OR 7 are selected from, and each R 7 became independent, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and heterocycloalkyl In some embodiments, the compound of formula (IIIb) is selected from the group consisting of alkyl, aryl, methyl ... or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: In some embodiments, the compound of formula (IIIb) or wherein m is 3 and , each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C1 -6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 aryl and heteroaryl In some embodiments, a compound of formula (IIIb), or wherein m is 3 and , each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 S Chloroalkyl, -NR 5 R 6 and-OR 7 The following are selected from several In embodiments, the compound of formula (IIIb), or a pharmaceutically acceptable salt or solvate thereof, is or a stereoisomer in which m is 3 and each R 1 are independently halogen, C 1-6 Al Kill, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7Selected from In some embodiments, the compound of formula (IIIb), or a pharmaceutically acceptable salt thereof, An acceptable salt, solvate or stereoisomer of 1 German Standing, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 cycloalkyl and-OR 7 are selected from, and each R 7 independently, C 1-6 Alkyl, C 1-6 Al Kill-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, hetero It is selected from cycloalkyl, aryl and heteroaryl. In an embodiment, the compound of formula (IIIb), or a pharmaceutically acceptable salt, solvate thereof, wherein m is 3 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 Choose from Each R 7 independently, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 S It is selected from cycloalkyl and heterocycloalkyl.

[0086] In some embodiments, a compound of Formula (IIIb), or a pharmaceutically acceptable salt thereof, A salt, solvate or stereoisomer of the formula wherein n is 0. In an embodiment, a compound of formula (IIIb), or a pharmaceutically acceptable salt, solvate thereof or a stereoisomer wherein n is 1. In some embodiments, , a compound of formula (IIIb), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof isomers, wherein n is 1 and R 1 But halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Shik alkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and heteroaryl. In some embodiments, the compound of formula (II) Ib) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof where n is 1 and R 1 But halogen, C 1-6 Alkyl, C 1-6 Hello Aruki Lu, C 3-8 Cycloalkyl, -NR 5 R 6 and-OR 7 is selected from In some embodiments, the compound of formula (IIIb), or a pharmaceutically acceptable salt thereof, A salt, solvate or stereoisomer of the formula: 1 But halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 Choose from In some embodiments, the compound of formula (IIIb) or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein n is 1; R 1 is a halogen. In some embodiments, the compound is of formula (IIIb): or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein n is 1 and R 1 is F. In some embodiments, the compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: n is 1 and R 1 In some embodiments, the compound of formula (IIIb) is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 In some embodiments, the compound of formula (I) IIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 C 1-6 Some examples are alkyl groups. In embodiments, the compound of formula (IIIb), or a pharmaceutically acceptable salt or solvate thereof, is or a stereoisomer, wherein n is 1 and R 1 is -CH3. In some embodiments, a compound of formula (IIIb), or a pharmaceutically acceptable salt thereof: solvates or stereoisomers, wherein n is 1 and R 1 Although -C≡CH In some embodiments, the compound of formula (IIIb), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 C 1- 6 alkyl-OR 7 In some embodiments, the compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: n is 1 and R 1 is —CH—O—CH. In some embodiments, , a compound of formula (IIIb), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof isomers, wherein n is 1 and R 1 C 1-6 It is a haloalkyl. In some embodiments, a compound of Formula (IIIb), or a pharmaceutically acceptable salt thereof: , solvates or stereoisomers, wherein n is 1 and R 1 Although it is -CF3 In some embodiments, the compound of formula (IIIb), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 C 3- 8 cycloalkyl. In some embodiments, the compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 Ga-NR 5 R 6 In some embodiments, the compound of formula (II) Ib) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof where n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 But combined with them Optionally, one or two R 10 Heterocyclo substituted with In some embodiments, the compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 But the nitrogen bonded to them together form an unsubstituted heterocycloalkyl. In the form of a compound of formula (IIIb), or a pharmaceutically acceptable salt, solvate or or a stereoisomer thereof, wherein n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 However, together with the nitrogen bonded to them, they independently form C 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Haloalkyl, halogen, oxo, -C(O)NR 8 R 9 ,- SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Choose one or two from R 10 In some embodiments, the heterocycloalkyl group is substituted with . In the form of a compound of formula (IIIb), or a pharmaceutically acceptable salt, solvate or or a stereoisomer thereof, wherein n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 However, together with the nitrogen bonded to them, they independently form C 1-6 Alkyl, C 3-8 Cycloalkyl and -C(O)NR 8 R9 Choose one or two R 10 Replaced with In some embodiments, the heterocycloalkyl of formula (I) IIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 -OR 7 In some embodiments, is a compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein n is 1 and R 1 -OR 7 and R 7 But C 1-6 Al Kill, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Shik and selected from the group consisting of cycloalkyl, heterocycloalkyl, aryl, and heteroaryl. In some embodiments, the compound of formula (IIIb), or a pharmaceutically acceptable salt thereof, and an acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 Ga-OC H3. In some embodiments, the compound of formula (IIIb), or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein n is 1; R 1 In some embodiments, the compound of formula (IIIb) is -OCF3. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 Ga-SO2R 12 In some embodiments, the compound of formula (I IIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 In some embodiments, is a compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein n is 1 and R 1 Ga-SR 8 Some In an embodiment, a compound of formula (IIIb), or a pharmaceutically acceptable salt, solvate thereof or a stereoisomer wherein n is 1 and R 1 are independently halogens, C 1- 6 alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 Choose one or two from In some embodiments, the aryl group is an aryl group optionally substituted with one or more groups of formula (I). IIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 optionally substituted with one or two groups selected from In some embodiments, the compound of formula (IIIb) is a heteroaryl. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: n is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and -C(O)NR 8 R 9 a thiazole optionally substituted with one or two groups selected from , pyrazine, pyrimidine, and pyridine. In one embodiment, a compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or is a stereoisomer where n is 2. In some embodiments, IIIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 2 and each R 1 are independently halogen, -CN, C 1-6 Archi Lu, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , Ant In some embodiments, the aryl is selected from aryl and heteroaryl. IIIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 2 and each R 1 are independently halogen, C 1-6 Alkyl, C1 -6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 and-OR 7 Selected from In some embodiments, a compound of formula (IIIb), or a pharmaceutical composition thereof, a commercially acceptable salt, solvate or stereoisomer of 1 are independently halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -NR 5 R 6 , -OR 7and heteroaryl. is a compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein n is 2 and each R 1 are independently halogen, C 1-6 Haloalkyl, -NR 5 R 6 , -OR 7 , thiazole, pyrazine, pyrimidine and pyridinium In some embodiments, the compound is selected from the group consisting of: or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein n is 2, and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 In some embodiments, In the present invention, a compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or stereoisomers, wherein n is 2 and each R 1 are independently halogen, C 1-6 Al Kill, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 It is selected from , each R 7 independently, C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and heterocycloalkyl In some embodiments, the aryl group is selected from the group consisting of aryl, ... or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 2 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Hello Lukil, C 3-8 Cycloalkyl and -OR 7 are selected from, and each R 7 became independent, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and heterocycloalkyl In some embodiments, the compound of formula (IIIb) is selected from the group consisting of alkyl, aryl, methyl ... or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: n is 3.

[0087] In some embodiments, a compound of formula (IV): [ka] During the ceremony, Each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C1 -6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -C(O)NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and and heteroaryl, wherein the aryl and heteroaryl are optionally independently selected from: and halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 from Substituted with one or two selected groups or two adjacent R 1 But, optional One or two R 11 forming a heterocycloalkyl ring substituted with R 3 But halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -NR 8 R 9 , -C(O)NR 8 R 9 , -NR 8 C(O)R 9 and -NR 9 SO2R 8 Selected from And, R 3a But halogen, C 1-6 Alkyl and C 1-6 haloalkyl , Each R 5 and R 6 are independent, H, C 1-6 Alkyl and C 3-8 Selected from cycloalkyl Selected or R 5 and R 6 However, together with the nitrogen bonded to them, One or two R's at will 10 forming a heterocycloalkyl substituted with Each R 7 are independent, H, C 1-6 Alkyl, C 1-6 Alkyl-OC 1-6 Alkyl , C 1-6 Haloalkyl, C 3-8 Cycloalkyl, heterocycloalkyl, aryl and and heteroaryl, wherein the heterocycloalkyl, aryl and heteroaryl are selected from the group consisting of: aryl optionally independently selected from halogen, C 1-6 Alkyl and C 1-6 From haloalkyl substituted with one or two selected groups, Each R 8 and R 9 are independent, H, C 1-6 Alkyl, C 3-8 Cycloalkyl, aryl and selected from aryl and heteroaryl; Each R 10 independently, C 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Haloal Chloride, halogen, oxo, -CN, -C(O)OR 8 , -C(O)R 8 , -C(O)NR 8 R 9 , -SO2R 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Selected from the law of nature, Each R 11 are independently halogen and C 1-6 alkyl, Each R 12 independently, C 1-6 Alkyl and C 3-8 cycloalkyl the law of nature, m is 0, 1, 2, 3, 4 or 5; a compound in which q is 0 or 1; or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

[0088] In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt thereof: solvates or stereoisomers of the formula 3 are halogens. In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt or solvate thereof, or a stereoisomer, wherein R 3is -CN. In this embodiment, a compound of formula (IV) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein R 3 C 1-6 Some embodiments are alkyl. In this embodiment, a compound of formula (IV) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein R 3 is -CH3. In some embodiments, A compound of formula (IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein R 3 C 1-6 In some embodiments, the alkyl group is haloalkyl. is a compound of formula (IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof isomer, wherein R 3 In some embodiments, the formula ( IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof In the formula, R 3 Ga-NR 8 R 9 In some embodiments, the compound of formula (IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, , where R 3 In some embodiments, the compound of formula (IV) is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: R 3 -C(O)NR 8 R 9 In some embodiments, the compound of formula (IV) A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula Medium, R 3In some embodiments, the compound of formula (IV) is -C(O)NH2. A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula Medium, R 3 Ga-NR 8 C(O)R 9 In some embodiments, the compound of formula (IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, , where R 3 In some embodiments, the formula ( IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein q is 0. In some embodiments, the compound of formula (IV): or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein q is 1. In some embodiments, the compound of formula (IV), or a pharmaceutical composition thereof, a commercially acceptable salt, solvate or stereoisomer of the compound of formula (I) wherein q is 1 and R 3a is halogen. In some embodiments, the compound of formula (IV), or wherein q is 1 and , R 3a C 1-6 In some embodiments, the group represented by formula (IV) is alkyl. A compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, of the formula In this case, q is 1 and R 3a C 1-6 It is a haloalkyl.

[0089] In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt thereof: solvates or stereoisomers, wherein m is 0. In the form of a compound of formula (IV), or a pharmaceutically acceptable salt, solvate or In some embodiments, the compound of formula (I) is a stereoisomer wherein m is 1. V) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 But halogen, -CN, C 1-6 Alkyl, C 2-6 Al Kinir, C. 1-6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and heteroaryl In some embodiments, the compound of formula (IV) is selected from: or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein m is 1 and R 1 But halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Shik alkyl, -NR 5 R 6 and-OR 7 Some implementations are selected from In the form of a compound of formula (IV), or a pharmaceutically acceptable salt, solvate or stereoisomers, wherein m is 1 and R 1 But halogen, C 1-6 Alkyl, C1 -6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 is selected from In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt thereof: solvates or stereoisomers, wherein m is 1 and R 1 is a halogen In some embodiments, the compound of formula (IV), or a pharmaceutically acceptable salt thereof, a salt, solvate or stereoisomer of the formula: 1 is F In some embodiments, the compound of formula (IV), or a pharmaceutically acceptable salt thereof, a salt, solvate or stereoisomer of the formula: 1 Although Cl In some embodiments, the compound of formula (IV), or a pharmaceutically acceptable salt thereof, and a suitable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 is -CN In some embodiments, the compound of formula (IV) or a pharmaceutically acceptable salt thereof is and an acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 C 1- In some embodiments, the compound of formula (IV) or A pharmaceutically acceptable salt, solvate or stereoisomer of the formula: , R 1 In some embodiments, the compound of formula (IV) or or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 In some embodiments, the compound of formula (IV) is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein , m is 1, and R 1 C 1-6 Alkyl-OR7 Some embodiments are In this embodiment, a compound of formula (IV) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein m is 1 and R 1 is -CH2-O-CH3 In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt thereof: solvates or stereoisomers, wherein m is 1 and R 1 C 1-6 Hello Aruki In some embodiments, the compound of formula (IV), or a pharmaceutical composition thereof, a commercially acceptable salt, solvate or stereoisomer of the compound of formula (I) wherein m is 1 and R 1 but In some embodiments, the compound of formula (IV) or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein m is 1; R 1 C 3-8 In some embodiments, the aryl group of formula (IV) is a cycloalkyl group. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 Ga-NR 5 R 6 In some embodiments, A compound of formula (IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 But with them Optionally, one or two R 10 Heterocyclic substituted with In some embodiments, the compound of formula (IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 But the nitrogen bonded to them together form an unsubstituted heterocycloalkyl. In the form of a compound of formula (IV), or a pharmaceutically acceptable salt, solvate or stereoisomers, wherein m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 but , together with the nitrogen bonded to them, independently C 1-6 Alkyl, C 3-8 Shik Roalkyl, C 1-6 Haloalkyl, halogen, oxo, -C(O)NR 8 R 9 , -SO 2nd Round 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Choose one or two R 10 In some embodiments, the heterocycloalkyl is substituted with In the present invention, a compound of formula (IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof is isomers, wherein m is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 But, Together with the nitrogen bonded to them, they independently form C 1-6 Alkyl, C 3-8 Cycloa -C(O)NR 8 R9 Choose one or two R 10 Hete replaced by In some embodiments, the compound of formula (IV) forms a cycloalkyl. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein , m is 1, and R 1 -OR 7 In some embodiments, the compound of formula (IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, , where m is 1 and R 1 -OR 7 and R 7 But C 1-6 Alkyl, C 1-6 a Rukill-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, Heteroalkyl and aryl and heteroaryl. In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt or solvate thereof, or a stereoisomer wherein m is 1 and R 1 is -OCH3 In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt thereof: solvates or stereoisomers, wherein m is 1 and R 1 Although it is -OCF3 In some embodiments, the compound of formula (IV), or a pharmaceutically acceptable salt thereof, and a suitable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 Ga-SO2R 12 In some embodiments, the compound of formula (IV), or a pharmaceutical thereof, a physiologically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R1 In some embodiments, the compound of formula (IV) or A pharmaceutically acceptable salt, solvate or stereoisomer of the formula: , R 1 Ga-SR 8 In some embodiments, the compound of formula (IV) or or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and -C (O)NR 8 R 9 and aryl optionally substituted with one or two groups selected from In some embodiments, the compound of formula (IV), or a pharmaceutically acceptable salt thereof, and a suitable salt, solvate or stereoisomer thereof, wherein m is 1 and R 1 But independently Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 Choose from Heteroaryl is optionally substituted with one or two groups as defined above. In this embodiment, the compound of formula (IV), or a pharmaceutically acceptable salt or solvate thereof, or a stereoisomer, wherein m is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 Choose one or two from and selected from thiazole, pyrazine, pyrimidine and pyridine optionally substituted with a group In some embodiments, the compound of formula (IV) or its pharmaceutically acceptable salts is Acceptable salts, solvates or stereoisomers are those in which m is 2. In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt thereof, a solvate or stereoisomer, wherein m is 2 and each R 1 are independently halogen , -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1- 6 haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 aryl and heteroaryl. In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt, solvate thereof, wherein m is 2 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 and- OR 7 In some embodiments, the compound is selected from the group consisting of: or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein m is 2, and each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 1-6 Haloal Kill, -NR 5 R 6 , -OR 7 and heteroaryl. In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt, solvate thereof, wherein m is 2 and each R 1 are independently halogen, C 1-6 Haloalkyl, -NR 5 R 6 , -OR 7 , thiazoles, pyrazines, pyrimidines and pyridine In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt thereof, , solvates or stereoisomers wherein m is 2 and each R 1 became independent and became Halo Gen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 In some embodiments, the compound is selected from the group consisting of: a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein m is 2; Each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 are selected from, and each R 7 independently, C 1-6 Alkyl , C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloa alkyl, heterocycloalkyl, aryl, and heteroaryl; In some embodiments, the compound of formula (IV), or a pharmaceutically acceptable salt thereof, A salt, solvate or stereoisomer of the formula: 1 became independent and Rogen, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 are selected from, and each R 7 independently, C 1-6 Alkyl, C 1-6 haloalkyl, C 3-8 It is selected from cycloalkyl and heterocycloalkyl. In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt, solvate thereof, In some embodiments, m is 3. is a compound of formula (IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 3 and each R 1 are independently halogen, -CN, C 1-6 a Lukil, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1-6 Haloalkyl, C3 -8 Cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , In some embodiments, the aryl group is selected from aryl and heteroaryl. A compound of formula (IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein m is 3 and each R 1 are independently halogen, C 1-6 Alkyl, C1 -6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 and-OR 7 Selected from In some embodiments, the compound of formula (IV) or its pharmaceutically acceptable salts is An acceptable salt, solvate or stereoisomer wherein m is 3 and each R 1 became independent , halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and - OR 7 In some embodiments, the compound is selected from the group consisting of: or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein m is 3, and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 are selected from, and each R 7 independently, C 1-6 a Lukil, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 S is selected from cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; In some embodiments, the compound of formula (IV), or a pharmaceutically acceptable salt thereof, and a possible salt, solvate or stereoisomer thereof, wherein m is 3 and each R 1 became independent Halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 are selected from, and each R 7 independently, C 1-6 Alkyl, C 1-6 Haloal Kill, C 3-8 is selected from cycloalkyl and heterocycloalkyl .

[0090] In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt thereof: solvates or stereoisomers, wherein n is 0. In the form of a compound of formula (IV), or a pharmaceutically acceptable salt, solvate or In some embodiments, the compound of formula (I) is a stereoisomer wherein n is 1. V) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 But halogen, -CN, C 1-6 Alkyl, C 2-6 Al Kinir, C. 1-6 Alkyl-OR 7 , C 1-6 Haloalkyl, C 3-8 cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 , aryl and heteroaryl In some embodiments, the compound of formula (IV) is selected from: or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein n is 1 and R 1 But halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Shik alkyl, -NR 5 R 6 and-OR 7 Some implementations are selected from In the form of a compound of formula (IV), or a pharmaceutically acceptable salt, solvate or A stereoisomer wherein n is 1 and R 1 But halogen, C1-6 Alkyl, C1 -6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 is selected from In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt thereof: solvates or stereoisomers, wherein n is 1 and R 1 is a halogen In some embodiments, the compound of formula (IV), or a pharmaceutically acceptable salt thereof, a salt, solvate or stereoisomer of the formula: 1 is F In some embodiments, the compound of formula (IV), or a pharmaceutically acceptable salt thereof, a salt, solvate or stereoisomer of the formula: 1 Although Cl In some embodiments, the compound of formula (IV), or a pharmaceutically acceptable salt thereof, and a suitable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 is -CN In some embodiments, the compound of formula (IV) or a pharmaceutically acceptable salt thereof is and an acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 C 1- In some embodiments, the compound of formula (IV) or A pharmaceutically acceptable salt, solvate or stereoisomer of the formula: , R 1 In some embodiments, the compound of formula (IV) or or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 In some embodiments, the compound of formula (IV) is or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein , n is 1, and R 1 C 1-6 Alkyl-OR 7 Some embodiments are In this embodiment, a compound of formula (IV) or a pharmaceutically acceptable salt, solvate or isoform thereof isomers, wherein n is 1 and R 1 is -CH2-O-CH3 In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt thereof: solvates or stereoisomers, wherein n is 1 and R 1 C 1-6 Hello Aruki In some embodiments, the compound of formula (IV), or a pharmaceutical composition thereof, a commercially acceptable salt, solvate or stereoisomer of the compound of formula (I) wherein n is 1 and R 1 but In some embodiments, the compound of formula (IV) or A pharmaceutically acceptable salt, solvate or stereoisomer of the compound of formula (I), wherein n is 1; R 1 C 3-8 In some embodiments, the aryl group of formula (IV) is a cycloalkyl group. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 Ga-NR 5 R 6 In some embodiments, A compound of formula (IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof wherein n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 But with them Optionally, one or two R 10 Heterocyclic substituted with In some embodiments, the compound of formula (IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 But the nitrogen bonded to them together form an unsubstituted heterocycloalkyl. In the form of a compound of formula (IV), or a pharmaceutically acceptable salt, solvate or A stereoisomer wherein n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6 but , together with the nitrogen bonded to them, independently C 1-6 Alkyl, C 3-8 Shik Roalkyl, C 1-6 Haloalkyl, halogen, oxo, -C(O)NR 8 R 9 , -SO 2nd Round 8 , -NR 9 C(O)R 8 and -NR 9 SO2R 8 Choose one or two R 10 In some embodiments, the heterocycloalkyl is substituted with In the present invention, a compound of formula (IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof is isomers, wherein n is 1 and R 1 Ga-NR 5 R 6 and R 5 and R 6But, Together with the nitrogen bonded to them, they independently form C 1-6 Alkyl, C 3-8 Cycloa -C(O)NR 8 R 9 Choose one or two R 10 Hete replaced by In some embodiments, the compound of formula (IV) forms a cycloalkyl. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein , n is 1, and R 1 -OR 7 In some embodiments, the compound of formula (IV) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, , where n is 1 and R 1 -OR 7 and R 7 But C 1-6 Alkyl, C 1-6 a Rukill-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, Heteroalkyl and aryl and heteroaryl. In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt or solvate thereof, or a stereoisomer wherein n is 1 and R 1 is -OCH3 In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt thereof: solvates or stereoisomers, wherein n is 1 and R 1 Although it is -OCF3 In some embodiments, the compound of formula (IV), or a pharmaceutically acceptable salt thereof, and a suitable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 Ga-SO2R 12 In some embodiments, the compound of formula (IV), or a pharmaceutical thereof, a physiologically acceptable salt, solvate or stereoisomer of 1 In some embodiments, the compound of formula (IV) or A pharmaceutically acceptable salt, solvate or stereoisomer of the formula: , R 1 Ga-SR 8 In some embodiments, the compound of formula (IV) or or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and -C (O)NR 8 R 9 and aryl optionally substituted with one or two groups selected from In some embodiments, the compound of formula (IV), or a pharmaceutically acceptable salt thereof, and a suitable salt, solvate or stereoisomer thereof, wherein n is 1 and R 1 But independently Halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9 Choose from Heteroaryl is optionally substituted with one or two groups as defined above. In this embodiment, the compound of formula (IV), or a pharmaceutically acceptable salt or solvate thereof, or a stereoisomer, wherein n is 1 and R 1 are independently halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and —C(O)NR 8 R 9Choose one or two from and selected from thiazole, pyrazine, pyrimidine and pyridine optionally substituted with a group In some embodiments, the compound of formula (IV) or its pharmaceutically acceptable salts is Acceptable salts, solvates or stereoisomers are those in which n is 2. In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt thereof, a solvate or stereoisomer, wherein n is 2 and each R 1 are independently halogen , -CN, C 1-6 Alkyl, C 2-6 Alkynyl, C 1-6 Alkyl-OR 7 , C 1- 6 haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 , -OR 7 , -SO2R 12 , -SF5, -SR 8 aryl and heteroaryl. In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt, solvate thereof, wherein n is 2 and each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl, -NR 5 R 6 and- OR 7 In some embodiments, the compound is selected from the group consisting of: or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein n is 2, and each R 1 are independently halogen, -CN, C 1-6 Alkyl, C 1-6 Haloal Kill, -NR 5 R 6 , -OR 7 and heteroaryl. In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt, solvate thereof, wherein n is 2 and each R 1 are independently halogen, C 1-6 Haloalkyl, -NR 5 R 6 , -OR 7 , thiazoles, pyrazines, pyrimidines and pyridine In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt thereof, , solvate or stereoisomer, wherein n is 2 and each R 1 became independent and became Halo Gen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 In some embodiments, the compound is selected from the group consisting of: a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein n is 2; Each R 1 are independently halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 are selected from, and each R 7 independently, C 1-6 Alkyl , C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloa alkyl, heterocycloalkyl, aryl, and heteroaryl; In some embodiments, the compound of formula (IV), or a pharmaceutically acceptable salt thereof, A salt, solvate or stereoisomer of the formula: 1 became independent and Rogen, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl and -OR 7 are selected from, and each R 7 independently, C 1-6 Alkyl, C 1-6 haloalkyl, C 3-8 It is selected from cycloalkyl and heterocycloalkyl. In some embodiments, a compound of formula (IV), or a pharmaceutically acceptable salt, solvate thereof, A compound or stereoisomer of the formula wherein n is 3.

[0091] Additionally, the embodiments presented herein may include one or more of the specific embodiments presented above. Includes combinations of the above.

[0092] In some embodiments, the compounds disclosed herein are any of Examples 1-86. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof. be.

[0093] Preparation of compounds The compounds used in the reactions described herein are commercially available chemicals and / or chemical Starting from compounds described in the literature, they are prepared according to known organic synthesis techniques. The chemicals are manufactured by Acros Organics (Geel, Belgium), Ald rich Chemical(Milwaukee,WI,Sigma Chemica l and Fluka), Apin Chemicals Ltd. (Milton Park, UK), Ark Pharm, Inc. (Libertyville, IL) , Avocado Research (Lancashire, U.K.), BDH I nc. (Toronto, Canada), Bionet (Cornwall, U.K. ), Chemservice Inc. (West Chester, PA), Comb i - blocks (San Diego, CA), Crescent Chemical Co. (Hauppauge, NY), eMolecules (San Diego, CA), Fisher Scientific Co. (Pittsburgh, PA) , Fisons Chemicals (Leicestershire, UK), Fro ntier Scientific (Logan, UT), ICN Biomedica ls, Inc. (Costa Mesa, CA), Key Organics (Corn wall, U.K.), Lancaster Synthesis (Windham, N H), Matrix Scientific, (Columbia, SC), Maybr idge Chemical Co. Ltd. (Cornwall, U.K.), Par ish Chemical Co. (Orem, UT), Pfaltz & Bauer , Inc. (Waterbury, CN), Polyorganix (Houston, TX), Pierce Chemical Co. (Rockford, IL), Rie del de Haen AG (Hanover, Germany), Ryan Sci entific, Inc. (Mount Pleasant, SC), Spectrum Chemicals (Gardena, CA), Sundia Meditech, ( Shanghai, China), TCI America (Portland, OR) , Trans World Chemicals, Inc. (Rockville, MD) ) and WuXi (Shanghai, China) .

[0094] The synthesis of reaction substrates useful for preparing the compounds described herein is detailed. Suitable reference books and treatises which describe this preparation For example, "Synthetic Organic Chemistry", hn Wiley & Sons, Inc., New York, SRSandle r et al., “Organic Functional Group Prepa rations,” 2nd Ed., Academic Press, New York. ,1983,HOHouse,“Modern Synthetic Reacti ons”, 2nd Ed., WABenjamin, Inc. Menlo Park ,Calif.1972, T.L.Gilchrist,“Heterocyclic Chemistry”,2nd Ed.,John Wiley & Sons,New York, 1992, J. March, “Advanced Organic Che mistry:Reactions, Mechanisms and Structure e”,4th Ed.,Wiley Interscience,New York,1 992. For the synthesis of reaction substrates useful for the preparation of the compounds described herein, Further articles detailing this preparation or refer to papers describing it are available. Suitable reference and technical books include, for example, Fuhrhop, J. and Penzl in G. “Organic Synthesis: Concepts, Methods ,Starting Materials”,Second,Revised and Enlarged Edition(1994)John Wiley & Sons ISBN:3-527-29074-5, Hoffman, RV “Organic Chemistry,An Intermediate Text”(1996)Oxf ord University Press, ISBN 0-19-509618-5, Larock,RC “Comprehensive Organic Transf. ormations:A Guide to Functional Group Pr eparations”2nd Edition(1999)Wiley-VCH,IS BN:0-471-19031-4, March, J. “Advanced Organ ic Chemistry:Reactions,Mechanisms,and St ructure”4th Edition(1992)John Wiley & So ns,ISBN:0-471-60180-2, Otera, J. (editor) “M Carbonyl Chemistry”(2000)Wiley-VCH ,ISBN:3-527-29871-1, Patai, S. “Patai's 199 2 Guide to the Chemistry of Functional G roups”(1992)Interscience ISBN:0-471-9302 2-9, Solomons,TWG “Organic Chemistry”7t h Edition(2000)John Wiley & Sons,ISBN:0- 471-19095-0, Stowell, JC, “Intermediate O rganic Chemistry”2nd Edition(1993)Wiley- Interscience,ISBN:0-471-57456-2, “Industr ial Organic Chemicals:Starting Materials and Intermediates:An Ullmann's Encyclop edia”(1999)John Wiley & Sons,ISBN:3-527- 29645-X,in 8 volumes, “Organic Reactions” (1942-2000)John Wiley & Sons,in over 55 volumes and "Chemistry of Functional Groups" ”John Wiley & Sons, in 73 volumes.

[0095] Specific and similar reaction substrates are also listed in Chemical Abstracts Ser. Vice of the American Chemical Society These substances are identified through an index of known chemicals, which is the basis for most public Available in community and university libraries and online databases (further For more information, see the American Chemical Society (Washington (You can contact us at gton, DC). Chemicals not listed are randomly prepared by custom chemical synthesis companies and are not commonly available. Many of the major chemical suppliers (e.g., those listed above) offer custom synthesis services. References for the preparation and selection of pharmaceutical salts of the compounds described herein is a PHStahl & C.G.Wermuth "Handbook of Ph armaceutical Salts”,Verlag Helvetica Chi mica Acta, Zurich, 2002.

[0096] Further forms of the compounds disclosed herein Isomers Additionally, in some embodiments, the compounds described herein may be present in the form of geometric isomers and In some embodiments, the compounds described herein are present as one or more The compounds shown herein include all cis isomers, trans isomers, Su isomers, syn isomers, anti isomers, entgegen (E) isomers and zusammen (Z ) isomers, as well as their corresponding mixtures. In some situations, compounds The compounds described herein may contain tautomers, such as tautomers, of the formula (I) and tautomers described herein. All possible tautomers of the formula shown are included. The compounds described herein have one or more chiral centers, and each chiral center may have the R configuration. or S configuration. The compounds described herein may be in any diastereomeric form. This includes mers, enantiomers, and epimers, as well as their corresponding mixtures. In further embodiments of the compounds and methods provided herein, Applications include enantiomers and / or derivatives resulting from a single preparation step, mixing or interconversion. Mixtures of diastereomers are useful. In some embodiments, the compounds described herein The compounds can be optically isolated by resolution of the racemic mixture by chiral chromatography. In some embodiments, the compounds described herein are prepared as pure enantiomers. The compound can be prepared by reacting a racemic mixture of the compound with an optically active resolving agent to obtain a pair of Diastereomeric compounds are formed, the diastereomers are separated, and optically pure enes are obtained. Some are prepared as their individual stereoisomers by recovering the enantiomers. In embodiments, dissociable complexes are preferred (e.g., crystalline diastereomeric salts). In some embodiments, diastereomers may have distinct physical properties (e.g., melting points, boiling points, solvents, etc.). In some embodiments, the molecules have different properties (e.g., decomposition ability, reactivity, etc.), and these differences are utilized to separate them. The diastereomers can be separated by chiral chromatography or, preferably, by solubility In some embodiments, the separation is then performed using a separation / splitting technique based on differences in By any practical means that does not cause racemization, the optically pure The enantiomers are recovered.

[0097] labeled compound In some embodiments, the compounds described herein may be used in combination with their isotopically labeled forms. In some embodiments, the methods disclosed herein include The present invention also includes methods for treating diseases by administering isotopically labeled compounds. In some embodiments, the methods disclosed herein include incorporating such isotopically labeled compounds into pharmaceutical compositions. This includes methods of treating diseases by administering them as pharmaceutical compositions. In some embodiments, the compounds disclosed herein include one or more atoms that are typically Substitution of atoms with atomic masses or mass numbers different from those found in nature Isotopically labeled compounds that are identical to the compounds shown herein except for the substitutions. Examples of isotopes that may be incorporated into the compounds described herein include: 2 H, 3 Isotopes of hydrogen such as H 13 C. 14 isotopes of carbon, such as C, l5 Like N isotopes of nitrogen, 18 O. 17 isotopes of oxygen, such as O 31 P, 32 P like phosphorus position, 35 sulfur isotopes such as S, 18 isotopes of fluorine, such as F, and 36 Cl's The compounds described herein and their pharmaceutical uses include isotopes of chlorine such as: Acceptable salts, esters, solvates, hydrates or derivatives of the above, including isotopic and / or or other isotopes of other atoms are within the scope of the present invention. Recognition compounds, e.g. 3 H and 14 Compounds containing radioisotopes such as C are drugs It is useful in drug and / or substrate tissue distribution assays. tium, i.e. 3 H and carbon-14, i.e. 14 The C isotope is particularly preferred. Furthermore, deuterium, i.e. 2 Substitution with heavy isotopes such as H can improve metabolic stability, e.g. These compounds may offer particular therapeutic advantages due to their increased in vivo half-life or reduced dosage requirements. In some embodiments, the isotopically labeled compound, its pharmaceutically acceptable salt, The esters, solvates, hydrates or derivatives are prepared by any suitable method.

[0098] In some embodiments, the compounds described herein are labeled by other means. These include chromophoric moieties, fluorescent moieties, bioluminescent labels, or chemiluminescent labels. Examples of uses include, but are not limited to, the use of

[0099] Pharmaceutically acceptable salts In some embodiments, the compounds described herein are In some embodiments, the methods disclosed herein include: Methods of treating diseases by administering such pharmaceutically acceptable salts are also included. In some embodiments, the methods disclosed herein include administering to a subject a pharmaceutical and methods of treating diseases by administering a physiologically acceptable salt thereof as a pharmaceutical composition. can be.

[0100] In some embodiments, the compounds described herein may contain an acidic or basic group. Since it has a structure of 1,000,000, it reacts with many inorganic or organic bases and inorganic or organic acids. In some embodiments, these salts are The compounds described herein may be prepared in situ during final isolation and purification. or by separately reacting the purified compound in free form with a suitable acid or base to produce the desired product. and isolating the resulting salt.

[0101] solvate In some embodiments, the compounds described herein exist as solvates. In some embodiments, administering such a solvate can be used to treat a disease. Further described herein are methods for incorporating such solvates into pharmaceutical compositions. This is a method of treating a disease by administering it as a substance.

[0102] Solvates contain either stoichiometric or non-stoichiometric amounts of solvent and may contain some In embodiments, the process is crystallized in a pharmaceutically acceptable solvent such as water, ethanol, etc. When the solvent is water, a hydrate is formed, and when the solvent is alcohol, In some cases, alcoholates are formed. Solvates of the compounds described herein are conveniently prepared or formed during the processes described herein. As an example, hydrates of the compounds described herein can be conveniently prepared using organic solvents. It is prepared by recrystallization from an aqueous / organic solvent mixture using this organic solvent. Examples include, but are not limited to, dioxane, tetrahydrofuran, or methanol. In addition, the compounds provided herein may exist in unsolvated and solvated forms. In general, the solvated forms are equivalent to unsolvated forms for the purposes of the compounds and methods provided herein. It is considered to be equivalent to the above.

[0103] Prodrug In some embodiments, the compounds described herein exist in prodrug form. Further described herein is the administration of such prodrugs. Also described herein is a method for treating a disease by This method involves administering a prodrug of the compound as a pharmaceutical composition to treat a disease.

[0104] In some embodiments, the prodrug contains one amino acid residue, or two or more ( For example, a polypeptide chain of 2, 3, or 4 amino acid residues is The free amino, hydroxy or carboxylic acid groups of the compound being treated are linked to an amide bond or an ester bond. It contains compounds covalently linked by ester bonds. There are 20 amino acid residues. Natural amino acids include, but are not limited to, 4-hydroxyproline, hydroxypropyl Roxylysine, desmosine, isodesmosine, 3-methylhistidine, norvaline, β- Alanine, gamma-aminobutyric acid, citrulline, homocysteine, homoserine, ornithine and In another embodiment, the prodrug includes one nucleic acid residue. a group, or an oligonucleotide of two or more (e.g., two, three, or four) nucleic acid residues The present invention also includes compounds in which a hydroxyl group is covalently bonded to a compound described herein.

[0105] Pharmaceutically acceptable prodrugs of the compounds described herein include esophageal steroids, steroids, steroid hormone ... Ternates, carbonates, thiocarbonates, N-acyl derivatives, N-acyloxyalkyl Derivatives, quaternary derivatives of tertiary amines, N-Mannich bases, Schiff bases, amino acid conjugates Also included are phosphate esters, metal salts and sulfonate esters. In some embodiments, the free amino, amido, hydroxy or carboxy groups Compounds with a carboxylic acid group have been converted into prodrugs. For example, are derivatized as amides or alkyl esters. In certain cases, these All of the prodrug moieties of the formula (I) have incorporated therein a group, which includes an ether functional group. , amine functional groups and carboxylic acid functional groups.

[0106] Hydroxyprodrugs include Advanced Drug Delivery Reagents. As reviewed in [views 1996, 19, 115], acyloxyalkyl ( For example, acyloxymethyl, acyloxyethyl esters, alkoxycarbonyloxy Dialkyl esters, alkyl esters, aryl esters, phosphate esters, sulfonate esters, sulfate esters, and disulfide-containing esters (except esters, ethers, amides, carbamates, hemisuccinates of (but not limited to) , dimethylaminoacetate, and phosphoryloxymethyloxycarbonyl can be.

[0107] Amine-derived prodrugs include the following groups and combinations of the following groups: [ka] and sulfonamides and phosphonamides.

[0108] In certain cases, the site of either aromatic ring moiety is susceptible to various metabolic reactions. Therefore, the introduction of appropriate substituents into the aromatic ring structure can reduce, minimize, or eliminate this metabolic pathway. Lose.

[0109] Pharmaceutical Composition In certain embodiments, the compound of formula (I), (II), (III) as described herein may be used. Compounds of formula (IIIa), (IIIb) or (IV) are administered as pure chemicals. In some embodiments, the compounds of formula (I), (II), (III) described herein may be used. ), (IIIa), (IIIb) or (IV) can be prepared, for example, by the method of Remingto n:The Science and Practice of Pharmacy(G ennaro,21 st Ed. Mack Pub. Co., Easton, PA (20 05)) based on the intended route of administration and standard pharmaceutical practice. , a pharmaceutically suitable or acceptable carrier (herein referred to as pharmaceutically suitable (or acceptable) a physiologically suitable (or tolerable) excipient, a physiologically suitable (or acceptable) excipient, or a physiologically in combination with a suitable (also referred to as an acceptable) carrier.

[0110] Accordingly, the present invention provides compounds of formula (I), (II), at least one compound of formula (III), (IIIa), (IIIb) or (IV); or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, together with one or more A pharmaceutical composition comprising a pharmaceutically acceptable carrier. The composition (or any number of ingredients) must be compatible with the other ingredients of the composition and be user-friendly (i.e., Something is acceptable or preferable if it is not harmful to the body (i.e., the subject).

[0111] One embodiment is a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula (I) or a pharmaceutical The present invention provides pharmaceutical compositions comprising physiologically acceptable salts thereof.

[0112] One embodiment is a compound of formula (II) or a pharmaceutical composition thereof, comprising a pharmaceutically acceptable excipient and a compound of formula (II) or a pharmaceutical composition thereof. Pharmaceutical compositions containing physiologically acceptable salts are provided.

[0113] One embodiment is a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula (III) or a preparation thereof. Pharmaceutical compositions including pharmaceutically acceptable salts are provided.

[0114] One embodiment is a compound of formula (IIIa) or a pharmaceutically acceptable carrier, comprising: Pharmaceutical compositions including pharmaceutically acceptable salts are provided.

[0115] One embodiment is a compound of formula (IIIb) or a pharmaceutically acceptable carrier, comprising: Pharmaceutical compositions including pharmaceutically acceptable salts are provided.

[0116] One embodiment is a compound of formula (IV) or a pharmaceutical composition thereof, comprising a pharmaceutically acceptable excipient and a compound of formula (IV) or a pharmaceutical composition thereof. Pharmaceutical compositions containing physiologically acceptable salts are provided.

[0117] Another embodiment is a compound of formula (I) or a pharmaceutical composition thereof, comprising a pharmaceutically acceptable excipient and a compound of formula (I) or a pharmaceutical composition thereof. Another embodiment provides a pharmaceutical composition consisting essentially of a pharmaceutically acceptable salt thereof. and a compound of formula (II) or a pharmaceutically acceptable salt thereof. Another embodiment provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient, and a pharmaceutical composition consisting essentially of a compound of formula (III) or a pharmaceutically acceptable salt thereof Another embodiment provides a compound of formula (IIIa) comprising a pharmaceutically acceptable excipient and a compound of formula (IIIa) or a pharmaceutically acceptable salt thereof. The embodiment comprises a pharmaceutically acceptable excipient and a compound of formula (IIIb) or a pharmaceutically acceptable salt thereof. In another embodiment, a pharmaceutical composition is provided that consists essentially of a pharmaceutically acceptable salt. and a compound of formula (IV) or a pharmaceutically acceptable salt thereof. The present invention provides a pharmaceutical composition comprising:

[0118] In certain embodiments, the compound of formula (I), (II), (III) as described herein may be used. ), (IIIa), (IIIb) or (IV) compounds can be prepared, for example, by the steps of the synthesis method Other small organic molecules, such as contaminant intermediates or by-products, produced in one or more steps are removed by less than about 5%. It is substantially pure in that it contains less than about 1%, less than about 0.1%.

[0119] These pharmaceutical compositions can be administered orally, rectally, topically, bucally, or parenterally ( For example, by subcutaneous, intramuscular, intradermal or intravenous administration, by vaginal administration, by eye drop administration or by aerosol administration. Examples of suitable compositions include those suitable for oral administration.

[0120] Exemplary pharmaceutical compositions include an organic or inorganic carrier suitable for topical, enteral, or parenteral application. or a pharmaceutical composition containing one or more of the disclosed compounds as an active ingredient in a mixture with an excipient. It is used in the form of a pharmaceutical preparation, for example in solid, semi-solid or liquid form. In this form, the active ingredient is formulated into tablets, pellets, capsules, suppositories, liquids, etc., suitable for use. , emulsions, suspensions and any other forms, for example, in accordance with conventional pharmaceutically acceptable The active compound is formulated with a suitable non-toxic carrier. It is included in the pharmaceutical composition in an amount sufficient to produce the desired effect.

[0121] In some embodiments for preparing solid compositions such as tablets, the primary active ingredient is Pharmaceutical carriers, such as corn starch, lactose, sucrose, sorbitol, and talc , stearic acid, magnesium stearate, dicalcium phosphate or gum The disclosed compounds may be mixed with conventional tableting ingredients such as PEG-100, PEG-100C, PEG-100D, PEG-100E, PEG-100F, PEG-100H ... and a solid precursor formulation comprising a homogeneous mixture of the compound or a pharmaceutically acceptable non-toxic salt thereof. When these precursor formulation compositions are referred to as homogeneous, it is understood that the compositions form a tablet. The dosage form is designed to be easily subdivided into unit dosage forms of equal potency, such as tablets, pills and capsules. This means that the active ingredient is uniformly dispersed throughout the composition.

[0122] In solid dosage forms for oral administration (capsules, tablets, pills, sugar-coated tablets, powders, granules, etc.), one or more pharmaceutical compounds such as sodium citrate or dicalcium phosphate acceptable carriers, and / or (1) starch, cellulose, microcrystalline cellulose, silica Modified microcrystalline cellulose, lactose, sucrose, glucose, mannitol and / or (2) fillers or extenders such as silicic acid, e.g., carboxymethyl cellulose, hydroxypropyl cellulose, Promellose, alginate, gelatin, polyvinylpyrrolidone, sucrose and / or (3) a humectant such as glycerol; (4) crospovidone. , Croscarmellose sodium, Sodium starch glycolate, Agar, Calcium Carbonates, potato starch, tapioca starch, alginic acid, certain silicates and disintegrants such as sodium carbonate; (5) dissolution retardants such as paraffin; (6) absorption enhancers such as quaternary ammonium compounds; (7) e.g., docusate sodium; (8) humectants such as cellulose, cetyl alcohol, and glycerol monostearate; (9) Absorbents such as phosphorus and bentonite clay, talc, calcium stearate, malic acid, Magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate (10) lubricants such as acetone and mixtures thereof, and (11) colorants, In the case of capsules, tablets and pills, some embodiments In some embodiments, the compositions of the present invention comprise a buffering agent. In tablets and hard gelatin capsules, excipients such as lactose or milk sugar and high and similar types of solid compositions using molecular weight polyethylene glycols as fillers. Use.

[0123] In some embodiments, the product may be prepared by compression or molding, optionally with one or more accessory ingredients. In some embodiments, a binder (e.g., gelatin or hydrogel) is added to form a tablet. hydroxypropyl methylcellulose), lubricants, inert diluents, preservatives, disintegrants (e.g., naphthalene sodium starch glycolate or cross-linked sodium carboxymethylcellulose), Surfactants or dispersants are used to prepare compressed tablets. In some embodiments, an inert liquid The mixture of the composition of the present invention moistened with diluent is molded in a suitable machine. In some embodiments, tablets, as well as dragees, capsules, pills, and Other solid dosage forms, such as granules, may be scored or these forms may be enterically coated. They are prepared with coatings and envelopes such as coatings and other coatings.

[0124] Compositions for inhalation or insufflation include pharmaceutically acceptable aqueous or organic solvents. or mixtures thereof, as well as solutions and suspensions thereof, and powders. Liquid dosage forms include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, Liquid dosage forms, including syrups and elixirs, may be used in addition to the compositions of the present invention. In some embodiments, an inert diluent such as water or other solvent, ethyl alcohol, alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol Cole, benzyl benzoate, propylene glycol, 1,3-butylene glycol, Oils (especially cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil and sesame oil) oil), glycerol, tetrahydrofuryl alcohol, polyethylene glycol and sol fatty acid esters of vitamins, solubilizers and emulsifiers such as cyclodextrin, and This includes mixtures of these.

[0125] In some embodiments, the suspending agent may comprise, in addition to the composition of the present invention, a suspending agent, e.g., oxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan Ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, Includes tragacanth and mixtures thereof.

[0126] In some embodiments, formulations for rectal or vaginal administration are provided as suppositories, The suppository may be prepared by mixing the composition of the present invention with, for example, cocoa butter, polyethylene glycol, suppository Mix one or more suitable non-irritating excipients or carriers, including waxes or salicylates. It is solid at room temperature but liquid at body temperature, so it melts in the body cavity. This will release the active agent.

[0127] The dosage form for transdermal administration of the composition of the present invention may be a powder, a spray, an ointment, a paste, a cream, or the like. Some embodiments include creams, lotions, gels, solutions, patches, and inhalants. In this form, the active ingredient is mixed under sterile conditions with a pharmaceutically acceptable carrier, if desired. The formulation is mixed with any preservative, buffer or propellant.

[0128] In some embodiments, ointments, pastes, creams, and gels are prepared using the compositions of the present invention. In addition to animal fats and oils, vegetable fats and oils, waxes, paraffins, starches, tragacanth Cellulose derivatives, polyethylene glycol, silicone, bentonite, silicic acid, It includes excipients such as talc and zinc oxide, or mixtures thereof.

[0129] In some embodiments, powders and sprays contain, in addition to the compositions of this invention, lactose, Talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder or a mixture of these substances. In some embodiments, in addition The propellant may be any of the usual propellants such as chlorofluorohydrocarbons, as well as butane and propane. This includes volatile unsubstituted hydrocarbons such as toluene.

[0130] In some embodiments, the compounds described herein can be administered in eye drops. It is formulated as follows.

[0131] Alternatively, the compositions and compounds disclosed herein may be administered by aerosol. This administration may be carried out using an aqueous aerosol, liposomal preparation, or solid formulation containing the compound of the present invention. In some embodiments, this is achieved by preparing particles in a non-aqueous (e.g., In some embodiments, a sonic nebulizer is used. The ultrasonic nebulizer is used because it minimizes the shearing of the drug. When shear force is applied, the compounds contained in the composition of the present invention are decomposed. The sols may be used in conjunction with conventional pharmaceutically acceptable carriers and stabilizers to form aqueous solutions of the compositions of the present invention. The carrier and stabilizer are used in the preparation of the present invention. Although the amount of surfactant varies depending on the specific composition requirements, typically, nonionic surfactants (Tween n, Pluronic or polyethylene glycol), harmless substances such as serum albumin Proteins, sorbitan esters, oleic acid, lecithin, amino acids such as glycine, These may include buffers, salts, sugars or sugar alcohols. Aerosols are generally prepared from isotonic solutions. To manufacture.

[0132] Pharmaceutical compositions suitable for parenteral administration may be prepared in the form of one or more pharmaceutically acceptable sterile isotonic aqueous solutions or or non-aqueous solution, dispersion, suspension or emulsion, or a sterile injectable solution or dispersion immediately before use. In some embodiments, the composition of the present invention is combined with a sterile powder to be reconstituted into a powder. In this case, antioxidants, buffers, bacteriostats, and solvents that make the formulation isotonic with the intended recipient's blood are used. The composition may contain a surfactant, suspending agent or thickening agent.

[0133] Examples of suitable aqueous and non-aqueous carriers for use in the pharmaceutical compositions of the present invention include water, ethanol, and the like. Polyols (glycerol, propylene glycol, polyethylene glycol, etc.) and suitable mixtures thereof, vegetable oils such as olive oil, injectable oils such as ethyl oleate Suitable flow properties include, for example, organic esters, as well as cyclodextrins. For example, by using a coating material such as lecithin, the dispersant This is maintained by maintaining the required particle size and by using surfactants.

[0134] Disclosed compounds, enteric materials, and pharmaceutically acceptable carriers or excipients thereof Enteric-coated materials are those that are substantially insoluble in the acidic environment of the stomach. The term refers to polymers that are soluble in intestinal fluids at a specific pH and are primarily soluble in intestinal fluids at a specific pH. The part of the gastrointestinal (digestive) tract that lies between the intestine and the duodenum, including the jejunum, duodenum, and ileum. The pH of the intestine is about 5.5, the pH of the jejunum is about 6.5, and the pH of the terminal ileum is about 7.5 Thus, the enteric material may have a viscosity of, for example, about 5.0, about 5.2, about 5.4, about 5.6 , about 5.8, about 6.0, about 6.2, about 6.4, about 6.6, about 6.8, about 7.0, about 7.2 , approx. 7.4, approx. 7.6, approx. 7.8, approx. 8.0, approx. 8.2, approx. 8.4, approx. 8.6, approx. 8.8 , about 9.0, about 9.2, about 9.4, about 9.6, about 9.8, or about 10.0 Exemplary enteric materials include cellulose acetate phthalate (CAP), Hydroxypropyl methylcellulose phthalate (HPMCP), polyvinyl acetate Phthalate (PVAP), Hydroxypropyl Methylcellulose Acetate Succinate (HPMCAS), cellulose acetate trimellitate, hydroxypropyl methylcellulose Cellulose succinate, cellulose acetate succinate, cellulose acetate hexa cellulose acetate maleate, cellulose propionate phthalate, cellulose acetate maleate cellulose acetate butyrate, cellulose acetate propionate, methyl copolymer of methyl methacrylic acid and methyl methacrylate, methyl acrylate, methyl methacrylate Copolymer of acrylate and methacrylic acid, methyl vinyl ether and maleic anhydride copolymer (Gantrez ES series), ethyl methacrylate-methyl methacrylate Acrylate-chlorotrimethylammonium ethyl acrylate copolymer, zein, cera Natural resins such as cloves and copallucosides, as well as some commercially available enteric-coated ingredients Dispersed systems (e.g., Eudragit L30D55, Eudragit FS30D, Eu dragit L100, Eudragit S100, Kollicoat EMM3 0D, Estacryl 30D, Coateric and Aquateric) The solubility of each of the above substances is known or can be readily determined in vivo. It is either that or that.

[0135] Formula (I), (II), (III), (IIIa), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IIIg), (IIIh), (IIIm ... The dosage of a composition comprising at least one compound of formula IIIb) or (IV) is administered to a patient (e.g. Depending on the condition of the patient (e.g., a human), i.e., stage of disease, general health, age, and other factors, It varies depending on the situation.

[0136] The pharmaceutical composition is administered in a manner appropriate to the disease to be treated (or prevented). The amount, and the preferred duration and frequency of administration, will depend on the condition of the patient, the type and severity of the patient's disease. The dosage will depend on factors such as the particular form of the active ingredient, as well as the method of administration. Generally, appropriate dosages and treatment regimens will provide therapeutic and / or prophylactic effects (e.g., Increased frequency of complete or partial remission, longer disease-free and / or overall survival, or or a reduction in the severity of symptoms. Optimal dosages are generally determined using experimental models and / or clinical trials. In some embodiments, the optimal dosage is determined based on the patient's body mass, weight, or blood pressure. Depends on the amount of liquid.

[0137] Oral dosages are typically about 1.0 mg to about 1000 mg, 1 to 4 times or more per day. The range is.

[0138] Methods and Uses The present invention discloses in vitro ( Contemplated methods include, for example, the use of the enzyme in the preparation of the enzyme described herein. In some embodiments, the method includes exposing the subject to a compound described in the document. The compounds used in one or more of the formulas (I), (II), (III), (IIIa), (III b) or (IV), or a pharmaceutically acceptable salt, solvate or Any generic, subgeneric or specific compound described herein, including stereoisomers, The compounds described herein are one of the most effective compounds for controlling MAGL and FAAH. The ability to inhibit or inhibit a given protein is known in the art and / or described herein. The embodiments of the present invention are characterized by the formula Compound (I), (II), (III), (IIIa), (IIIb) or (IV) and any subgroup thereof, or a pharmaceutically acceptable salt or solvate thereof. or stereoisomers that are associated with unhealthy or abnormal levels of MAGL and / or FAAH The present invention also relates to use in methods of treating conditions characterized by abnormal levels of ATP. "Characterized by unhealthy or abnormal levels of MAGL and FAAH" Conditions include neuropathic pain, anxiety and inflammatory bowel disease, as well as the treatment of cancer cells. These include proliferation and migration.

[0139] In some embodiments, a method of treating pain in a patient in need thereof, comprising: and (IIIa) or (IIIb) as described herein. IIb) or (IV), or a pharmaceutically acceptable salt, solvate or An embodiment of the present invention is a method for treating a rheumatoid arthritis, comprising administering a therapeutically effective amount of a rheumatoid arthritis or ... Formulas (I), (II), (III), (IIIa), and (IIIb) described in the specification or (IV), and any subgroup thereof, or a pharmaceutically acceptable salt thereof An acceptable salt, solvate or stereoisomer thereof for use in a method for treating pain in a patient. In some embodiments, the present invention relates to the treatment of pain in a patient in need thereof. The method comprises administering to the patient a compound of formula (I) or a compound thereof as described herein. administering a therapeutically effective amount of a pharmaceutically acceptable salt, solvate, or stereoisomer thereof. In some embodiments, the method is a method for treating pain in a patient in need thereof. and administering to the patient a compound of formula (II) described herein or a pharmaceutically acceptable salt thereof. a therapeutically effective amount of an acceptable salt, solvate, or stereoisomer thereof. In some embodiments, there is provided a method of treating pain in a patient in need thereof, the method comprising: to a subject administering to the subject a compound of formula (III) as described herein, or a pharmaceutically acceptable salt thereof The method comprises administering a therapeutically effective amount of a suitable salt, solvate or stereoisomer of the compound of formula (I). In some embodiments, a method for treating pain in a patient in need thereof comprises administering to the patient a a compound of formula (IIIa) as described herein, or a pharmaceutically acceptable salt thereof; The method comprises administering a therapeutically effective amount of a solvate or stereoisomer. In embodiments, a method of treating pain in a patient in need thereof comprises administering to the patient a pain reliever comprising ... or a pharmaceutically acceptable salt or solvate thereof. In some embodiments, the method comprises administering a therapeutically effective amount of a compound or stereoisomer thereof.

[0013] The present invention provides a method for treating pain in a patient in need thereof, comprising administering to the patient a painkiller as described herein. The compound of formula (IV) or a pharmaceutically acceptable salt, solvate or The method comprises administering a therapeutically effective amount of a stereoisomer.

[0140] In some embodiments, a method of treating a neuropathy in a patient in need thereof, comprising: and administering to the patient a compound of formula (I), (II), (III), (IIIa) or (IIIb) as described herein. ), (IIIb) or (IV), or a pharmaceutically acceptable salt thereof, a solvent The method comprises administering a therapeutically effective amount of a solvate or stereoisomer of the compound of the present invention. is a compound represented by formula (I), (II), (III), (IIIa), (II Compounds of formula Ib) or (IV) and any subgroups thereof, or preparations thereof A pharmaceutically acceptable salt, solvate or stereoisomer thereof for use in treating a neurological disorder in a patient. In some embodiments, the present invention relates to a method for treating a neurological disorder. 2. A method for treating a neurological disorder in a patient, comprising administering to the patient a compound of formula (I) as described herein. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, In some embodiments, the method comprises administering to a patient in need of treatment for a neurological disorder. 2. A method for treating a neurological disorder in a patient, comprising administering to the patient a compound of formula (II) as described herein. a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof. In some embodiments, a patient in need of treatment for a neurological disorder is treated using a method comprising administering 20. A method for treating a neurological disorder comprising administering to a patient a compound of formula (III) as described herein. a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof. In some embodiments, a patient in need of treatment for a neurological disorder is treated using a method comprising administering a method for treating a neurological disorder of the present invention, comprising administering to the patient a compound of formula (IIIa) as described herein. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, In some embodiments, the method comprises administering to a patient in need of treatment for a neurological disorder. 1. A method for treating a neurological disorder in a patient, comprising administering to the patient a compound of formula (IIIb) or a pharmaceutically acceptable salt, solvate or stereoisomer thereof for therapeutic use. In some embodiments, the method comprises administering an effective amount of A method for treating a neurological disorder in a patient, comprising administering to the patient a compound of formula (IV) as described herein. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, The method includes administering an amount of

[0141] In certain embodiments, the disclosed compounds are used in one or more of the above methods. The compound may be a compound represented by formula (I), (II), (III), (IIIa), (IIIb) or (IV) Any generic, subgeneric or specific compound described herein, such as the compounds of An embodiment of the present invention is a compound of formula (I), (II) ), (III), (IIIa), (IIIb) or (IV), and their Any subgroup thereof, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof The present invention also relates to a compound for use in one or more of the above methods of treatment. Embodiments include those of formula (I), (II), (III), (IIIa), Compounds of formula (IIIb) or (IV), and any subgroups thereof, or pharmaceutically acceptable salts, solvates or stereoisomers thereof, It also concerns things used in law.

[0142] The disclosed compounds are useful in treating such conditions at dosages that provide optimal pharmaceutical efficacy. Administer to patients (animals and humans) who require the use of the product. The dosage will depend not only on the particular compound or composition selected, but also on the route of administration, the condition being treated, and the nature, age and condition of the patient, any concomitant medications or special diets the patient is following at the time, and The appropriate dosage will vary from patient to patient depending on other factors and is ultimately at the discretion of the attending physician. It is clear that the treatment of the above conditions and diseases is dependent on the amount of the drug used. and a dosage unit formulation comprising a physiologically acceptable non-toxic carrier, adjuvant, and vehicle as described herein. The compounds disclosed in the above can be administered orally, subcutaneously, topically, parenterally, by inhalation or by spray. Parenteral administration may include subcutaneous injection, intravenous or intramuscular injection or infusion. This includes techniques for:

[0143] Also contemplated by the present invention are, for example, compounds that combine the disclosed compounds with additional active compounds. A part of a prescribed treatment regimen intended to produce a beneficial effect through the interaction of drugs. One example is combination therapy, in which these therapeutic agents are administered in combination. Beneficial effects of combination therapy include: These include pharmacokinetic or pharmacodynamic interactions resulting from the concomitant use of therapeutic agents. Coadministration of these therapeutic agents is typically for a predetermined period of time (depending on the combination selected). Combination therapy involves multiple treatments. administering the agents sequentially, i.e., administering each therapeutic agent at a different time, and or at least two of the therapeutic agents are administered substantially simultaneously. It is intended to.

[0144] Substantially simultaneous administration can be achieved, for example, by administering the therapeutic agents in a single formulation or composition having a fixed ratio of each therapeutic agent. A single dose (e.g., a tablet or capsule) may be administered to the subject, or a single dose ... This is done by administering multiple doses of the formulation (e.g., capsules) of each therapeutic agent. The substantially simultaneous administration may be by any suitable route, including oral administration. These include intravenous, intramuscular, and direct absorption through mucosal tissues. The therapeutic agents may be administered by the same route or by different routes. For example, the selected combination The first therapeutic agent of the combination is administered by intravenous injection, and the second therapeutic agent of the combination is administered by intravenous injection. Another therapeutic agent is administered orally. Alternatively, for example, all therapeutic agents are administered orally or All therapeutic agents are administered by intravenous injection.

[0145] Combination therapy involves combining the above therapeutic agents with other bioactive ingredients and non-drug therapies. When the combination therapy further includes a non-drug treatment, Therapy is based on the premise that beneficial effects can be achieved through the interaction of a combination of therapeutic agents and non-pharmacological treatments. In some cases, the administration of the therapeutic agent may be performed at any suitable time. Temporarily omitting non-pharmacological treatment, perhaps for days or even weeks, may not result in beneficial effects. It can be useful.

[0146] The components of the combination may be administered to a patient simultaneously or sequentially. It will be apparent that simultaneous administration may be achieved by being in the same acceptable carrier. The active ingredients are administered either simultaneously or sequentially in separate formulations, as in conventional oral dosage forms. It is present in the carrier.

[0147] For example, the disclosed compounds are useful in the treatment of pain, e.g., as opioids, Cannabinoid receptor (CB-1 or CB-2) modulators, COX-2 inhibitors Other pain medications such as pain inhibitors, acetaminophen, and / or nonsteroidal anti-inflammatory drugs Additional therapeutic agents that may be co-administered, for example for the treatment of pain, include morphine. Ne, codeine, hydromorphone, hydrocodone, oxymorphone, fentanyl, These include ramadol and levorphanol.

[0148] Other potential co-administration therapies include aspirin, naproxen, and evelopharyn profen, salsalate, diflunisal, dexibuprofen, fenoprofen, Toprofen, oxaprozin, loxoprofen, indomethacin, tolmetin, suriconazole Ndac, etodolac, ketorolac, piroxicam, meloxicam, tenoxicam, drochlor cicam, lornoxicam, celecoxib, parecoxib, rimonabant and / or etoposide Ricoxib is an example.

[0149] The following examples are given merely as illustrations of various embodiments and in no way represent a limitation on the scope of the invention. It is not to be construed as limiting the invention. [Example]

[0150] List of abbreviations As used above and throughout the description of the present invention, the following abbreviations are used unless otherwise indicated: Unless otherwise specified, they shall be understood to have the following meanings: ACN or MeCN: acetonitrile Bn: Benzyl BOC or Boc: tert-butylcarbamate CDI: 1,1'-carbonyldiimidazole Cy: Cyclohexyl DCE: dichloroethane (ClCH2CH2Cl) DCM: dichloromethane (CH2Cl2) DIPEA or DIEA: Diisopropylethylamine DMAP: 4-(N,N-dimethylamino)pyridine DMF: dimethylformamide DMA: N,N-dimethylacetamide DMSO: dimethyl sulfoxide equiv: equivalent (plural) Et: Ethyl EtOH: ethanol EtOAc: ethyl acetate HATU: 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo [4,5-b]pyridinium 3-oxide hexafluorophosphate HPLC: High-performance liquid chromatography LAH: Lithium aluminum hydride Me: Methyl MeOH: Methanol MS: Mass spectrometry NMM: N-methylmorpholine NMR: nuclear magnetic resonance PMB: para-methoxybenzyl TEA: Triethylamine TFA: Trifluoroacetic acid THF: tetrahydrofuran TLC: Thin Layer Chromatography

[0151] I. Chemical synthesis Unless otherwise noted, reagents and solvents were used as received from commercial suppliers. and / or for oxygen-sensitive synthetic transformations, anhydrous solvents and oven-dried glass Instruments used. Yields not optimized. Reaction times are approximate and not optimized. Unless otherwise stated, column chromatography and thin layer chromatography (TL C) was performed on silica gel. Spectra are given in ppm (δ) and coupling constants (J ) are reported in Hertz. In the proton spectrum, the solvent peak is used as the base peak. Used.

[0152] Example 1: 5-(trifluoromethyl)pyridin-3-yl 2-(3-(trifluoromethyl)pyridin-3-yl) Methyl)phenoxy)-7-azaspiro[3.5]nonane-7-carboxylate [ka] Step 1: tert-Butyl 2-((methylsulfonyl)oxy)-7-azaspiro[3 Preparation of .5]nonane-7-carboxylate [ka] In a 250 mL round-bottom flask, add tert-butyl 2-hydroxy-7-azaspiro[3 .5]nonane-7-carboxylate (3.00 g, 12.4 mmol, 1.00 equ iv), triethylamine (3.77g, 37.3mmol, 3.00equiv), and Methanesulfonyl chloride (2.13 g, 1 mL) and dichloromethane (50 mL) were added. (8.7 mmol, 1.50 equiv) was added at 0° C. The reaction was stirred overnight at room temperature. The resulting solution was diluted with dichloromethane (3×100 mL). The organic layers were combined, washed with brine (3 x 100 mL), and The extract was dried over sodium sulfate, filtered, and concentrated under reduced pressure to give 4.55 g of tert-butyl 2-( (Methylsulfonyl)oxy)-7-azaspiro[3.5]nonane-7-carboxylate The compound was obtained as a brown oil. LCMS (ESI, m / z): 320 [M+H] +

[0153] Step 2: tert-Butyl 2-(3-(trifluoromethyl)phenoxy)-7-aza Preparation of spiro[3.5]nonane-7-carboxylate [ka] In a 50 mL round-bottom flask, add tert-butyl 2-((methylsulfonyl)oxy)- 7-Azaspiro[3.5]nonane-7-carboxylate (0.909g, 2.85mm ol, 1.00 equiv), 3-(trifluoromethyl)phenol (0.554 g, 3.42 mmol, 1.20 equiv), cesium carbonate (2.79 g, 8.5 5 mmol, 3.00 equiv) and DMF (20 mL). The mixture was stirred overnight at 80°C and quenched with water (20 mL). (3 x 20 mL), the organic layers were combined and washed with brine (1 x 100 mL), and The mixture was dried over aqueous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was evaporated on silica gel. Column chromatography gave 0.880 g (80% yield) of tert-butyl 2 -(3-(trifluoromethyl)phenoxy)-7-azaspiro[3.5]nonane-7- The carboxylate was obtained as a pale yellow oil. LCMS (ESI, m / z): 386 [M +H] +

[0154] Step 3: 2-(3-(trifluoromethyl)phenoxy)-7-azaspiro[3.5] Preparation of nonane [ka] In a 50 mL round-bottom flask, add tert-butyl 2-(3-(trifluoromethyl)phenyl)- noxy)-7-azaspiro[3.5]nonane-7-carboxylate (880 mg, 2. 28 mmol, 1.00 equiv), dichloromethane (20 mL), and trifluoro Acetic acid (12 mL) was charged, and the resulting solution was stirred for 2 hours at room temperature and concentrated under reduced pressure. The crude product was dissolved in 1 M sodium hydroxide solution (10 mL) and The organic layers were combined, washed with brine (10 mL), and Dried over sodium sulfate, filtered, and concentrated under reduced pressure to give 638 mg (98% yield) ) 2-(3-(trifluoromethyl)phenoxy)-7-azaspiro[3.5]nonane was obtained as a yellow oil. LCMS (ESI, m / z): 286 [M+H] +

[0155] Step 4: 5-(trifluoromethyl)pyridin-3-yl 2-(3-(trifluoromethyl)pyridin-3-yl) Preparation of (ethyl)phenoxy)-7-azaspiro[3.5]nonane-7-carboxylate [ka] In a 50 mL round-bottom flask, add triphosgene (158 mg, 0.530 mmol, 0.7 0 equiv) and dichloromethane (20 mL). ) Pyridin-3-ol (248 mg, 1.52 mmol, 2.00 equiv) and pyridin-3-ol The mixture was stirred for 2 hours at 0°C, and then 2-(3-(trimethylsilyl)-2-methyl-2-propanol)-2-one was added. Fluoromethyl)phenoxy)-7-azaspiro[3.5]nonane (217 mg, 0.7 The resulting solution was stirred overnight at room temperature and then diluted with water. (20 mL). The mixture was extracted with dichloromethane (3 x 20 mL). The organic layers were combined, washed with brine (1 x 100 mL) and extracted with anhydrous sodium sulfate. The crude product (900 mg) was purified by preparative HPLC. and purified to give 206.5 mg (57% yield) of 5-(trifluoromethyl)pyridine-3 -yl 2-(3-(trifluoromethyl)phenoxy)-7-azaspiro[3.5]nona The amine-7-carboxylate was obtained as a brown oil. 1 H NMR (300 MHz, chloro Form-d) δ 8.75(s, 1H), 8.66(s, 1H), 7.81(s, 1 H), 7.38 - 7.43 (m, 1H), 7.22 - 7.25 (m, 1H), 6.99 - 7.04 (m, 2H), 4.74 - 4.82 (m, 1H), 3. 51 - 3.68 (m, 4H), 2.49 - 2.56 (m, 2H), 2.03 - 2.10 (m, 2H), 1.78 (s, 4H). LCMS (ESI, m / z ): 516 [M+H+MeCN] +

[0156] Example 2: 5-(trifluoromethyl)pyridin-3-yl 2-(4-(3-chlorophenyl)-2-methyl ... (Benzyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate [ka] Step 1: Preparation of 3-(benzyloxy)-5-(trifluoromethyl)pyridine [ka] In a 250 mL three-neck round-bottom flask, add 3-chloro-5-(trifluoromethyl)pyridine (5.04g, 27.5mmol, 1.00equiv), phenylmethanol (2.9 (8 g, 27.6 mmol, 1.00 equiv) and DMF (30 mL) were added under nitrogen. Sodium hydride (60% mineral oil dispersion, 2.32 g, 55.8 mmol, 2 0.00 equiv) was added portionwise at 0° C. The resulting solution was stirred for 2 hours at 40° C. Quenched with water (20 mL), the mixture was extracted with dichloromethane (3 x 30 mL). The organic layers were combined, washed with water (3 x 30 mL), and dried over anhydrous sodium sulfate. , filtered, and concentrated under reduced pressure to give 3.00 g (43% yield) of 3-(benzyloxy)-5 -(trifluoromethyl)pyridine was obtained as a yellow oil. LCMS (ESI, m / z) : 254 [M+H] +

[0157] Step 2: Preparation of 5-(trifluoromethyl)pyridin-3-ol [ka] In a 250 mL three-necked round-bottom flask, add 3-(benzyloxy)-5-(trifluoromethyl) (3.00 g, 11.9 mmol, 1.00 equiv.), methanol (3 The resulting solution was stirred for 4 hours. The mixture was stirred under hydrogen at 50° C. The solid was filtered and washed with methanol (3×30 mL). The filtrate was concentrated under reduced pressure to give 1.60 g (83% yield) of 5-(trifluoromethyl)-2-(2-(2-methyl-2-propanol). (I)pyridin-3-ol was obtained as a white solid. LCMS (ESI, m / z): 1 64 [M+H] +

[0158] Step 3: 2-(tert-butyl)7-(5-(trifluoromethyl)pyridine-3- Preparation of (( ... [ka] In a 100 mL round-bottom flask, add triphosgene (0.971 mg, 3.27 mmol, 0 37 equiv), 5-(trifluoromethyl)pyridin-3-yl chloroformate methylpropane (2.08 g, 8.87 mmol, 1.10 equiv), and dichloromethane (30 Pyridine (1.94 g, 24.5 mmol, 3.00 equiv) was added to the The resulting solution was stirred for 2 hours at 0°C, and then tert-butyl 2,7- Diazaspiro[3.5]nonane-2-carboxylate (1.85 g, 8.17 mmol) , 1.00 equiv) was added. The reaction was stirred overnight at room temperature and diluted with water (10 mL). The mixture was extracted with dichloromethane (3 x 20 mL) and the organic layers were combined. , washed with water (3 x 20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 1.40 g (yield 41% yield of 2-(tert-butyl)7-(5-(trifluoromethyl)pyridine-3 -yl)2,7-diazaspiro[3.5]nonane-2,7-dicarboxylate, LCMS (ESI, m / z): 416 [M+H] +

[0159] Step 4: 5-(trifluoromethyl)pyridin-3-yl 2,7-diazaspiro[3. Preparation of 5]nonane-7-carboxylate [ka] In a 100 mL round-bottom flask, add 2-(tert-butyl) 7-(5-(trifluoromethyl)methyl)-2-(2-methyl-2-propanol)-2-one. (ethyl)pyridin-3-yl)2,7-diazaspiro[3.5]nonane-2,7-dicarboxamide xylate (1.40 g, 3.37 mmol, 1.00 equiv), dichloromethane ( The resulting solution was stirred at room temperature for 2 hours. The mixture was stirred at rt and concentrated under reduced pressure to give 1.02 g of 5-(trifluoromethyl)pyridine-3- Il 2,7-diazaspiro[3.5]nonane-7-carboxylate was obtained as a yellow oil. LCMS (ESI, m / z): 316 [M+H] +

[0160] Step 5: 5-(trifluoromethyl)pyridin-3-yl 2-(4-(3-chlorophenyl)-2-methylpropional) (Noxy)benzyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate preparation [ka] In a 40 mL round-bottom flask, add 4-(3-chlorophenoxy)benzaldehyde (100 mg, 0.431 mmol, 1.00 equiv), 5-(trifluoromethyl)pyridin Non-3-yl 2,7-diazaspiro[3.5]nonane-7-carboxylate (164m g, 0.522 mmol, 1.20 equiv), triethylamine (130 mg, 1. 28 mmol, 3.0 equiv) and 1,2-dichloroethane (10 mL) were added. The resulting solution was stirred for 2 hours at room temperature and then added sodium triacetoxyborohydride. Iodide (228 mg, 1.08 mmol, 2.50 equiv) was added. The mixture was stirred overnight at room temperature and quenched with water (10 mL), and extracted with dichloromethane. The organic layers were combined and washed with water (3 x 10 mL), and The crude product was purified by preparative HPLC. Purification gave 36.4 mg (16% yield) of 5-(trifluoromethyl)pyridin-3-yl 2-(4-(3-chlorophenoxy)benzyl)-2,7-diazaspiro[3.5] Nan-7-carboxylate was obtained as a colorless oil. 1 H NMR (300 MHz, C1H-d) δ 8.72 (s, 1H), 8.62 (s, 1H), 7.77 (s, 1H), 7.28 - 7.31 (m, 2H), 7.22 - 7.27 (m, 1H), 7.05 - 7.12 (m, 1H), 6.90 - 7.00 (m, 3H) ), 6.88 - 6.90 (m, 1H), 3.68 (s, 2H), 3.61 (b r, 2H), 3.50 (br, 2H), 3.04 - 3.15 (m, 4H), 1 .87 (br, 4H). LCMS (ESI, m / z): 532 [M+H] +

[0161] Example 3: 5-Carbamoylpyridin-3-yl 2-(3-chloro-5-(trifluoromethyl)methyl)-2-(2-methyl-2-pyridin-3-yl)- ...2-methyl-2-pyridin-3-yl)-2-(2-methyl-2-pyridin-3-yl)-2- (trimethyl)benzyl)-2,8-diazaspiro[4.5]decane-8-carboxylate [ka] Step 1: tert-Butyl 2-(3-chloro-5-(trifluoromethyl)benzyl) Preparation of 2,8-diazaspiro[4.5]decane-8-carboxylate [ka] In a 250 mL round-bottom flask, add 3-chloro-5-(trifluoromethyl)benzaldehyde. Hydride (2.08g, 10.0mmol, 1.00equiv), tert-butyl 2,8 -diazaspiro[4.5]decane-8-carboxylate (2.40 g, 10.0 mmol) 1,000 equiv) and 1,2-dichloroethane (50 mL). The resulting solution was stirred for 2 hours at room temperature and then added sodium triacetoxyborohydride (4 (0.24g, 20.0mmol, 2.00equiv) was added. The reaction was allowed to stand overnight at room temperature. The mixture was stirred at rt and quenched with water (150 mL). The mixture was diluted with dichloromethane (3×100 The organic layers were combined, washed with brine (3 x 100 mL), and The mixture was dried over methylsulfate, filtered, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography. 3.67 g (90% yield) of tert-butyl 2-(3-chloro-5- (Trifluoromethyl)benzyl)-2,8-diazaspiro[4.5]decane-8-carbohydrate The carboxylate was obtained as a white solid. LCMS (ESI, m / z): 433 [M+H ] +

[0162] Step 2: 2-(3-chloro-5-(trifluoromethyl)benzyl)-2,8-diaza Preparation of spiro[4.5]decane [ka] In a 100 mL round-bottom flask, add tert-butyl 2-(3-chloro-5-(trifluoromethyl)methyl) (trimethyl)benzyl)-2,8-diazaspiro[4.5]decane-8-carboxylate (3.67 g, 9.20 mmol, 1.00 equiv), concentrated hydrochloric acid (10 mL), and 1 4-Dioxane (20 mL) was added. The resulting solution was stirred at room temperature for 3 hours and then heated under reduced pressure. Concentration with 2.82 g of 2-(3-chloro-5-(trifluoromethyl)benzyl)- 2,8-Diazaspiro[4.5]decane was obtained as a white solid. LCMS (ESI, m / z): 333 [M+H] +

[0163] Step 3: 5-carbamoylpyridin-3-yl 2-(3-chloro-5-(trifluoromethyl)methyl)pyridin-3-yl Methyl)benzyl)-2,8-diazaspiro[4.5]decane-8-carboxylate preparation [ka] In a 40 mL vial, 5-hydroxypyridine-3-carboxamide (207 mg, 1.50 mmol, 1.50 equiv), triphosgene (93.0 mg, 0.330 m mol, 0.33 equiv) and tetrahydrofuran (5 mL). (395 mg, 4.99 mmol, 5.00 equiv) was added dropwise at 0°C, and the resulting solution The mixture was stirred for 3 hours at 0° C. 2-(3-chloro-5-(trifluoromethyl)benzyl) -2,8-diazaspiro[4.5]decane (333 mg, 1.00 mmol, 1.00 e quiv) in sodium hydride (60% mineral oil dispersion, 48.0 mg, 1.20 mo 1, 1.20 equiv) in tetrahydrofuran (5 mL), and this solution was added to The reaction was stirred overnight at room temperature and quenched with water (20 mL). The mixture was extracted with ethyl acetate (3 x 10 mL), and the organic layers were combined and washed with brine. (3 x 10 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by preparative HPLC to give 50.1 mg (10% yield). 5-Carbamoylpyridin-3-yl 2-(3-chloro-5-(trifluoromethyl)benzyl) (Benzyl)-2,8-diazaspiro[4.5]decane-8-carboxylate was obtained as a white solid. And got it. 1 H NMR (300 MHz, chloroform-d) δ 8.83 (s, 1 H), 8.57 (d, J = 2.3 Hz, 1H), 7.96 (t, J =2.2 Hz, 1H), 7.50 - 7.61 (m, 3H), 6.29 (br, 1H), 5.91 (br, 1H), 3.45 - 3.70 (m, 6H), 2.64 (br , 2H), 2.44 (br, 2H), 1.67 - 1.76 (m, 6H).LC MS (ESI, m / z): 497 [M+H] +

[0164] Example 4: 5-Carbamoylpyridin-3-yl 2-(5-chloro-2-(trifluoromethyl)methyl)-2-(2-methyl- ... (trimethyl)benzyl)-2,8-diazaspiro[4.5]decane-8-carboxylate [ka] Step 1: tert-Butyl 2-(5-chloro-2-(trifluoromethyl)benzyl) Preparation of 2,8-diazaspiro[4.5]decane-8-carboxylate [ka] In a 250 mL round-bottom flask, add 5-chloro-2-(trifluoromethyl)benzaldehyde. Hydride (0.860g, 4.12mmol, 1.00equiv), tert-butyl 2, 8-Diazaspiro[4.5]decane-8-carboxylate (1.00 g, 4.16 mm ol, 1.00 equiv) and 1,2-dichloroethane (50 mL). The mixture was stirred for 2 hours at room temperature and then added sodium triacetoxyborohydride (3 The resulting solution was stirred overnight at room temperature. The mixture was stirred at room temperature and quenched with water (50 mL). The mixture was extracted with dichloromethane (3 × 50 mL), the organic layers were combined and washed with water (3 × 50 mL), and anhydrous sodium sulfate The mixture was dried over ethyl acetate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography. 1.50 g (84% yield) of tert-butyl 2-(5-chloro-2-( (Trifluoromethyl)benzyl)-2,8-diazaspiro[4.5]decane-8-carbo The xylate was obtained as a white oil. LCMS (ESI, m / z): 433 [M+H] +

[0165] Step 2: 2-(5-chloro-2-(trifluoromethyl)benzyl)-2,8-diaza Preparation of spiro[4.5]decane [ka] In a 250 mL round-bottom flask, add tert-butyl 2-(5-chloro-2-(trifluoromethyl)methyl) (trimethyl)benzyl)-2,8-diazaspiro[4.5]decane-8-carboxylate (1.50 g, 3.46 mmol, 1.00 equiv), 1,4-dioxane (50 m The resulting solution was stirred at room temperature for 2 hours, and then concentrated hydrogen chloride (20 mL) was added. Concentration under reduced pressure gave 1.20 g of 2-(5-chloro-2-(trifluoromethyl)benzene (4.5)-2,8-diazaspiro[4.5]decane was obtained as a white solid. LCMS (ES I, m / z): 333 [M+H] +

[0166] Step 3: 2-(5-chloro-2-(trifluoromethyl)benzyl)-2,8-diaza Preparation of spiro[4.5]decane-8-carbonyl chloride [ka] In a 40 mL round-bottom flask, add 2-(5-chloro-2-(trifluoromethyl)benzyl )-2,8-diazaspiro[4.5]decane (1.00 g, 3.00 mmol, 1.00 equiv), triphosgene (0.358g, 1.21mmol, 0.40equiv) , and dichloromethane (10 mL). DIPEA (0.777 g, 6.01 mm ol, 2.00 equiv) was added dropwise at 0°C, and the resulting solution was stirred for 2 hours at 0°C. The mixture was then quenched with water (5 mL). The mixture was extracted with dichloromethane (3 × 10 mL). ), the organic layers were combined, washed with water (3 x 10 mL), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to give 1.18 g of 2-(5-chloro-2-(trifluoromethyl)methyl)- (ethyl)benzyl)-2,8-diazaspiro[4.5]decane-8-carbonyl chloride was obtained as a yellow oil.

[0167] Step 4: 5-carbamoylpyridin-3-yl 2-(5-chloro-2-(trifluoromethyl)methyl) Methyl)benzyl)-2,8-diazaspiro[4.5]decane-8-carboxylate preparation [ka] In a 40 mL vial, add 5-hydroxypyridine-3-carboxamide (83.0 mg , 0.600mmol, 1.00equiv), sodium hydride (60% mineral oil dispersion, 120 mg, 3.00 mmol, 3.00 equiv), and tetrahydrofuran (10 mL) was added under nitrogen. The mixture was stirred at room temperature for 2 hours, and then 2-(5- Chloro-2-(trifluoromethyl)benzyl)-2,8-diazaspiro[4.5]deca Benzene-8-carbonyl chloride (237 mg, 0.600 mmol, 1.00 equiv ) was added. The resulting solution was stirred overnight at 60°C and quenched with water (30 mL). The mixture was extracted with dichloromethane (3 x 20 mL), and the organic layers were combined and washed with water (3 × 20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by preparative HPLC to give 42.6 mg (14% yield) of 5-carbamoyl 2-(5-chloro-2-(trifluoromethyl)benzyl)-2-ylpyridin-3-yl ,8-diazaspiro[4.5]decane-8-carboxylate was obtained as a white solid. 1 H NMR (300 MHz, chloroform-d) δ 8.84 (d, J = 1.8 Hz, 1H), 8.60 (d, J = 2.4 Hz, 1H), 7.98- 8.00 (m, 1H), 7.84 - 7.86 (m, 1H), 7.60 (d, J = 8. 4 Hz, 1H), 7.28 - 7.36 (m, 1H), 5.70 - 6.40 ( m, 2H), 3.50 - 3.80 (m, 6H), 2.50 - 2.72 (m, 4H), 1.66 - 1.74 (m, 6H). LCMS (ESI, m / z): 4 97 [M+H] +

[0168] Example 5: 5-Carbamoylpyridin-3-yl 2-(3-(4-chlorophenoxy) Benzyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate [ka] Step 1: 5-carbamoylpyridin-3-yl(4-nitrophenyl)carbonate preparation [ka] In a 40 mL vial, 5-hydroxypyridine-3-carboxamide (138 mg, 1.00mmol, 1.00equiv), pyridine (158mg, 2.00mmol, 2.00 equiv) and acetonitrile (5 mL). Add 222 mg of methylformate (1.10 mmol, 1.10 equiv) at 0°C. The resulting solution was stirred for 2 hours at 0°C and concentrated under reduced pressure to give 303 mg of 5-carbamoyl methylcellulose. Moylpyridin-3-yl(4-nitrophenyl)carbonate was obtained as a yellow solid.

[0169] Step 2: tert-Butyl 2-(3-(4-chlorophenoxy)benzyl)-2,7- Preparation of diazaspiro[3.5]nonane-7-carboxylate [ka] In a 100 mL round-bottom flask, add tert-butyl 2,7-diazaspiro[3.5]nonaphthalene. Benzene-7-carboxylate (452 ​​mg, 2.00 mmol, 1.00 equiv), 3 -(4-chlorophenoxy)benzaldehyde (466 mg, 2.00 mmol, 1.0 0 equiv), and 1,2-dichloroethane (10 mL). The mixture was stirred for 2 h. Stir at room temperature for 1 hour, then add sodium triacetoxyborohydride (848 mg, 4 The resulting solution was stirred overnight at room temperature. Quenched with water (50 mL), the mixture was extracted with dichloromethane (3 x 50 mL). The organic layers were combined, washed with brine (3 x 50 mL) and extracted with anhydrous sodium sulfate. The mixture was dried, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography. Over the course of 1 hour, 700 mg (79% yield) of tert-butyl 2-(3-(4-chlorophenoxy)methyl)propanol was obtained. Benzyl-2,7-diazaspiro[3.5]nonane-7-carboxylate (white) Obtained as a semi-solid. LCMS (ESI, m / z): 443 [M+H] +

[0170] Step 3: 2-(3-(4-chlorophenoxy)benzyl)-2,7-diazaspiro[3 Preparation of .5]nonane [ka] In a 100 mL round-bottom flask, add tert-butyl 2-(3-(4-chlorophenoxy) benzyl)-2,7-diazaspiro[3.5]nonane (443 mg, 1.00 mmol, 1.00 equiv), 1,4-dioxane (20 mL), and concentrated hydrogen chloride (5 mL) The resulting solution was stirred for 4 hours at room temperature and concentrated under reduced pressure to give 343 mg of 2- (3-(4-chlorophenoxy)benzyl)-2,7-diazaspiro[3.5]nonane Obtained as a white solid. LCMS (ESI, m / z): 343 [M+H] +

[0171] Step 4: 5-carbamoylpyridin-3-yl 2-(3-(4-chlorophenoxy)benzyl)benzoate Preparation of (2,7-diazasipiro[3.5]nonane-7-carboxylate [ka] In a 40 mL vial, add 2-(3-(4-chlorophenoxy)benzyl)-2,7-dichlorobenzoate. Azaspiro[3.5]nonane (343 mg, 1.00 mmol, 1.00 equiv), Tetrahydrofuran (5 mL) and sodium hydride (60% mineral oil dispersion, 10 0 mg, 2.50 mmol, 2.50 equiv) was added under nitrogen. The resulting solution was After stirring for 10 minutes at room temperature, 5-carbamoylpyridin-3-yl 4-nitrophenylcarbamoyl Carbonate (303 mg, 1.00 mmol, 1.00 equiv) was added. The mixture was stirred overnight at 60°C and quenched with water (10 mL). The organic layers were combined and washed with brine (3 x 10 mL). The mixture was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. Purification by HPLC gave 21.2 mg (4% yield) of 5-carbamoylpyridine-3 -yl 2-(3-(4-chlorophenoxy)benzyl)-2,7-diazaspiro[3.5 ]nonane-7-carboxylate as a white solid. 1 H NMR (300 MHz , chloroform-d) δ 8.83 (d, J = 1.8 Hz, 1H), 8.57 (d, J = 2.5 Hz, 1H), 7.94 (t, J = 2.2 Hz, 1H), 7.26 - 7.32 (m, 3H), 7.05 - 7.08 (m, 1H), 6. 86 - 6.96 (m, 4H), 6.23 (br, 1H), 5.78 (br, 1 H), 3.39 - 3.74 (m, 6H), 3.27 (br, 4H), 1.87 (br, 4H). LCMS (ESI, m / z): 507 [M+H] +

[0172] Example 6: 5-aminopyridin-3-yl 4-(4-chloro-3-isopropoxybenzyl)benzoate Di(di)piperazine-1-carboxylate [ka] Step 1: Preparation of 4-chloro-3-isopropoxybenzaldehyde [ka] In a 250 mL round-bottom flask, add 4-chloro-3-hydroxybenzaldehyde (2.0 mL). 0g, 12.8mmol, 1.00equiv), 2-iodopropane (4.30g, 2 5.3 mmol, 2.00 equiv), cesium carbonate (12.4 g, 38.1 The resulting solution was added with 100 mmol, 3.00 equiv) and DMF (80 mL). The mixture was stirred overnight at 80°C and quenched with water (50 mL). Extract (3 x 100 mL), combine the organic layers, wash with water (3 x 30 mL), and The mixture was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography. Chromatography revealed 2.37 g (93% yield) of 4-chloro-3-isopropoxy Dibenzaldehyde was obtained as a yellow oil. LCMS (ESI, m / z): 199 [M +H] +

[0173] Step 2: tert-Butyl 4-(4-chloro-3-isopropoxybenzyl)piperazine Preparation of benzophenone-1-carboxylate [ka] In a 100 mL round-bottom flask, add 4-chloro-3-isopropoxybenzaldehyde (1 0.00g, 5.03mmol, 1.00equiv), tert-butylpiperazine-1 -carboxylate (1.40 g, 7.52 mmol, 1.50 equiv), and 1, 2-Dichloroethane (30 mL) was added. The resulting solution was stirred at room temperature for 1 hour, then , sodium triacetoxyborohydride (2.20 g, 10.4 mmol, 2.0 0 equiv) was added. The reaction was stirred overnight at room temperature and quenched with water (30 mL). The mixture was extracted with dichloromethane (3 x 50 mL), and the organic layers were combined and washed with water. The extract was washed (3 x 30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 1.49 g (yield 80%). ) tert-butyl 4-(4-chloro-3-isopropoxybenzyl)piperazine-1 -carboxylate was obtained as a yellow oil. LCMS (ESI, m / z): 369 [M +H] +

[0174] Step 3: Preparation of 1-(4-chloro-3-isopropoxybenzyl)piperazine [ka] In a 50 mL round-bottom flask, add tert-butyl 4-(4-chloro-3-isopropoxy) benzyl)piperazine-1-carboxylate (1.11 g, 3.00 mmol, 1.0 0 equiv), trifluoroacetic acid (1 mL), and dichloromethane (10 mL) were added. The resulting solution was stirred for 3 hours at room temperature and concentrated under reduced pressure to give 0.807 g of 1-(4 (3-chloro-3-isopropoxybenzyl)piperazine was obtained as a yellow oil. LCMS ( ESI, m / z): 269 [M+H] +

[0175] Step 4: 4-(4-chloro-3-isopropoxybenzyl)piperazine-1-carbonyl Preparation of benzoyl chloride [ka] In a 50 mL round-bottom flask, add 1-(4-chloro-3-isopropoxybenzyl)piperazine gin (538 mg, 2.00 mmol, 1.00 equiv), triphosgene (298 m g, 1.00 mmol, 0.50 equiv) and dichloromethane (10 mL) DIPEA (516 mg, 4.00 mmol, 2.00 equiv) was added dropwise at 0°C. The resulting solution was stirred for 3 hours at room temperature and quenched with water (10 mL). was extracted with dichloromethane (3 × 30 mL), and the organic layers were combined and washed with water (3 × 10 mL). L), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give 662 mg of 4-(4-chloro-3-isopropoxybenzyl)piperazine-1-carbonyl chloride The compound was obtained as a yellow solid.

[0176] Step 5: 5-aminopyridin-3-yl 4-(4-chloro-3-isopropoxybenzoyl) Preparation of (I)piperazine-1-carboxylate [ka] In a 50 mL round-bottom flask, add 4-(4-chloro-3-isopropoxybenzyl)piperazine Diazin-1-carbonyl chloride (390 mg, 1.18 mmol, 1.20 equiv ), 5-aminopyridin-3-ol (108 mg, 0.980 mmol, 1.00 eq uiv), 4-dimethylaminopyridine (23.9 mg, 0.200 mmol, 0.20 equiv), DIPEA (457mg, 3.54mmol, 3.00equiv), and The resulting solution was stirred overnight at 60°C and then cooled to 100°C. (10 mL). The mixture was extracted with ethyl acetate (3 x 30 mL). The organic layers were combined, washed with water (3 x 10 mL), and dried over anhydrous sodium sulfate. , filtered, and concentrated under reduced pressure. The crude product was purified by preparative HPLC to give 249. 0 mg (63% yield) of 5-aminopyridin-3-yl 4-(4-chloro-3-isopropyl)propionate (Oxybenzyl)piperazine-1-carboxylate was obtained as a yellow solid. 1 HNM R: (300 MHz, chloroform-d) δ 7.71 - 7.93 (m, 2H) , 7.34 - 7.38 (m, 1H), 6.89 - 7.01 (s, 1H), 6 .74 - 6.89 (m, 2H), 4.42 - 4.71 (m, 1H), 3.34 - 3.90 (m, 8H), 2.30 - 2.61 (m, 4H), 1.24 - 1 .40 (m, 6H). LCMS (ESI, m / z): 405 [M+H] +

[0177] Example 7: 5-(trifluoromethyl)pyridin-3-yl 2-(3-(benzo[d] Thiazol-2-yloxy)benzyl)-2,7-diazaspiro[3.5]nonane-7 -carboxylate [ka] Step 1: Preparation of 3-(benzo[d]thiazol-2-yloxy)benzaldehyde [ka] In a 100 mL round-bottom flask, add 3-hydroxybenzaldehyde (1.00 g, 8.2 mL) 0mmol, 1.00equiv), 2-chlorobenzo[d]thiazole (2.08g, 12.3 mmol, 1.50 equiv), DMF (25 mL), and potassium carbonate A solution of 1.4g (3.40g, 24.6mmol, 3.00 equiv) was added under nitrogen. The reaction mixture was stirred overnight at 80° C. and quenched with water (25 mL). Extract with acetate (3 x 25 mL), combine the organic layers and wash with brine (2 x 50 mL ), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. Column chromatography gave 0.800 g (38% yield) of 3-(benzo[a]thiazolinone). [d]Thiazol-2-yloxy)benzaldehyde was obtained as a yellow oil. LCMS (ESI, m / z): 256 [M+H] +

[0178] Step 2: 2-(tert-butyl)7-(5-(trifluoromethyl)pyridine-3- Preparation of (( ... [ka] In a 100 mL round-bottom flask, add triphosgene (0.986 g, 3.32 mmol, 0. 50 equiv) and tetrahydrofuran (15 mL). ,7-diazaspiro[3.5]nonane-2-carboxylate (1.50 g, 6.64 m mol, 1.00 equiv) was added at 0°C, and then DIPEA (3.43 g, 26.6 The reaction was stirred for 2 hours at room temperature and water (1 The resulting solution was extracted with dichloromethane (3 x 15 mL). The layers were combined, washed with brine (2 x 50 mL), and dried over anhydrous sodium sulfate. The crude product was dissolved in tetrahydrofuran (15 mL) and concentrated under reduced pressure. and 5-(trifluoromethyl)pyridin-3-ol (1.30 g, 7.97 mmol) , 1.20 equiv) and potassium tert-butoxide (1.12 g, 9.96 mm The resulting solution was stirred overnight at room temperature and then diluted with water (15 ml The mixture was extracted with dichloromethane (3 x 100 mL), and the organic layer The combined extracts were washed with brine (2 x 75 mL), dried over anhydrous sodium sulfate, and The mixture was filtered and concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography to obtain 1.60 g (58% yield) of 2-(tert-butyl) 7-(5-(trifluoromethyl) )pyridin-3-yl)2,7-diazaspiro[3.5]nonane-2,7-dicarboxy The compound was obtained as a yellow oil. LCMS (ESI, m / z): 416 [M+H] +

[0179] Step 3: 5-(trifluoromethyl)pyridin-3-yl 2-(3-(benzo[d]thiazolinone) Azol-2-yloxy)benzyl)-2,7-diazaspiro[3.5]nonane-7- Preparation of carboxylates [ka] In step 5, 3-(benzo[d]thiazolinone) was prepared as described in steps 4-5 of Example 2. The title compound was synthesized using (azol-2-yloxy)benzaldehyde, 111 mg (50% yield) of 5-(trifluoromethyl)pyridin-3-yl 2-(3-(benzoyl)-2-methyl ... (D)thiazol-2-yloxy)benzyl)-2,7-diazaspiro[3.5]no Nan-7-carboxylate was obtained as a colorless oil. 1 H NMR (300 MHz, Fluoroform-d) δ 8.62 - 8.71 (m, 2H), 7.66 - 7.76 ( m, 3H), 7.30 - 7.48 (m, 2H), 7.32 (s, 1H), 7. 12 - 7.24 (m, 3H), 3.71 (s, 2H), 3.59 (br, 2H) ), 3.49 (br, 2H), 3.11 - 3.14 (m, 4H), 1.75 - 1.85 (m, 4H). LCMS (ESI, m / z): 555 [M+H] +

[0180] Example 8: 5-(trifluoromethyl)pyridin-3-yl 2-(4-(2-chlorophenyl)-2-methylpropional) (Benzyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate [ka] Step 1: Preparation of 4-(2-chlorophenoxy)benzaldehyde [ka] In a 250 mL round-bottom flask, add potassium carbonate (4.30 g, 31.1 mmol) , 2.00 equiv), 2-chlorophenol (2.00 g, 15.6 mmol, 1. 00 equiv), 4-fluorobenzaldehyde (1.94 g, 15.6 mmol, 1 0.00 equiv), and acetonitrile (50 mL) were added under nitrogen. The mixture was stirred at 80° C. overnight and quenched with water (100 mL). The organic layers were combined, washed with water (3 x 50 mL), and The residue was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Chromatography gave 2.20 g (61% yield) of 4-(2-chlorophenoxy)-2-methylpropional. ) benzaldehyde was obtained as a yellow oil. LCMS (ESI, m / z): 233 [M +H] +

[0181] Step 2: 5-(trifluoromethyl)pyridin-3-yl 2-(4-(2-chlorophenyl)-2-methylpropional) (Noxy)benzyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate preparation [ka] In a 50 mL round-bottom flask, add 4-(2-chlorophenoxy)benzaldehyde (100 mg, 0.432 mmol, 1.00 equiv), 5-(trifluoromethyl)pyridin Non-3-yl 2,7-diazaspiro[3.5]nonane-7-carboxylate (164m g, 0.522 mmol, 1.20 equiv, as described in steps 1-4 of Example 2 (prepared as described above), triethylamine (130 mg, 1.28 mmol, 3.00 eq iv) and 1,2-dichloroethane (10 mL). The resulting solution was heated at room temperature for 2 hours. After stirring at room temperature, sodium triacetoxyborohydride (228 mg, 1.08 The reaction was stirred overnight at room temperature and water (10 The mixture was extracted with dichloromethane (3 x 10 mL), and the organic layer The combined extracts were washed with water (3 x 10 mL), dried over anhydrous sodium sulfate, and filtered. The crude product was purified by preparative HPLC to give 56.2 mg (yield). 25% yield of 5-(trifluoromethyl)pyridin-3-yl 2-(4-(2-chlorofluoromethyl)pyridin-3-yl) (Benzyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate was obtained as a yellow oil. 1 H NMR (300 MHz, chloroform-d) δ 8.72 (s, 1H), 8.62 (s, 1H), 7.76 (s, 1H), 7.44 - 7.48 (m, 1H), 7.19 - 7.26 (m, 3H), 7.06 - 7.1 1 (m, 1H), 6.90 - 7.00 (m, 3H), 3.50 - 3.64 ( m, 4H), 3.49 (br, 2H), 3.10 - 3.11 (m, 4H), 1 .85 - 1.97 (m, 4H). LCMS (ESI, m / z): 532 [M+ H] +

[0182] Example 9: 5-(trifluoromethyl)pyridin-3-yl 2-(3-(2-chlorophenyl)-2-methylpropional) (Benzyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate [ka] Step 1: Preparation of 3-(2-chlorophenoxy)benzaldehyde [ka] In a 250 mL round-bottom flask, add 2-chlorophenol (1.28 g, 9.96 mmol) , 1.00 equiv), (3-formylphenyl)boronic acid (1.50 g, 10.0 m mol, 1.00 equiv), triethylamine (5.05 g, 49.9 mmol, 5 0.00 equiv), 1,2-dichloroethane (100 mL), and copper(II) acetate The resulting solution was added to the flask. The mixture was stirred overnight at room temperature and concentrated under reduced pressure. The residue was purified by silica gel column chromatography. 760 mg (33% yield) of 3-(2-chlorophenoxy)benzaldehyde was obtained as a yellow oil. LCMS (ESI, m / z): 233 [M+H] +

[0183] Step 2: 5-(trifluoromethyl)pyridin-3-yl 2-(3-(2-chlorophenyl)-2-methylpropional) (Noxy)benzyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate preparation [ka] In a 50 mL round-bottom flask, add 3-(2-chlorophenoxy)benzaldehyde (100 mg, 0.432 mmol, 1.00 equiv), 5-(trifluoromethyl)pyridin Non-3-yl 2,7-diazaspiro[3.5]nonane-7-carboxylate (164m g, 0.522 mmol, 1.20 equiv, as described in steps 1-4 of Example 2 (prepared as described above), triethylamine (130 mg, 1.28 mmol, 3.00 eq iv) and 1,2-dichloroethane (10 mL). The resulting solution was heated at room temperature for 2 hours. After stirring at room temperature, sodium triacetoxyborohydride (228 mg, 1.08 The reaction was stirred overnight at room temperature and water (5m The mixture was extracted with dichloromethane (3×10 mL) and the organic layer was The combined extracts were washed with water (3 x 10 mL), dried over anhydrous sodium sulfate, filtered, and Concentrated under reduced pressure. The crude product was purified by preparative HPLC to give 16.5 mg (yield 7%) of 5-(trifluoromethyl)pyridin-3-yl 2-(3-(2-chlorophenoxy)methyl)pyridin-3-yl (Oxy)benzyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate Obtained as a colored oil. 1 H NMR (300 MHz, chloroform-d) δ 8.72 (s, 1H), 8.62 (s, 1H), 7.76 (s, 1H), 7.48 - 7 .60 (m, 1H), 7.36 - 7.45 (m, 1H), 7.26 - 7.31 (m, 1H), 7.07 - 7.20 (m, 2H), 7.01 - 7.05 (m , 1H), 6.94 - 6.99 (m, 1H), 6.84 - 6.91 (m, 1 H), 3.71 (s, 2H), 3.40 - 3.59 (m, 4H), 3.01 - 3.35 (m, 4H), 1.86 (br, 4H). LCMS (ESI, m / z ): 532 [M+H] +

[0184] Example 10: 5-(trifluoromethyl)pyridin-3-yl 2-(3-(3-chloro)methyl)pyridin-3-yl 2-(3-chloro)methyl ... (Phenoxy)benzyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate to [ka] Step 1: Preparation of 3-(3-chlorophenoxy)benzaldehyde [ka] In a 500 mL round-bottom flask, add 3-chlorophenol (1.53 g, 11.9 mmol) , 1.10 equiv), potassium carbonate (11.2 g, 81.0 mmol, 8. 00 equiv), 3-bromobenzaldehyde (2.00 g, 10.8 mmol, 1. 00 equiv), quinoline (50 mL), pyridine (100 mL), and copper(II) ion HCl (6.50 g, 81.2 mmol, 8.00 equiv) was added under nitrogen. The resulting solution was stirred at 170° C. for 2 days, concentrated under reduced pressure, and diluted with water (100 mL). The mixture was extracted with ethyl acetate (3 x 100 mL), and the organic layers were combined and washed with brine. (3 x 100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 500 mg (yield 20%) of 3-(3-chlorophenoxy)benzaldehyde was obtained as a yellow oil. LCM S (ESI, m / z): 233 [M+H]+

[0185] Step 2: 5-(trifluoromethyl)pyridin-3-yl 2-(3-(3-chlorophenyl)-2-methyl ... (Noxy)benzyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate preparation [ka] In a 50 mL round-bottom flask, add 3-(3-chlorophenoxy)benzaldehyde (100 mg, 0.432 mmol, 0.83 equiv), 5-(trifluoromethyl)pyridin Non-3-yl 2,7-diazaspiro[3.5]nonane-7-carboxylate (164m g, 0.522 mmol, 1.00 equiv, as described in steps 1-4 of Example 2 (prepared as described above), triethylamine (130 mg, 1.28 mmol, 2.50 eq iv) and 1,2-dichloroethane (10 mL). The resulting solution was heated at room temperature for 2 hours. After stirring at room temperature, sodium triacetoxyborohydride (228 mg, 1.08 The reaction was stirred overnight at room temperature and water (10 The mixture was extracted with dichloromethane (3 x 10 mL), and the organic layer The combined extracts were washed with water (3 x 10 mL), dried over anhydrous sodium sulfate, and filtered. The crude product was purified by preparative HPLC to give 10.8 mg (yield). 4% yield of 5-(trifluoromethyl)pyridin-3-yl 2-(3-(3-chlorophenyl)-2-methyl ... (Noxy)benzyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate Obtained as a colorless oil. 1 H NMR (300 MHz, chloroform-d) δ 8.12 (s, 1H), 8.62 (s, 1H), 7.76 (s, 1H), 7.31 (m , 1H), 7.28 - 7.31 (m, 1H), 7.00 - 7.12 (m, 2 H), 6.88 - 6.98 (m, 4H), 3.87 (s, 2H), 3.49 - 3.77 (m, 4H), 3.14 - 3.42 (m, 4H), 1.87 - 1. 89 (m, 4H). LCMS (ESI, m / z): 532 [M+H] +

[0186] Example 11: 5-(trifluoromethyl)pyridin-3-yl 2-(3-(pyrimidine) -5-yloxy)benzyl)-2,7-diazaspiro[3.5]nonane-7-carbox Silate [ka] Step 1: Preparation of 3-(pyrimidin-5-yloxy)benzaldehyde [ka] In a 250 mL round-bottom flask, add 5-bromopyrimidine (3.18 g, 20.0 mmol) , 1.00 equiv), 3-hydroxybenzaldehyde (2.44 g, 20.0 mm ol, 1.00 equiv), cesium carbonate (13.0 g, 40.0 mmol, 2.00 equiv), copper(I) iodide (380 mg, 2.00 mmol, 0.1 0 equiv), L-proline (460 mg, 4.00 mmol, 0.20 equiv) and dimethyl sulfoxide (10 mL) were added under nitrogen. The resulting solution was stirred overnight for 12 hours. The mixture was stirred at 0°C and quenched with water (50 mL). The mixture was extracted with ethyl acetate. (3 x 50 mL), the organic layers were combined and washed with brine (3 x 50 mL) and anhydrous sodium The mixture was dried over methylsulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography. Chromatography yielded 1.00 g (25% yield) of 3-(pyrimidin-5-yloxy)- Benzaldehyde was obtained as a yellow oil. LCMS (ESI, m / z): 201 [ M+H] +

[0187] Step 2: 5-(trifluoromethyl)pyridin-3-yl 2-(3-(pyrimidine-5 -(I)benzyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate Preparation of the acetone [ka] In a 50 mL round-bottom flask, add 3-(pyrimidin-5-yloxy)benzaldehyde ( 100mg, 0.501mmol, 1.00equiv), 5-(trifluoromethyl) Pyridin-3-yl 2,7-diazaspiro[3.5]nonane-7-carboxylate (1 89 mg, 0.602 mmol, 1.20 equiv, as described in steps 1 to 4 of Example 2 (prepared as described), triethylamine (151 mg, 1.49 mmol, 3.00 equiv) and 1,2-dichloroethane (10 mL). The resulting solution was stirred for 2 h. Stir at room temperature for 1 hour, then add sodium triacetoxyborohydride (265 mg, 1 The resulting solution was stirred overnight at room temperature. Quenched with water (10 mL), the mixture was extracted with dichloromethane (3 x 10 mL). The organic layers were combined, washed with water (3 x 10 mL), and dried over anhydrous sodium sulfate. The crude product was purified by preparative HPLC to give 36.5% mp 180°C (95°F), filtrated and concentrated under reduced pressure. mg (15% yield) of 5-(trifluoromethyl)pyridin-3-yl 2-(3-(pyridinyl)-2-yl) (Imidin-5-yloxy)benzyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate The carboxylate was obtained as a grey semi-solid. 1 H NMR (300 MHz, chloroform -d) δ 8.98 (s, 1H), 8.72 (s, 1H), 8.62 (s, 1H ), 8.48 (s, 2H), 7.77 (s, 1H), 7.34 - 7.39 (m , 1H), 7.15 - 7.18 (m, 1H), 7.05 (s, 1H), 6.9 5 - 6.98 (m, 1H), 3.70 (s, 2H), 3.49 - 3.60 ( m, 4H), 3.14 (br, 4H), 1.87 (b...

Claims

1. A compound having the structure of formula (III): 【Chemistry 1】 During the ceremony, Each R １ are independently halogen, —CN, C １－６ Alkyl, C ２－６ Alkynyl, C １ －６ Alkyl-OR ７ , C １－６ Haloalkyl, C ３－８ Cycloalkyl, —NR ５ R ６ 、-C(O)NR ５ R ６ 、-OR ７ -SO ２ R １２ -SF ５ -SR ８ , ARIRA and and heteroaryl, wherein the aryl and heteroaryl are optionally independently selected from: and halogens, C １－６ Alkyl, C １－６ Haloalkyl and —C(O)NR ８ R ９ from substituted with one or two selected groups, or two adjacent R １ But, optional One or two R １１ forming a heterocycloalkyl ring substituted with R ３ But halogen, -CN, C １－６ Alkyl, C １－６ Haloalkyl, —NR ８ R ９ , —C(O)NR ８ R ９ , -NR ８ C(O)R ９ and -NR ９ SO ２ R ８ Selected from And, R ３ａ But halogen, C １－６ Alkyl and C １－６ haloalkyl 、 Each R ５ and R ６ are independent, H, C １－６ Alkyl and C ３－８ Selected from cycloalkyl Selected or R ５ and R ６ However, together with the nitrogen bonded to them, One or two R's at will １０ forming a heterocycloalkyl substituted with Each R ７ are independent, H, C １－６ Alkyl, C １－６ Alkyl-O-C １－６ Alkyl , C １－６ Haloalkyl, C ３－８ Cycloalkyl, heterocycloalkyl, aryl and and heteroaryl, wherein the heterocycloalkyl, aryl and heteroaryl are selected from the group consisting of: aryl optionally independently selected from halogen, C １－６ Alkyl and C １－６ From haloalkyl substituted with one or two selected groups; Each R ８ and R ９ are independent, H, C １－６ Alkyl, C ３－８ Cycloalkyl, aryl and selected from aryl and heteroaryl; Each R １０ became independent and C １－６ Alkyl, C ３－８ Cycloalkyl, C １－６ Haloal alkyl, halogen, oxo, -CN, -C(O)OR ８ , -C(O)R ８ , —C(O)NR ８ R ９ , -SO ２ R ８ , -NR ９ C(O)R ８ and -NR ９ SO ２ R ８ Selected from the law of nature, Each R １１ are independently halogen and C １－６ alkyl, Each R １２ became independent and C １－６ Alkyl and C ３－８ cycloalkyl the law of nature, m is 0, 1, 2, 3, 4 or 5; q is 0 or 1; w is 1 or 2; x is 0 or 1; y is 0 or 1; z is 0 or 1; when y and z are 0, x is 1 and w is 2; when y and z are 1, w is 1; When y is 1 and z is 0, or when y is 0 and z is 1, then x is 1. the compound, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

2. The compound according to claim 1, which is a compound of the following formula (IIIa): Pharmaceutically acceptable salts, solvates or stereoisomers 【Chemistry 2】 。

3. The compound according to claim 1, which is a compound having the structure of the following formula (IIIb): Pharmaceutically acceptable salts, solvates or stereoisomers 【Transformation 3】 。

4. A compound having the structure of formula (IV): 【Chemistry 4】 During the ceremony, Each R １ are independently halogen, —CN, C １－６ Alkyl, C ２－６ Alkynyl, C １ －６ Alkyl-OR ７ , C １－６ Haloalkyl, C ３－８ Cycloalkyl, —NR ５ R ６ 、-C(O)NR ５ R ６ 、-OR ７ -SO ２ R １２ -SF ５ -SR ８ , ARIRA and and heteroaryl, wherein the aryl and heteroaryl are optionally independently selected from: and halogens, C １－６ Alkyl, C １－６ Haloalkyl and —C(O)NR ８ R ９ from substituted with one or two selected groups, or two adjacent R １ But, optional One or two R １１ forming a heterocycloalkyl ring substituted with R ３ But halogen, -CN, C １－６ Alkyl, C １－６ Haloalkyl, —NR ８ R ９ , —C(O)NR ８ R ９ , -NR ８ C(O)R ９ and -NR ９ SO ２ R ８ Selected from And, R ３ａ But halogen, C １－６ Alkyl and C １－６ haloalkyl 、 Each R ５ and R ６ are independent, H, C １－６ Alkyl and C ３－８ Selected from cycloalkyl Selected or R ５ and R ６ However, together with the nitrogen bonded to them, One or two R's at will １０ forming a heterocycloalkyl substituted with Each R ７ are independent, H, C １－６ Alkyl, C １－６ Alkyl-O-C １－６ Alkyl , C １－６ Haloalkyl, C ３－８ Cycloalkyl, heterocycloalkyl, aryl and and heteroaryl, wherein the heterocycloalkyl, aryl and heteroaryl are selected from the group consisting of: aryl optionally independently selected from halogen, C １－６ Alkyl and C １－６ From haloalkyl substituted with one or two selected groups; Each R ８ and R ９ are independent, H, C １－６ Alkyl, C ３－８ Cycloalkyl, aryl and selected from aryl and heteroaryl; Each R １０ became independent and C １－６ Alkyl, C ３－８ Cycloalkyl, C １－６ Haloal alkyl, halogen, oxo, -CN, -C(O)OR ８ , -C(O)R ８ , —C(O)NR ８ R ９ , -SO ２ R ８ , -NR ９ C(O)R ８ and -NR ９ SO ２ R ８ Selected from the law of nature, Each R １１ are independently halogen and C １－６ alkyl, Each R １２ became independent and C １－６ Alkyl and C ３－８ cycloalkyl the law of nature, m is 0, 1, 2, 3, 4 or 5; The compound wherein q is 0 or 1. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

5. The compound according to any one of claims 1 to 4, wherein m is 1, or a pharmaceutical composition thereof. A physiologically acceptable salt, solvate or stereoisomer thereof.

6. The compound according to any one of claims 1 to 4, wherein m is 2, or a pharmaceutical composition thereof. A physiologically acceptable salt, solvate or stereoisomer thereof.

7. In the formula, R ３ But C １－６ The compound according to any one of claims 1 to 6, which is haloalkyl. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

8. In the formula, R ３ Ga-CF ３ or a pharmaceutically acceptable salt thereof. Possible salts, solvates or stereoisomers.

9. In the formula, R ３ is a halogen; or A pharmaceutically acceptable salt, solvate or stereoisomer thereof.

10. In the formula, R ３ is -C(O)NH ２ The compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

11. In the formula, R ３ is —CN, or a compound thereof according to any one of claims 1 to 6. A pharmaceutically acceptable salt, solvate or stereoisomer of:

12. A compound according to any one of claims 1 to 11, wherein q is 0, or a pharmaceutical preparation thereof. A physiologically acceptable salt, solvate or stereoisomer.

13. A compound according to any one of claims 1 to 11, wherein q is 1, or a pharmaceutical preparation thereof. A physiologically acceptable salt, solvate or stereoisomer.

14. In the formula, each R １ are independently halogen, —CN, C １－６ Alkyl, C １－６ Hello Aruki Ru, -NR ５ R ６ , -OR ７ and heteroaryl. A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt, solvate or isoform thereof. Somatic isomers.

15. In the formula, each R １ are independently halogen, C １－６ Haloalkyl, —NR ５ R ６ and -OR ７ A compound according to any one of claims 1 to 14, or a pharmaceutical composition thereof, selected from A physiologically acceptable salt, solvate or stereoisomer.

16. In the formula, R ５ and R ６ together with the nitrogen to which they are bonded, may optionally be one or Two R's １０ 16. The method of claim 1, wherein the heterocycloalkyl is substituted with A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof. Gender body.

17. In the formula, R ５ and R ６ However, together with the nitrogen bonded to them, they independently form C １－６ Alkyl and —C(O)NR ８ R ９ One or two R selected from １０ Replaced with The compound according to any one of claims 1 to 16, which forms a telocycloalkyl ring. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

18. In the formula, R ５ and R ６ together with the nitrogen to which they are attached to form an unsubstituted heterocyclic The compound according to any one of claims 1 to 15, wherein the compound forms a hydroxyl group, or A pharmaceutically acceptable salt, solvate or stereoisomer.

19. In the formula, R ５ and R ６ together with the nitrogen to which they are bonded to form a group represented by the formula 【Transformation 5】 16. The compound according to claim 1, wherein the heterocycloalkyl is selected from the group consisting of or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

20. In the formula, each R １ are independently halogen, C １－６ Alkyl, C １－６ Haloalkyl and - OR ７ or a compound according to any one of claims 1 to 14 selected from A pharmaceutically acceptable salt, solvate or stereoisomer.

21. In the formula, R ７ became independent and C １－６ Alkyl, C １－６ Haloalkyl, C ３－８ Cycloa 21. Any one of claims 1 to 20, wherein the aryl is selected from alkyl, aryl and heteroaryl.

2. A compound according to claim 1, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

22. In the formula, R ７ became independent and C １－６ Alkyl, C １－６ Selected from haloalkyl and aryl A compound according to any one of claims 1 to 21, or a pharmaceutically acceptable salt thereof, Acceptable salts, solvates or stereoisomers.

23. In the formula, two adjacent R １ optionally one or two R １１ Heterocyclic substituted with The compound according to any one of claims 1 to 13, wherein the compound forms a hydroxyl group, or A pharmaceutically acceptable salt, solvate or stereoisomer of:

24. In the formula, each R １１ is a halogen; or a pharmaceutical composition thereof A commercially available salt, solvate or stereoisomer thereof.

25. A compound represented by the following formula: 【Transformation 6】 【change】 【change】 or a pharmaceutically acceptable salt, solvate or stereoisomer thereof. body.

26. A compound according to any one of claims 1 to 25, or a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprising a solvate or stereoisomer.

27. A pharmaceutical composition for use in treating pain in a patient, comprising any one of claims 1 to 25. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof. The pharmaceutical composition comprising

28. A pharmaceutical composition for use in treating a neurological disorder in a patient, comprising:

1. A compound according to claim 1, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof. The pharmaceutical composition comprising the body.

29. A compound according to any one of claims 1 to 25 for use in treating pain in a patient. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

30. A compound according to any one of claims 1 to 25 for use in treating a neurological disorder in a patient. or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

31. Claims 1-2 for use in the treatment of neuropathic pain, anxiety, inflammatory bowel disease and cancer 5 or a pharmaceutically acceptable salt, solvate or is a stereoisomer.

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