Muscarinic acetylcholine M1 receptor antagonists

Abstract

The invention relates to muscarinic acetylcholine M1 receptor antagonists. Provided herein, inter alia, are compounds useful as antagonists of muscarinic acetylcholine receptor M1 (mAChRM1); synthetic methods for preparing the compounds; a pharmaceutical composition including the compound; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and the compositions.

Description

[0001] This application is a divisional application, with the parent application number 202080078984.9 and application date 2020.10.06, entitled "Muscary Acetylcholine M1 Receptor Antagonist".

[0002] Cross-reference to related applications

[0003] This application claims priority to U.S. Provisional Application No. 62 / 911,807, filed October 7, 2019, which is incorporated herein by reference in its entirety and for all purposes. Background Technology

[0004] Human muscarinic acetylcholine receptor M1 (mAChRM1) is a 479-amino acid protein encoded by the CHRM1 gene. mAChR M1 is one of five members (M1-M5) of the muscarinic acetylcholine receptor family, which are widely expressed throughout the body and play distinct roles in cognition, sensation, motor function, and autonomic function. M1 mAChR is present in the central and peripheral nervous systems, specifically in the cerebral cortex and sympathetic ganglia. Based on the potential role of mAChRM1 in epileptic seizure activity and motor control, highly selective mAChR M1 antagonists may have potential utility in treating some epileptic disorders and certain motor disorders, including Parkinson's disease, dystonia, and Fragile X syndrome. Summary of the Invention

[0005] This disclosure provides compounds and compositions, for example, as antagonists of muscarinic acetylcholine M1 receptors (mAChR M1), and their use as pharmaceutical agents, methods of their preparation, and pharmaceutical compositions comprising the disclosed compounds as at least one active ingredient. This disclosure also provides the use of the disclosed compounds as pharmaceuticals for inhibiting the activity of muscarinic acetylcholine M1 receptors in patients and / or in the manufacture of said pharmaceuticals.

[0006] One aspect provides a compound or a pharmaceutically acceptable salt or solvation thereof having a structure of formula (IA-1) or (IB-1):

[0007]

[0008] in:

[0009] X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 )-、-O-、-S(O) n -, -CH2N(R) 11)-, substituted or unsubstituted alkylene, substituted or unsubstituted alkenyl, substituted or unsubstituted ynylene, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl or substituted or unsubstituted heteroalkenyl;

[0010] Y is a substituted or unsubstituted alkylene group, a substituted or unsubstituted alkenyl group, or a substituted or unsubstituted heteroalkylene group;

[0011] R 1 for Wherein ring A is optionally substituted with the following heteroaryl ring or heterocyclic alkyl ring: hydroxyl, halogen, cyano, -N(R) 14 (R) 15 ), substituted or unsubstituted alkyl groups, substituted or unsubstituted alkoxy groups, substituted or unsubstituted haloalkyl groups, substituted or unsubstituted haloalkoxy groups, substituted or unsubstituted cycloalkyl groups, substituted or unsubstituted cycloalkoxy groups, substituted or unsubstituted halocycloalkyl groups, substituted or unsubstituted halocycloalkoxy groups, substituted or unsubstituted heterocycloalkyl groups, substituted or unsubstituted aryl groups, substituted or unsubstituted heteroaryl groups, -S(O) n (R 16 ) or -SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S;

[0012] R 2 It can be hydrogen, deuterium, halogen, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted haloalkyl, substituted or unsubstituted haloalkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted halocycloalkyl, substituted or unsubstituted halocycloalkoxy, substituted or unsubstituted alkylhydroxy, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;

[0013] R 3 Halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted haloalkyl, substituted or unsubstituted haloalkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted halocycloalkyl, substituted or unsubstituted halocycloalkoxy, substituted or unsubstituted alkylhydroxy, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or R2 and R 3 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl;

[0014] R 4 and R 5 Independently selected from hydrogen, deuterium, halogens, and substituted or unsubstituted alkyl groups; or R 3 and R 4 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 4 and R 5 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl;

[0015] R 6 and R 7 Independently selected from hydrogen, deuterium, halogens, and substituted or unsubstituted alkyl groups; or R 3 and R 7 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 4 and R 6 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 5 and R 7 Combining to form bonds;

[0016] R 8 for

[0017] R 9 and R 10 Independently selected from hydrogen, deuterium, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted haloalkyl, substituted or unsubstituted haloalkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted halocycloalkyl, substituted or unsubstituted halocycloalkoxy, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or R 3 and R 10 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R4 and R 10 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 6 and R 10 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 9 and R 10 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl;

[0018] R 11 It is hydrogen, a substituted or unsubstituted alkyl group, a substituted or unsubstituted haloalkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted halocycloalkyl group, a substituted or unsubstituted heterocycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group; or R 3 and R 11 Combining to form a heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 4 and R 11 Combining to form a heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 6 and R 11 Combining to form heteroalkyl rings optionally substituted with: halogens, substituted or unsubstituted alkyl groups, or substituted or unsubstituted cycloalkyl groups;

[0019] Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 ), substituted or unsubstituted alkyl groups, substituted or unsubstituted alkoxy groups, substituted or unsubstituted haloalkyl groups, substituted or unsubstituted haloalkoxy groups, substituted or unsubstituted cycloalkyl groups, substituted or unsubstituted cycloalkoxy groups, substituted or unsubstituted halocycloalkyl groups, substituted or unsubstituted halocycloalkoxy groups, substituted or unsubstituted alkylhydroxy groups, substituted or unsubstituted heterocycloalkyl groups, substituted or unsubstituted aryl groups, substituted or unsubstituted heteroaryl groups, -S(O) n (R 16 ) or -SF5; or R 3 And an R 12Combining to form a cycloalkyl or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 10 And an R 12 Combining to form a cycloalkyl or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 11 And an R 12 Combining to form heteroalkyl rings optionally substituted with: halogens, substituted or unsubstituted alkyl groups, or substituted or unsubstituted cycloalkyl groups;

[0020] R 13 It is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted halocycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;

[0021] R 14 and R 15 Independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted halocycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or R 14 and R 15 Combining to form a heterocyclic alkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl;

[0022] R 16 It can be a substituted or unsubstituted alkyl group, a substituted or unsubstituted haloalkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted halocycloalkyl group, a substituted or unsubstituted heterocycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group.

[0023] m is 0 or 1;

[0024] n is 0, 1, or 2;

[0025] o is 0, 1, 2, or 3; and

[0026] p is 0 or 1.

[0027] One aspect provides: a compound of formula (IA) or (IB):

[0028]

[0029] in:

[0030] X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 )-、-O-、-S(O) n -, -CH2N(R) 11 - or -CH2O-;

[0031] Y is -CH2-, -CH2CH2-, -CH=CH-, or -CH2OCH2-;

[0032] R 1 for Wherein ring A is optionally substituted with a 5- or 6-membered heteroaryl ring or a 5- or 6-membered heterocyclic alkyl ring: halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S;

[0033] R 2 Hydrogen, deuterium, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl;

[0034] R 3 Halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; or R 2 and R 3 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0035] R 4 and R 5 Independently selected from hydrogen, deuterium, halogens and C 1-3 Alkyl; or R 3 and R 4 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 5 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0036] R 6 and R 7 Independently selected from hydrogen, deuterium, halogens and C 1-3 Alkyl; or R 3 and R 7 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 6 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 5 and R 7 Combining to form bonds;

[0037] R 8 for

[0038] R 9 and R 10 Independently selected from hydrogen, deuterium, halogens, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6Halogenated cycloalkoxy, heterocyclic alkyl, aryl or heteroaryl; or R 3 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 6 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 9 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0039] R 11 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 3 and R 11 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 11 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 6 and R 11 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0040] Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5; or R 3 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 10 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 11 And an R 12 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0041] R 13 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0042] R 14 and R 15 Independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 14 and R 15 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0043] R 16 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0044] m is 0 or 1;

[0045] n is 0, 1, or 2; and

[0046] o can be 0, 1, 2, or 3;

[0047] Or a pharmaceutically acceptable salt or solvate thereof, provided that the above combination does not violate the rules of value known to those skilled in the art.

[0048] In one aspect, a compound of formula (IIA) or (IIB) is provided:

[0049]

[0050] in:

[0051] X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 )-、-O-、-S(O) n -, -CH2N(R) 11 - or -CH2O-;

[0052] Y is -CH2-, -CH2CH2-, -CH=CH-, or -CH2OCH2-;

[0053] R 1 for Wherein ring A is optionally substituted with a 5- or 6-membered heteroaryl ring or a 5- or 6-membered heterocyclic alkyl ring: halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S;

[0054] R 2 Hydrogen, deuterium, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl;

[0055] R 3 Halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; or R 2 and R 3 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0056] R 8 for

[0057] R 9 and R 10 Independently selected from hydrogen, deuterium, halogens, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl or heteroaryl; or R 3 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 9 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0058] R 11 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 3 and R 11 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C3-6 cycloalkyl;

[0059] Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5; or R 3 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 10 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 11 And an R 12 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0060] R 13 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0061] R 14 and R 15 Independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 14 and R 15 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0062] R16 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0063] m is 0 or 1;

[0064] n is 0, 1, or 2; and

[0065] o can be 0, 1, 2, or 3;

[0066] Or a pharmaceutically acceptable salt or solvate thereof, provided that the above combination does not violate the rules of value known to those skilled in the art.

[0067] On the other hand, a compound of formula (III) is provided:

[0068]

[0069] in:

[0070] X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 )-、-O-、-S(O) n -, -CH2N(R) 11 - or -CH2O-;

[0071] R 1 for Wherein ring A is optionally substituted with a 5- or 6-membered heteroaryl ring or a 5- or 6-membered heterocyclic alkyl ring: halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S;

[0072] R 2 Hydrogen, deuterium, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, C1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl;

[0073] R 3 Halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; or R 2 and R 3 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0074] R 8 for

[0075] R 9 and R 10 Independently selected from hydrogen, deuterium, halogens, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl or heteroaryl; or R 3 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 9 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0076] R 11 For hydrogen, C 1-6 Alkyl, C1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 3 and R 11 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0077] Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5; or R 3 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 10 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 11 And an R 12 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0078] R 13 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0079] R 14 and R 15 Independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 14 and R 15 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0080] R 16 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0081] m is 0 or 1;

[0082] n is 0, 1, or 2; and

[0083] o can be 0, 1, 2, or 3;

[0084] Or a pharmaceutically acceptable salt or solvate thereof, provided that the above combination does not violate the rules of value known to those skilled in the art.

[0085] In some embodiments of compounds of formula (IA), (IB), (IIA), (IIB), or (III) or their pharmaceutically acceptable salts or solvates, X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 - or -O-. In some embodiments, X is a key, -N(R) 11 )- or -O-.

[0086] In some embodiments of compounds of formula (IA), (IB), (IIA), (IIB), or (III) or their pharmaceutically acceptable salts or solvates, R 1 for In some embodiments, R 1 for

[0087] In some embodiments of compounds of formula (IA), (IB), (IIA), (IIB), or (III) or their pharmaceutically acceptable salts or solvates, R 8 for In some embodiments, R 8 for

[0088] This document envisions any combination of groups described above or below for various variables. Throughout the specification, those skilled in the art have selected their groups and substituents to provide stable moieties and compounds.

[0089] In another aspect, it is a pharmaceutical composition comprising a compound of formula (IA), (IB), (IIA), (IIB) or (III), a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.

[0090] In another aspect, there is a method for treating a subject with neurodegenerative disease, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (IA), (IB), (IIA), (IIB), or (III) or a pharmaceutically acceptable salt or solvate thereof.

[0091] In another aspect, a method for treating neuropathy in a subject in need includes administering to the subject a therapeutically effective amount of a compound of formula (IA), (IB), (IIA), (IIB), or (III) or a pharmaceutically acceptable salt or solvation thereof. In some embodiments, a method for treating neuropathy in a subject in need includes administering to the subject a therapeutically effective amount of a compound of formula (IA), (IB), (IIA), (IIB), or (III) or a pharmaceutically acceptable salt or solvation thereof, wherein the neuropathy is a peripheral neuropathy. In some embodiments, a method for treating neuropathy in a subject in need includes administering to the subject a therapeutically effective amount of a compound of formula (IA), (IB), (IIA), (IIB), or (III) or a pharmaceutically acceptable salt or solvation thereof, wherein the neuropathy is diabetic neuropathy.

[0092] In another aspect, a method for treating a demyelinating disease in a subject of need includes administering to the subject a therapeutically effective amount of a compound of formula (IA), (IB), (IIA), (IIB), or (III) or a pharmaceutically acceptable salt or solvation thereof. In some embodiments, a method for treating a demyelinating disease in a subject of need includes administering to the subject a therapeutically effective amount of a compound of formula (IA), (IB), (IIA), (IIB), or (III) or a pharmaceutically acceptable salt or solvation thereof, wherein the demyelinating disease is a demyelinating disease of the central nervous system. In some embodiments, a method for treating a demyelinating disease in a subject of need includes administering to the subject a therapeutically effective amount of a compound of formula (IA), (IB), (IIA), (IIB), or (III) or a pharmaceutically acceptable salt or solvation thereof, wherein the demyelinating disease is multiple sclerosis. In some embodiments, a method for treating a subject with a demyelinating disease includes administering to the subject a therapeutically effective amount of a compound of formula (IA), (IB), (IIA), (IIB), or (III) or a pharmaceutically acceptable salt or solvate thereof, wherein the demyelinating disease is a demyelinating disease of the peripheral nervous system.

[0093] In some embodiments of the methods described herein, the methods further include administering one or more immunomodulators. In some embodiments, the one or more immunomodulators are selected from: IFN-β1 molecules, etc.; corticosteroids, etc.; polymers of glutamate, lysine, alanine, and tyrosine, or glatiramer, etc.; antibodies or fragments thereof against α-4 integrin, or natalizumab, etc.; anthrone molecules, or mitoxantrone, etc.; S1P1 function modulators, or fingolimod, etc.; NRF2 function modulators, or dimethyl fumarate, etc.; antibodies against the T-cell IL-2 receptor α subunit (CD25), or daclizumab, etc.; antibodies against CD52, or alemtuzumab, etc.; antibodies against CD20, or ocrelizumab, etc.; inhibitors of dihydroorotate dehydrogenase, or teriflunomide, etc.

[0094] In another aspect, a method for modulating the activity of muscarinic acetylcholine receptor M1 in a subject is provided, the method comprising administering to the subject a compound of formula (IA), (IB), (IIA), (IIB), or (III), or a pharmaceutically acceptable salt or solvate thereof. In some embodiments, the compound of formula (IA), (IB), (IIA), (IIB), or (III), or a pharmaceutically acceptable salt or solvate thereof, acts as a selective M1 antagonist. Detailed Implementation

[0095] This disclosure relates, at least in part, to compounds capable of inhibiting muscarinic acetylcholine M1 receptors.

[0096] As used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural indicators unless the context clearly indicates otherwise. Thus, for example, reference to “pharmaceutical” includes a variety of such pharmaceuticals, and reference to “cell” includes reference to one or more cells (or a variety of cells) and their equivalent effects. When the scope is used herein to refer to physical properties, such as molecular weight, or chemical properties, such as chemical formulas, it is intended to include all combinations and sub-combinations of the scope, as well as specific embodiments thereof. When referring to a number or numerical range, the term “about” means that the referenced number or numerical range is an approximation within experimental variability (or within statistical experimental error), and therefore the number or numerical range varies between 1% and 15% of said number or numerical range. In embodiments, about means within the standard deviation of measurements generally acceptable in the art. In embodiments, about means a range extended to + / - 10% of a specified value. In embodiments, about includes the specified value. The term “comprising” (and related terms such as “comprise”, “comprises”, “having”, or “including”) is not intended to exclude embodiments in which, for example, any embodiment of a substance composition, composition, method, or process described herein “may consist of the described features” or “consistently consists of the described features”.

[0097] I. Definition

[0098] As used in this specification and the appended claims, unless otherwise indicated, the following terms have the meanings indicated below.

[0099] As used in this article, C1-C x Includes C1-C2, C1-C3...C1-C x C1-C x This refers to the number of carbon atoms that constitute its designated portion (excluding optional substituents). Similarly, C1-x Includes C 1-2 C 1-3 ...C 1-x C 1-x It refers to the number of carbon atoms that make up its specified part (excluding optional substituents).

[0100] "Amino" refers to the -NH2 group.

[0101] "Cyano" refers to the -CN group.

[0102] "Hydroxy group" refers to the -OH group.

[0103] "Nitro" refers to the -NO2 group.

[0104] "O-" refers to the -O- group.

[0105] "Oxygen group" refers to the =O group.

[0106] "Thiokine group" refers to the =S group.

[0107] "Imine" refers to the =NH group.

[0108] "Oxime group" refers to the =N-OH group.

[0109] "Alkyl" or "alkylene" refers to a compound consisting only of carbon and hydrogen atoms, without any unsaturation, and having one to fifteen carbon atoms (e.g., C1-C1). 15 Alkyl or C 1-15 Alkyl groups are straight-chain or branched hydrocarbon chain groups. In some embodiments, the alkyl group comprises one to thirteen carbon atoms (e.g., C1-C1). 13 Alkyl or C 1-13 Alkyl group). In some embodiments, the alkyl group comprises one to eight carbon atoms (e.g., C1-C8 alkyl or C... 1-8 Alkyl group). In other embodiments, the alkyl group comprises one to six carbon atoms (e.g., C1-C6 alkyl or C6 alkyl). 1-6 Alkyl group). In other embodiments, the alkyl group comprises one to five carbon atoms (e.g., C1-C5 alkyl or C... 1-5 Alkyl group). In other embodiments, the alkyl group comprises one to four carbon atoms (e.g., C1-C4 alkyl or C4 alkyl). 1-4 Alkyl group). In other embodiments, the alkyl group comprises one to three carbon atoms (e.g., C1-C3 alkyl or C... 1-3 Alkyl group). In other embodiments, the alkyl group comprises one to two carbon atoms (e.g., C1-C2 alkyl or C2-C2 alkyl). 1-2 Alkyl group). In other embodiments, the alkyl group comprises one carbon atom (e.g., C1 alkyl). In other embodiments, the alkyl group comprises five to fifteen carbon atoms (e.g., C5-C1 alkyl). 15Alkyl or C 5-15 Alkyl group). In other embodiments, the alkyl group comprises five to eight carbon atoms (e.g., C5-C8 alkyl or C...). 5-8 Alkyl group). In other embodiments, the alkyl group comprises two to five carbon atoms (e.g., C2-C5 alkyl or C2-C5 alkyl). 2-5 Alkyl group). In other embodiments, the alkyl group comprises three to five carbon atoms (e.g., C3-C5 alkyl or C... 3-5 Alkyl group. In other embodiments, the alkyl group is selected from methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (isopropyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl), 1,1-dimethylethyl (tert-butyl), and 1-pentyl (n-pentyl). The alkyl group is connected to the rest of the molecule by a single bond. Unless otherwise specified in the specification, the alkyl group is optionally substituted with one or more of the following substituents: halogen, cyano, nitro, oxy, thiooxy, imino, oxime, trimethylsilyl, -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 2), -S(O) t OR a (where t is 1 or 2), -S(O) t R f (where t is 1 or 2) and -S(O) t N(R a )2 (where t is 1 or 2), where each R a Independently hydrogen, alkyl, haloalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl, and each R fIndependently, it is an alkyl, haloalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl. Therefore, the alkyl group may be substituted or unsubstituted. In embodiments, the alkyl group is substituted with at least one substituent, wherein if the alkyl group is substituted with multiple substituents, each substituent may optionally be different. In embodiments, the alkyl group is substituted with at least one size-restricted substituent, wherein if the alkyl group is substituted with multiple size-restricted substituents, each size-restricted substituent may optionally be different. In embodiments, the alkyl group is substituted with at least one lower substituent, wherein if the alkyl group is substituted with multiple lower substituents, each lower substituent may optionally be different.

[0110] "Alkoxy" refers to a group bonded by an oxygen atom of the formula -O-alkyl, wherein the alkyl is an alkyl chain as defined above.

[0111] "Alkenyl" refers to a straight-chain or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and having two to twelve carbon atoms. In some embodiments, the alkenyl group comprises two to eight carbon atoms. In other embodiments, the alkenyl group comprises two to four carbon atoms. The alkenyl group is connected to the rest of the molecule by a single bond, such as ethenyl (i.e., vinyl), propenyl (i.e., allyl), butenyl, pentenyl, penta-1,4-dienyl, etc. Unless otherwise specifically stated in the specification, the alkenyl group may optionally be substituted with one or more of the following substituents: halogen, cyano, nitro, oxy, thiooxy, imino, oxime, trimethylsilyl, -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 (where t is 1 or 2), -S(O) t OR a (where t is 1 or 2), -S(O) t R f (where t is 1 or 2) and -S(O) t N(R a)2 (where t is 1 or 2), where each R a Independently hydrogen, alkyl, haloalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl, and each R f The alkenyl group is independently alkyl, haloalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl. Therefore, the alkenyl group can be substituted or unsubstituted. In embodiments, the alkenyl group is substituted by at least one substituent, wherein if the alkenyl group is substituted by multiple substituents, each substituent may optionally be different. In embodiments, the alkenyl group is substituted by at least one size-restricted substituent, wherein if the alkenyl group is substituted by multiple size-restricted substituents, each size-restricted substituent may optionally be different. In embodiments, the alkenyl group is substituted by at least one lower substituent, wherein if the alkenyl group is substituted by multiple lower substituents, each lower substituent may optionally be different.

[0112] "Alynyl" refers to a straight-chain or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, and having two to twelve carbon atoms. In some embodiments, the alkynyl group comprises two to eight carbon atoms. In other embodiments, the alkynyl group has two to four carbon atoms. The alkynyl group is connected to the rest of the molecule by a single bond, such as ethynyl, propynyl, butynyl, pentylyl, hexynyl, etc. Unless otherwise specifically stated in the specification, the alkynyl group may optionally be substituted with one or more of the following substituents: halogen, cyano, nitro, oxy, thiooxy, imino, oxime, trimethylsilyl, -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 2), -S(O) t OR a (where t is 1 or 2), -S(O) t R f (where t is 1 or 2) and -S(O) t N(R a )2 (where t is 1 or 2), where each R aIndependently hydrogen, alkyl, haloalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl, and each R f Independently, it is an alkyl, haloalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl group. Therefore, the alkynyl group can be substituted or unsubstituted. In embodiments, the alkynyl group is substituted by at least one substituent, wherein if the alkynyl group is substituted by multiple substituents, each substituent may optionally be different. In embodiments, the alkynyl group is substituted by at least one size-restricted substituent, wherein if the alkynyl group is substituted by multiple size-restricted substituents, each size-restricted substituent may optionally be different. In embodiments, the alkynyl group is substituted by at least one lower substituent, wherein if the alkynyl group is substituted by multiple lower substituents, each lower substituent may optionally be different.

[0113] Unless otherwise stated, the term "heteroalkyl" on its own or in combination with another term means comprising at least one carbon atom and at least one heteroatom (e.g., O, N, P, Si, and S), wherein the nitrogen and sulfur atoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quaternized, and does not contain a stable straight or branched chain or combination thereof with saturation. The heteroatom (e.g., O, N, S, Si, or P) may be placed at any internal position of the heteroalkyl group or at a position where the alkyl group is attached to the remainder of the molecule. The heteroalkyl group is an uncyclic chain. Examples include, but are not limited to: -CH2-CH2-O-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -CH2-S-CH2, -S(O)-CH3, -CH2-CH2-S(O)2-CH3, -Si(CH3)3, -O-CH3, -O-CH2-CH3, and -CN. At most two or three heteroatoms can be sequential, such as -CH2-NH-OCH3 and -CH2-O-Si(CH3)3. The heteroalkyl moiety may contain one heteroatom (e.g., O, N, S, Si, or P). The heteroalkyl moiety may contain two optionally different heteroatoms (e.g., O, N, S, Si, or P). The heteroalkyl moiety may contain three optionally different heteroatoms (e.g., O, N, S, Si, or P). The heteroalkyl moiety may contain four optionally different heteroatoms (e.g., O, N, S, Si, or P). The heteroalkyl moiety may contain five optionally different heteroatoms (e.g., O, N, S, Si, or P). The heteroalkyl moiety may contain up to eight optionally different heteroatoms (e.g., O, N, S, Si, or P). The heteroalkyl group may be substituted or unsubstituted. In embodiments, the heteroalkyl group is substituted with at least one substituent, wherein if the heteroalkyl group is substituted with multiple substituents, each substituent may be optionally different. In embodiments, the heteroalkyl group is substituted with at least one size-restricted substituent, wherein if the heteroalkyl group is substituted with multiple size-restricted substituents, each size-restricted substituent may optionally be different. In embodiments, the heteroalkyl group is substituted with at least one lower substituent, wherein if the heteroalkyl group is substituted with multiple lower substituents, each lower substituent may optionally be different.

[0114] "Heteroalkenyl" refers to a substance comprising at least one carbon-carbon double bond and at least one heteroatom (e.g., O, N, P, Si, and S), wherein the nitrogen and sulfur atoms may optionally be oxidized, and the nitrogen heteroatom may optionally be a quaternized stable straight-chain or branched chain or a combination thereof. The heteroalkenyl group may be substituted or unsubstituted. In embodiments, the heteroalkenyl group is substituted with at least one substituent, wherein if the heteroalkenyl group is substituted with multiple substituents, each substituent may optionally be different. In embodiments, the heteroalkenyl group is substituted with at least one size-restricted substituent, wherein if the heteroalkenyl group is substituted with multiple size-restricted substituents, each size-restricted substituent may optionally be different. In embodiments, the heteroalkenyl group is substituted with at least one lower substituent, wherein if the heteroalkenyl group is substituted with multiple lower substituents, each lower substituent may optionally be different.

[0115] "Hydynyl" refers to a group comprising at least one carbon-carbon triple bond and at least one heteroatom (e.g., O, N, P, Si, and S), wherein the nitrogen and sulfur atoms may optionally be oxidized, and the nitrogen heteroatom may optionally be a quaternized stable straight-chain or branched chain or a combination thereof. The hydynyl group may be substituted or unsubstituted. In embodiments, the hydynyl group is substituted with at least one substituent, wherein if the hydynyl group is substituted with multiple substituents, each substituent may optionally be different. In embodiments, the hydynyl group is substituted with at least one size-restricted substituent, wherein if the hydynyl group is substituted with multiple size-restricted substituents, each size-restricted substituent may optionally be different. In embodiments, the hydynyl group is substituted with at least one lower substituent, wherein if the hydynyl group is substituted with multiple lower substituents, each lower substituent may optionally be different.

[0116] Unless otherwise stated, the term "heteroalkylene" itself, or as part of another substituent, refers to a divalent group derived from a heteroalkylene group, such as (but not limited to) those exemplified by -CH2-CH2-S-CH2-CH2- and -CH2-S-CH2-CH2-NH-CH2-. For heteroalkylene groups, the heteroatom may also occupy any or both of the chain terminus (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, etc.). Furthermore, for alkylene and heteroalkylene linking groups, the direction in which the formula of the linking group is written does not imply the orientation of the linking group. For example, the formula -C(O)2R'- represents both -C(O)2R'- and -R'C(O)2-. As stated above, the heteroalkyl groups used herein include those groups attached to the remainder of the molecule via heteroatoms, such as -C(O)R', -C(O)NR', ​​-NR'R", -OR', -SR', and / or -SO2R'. Where the term "heteroalkyl" is followed by a specific heteroalkyl group, such as -NR'R", it should be understood that the terms heteroalkyl and -NR'R" are not redundant or mutually exclusive. Rather, the specific heteroalkyl group is described for clarity. Therefore, the term "heteroalkyl" should not be construed herein as excluding specific heteroalkyl groups such as -NR'R".

[0117] Unless otherwise stated, the term "hesylene" itself, or as part of another substituent, refers to a divalent group derived from hesylene.

[0118] Unless otherwise stated, the term "neodyneyl" itself, or as part of another substituent, refers to a divalent group derived from a neodyneyl group.

[0119] "Aryl" refers to a group derived from an aromatic monocyclic or polycyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. An aromatic monocyclic or polycyclic hydrocarbon ring system contains only hydrogen and carbon atoms consisting of six to eighteen carbon atoms, wherein at least one ring in the ring system is fully unsaturated, i.e., it contains a cyclic, delocalized (4n+2)π electron system conforming to Hückel theory. Ring systems derived from aryl include, but are not limited to, groups such as benzene, fluorene, indene, indene, naphthalene, and naphthalene. Unless otherwise specifically stated in the specification, the term "aryl" or the prefix "aryl-" (as in "arylalkyl") is intended to include an aryl group optionally substituted with one or more substituents independently selected from: alkyl, alkenyl, ynyl, halogen, haloalkyl, cyano, nitro, aryl, aralkyl, aryl-alkenyl, arylynyl, 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 -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 (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2) and -R b -S(O) t N(R a )2 (where t is 1 or 2), where each R a Independently, each R is hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl (optionally substituted with one or more halogen groups), aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl. b Independently, it is a direct bond or a straight-chain or branched alkylene or alkenylene chain, and R c The aryl group is a straight-chain or branched alkylene or alkenylene chain. Therefore, the aryl group can be substituted or unsubstituted. In embodiments, the aryl group is substituted by at least one substituent, wherein if the aryl group is substituted by multiple substituents, each substituent may optionally be different. In embodiments, the aryl group is substituted by at least one size-restricted substituent, wherein if the aryl group is substituted by multiple size-restricted substituents, each size-restricted substituent may optionally be different. In embodiments, the aryl group is substituted by at least one lower substituent, wherein if the aryl group is substituted by multiple lower substituents, each lower substituent may optionally be different.

[0120] "Aryloxy group" refers to a group bonded by an oxygen atom of the formula -O-aryl, where the aryl group is as defined above.

[0121] "Aryl group" refers to the formula -R c -aryl groups, where R c The alkylene chain is as defined above, such as methylene, ethylene, etc. The alkylene chain portion of the aralkyl group is optionally substituted as described above for the alkylene chain. The aryl portion of the aralkyl group is optionally substituted as described above for the aryl group.

[0122] "Arylalkyloxy group" refers to a group bonded by an oxygen atom of the formula -O-aryl group, wherein the aryl group is as defined above.

[0123] "Aryl" refers to the formula -R d -aryl groups, where R d It is an alkenyl chain as defined above. The aryl portion of the aryl group is optionally substituted as described above for the aryl group. The alkenyl chain portion of the aryl group is optionally substituted as defined above for the alkenyl group.

[0124] "Arotyne group" refers to the formula -R e -aryl groups, where R e The aryynyl chain is as defined above. The aryl portion of the aryynyl group is optionally substituted as described above for the aryl group. The aryynyl chain portion of the aryynyl group is optionally substituted as defined above for the aryynyl chain.

[0125] "Cycloalkyl" refers to a stable non-aromatic monocyclic or polycyclic hydrocarbon group consisting only of carbon and hydrogen atoms, comprising a fused ring, bridged ring, or spirocyclic system, and having three to fifteen carbon atoms. In some embodiments, the cycloalkyl group comprises three to ten carbon atoms. In other embodiments, the cycloalkyl group comprises five to seven carbon atoms. The cycloalkyl group is connected to the rest of the molecule by a single bond. The cycloalkyl group is saturated (i.e., containing only a single C-C bond) or partially unsaturated (i.e., containing one or more double or triple bonds). Examples of monocyclic cycloalkyl groups include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. In some embodiments, the cycloalkyl group comprises three to eight carbon atoms (e.g., C3-C8 cycloalkyl or C... 3-8 Cycloalkyl groups. In other embodiments, cycloalkyl groups comprise three to seven carbon atoms (e.g., C3-C7 cycloalkyl or C...). 3-7 Cycloalkyl groups. In other embodiments, cycloalkyl groups comprise three to six carbon atoms (e.g., C3-C6 cycloalkyl or C6 cycloalkyl). 3-6 Cycloalkyl groups. In other embodiments, cycloalkyl groups comprise three to five carbon atoms (e.g., C3-C5 cycloalkyl or C…). 3-5Cycloalkyl groups. In other embodiments, cycloalkyl groups comprise three to four carbon atoms (e.g., C3-C4 cycloalkyl or C4-C4 cycloalkyl). 3-4 Cycloalkyl. Partially unsaturated cycloalkyl groups are also referred to as "cycloalkenyl". Examples of monocyclic cycloalkenyl groups include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Polycyclic cycloalkyl groups include, for example, adamantyl, norbornyl (i.e., bicyclo[2.2.1]heptyl), norbornyl, decahydronaphthyl, 7,7-dimethyl-bicyclo[2.2.1]heptyl, bicyclo[1.1.1]pentyl, spiro[3.3]heptyl, spiro[4.4]nonyl, etc. Unless otherwise specifically stated in the specification, the term "cycloalkyl" is intended to include cycloalkyl groups optionally substituted with one or more substituents, said one or more substituents being independently selected from: alkyl, alkenyl, ynyl, halogen, haloalkyl, cyano, nitro, aryl, aralkyl, arylenyl, aryynyl, 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 -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 (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2) and R b -S(O) tN(R a )2 (where t is 1 or 2), where each R a Independently, each R is hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl (optionally substituted with one or more halogen groups), aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl. b Independently, it is a direct bond or a straight-chain or branched alkylene or alkenylene chain, and R c The cycloalkyl group is a straight-chain or branched alkylene or alkenylene chain. Therefore, the cycloalkyl group can be substituted or unsubstituted. In embodiments, the cycloalkyl group is substituted with at least one substituent, wherein if the cycloalkyl group is substituted with multiple substituents, each substituent may optionally be different. In embodiments, the cycloalkyl group is substituted with at least one size-restricted substituent, wherein if the cycloalkyl group is substituted with multiple size-restricted substituents, each size-restricted substituent may optionally be different. In embodiments, the cycloalkyl group is substituted with at least one lower substituent, wherein if the cycloalkyl group is substituted with multiple lower substituents, each lower substituent may optionally be different.

[0126] "Cycloalkoxy" refers to a group bonded by an oxygen atom of the formula -O-cycloalkyl, wherein the cycloalkyl group is as defined above.

[0127] "Halogen" or "halogen" refers to a bromine, chlorine, fluorine, or iodine substituent.

[0128] "Halogenated alkyl" refers to an alkyl group that is substituted with one or more halogen groups as defined above.

[0129] "Haloalkoxy" refers to an alkoxy group that is substituted with one or more halogen groups as defined above.

[0130] "Halogenated cycloalkyl" refers to a cycloalkyl group that is substituted with one or more halogen groups as defined above.

[0131] "Halogenated cycloalkoxy" refers to an alkoxy group that is substituted with one or more halogen groups as defined above.

[0132] "alkylhydroxyl" refers to an alkyl group that is substituted with one or more halogen groups as defined above.

[0133] "Heterocyclic alkyl" refers to a stable 3- to 18-membered non-aromatic ring group comprising two to twelve carbon atoms and one to six heteroatoms selected from nitrogen, oxygen, and sulfur. Unless otherwise specified in the specification, heterocyclic alkyl groups are monocyclic, bicyclic, tricyclic, or tetracyclic systems, including fused-ring, spirocyclic, or bridged-ring systems. The heteroatoms in the heterocyclic alkyl group are optionally oxidized. One or more nitrogen atoms (if present) are optionally quaternized. The heterocyclic alkyl group is partially or fully saturated. In some embodiments, the heterocyclic alkyl group is attached to the remainder of the molecule by any atom of the ring. Examples of such heterocyclic alkyl groups include, but are not limited to, dioxolane, thienyl[1,3]dithiaalkyl, decahydroisoquinolinyl, imidazolinyl, imidazoalkyl, isothiazolinyl, isoxazolinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperidinyl, 2-oxopiperidinyl, 2-oxopiperidinyl, 2-oxopiperylalkyl, oxazolinyl, piperidinyl, piperazine, 4-piperidinoneyl, pyrrolylalkyl, pyrazolyl, quinine cycloesteryl, thiazoalkyl, tetrahydrofuranyl, trithienyl, tetrahydropyranyl, thiomorpholinyl, thiomorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. Unless otherwise specified in the specification, the term "heterocyclic alkyl" is intended to include heterocyclic alkyl groups as defined above, optionally substituted with one or more substituents selected from: alkyl, alkenyl, alkynyl, halogen, haloalkyl, oxy, thiooxy, cyano, nitro, aryl, aralkyl, aryl-alkenyl, arylynyl, cycloalkyl, heterocyclic 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 aS(O) t R a (where t is 1 or 2), -R b -S(O) t OR a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2) and -R b -S(O) t N(R a )2 (where t is 1 or 2), where each R a Independently, each R is hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl. b Independently, it is a direct bond or a straight-chain or branched alkylene or alkenylene chain, and R c The heterocyclic alkyl group is a straight-chain or branched alkylene or alkenylene chain. In embodiments, the heterocyclic alkyl group may be substituted or unsubstituted. In embodiments, the heterocyclic alkyl group is substituted with at least one substituent, wherein if the heterocyclic alkyl group is substituted with multiple substituents, each substituent may optionally be different. In embodiments, the heterocyclic alkyl group is substituted with at least one size-restricted substituent, wherein if the heterocyclic alkyl group is substituted with multiple size-restricted substituents, each size-restricted substituent may optionally be different. In embodiments, the term "heterocyclic alkyl ring" is used herein as a heterocyclic alkyl ring.

[0134] "Heteroaryl" refers to a group derived from a 5- to 18-membered aromatic ring group comprising one to seventeen carbon atoms and one to six heteroatoms selected from nitrogen, oxygen, and sulfur. As used herein, a heteroaryl is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system in which at least one ring in the ring system is fully unsaturated, i.e., it contains a cyclic, delocalized (4n+2)π electron system conforming to Hückel's theory. Heteroaryls contain fused or bridged ring systems. The heteroatoms in the heteroaryl are optionally oxidized. One or more nitrogen atoms (if present) are optionally quaternized. The heteroaryl is attached to the remainder of the molecule via any atom of the ring. Unless otherwise specified in the specification, the term "heteroaryl" is intended to include heteroaryl groups as described above, optionally substituted with one or more substituents selected from: alkyl, alkenyl, ynyl, halogen, haloalkyl, oxy, thiooxy, cyano, nitro, aryl, aralkyl, aryl-alkenyl, arylynyl, cycloalkyl, heterocycloalkyl, heteroaryl, heteroaryl, -R b -OR a -R b -OC(O)-Ra -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 (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2) and -R b -S(O) t N(R a )2 (where t is 1 or 2), where each R a Independently, each R is hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl. b Independently, it is a direct bond or a straight-chain or branched alkylene or alkenylene chain, and R c The heteroaryl group is a straight-chain or branched alkylene or alkenylene chain. Therefore, the heteroaryl group can be substituted or unsubstituted. In embodiments, the heteroaryl group is substituted by at least one substituent, wherein if the heteroaryl group is substituted by multiple substituents, each substituent may optionally be different. In embodiments, the heteroaryl group is substituted by at least one size-restricted substituent, wherein if the heteroaryl group is substituted by multiple size-restricted substituents, each size-restricted substituent may optionally be different. In embodiments, the heteroaryl group is substituted by at least one lower substituent, wherein if the heteroaryl group is substituted by multiple lower substituents, each lower substituent may optionally be different.

[0135] "N-Heteroaryl" refers to a heteroaryl group as defined above, containing at least one nitrogen atom and wherein the connection point between the heteroaryl group and the rest of the molecule is through the nitrogen atom in the heteroaryl group. The N-heteroaryl group may optionally be substituted, as described above for heteroaryl groups.

[0136] "C-heteroaryl" refers to a heteroaryl group as defined above, wherein the connection point between the heteroaryl group and the rest of the molecule is through a carbon atom in the heteroaryl group. The C-heteroaryl group may optionally be substituted, as described above for heteroaryl groups.

[0137] "Heteroaryloxy group" refers to a group bonded by an oxygen atom of the formula -O-heteroaryl, wherein the heteroaryl group is as defined above.

[0138] "Heteroarylalkyl" formula -R c - A heteroaryl group, wherein R c The alkylene chain is as defined above. If the heteroaryl group is a nitrogen-containing heteroaryl group, the heteroaryl group is optionally linked to an alkyl group at the nitrogen atom. The alkylene chain of the heteroaryl alkyl group is optionally substituted as defined above for the alkylene chain. The heteroaryl moiety of the heteroaryl alkyl group is optionally substituted as defined above for the heteroaryl group.

[0139] "Heteroarylalkoxy" refers to the compound with the formula -OR c - A heteroaryl group bonded to an oxygen atom, wherein R c The alkylene chain is as defined above. If the heteroaryl group is a nitrogen-containing heteroaryl group, the heteroaryl group is optionally linked to an alkyl group at the nitrogen atom. The alkylene chain of the heteroarylalkoxy group is optionally substituted as defined above for the alkylene chain. The heteroaryl moiety of the heteroarylalkoxy group is optionally substituted as defined above for the heteroaryl group.

[0140] "Optional" or "optionally" means that the event or situation described below may or may not occur, and the description includes both the case where the event or situation occurs and the case where it does not occur. For example, "optionally substituted aryl" means that the aryl group is substituted or not substituted, and the description includes both substituted and unsubstituted aryl groups.

[0141] In the embodiments, each of the above terms (e.g., "alkyl", "alkenyl", "ynyl", "heteroalkyl", "heteroalkenyl", "heteroynyl", "cycloalkyl", "heterocycloalkyl", "aryl", and "heteroaryl") comprises the indicated group in both substituted and unsubstituted forms. Preferred substituents for each type of group are provided below.

[0142] As used herein, “substituted group” means a group selected from the following:

[0143] (A) Oxygen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, unsubstituted alkyl (e.g., C1-C8 alkyl, C1-C6 alkyl or C1 -C4 alkyl), unsubstituted alkenyl (e.g., C2-C8 alkenyl, C2-C6 alkenyl, or C2-C4 alkenyl), unsubstituted alkynyl (e.g., C2-C8 alkenyl, C2-C6 alkenyl, or C2-C4 alkenyl), unsubstituted heteroalkyl (e.g., 2- to 8-membered heteroalkyl, 2- to 6-membered heteroalkyl, or 2- to 4-membered heteroalkyl), unsubstituted heteroalkenyl (e.g., 3- to 8-membered heteroalkenyl, 3- to 6-membered heteroalkenyl, or... 3- to 4-membered heteroalkyl), unsubstituted heteroalkylyl (e.g., 3- to 8-membered heteroalkyl, 3- to 6-membered heteroalkyl, or 3- to 4-membered heteroalkyl), unsubstituted cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), unsubstituted heteroalkyl (e.g., 3- to 8-membered heteroalkyl, 3- to 6-membered heteroalkyl, or 5- to 6-membered heteroalkyl), unsubstituted aryl (e.g., C6-C... 10 Aryl, C 10 Aryl, or phenyl) or unsubstituted heteroaryl (e.g., 5- to 10-membered heteroaryl, 5- to 9-membered heteroaryl, or 5- to 6-membered heteroaryl); and

[0144] (B) Alkyl groups substituted with at least one substituent (e.g., C1-C1) 20 C1-C 12 C1-C8, C1-C6, C1-C4 or C1-C2), alkenyl (e.g., C2-C) 20 C2-C 12 (C2-C8, C2-C6, or C2-C4), alkynyl groups (e.g., C2-C...). 20 C2-C 12C2-C8, C2-C6, or C2-C4), heteroalkyl (e.g., 2 to 20, 2 to 12, 2 to 8, 2 to 6, 4 to 6, 2 to 3, or 4 to 5), heteroalkenyl (e.g., 3 to 20, 3 to 12, 3 to 8, 3 to 6, 4 to 6, or 4 to 5), heteroynyl (e.g., 3 to 20, 3 to 12, 3 to 8, 3 to 6, 4 to 6, or 4 to 5), cycloalkyl (e.g., C3-C4), cycloalkyl (e.g., C2-C8, C2-C6, or C2-C4), heteroalkyl (e.g., C2 to 20, 3 to 12, 3 to 8, 3 to 6, 4 to 6, or 4 to 5), cycloalkyl (e.g., C3-C4), cycloalkyl (e.g., C2 ... 10 C3-C8, C3-C6, C4-C6 or C5-C6), heterocyclic alkyl (e.g., ternary to decacyclic, ternary to octyl, ternary to octyl, ternary to octyl, quaternary to octyl, quaternary to quinary or quinary to quinary), aryl (e.g., C6-C4, C5-C6, C3-C8, C3-C6, C4-C6 or C5-C6), heterocyclic alkyl (e.g., ternary to decacyclic, ternary to octyl, ternary to octyl, qua ... 12 C6-C 10 (or phenyl) or heteroaryl (e.g., 5- to 12-membered, 5- to 10-membered, 5- to 9-membered, or 5- to 6-membered), wherein the at least one substituent is selected from:

[0145] (i) Oxygen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, unsubstituted alkyl (e.g., C1-C8 alkyl, C1-C6 alkyl or C1 -C4 alkyl), unsubstituted alkenyl (e.g., C2-C8 alkenyl, C2-C6 alkenyl, or C2-C4 alkenyl), unsubstituted alkynyl (e.g., C2-C8 alkenyl, C2-C6 alkenyl, or C2-C4 alkenyl), unsubstituted heteroalkyl (e.g., 2- to 8-membered heteroalkyl, 2- to 6-membered heteroalkyl, or 2- to 4-membered heteroalkyl), unsubstituted heteroalkenyl (e.g., 3- to 8-membered heteroalkenyl, 3- to 6-membered heteroalkenyl, or... 3- to 4-membered heteroalkyl), unsubstituted heteroalkylyl (e.g., 3- to 8-membered heteroalkyl, 3- to 6-membered heteroalkyl, or 3- to 4-membered heteroalkyl), unsubstituted cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), unsubstituted heteroalkyl (e.g., 3- to 8-membered heteroalkyl, 3- to 6-membered heteroalkyl, or 5- to 6-membered heteroalkyl), unsubstituted aryl (e.g., C6-C... 10 Aryl, C10 Aryl, or phenyl) or unsubstituted heteroaryl (e.g., 5- to 10-membered heteroaryl, 5- to 9-membered heteroaryl, or 5- to 6-membered heteroaryl); and

[0146] (ii) Alkyl groups substituted with at least one substituent (e.g., C1-C1) 20 C1-C 12 C1-C8, C1-C6, C1-C4 or C1-C2), alkenyl (e.g., C2-C) 20 C2-C 12 (C2-C8, C2-C6, or C2-C4), alkynyl groups (e.g., C2-C...). 20 C2-C 12 C2-C8, C2-C6, or C2-C4), heteroalkyl (e.g., 2 to 20, 2 to 12, 2 to 8, 2 to 6, 4 to 6, 2 to 3, or 4 to 5), heteroalkenyl (e.g., 3 to 20, 3 to 12, 3 to 8, 3 to 6, 4 to 6, or 4 to 5), heteroynyl (e.g., 3 to 20, 3 to 12, 3 to 8, 3 to 6, 4 to 6, or 4 to 5), cycloalkyl (e.g., C3-C4), cycloalkyl (e.g., C2-C8, C2-C6, or C2-C4), heteroalkyl (e.g., C2 to 20, 3 to 12, 3 to 8, 3 to 6, 4 to 6, or 4 to 5), cycloalkyl (e.g., C3-C4), cycloalkyl (e.g., C2 ... 10 C3-C8, C3-C6, C4-C6 or C5-C6), heterocyclic alkyl (e.g., ternary to decacyclic, ternary to octyl, ternary to octyl, ternary to octyl, quaternary to octyl, quaternary to quinary or quinary to quinary), aryl (e.g., C6-C4, C5-C6, C3-C8, C3-C6, C4-C6 or C5-C6), heterocyclic alkyl (e.g., ternary to decacyclic, ternary to octyl, ternary to octyl, qua ... 12 C6-C 10 (or phenyl) or heteroaryl (e.g., 5- to 12-membered, 5- to 10-membered, 5- to 9-membered, or 5- to 6-membered), wherein the at least one substituent is selected from:

[0147] (a) Oxygen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, unsubstituted alkyl (e.g., C1-C8 alkyl, C1-C6 alkyl or C1 -C4 alkyl), unsubstituted alkenyl (e.g., C2-C8 alkenyl, C2-C6 alkenyl, or C2-C4 alkenyl), unsubstituted alkynyl (e.g., C2-C8 alkenyl, C2-C6 alkenyl, or C2-C4 alkenyl), unsubstituted heteroalkyl (e.g., 2- to 8-membered heteroalkyl, 2- to 6-membered heteroalkyl, or 2- to 4-membered heteroalkyl), unsubstituted heteroalkenyl (e.g., 3- to 8-membered heteroalkenyl, 3- to 6-membered heteroalkenyl, or... 3- to 4-membered heteroalkyl), unsubstituted heteroalkylyl (e.g., 3- to 8-membered heteroalkyl, 3- to 6-membered heteroalkyl, or 3- to 4-membered heteroalkyl), unsubstituted cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), unsubstituted heteroalkyl (e.g., 3- to 8-membered heteroalkyl, 3- to 6-membered heteroalkyl, or 5- to 6-membered heteroalkyl), unsubstituted aryl (e.g., C6-C... 10 Aryl, C 10 Aryl, or phenyl) or unsubstituted heteroaryl (e.g., 5- to 10-membered heteroaryl, 5- to 9-membered heteroaryl, or 5- to 6-membered heteroaryl); and

[0148] (b) Alkyl groups substituted with at least one substituent (e.g., C1-C1) 20 C1-C 12 C1-C8, C1-C6, C1-C4 or C1-C2), alkenyl (e.g., C2-C) 20 C2-C 12 (C2-C8, C2-C6, or C2-C4), alkynyl groups (e.g., C2-C...). 20 C2-C 12C2-C8, C2-C6, or C2-C4), heteroalkyl (e.g., 2 to 20, 2 to 12, 2 to 8, 2 to 6, 4 to 6, 2 to 3, or 4 to 5), heteroalkenyl (e.g., 3 to 20, 3 to 12, 3 to 8, 3 to 6, 4 to 6, or 4 to 5), heteroynyl (e.g., 3 to 20, 3 to 12, 3 to 8, 3 to 6, 4 to 6, or 4 to 5), cycloalkyl (e.g., C3-C4), cycloalkyl (e.g., C2-C8, C2-C6, or C2-C4), heteroalkyl (e.g., C2 to 20, 3 to 12, 3 to 8, 3 to 6, 4 to 6, or 4 to 5), cycloalkyl (e.g., C3-C4), cycloalkyl (e.g., C2 ... 10 C3-C8, C3-C6, C4-C6 or C5-C6), heterocyclic alkyl (e.g., ternary to decacyclic, ternary to octyl, ternary to octyl, ternary to octyl, quaternary to octyl, quaternary to quinary or quinary to quinary), aryl (e.g., C6-C4, C5-C6, C3-C8, C3-C6, C4-C6 or C5-C6), heterocyclic alkyl (e.g., ternary to decacyclic, ternary to octyl, ternary to octyl, qua ... 12 C6-C 10 (or phenyl) or heteroaryl (e.g., 5- to 12-membered, 5- to 10-membered, 5- to 9-membered, or 5- to 6-membered), wherein the at least one substituent is selected from: oxy, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCH Cl2, -OCHBr2, -OCHI2, -OCHF2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, unsubstituted Alkyl (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), unsubstituted alkenyl (e.g., C2-C8 alkenyl, C2-C6 alkenyl, or C2-C4 alkenyl), unsubstituted alkynyl (e.g., C2-C8 alkynyl, C2-C6 alkynyl, or C2-C4 alkynyl), unsubstituted heteroalkyl (e.g., 2- to 8-membered heteroalkyl, 2- to 6-membered heteroalkyl, or 2- to 4-membered heteroalkyl), unsubstituted heteroalkenyl (e.g., 3- to 8-membered heteroalkyl). Alkenyl, 3- to 6-membered heteroalkenyl or 3- to 4-membered heteroalkenyl), unsubstituted heterocycloalkyl (e.g., 3- to 8-membered heterocycloalkyl, 3- to 6-membered heterocycloalkyl or 3- to 4-membered heterocycloalkyl), unsubstituted cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl or C5-C6 cycloalkyl), unsubstituted heterocycloalkyl (e.g., 3- to 8-membered heterocycloalkyl, 3- to 6-membered heterocycloalkyl or 5- to 6-membered heterocycloalkyl), unsubstituted aryl (e.g., C6-C... 10 Aryl, C 10Aryl or phenyl) or unsubstituted heteroaryl (e.g., 5- to 10-membered heteroaryl, 5- to 9-membered heteroaryl or 5- to 6-membered heteroaryl).

[0149] As used herein, “size-limited substituent” or “size-limited substituent group” refers to a group selected from all the substituents described above for “substituent”, wherein each substituted or unsubstituted alkyl group is a substituted or unsubstituted C1-C. 20 Alkyl group, each substituted or unsubstituted alkenyl group being a substituted or unsubstituted C2-C group. 20 Alkenyl group, each substituted or unsubstituted alkynyl group being a substituted or unsubstituted C2-C group. 20 The alkynyl group, each substituted or unsubstituted heteroalkyl group being a substituted or unsubstituted 2- to 20-membered heteroalkyl group, each substituted or unsubstituted heteroenyl group being a substituted or unsubstituted 3- to 20-membered heteroenyl group, each substituted or unsubstituted heteroynyl group being a substituted or unsubstituted 3- to 20-membered heteroynyl group, each substituted or unsubstituted cycloalkyl group being a substituted or unsubstituted C3-C8 cycloalkyl group, each substituted or unsubstituted heterocycloalkyl group being a substituted or unsubstituted 3- to 8-membered heterocycloalkyl group, and each substituted or unsubstituted aryl group being a substituted or unsubstituted C6-C8 cycloalkyl group. 10 Aryl group, and each substituted or unsubstituted heteroaryl group is a substituted or unsubstituted 5- to 10-membered heteroaryl group.

[0150] As used herein, “lower substituent” or “lower substituent group” means a group selected from all the substituents described above for “substituent”, wherein each substituted or unsubstituted alkyl group is a substituted or unsubstituted C1-C8 alkyl group, each substituted or unsubstituted alkenyl group is a substituted or unsubstituted C2-C8 alkenyl group, each substituted or unsubstituted ynyl group is a substituted or unsubstituted C2-C8 ynyl group, and each substituted or unsubstituted heteroalkyl group is a substituted or unsubstituted heteroalkyl group. The substituted 2- to 8-membered heteroalkyl group, each substituted or unsubstituted heteroalkenyl group being a substituted or unsubstituted 3- to 8-membered heteroalkenyl group, each substituted or unsubstituted heteroynyl group being a substituted or unsubstituted 3- to 8-membered heteroynyl group, each substituted or unsubstituted cycloalkyl group being a substituted or unsubstituted C3-C7 cycloalkyl group, each substituted or unsubstituted heterocycloalkyl group being a substituted or unsubstituted 3- to 7-membered heterocycloalkyl group, each substituted or unsubstituted aryl group being a substituted or unsubstituted phenyl group, and each substituted or unsubstituted heteroaryl group being a substituted or unsubstituted 5- to 6-membered heteroaryl group.

[0151] In some embodiments, each substituted group in the compounds described herein is substituted with at least one substituent. More specifically, in some embodiments, each substituted alkyl, substituted alkenyl, substituted alkynyl, substituted heteroalkyl, substituted heteroalkenyl, substituted heteroalkynyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted alkenyl, substituted alkynyl, substituted heteroalkylene, substituted heteroalkenyl, substituted heteroalkynyl, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and / or substituted heteroarylene is substituted with at least one substituent. In other embodiments, at least one or all of these groups are substituted with at least one size-restricted substituent. In other embodiments, at least one or all of these groups are substituted with at least one lower substituent.

[0152] In other embodiments of the compounds herein, each substituted or unsubstituted alkyl group may be a substituted or unsubstituted C1-C2. 20 Alkyl groups, each substituted or unsubstituted alkenyl group can be substituted or unsubstituted C2-C. 20 Alkenyl groups, each substituted or unsubstituted alkynyl group can be substituted or unsubstituted C2-C. 20The alkynyl group, each substituted or unsubstituted heteroalkyl group being a substituted or unsubstituted 2- to 20-membered heteroalkyl group, each substituted or unsubstituted heteroenyl group being a substituted or unsubstituted 3- to 20-membered heteroenyl group, each substituted or unsubstituted heteroynyl group being a substituted or unsubstituted 3- to 20-membered heteroynyl group, each substituted or unsubstituted cycloalkyl group being a substituted or unsubstituted C3-C8 cycloalkyl group, each substituted or unsubstituted heterocycloalkyl group being a substituted or unsubstituted 3- to 8-membered heterocycloalkyl group, and each substituted or unsubstituted aryl group being a substituted or unsubstituted C6-C8 cycloalkyl group. 10 The aryl group, and / or each substituted or unsubstituted heteroaryl group, is a substituted or unsubstituted 5- to 10-membered heteroaryl group. In other embodiments of the compounds herein, each substituted or unsubstituted alkylene group is a substituted or unsubstituted C1-C... 20 Alkylene, each substituted or unsubstituted alkenyl group being a substituted or unsubstituted C2-C 20 Alkenylyl group, each substituted or unsubstituted alkyneylyl group being a substituted or unsubstituted C2-C 20 The alkylene group, each substituted or unsubstituted heteroalkyl group being a substituted or unsubstituted 2- to 20-membered heteroalkylene group, each substituted or unsubstituted heteroenyl group being a substituted or unsubstituted 3- to 20-membered heteroenylene group, each substituted or unsubstituted cycloalkylene group being a substituted or unsubstituted C3-C8 cycloalkylene group, each substituted or unsubstituted heteroalkylene group being a substituted or unsubstituted 3- to 8-membered heteroalkylene group, and each substituted or unsubstituted arylene group being a substituted or unsubstituted C6-C8 cycloalkylene group. 10 The aryl group, and / or each substituted or unsubstituted heteroaryl group is a substituted or unsubstituted 5- to 10-membered heteroaryl group.

[0153] In some embodiments, each substituted or unsubstituted alkyl group is a substituted or unsubstituted C1-C8 alkyl group, each substituted or unsubstituted alkenyl group is a substituted or unsubstituted C2-C8 alkenyl group, each substituted or unsubstituted alkynyl group is a substituted or unsubstituted C2-C8 alkynyl group, each substituted or unsubstituted heteroalkyl group is a substituted or unsubstituted 2- to 8-membered heteroalkyl group, each substituted or unsubstituted heteroalkenyl group is a substituted or unsubstituted 3- to 8-membered heteroalkenyl group, each substituted or unsubstituted heteroynyl group is a substituted or unsubstituted 3- to 8-membered heteroynyl group, each substituted or unsubstituted cycloalkyl group is a substituted or unsubstituted C3-C7 cycloalkyl group, each substituted or unsubstituted heterocycloalkyl group is a substituted or unsubstituted 3- to 7-membered heterocycloalkyl group, and each substituted or unsubstituted aryl group is a substituted or unsubstituted C6-C8 cycloalkyl group. 10 The aryl group, and / or each substituted or unsubstituted heteroaryl group is a substituted or unsubstituted 5- to 9-membered heteroaryl group. In some embodiments, each substituted or unsubstituted alkylene group is a substituted or unsubstituted C1-C8 alkylene group, each substituted or unsubstituted alkenyl group is a substituted or unsubstituted C2-C8 alkenylene group, each substituted or unsubstituted ynyne group is a substituted or unsubstituted C2-C8 ynyneene group, each substituted or unsubstituted heteroalkylene group is a substituted or unsubstituted 2- to 8-membered heteroalkylene group, and each substituted or unsubstituted heteroenylene group is a substituted or unsubstituted 3- to 8-membered heteroenylene group. Each substituted or unsubstituted heterocyclic group is a substituted or unsubstituted 3- to 8-membered heterocyclic group, each substituted or unsubstituted cycloalkyl group is a substituted or unsubstituted C3-C7 cycloalkyl group, each substituted or unsubstituted heterocyclic group is a substituted or unsubstituted 3- to 7-membered heterocyclic group, each substituted or unsubstituted aryl group is a substituted or unsubstituted phenylene group, and / or each substituted or unsubstituted heteroaryl group is a substituted or unsubstituted 5- to 6-membered heteroaryl group. In some embodiments, the compound is a chemical species described in the application (e.g., examples in the following sections or tables).

[0154] In the embodiments, substituted or unsubstituted portions (e.g., substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkylene, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkyn ... The substituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and / or substituted or unsubstituted heteroaryl) are unsubstituted (e.g., unsubstituted alkyl, unsubstituted alkenyl, unsubstituted alkynyl, unsubstituted heteroalkyl, unsubstituted heteroalkenyl, unsubstituted heteroalkynyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, unsubstituted heteroaryl, unsubstituted alkylene, unsubstituted alkenyl, unsubstituted alkynyl, unsubstituted heteroalkyl, unsubstituted heteroalkenyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl and / or unsubstituted heteroaryl). In the embodiments, substituted or unsubstituted portions (e.g., substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkylene, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkylene, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkylene, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted heteroalkylene The alkynyl group, substituted or unsubstituted cycloalkylene group, substituted or unsubstituted heteroalkylene group, substituted or unsubstituted arylene group and / or substituted or unsubstituted heteroarylene group are substituted (e.g., respectively substituted alkyl group, substituted alkenyl group, substituted alkynyl group, substituted heteroalkyl group, substituted heteroalkynyl group, substituted cycloalkyl group, substituted heteroalkyl group, substituted aryl group, substituted heteroaryl group, substituted alkylene group, substituted alkenylene group, substituted alkynylene group, substituted heteroalkylene group, substituted heteroalkynylene group, substituted cycloalkylene group, substituted heteroalkylene group, substituted arylene group and / or substituted heteroarylene group).

[0155] In embodiments, the substituted portion (e.g., substituted alkyl, substituted alkenyl, substituted alkynyl, substituted heteroalkyl, substituted heteroalkenyl, substituted heteroalkynyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted alkenyl, substituted alkynyl, substituted heteroalkylene, substituted heteroalkenyl, substituted heteroalkynyl, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene and / or substituted heteroarylene) is substituted with at least one substituent, wherein if the substituted portion is substituted with multiple substituents, each substituent may optionally be different. In embodiments, if the substituted portion is substituted with multiple substituents, each substituent is different.

[0156] In embodiments, the substituted portion (e.g., substituted alkyl, substituted alkenyl, substituted alkynyl, substituted heteroalkyl, substituted heteroalkenyl, substituted heteroalkynyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted alkenyl, substituted alkynyl, substituted heteroalkylene, substituted heteroalkenyl, substituted heteroalkynyl, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene and / or substituted heteroarylene) is substituted with at least one size-restricted substituent, wherein if the substituted portion is substituted with multiple size-restricted substituents, each size-restricted substituent may optionally be different. In embodiments, if the substituted portion is substituted with multiple size-restricted substituents, each size-restricted substituent is different.

[0157] In the embodiments, the substituted portion (e.g., substituted alkyl, substituted alkenyl, substituted alkynyl, substituted heteroalkyl, substituted heteroalkenyl, substituted heteroalkynyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted alkenyl, substituted alkynyl, substituted heteroalkylene, substituted heteroalkenyl, substituted heteroalkynyl, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene and / or substituted heteroarylene) is substituted with at least one lower substituent, wherein if the substituted portion is substituted with multiple lower substituents, each lower substituent may optionally be different. In the embodiments, if the substituted portion is substituted with multiple lower substituents, each lower substituent is different.

[0158] In the embodiments, the substituted portion (e.g., substituted alkyl, substituted alkenyl, substituted alkynyl, substituted heteroalkyl, substituted heteroalkenyl, substituted heteroalkynyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted alkenyl, substituted alkynyl, substituted heteroalkylene, substituted heteroalkynyl, substituted heteroalkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene and / or substituted heteroaryl) is substituted by at least one substituent, a size-restricted substituent, or a lower substituent; wherein if the substituted portion is substituted by a plurality of groups selected from substituents, size-restricted substituents, and lower substituents, each substituent, size-restricted substituent, and / or lower substituent may optionally be different. In the embodiments, if the substituted portion is replaced by a plurality of groups selected from substituents, size-restricted substituents, and / or lower substituents, then each substituent, size-restricted substituent, and lower substituent is different.

[0159] A "tautomer" is a molecule in which a proton can be transferred from one atom of the molecule to another atom of the same molecule. In some embodiments, the compounds provided herein exist as tautomers. In cases where tautomerization is possible, a chemical equilibrium of tautomers will exist. The exact proportions of tautomers depend on several factors, including physical state, temperature, solvent, and pH. Some examples of tautomeric equilibria include:

[0160]

[0161] "Pharmaceutically acceptable salt" includes both acid addition salts and base addition salts. The term "pharmaceutically acceptable salt" for any of the compounds described herein is intended to cover any and all pharmaceutically suitable salt forms. Preferred pharmaceutically acceptable salts of the compounds described herein are pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts.

[0162] "Pharmaceutically acceptable acid addition salts" refer to those salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, hydroiodic acid, hydrofluoric acid, and phosphorous acid, while retaining the biologically or otherwise desired bioavailability and properties of the free base. This also includes salts formed with organic acids such as aliphatic monocarboxylic acids and dicarboxylic acids, phenyl-substituted alkanes, hydroxyalkanes, alkanedioic acids, aromatic acids, aliphatic and aromatic sulfonic acids, and including, for example, acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, and salicylic acid. Therefore, exemplary salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, hydrogen monophosphate, dihydrogen phosphate, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, trifluoroacetates, propionates, octanoates, isobutyrates, oxalates, malonates, succinates, octanoates, fumarates, maleates, mandelates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, phthalates, benzenesulfonates, toluenesulfonates, phenylacetates, citrates, lactates, malates, tartrates, methanesulfonates, etc. Salts of amino acids, such as arginine salts, gluconates, and galacturons, have also been envisioned (see, for example, Berge S.M. et al., “Pharmaceutical Salts,” Journal of Pharmaceutical Science, 66:1-19 (1997). Acid addition salts of basic compounds are prepared by contacting the free base form with a sufficient amount of the desired acid to produce the salt.

[0163] "Pharmaceutically acceptable base addition salts" are those salts that retain the biological effectiveness and properties of the free acid as desired biologically or otherwise. These salts are prepared by adding an inorganic or organic base to the free acid. In some embodiments, pharmaceutically acceptable base addition salts form with a metal or amine such as an alkali metal or alkaline earth metal, or an organic amine. Salts derived from inorganic bases include, but are not limited to, salts of sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, etc. Salts derived from organic bases include, but are not limited to, salts of the following: primary, secondary, and tertiary amines; substituted amines, including naturally occurring substituted amines; cyclic amines; and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, N,N-dibenzylethylenediamine, chloroprocaine, hydroxylamine, choline, betaine, ethylenediamine, ethylenediphenylamine, N-methylglucosamine, glucosamine, methylglucosamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, polyamine resins, etc. See Berge et al., ibid.

[0164] "Prodrug" refers to a compound that, in some embodiments, is converted into the bioactive compound described herein under physiological conditions or by solvent degradation. Therefore, the term "prodrug" refers to a precursor of a pharmaceutically acceptable bioactive compound. Prodrugs are typically inactive when administered to a subject, but are converted into the active compound in vivo, for example, through hydrolysis. Prodrug compounds often offer advantages such as solubility, tissue compatibility, or delayed release in mammalian organisms (see, for example, Bundgard, H., Design of Prodrugs, Amsterdam: Elsevier, 1985). Discussions of prodrugs can also be found in Higuchi, T. et al., “Pro-drugs as Novel Delivery Systems,” ACS Symposium Series, Vol. 14, and Roche, EB., ed., “Bioreversible Carriers in Drug Design,” Oxford: Pergamon Press, 1987.

[0165] The term "prodrug" is also intended to include any covalently bonded carrier that releases the active compound in vivo when such a prodrug is administered to a mammalian subject. Prodrugs of the active compounds described herein can be prepared by modifying the functional groups present in the active compound in such a way that the modified compound cleaves into the parent active compound under normal handling or in vivo. Prodrugs comprise compounds in which a hydroxyl, amino, or thiol group is bonded to any group that, when the prodrug of the active compound is administered to a mammalian subject, cleaves to form a free hydroxyl, free amino, or free thiol group, respectively. Examples of prodrugs include, but are not limited to, acetate, formate, and benzoate derivatives of alcohols in the active compound.

[0166] "Pharmaceutically acceptable solvates" refer to compositions of substances in the form of solvation addition. In some embodiments, the solvate contains a stoichiometric or non-stoichiometric amount of solvent and is formed during preparation using a pharmaceutically acceptable solvent (such as water, ethanol, etc.). When the solvent is water, an "hydrate" is formed, or when the solvent is ethanol, an alcohol is formed. The solvates of the compounds described herein are conveniently prepared or formed in the methods described herein. The compounds provided herein are optionally present in both non-solventized and solvated forms.

[0167] The terms "alteric site" and "alteric binding site" refer to ligand binding sites that are topologically different from orthogonal binding sites.

[0168] The terms "orthogonal site" and "orthogonal binding site" refer to the primary binding site on a receptor that is recognized by the receptor's endogenous ligand or agonist. For example, the orthogonal site on the muscarinic acetylcholine M1 receptor is the site where acetylcholine binds.

[0169] The term "ligand" refers to a natural or synthetic molecule that can bind to or associate with a receptor to form a complex and mediate, prevent, or alter biological effects. The term "ligand" is intended to encompass allosteric modulators, inhibitors, activators, agonists, antagonists, natural substrates, and analogues of natural substrates.

[0170] The terms “natural ligand” and “endogenous ligand” refer to naturally occurring ligands that bind to receptors.

[0171] In the embodiments, the terms “inhibition,” “inhibit,” “inhibiting,” etc., relating to protein-inhibitor interactions, mean a negative impact (e.g., reduction) on the activity or function of a protein relative to the absence of an inhibitor. In the embodiments, inhibition means a negative impact (e.g., reduction) on the concentration or level of a protein relative to the absence of an inhibitor. In the embodiments, inhibition refers to a reduction in disease or symptoms of disease. In the embodiments, inhibition refers to a reduction in the activity of a specific protein target. Therefore, inhibition at least partially or completely comprises partially or completely blocking stimulation, reducing, preventing or delaying activation, desensitizing, or downregulating signal transduction or enzyme activity or the amount of protein. In the embodiments, inhibition refers to a reduction in the activity of a target protein caused by a direct interaction (e.g., the inhibitor binding to the target protein). In the embodiments, inhibition refers to a reduction in the activity of a target protein caused by an indirect interaction (e.g., the inhibitor binding to a protein that activates the target protein, thereby preventing the target protein from activating).

[0172] In the embodiments, the terms "inhibitor," "repressor," "antagonist," or "downregulator" are interchangeable as substances capable of detectably reducing the expression or activity of a given gene or protein. Antagonists can reduce expression or activity by 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or more compared to a control without an antagonist. In some cases, expression or activity is 1 / 1.5, 1 / 2, 1 / 3, 1 / 4, 1 / 5, 1 / 10, or even less than the expression or activity without an antagonist.

[0173] In this embodiment, the term "expression" encompasses any step involved in the production of a polypeptide, including but not limited to transcription, post-transcriptional modification, translation, post-translational modification, and secretion. Expression can be detected using conventional techniques for protein detection, such as ELISA, Western blotting, flow cytometry, immunofluorescence, immunohistochemistry, etc.

[0174] The term "mAChRM1 receptor antagonist" refers to any exogenously administered compound or agent capable of partially or completely inhibiting or reversing the effect of an agonist (e.g., acetylcholine) on the mAChRM1 receptor. This term encompasses compounds or agents characterized as antagonists, partial antagonists, and negative allosteric modulators (or described as having the aforementioned characteristics). For example, mAChRM1 receptor antagonists may mediate their action by binding to an ortho- or allosteric site, or they may interact at unique binding sites that are not normally involved in the biological regulation of receptor activity. Thus, in animals, particularly mammals (e.g., humans), mAChRM1 receptor antagonists directly or indirectly inhibit the activity of the mAChRM1 receptor in the presence or absence of acetylcholine or another agonist. In various respects, mAChRM1 receptor antagonists reduce the activity of the cellular mAChRM1 receptor in the presence of extracellular acetylcholine. In some embodiments, the compound as a “mAChRM1 receptor antagonist” includes compounds as “mAChRM1 receptor competitive antagonist”, “mAChRM1 receptor non-competitive antagonist”, “mAChRM1 receptor partial antagonist”, or “mAChRM1 receptor negative allosteric regulator”.

[0175] The term "mAChRM1 receptor competitive antagonist" refers to any exogenously applied compound or agent that can bind to the orthotopic site of the mAChRM1 receptor without activating the receptor. Therefore, competitive antagonists can interact with the mAChRM1 receptor and compete with the endogenous ligand acetylcholine for receptor binding, reducing the receptor's ability to transduce intracellular signals in response to endogenous ligand binding.

[0176] The term "mAChRM1 receptor noncompetitive antagonist" refers to any exogenously applied compound or agent that binds to a site that is not an ortho-binding site of the mAChRM1 receptor and is capable of partially or completely inhibiting or reversing the effect of an agonist (e.g., acetylcholine) on the mAChRM1 receptor. Therefore, noncompetitive antagonists can interact with the mAChRM1 receptor and reduce the binding of the endogenous ligand acetylcholine to the receptor and / or reduce the receptor's ability to transduce intracellular signals in response to endogenous ligand binding.

[0177] The term "mAChRM1 partial antagonist" refers to any exogenously administered compound or agent that can bind to either the ortho- or allosteric site, but whose binding effect only partially blocks the response of the mAChRM1 receptor to an agonist, such as acetylcholine. Therefore, partial antagonists can interact with the mAChRM1 receptor but cannot completely inhibit its response to an agonist, such as acetylcholine.

[0178] The term "mAChR M1 negative allosteric modulator" refers to any exogenously administered compound or agent that binds to an allosteric site that directly or indirectly inhibits the activity of the mAChR M1 receptor in the body of animals, particularly mammals such as humans, in the presence of acetylcholine or another agonist. For example, while not intended to limit this disclosure, selective muscarinic M1 negative allosteric modulators can preferentially bind to muscarinic M1 receptors and reduce muscarinic M1 signaling by acting as non-competitive antagonists. In one aspect, mAChR M1 receptor negative allosteric modulators reduce the cellular activity of the mAChRM1 receptor in the presence of extracellular acetylcholine.

[0179] In the embodiments, the terms "selective" or "selectivity" in relation to a compound or agent refer to the ability of a compound or agent to preferentially increase or decrease the activity of a specific molecular target (e.g., protein, enzyme, etc.) over one or more different molecular targets (e.g., a compound selective for the muscarinic acetylcholine M1 receptor (mAChRM1) will preferentially inhibit mAChR M1 rather than other muscarinic receptors). In the embodiments, "muscarinic acetylcholine M1 receptor selective compound" or "mAChR M1 selective compound" refers to a compound selective for the muscarinic acetylcholine M1 receptor (mAChRM1) (e.g., the compound described herein). In the embodiments, the selectivity of the compound (e.g., the compound described herein) for the muscarinic acetylcholine M1 receptor (mAChRM1) is about 5, 10, 20, 30, 40, 50, or about 100 times that of one or more of the mAChR M2, M3, M4, or M5 receptors. In the embodiments, the compounds (e.g., those described herein) are selective for muscarinic acetylcholine M1 receptors (mAChRM1) by at least 5, 10, 20, 30, 40, 50, or at least 100 times more than one or more of the mAChRM2, M3, M4, or M5 receptors.

[0180] The terms "subject" or "patient" encompass mammals. Examples of mammals include, but are not limited to, any member of the mammal class: humans, non-human primates such as chimpanzees and other apes and monkeys; livestock such as cattle, horses, sheep, goats, and pigs; domestic animals such as rabbits, dogs, and cats; and laboratory animals, including rodents such as rats, mice, and guinea pigs. In one respect, a subject is a human.

[0181] As used herein, the terms “treatment,” “treating,” “relief,” or “improvement” are used interchangeably. These terms refer to methods used to obtain beneficial or desired outcomes, including, but not limited to, therapeutic and / or preventive benefits. A “therapeutic benefit” means the eradication or improvement of the underlying condition being treated. Furthermore, a therapeutic benefit is achieved by eradicating or improving one or more physical symptoms associated with the underlying condition, resulting in an improvement observed in the patient, even though the patient still has the underlying condition. For preventive benefits, the composition is given to a patient at risk of developing a specific disease, or to a patient who reports one or more physical symptoms of a disease, even if the disease has not yet been diagnosed.

[0182] As used in this article, "EC" 50 "This refers to a concentration of 50% of the substances (e.g., compounds or drugs) required to activate or enhance a biological process or its components, including proteins, subunits, organelles, ribonucleoproteins, etc." For example, EC 50 This can refer to the concentration of an agonist that elicits a response in an in vitro assay that is half between the baseline and maximum response. In some embodiments, the in vitro assay system utilizes a cell line that has been transfected with an endogenous expression of the target of interest or with a suitable expression vector that guides the expression of the target in a recombinant form.

[0183] As used in this article, "IC" 50 "Intended to refer to a concentration of 50% of the substances (e.g., compounds or drugs) required to inhibit a biological process or its components, including proteins, subunits, organelles, ribonucleoproteins, etc." For example, IC50. 50 The half-maximal (50%) inhibitory concentration (IC) of a substance is determined in a suitable assay. For example, the IC50 of the mAChRM1 receptor. 50 It can be determined in an in vitro assay system.

[0184] II.Compounds

[0185] This disclosure provides compounds that act as antagonists of the muscarinic acetylcholine M1 receptor (mAChRM1). These compounds and compositions comprising these compounds can be used to treat or prevent neurological disorders. In some embodiments, the compounds described herein can be used to treat multiple sclerosis.

[0186] One aspect provides a compound or a pharmaceutically acceptable salt or solvation thereof having a structure of formula (IA-1) or (IB-1):

[0187]

[0188] in:

[0189] X is a bond, -C(R) 9(R) 10 )-、-N(R 11 )-、-O-、-S(O) n -, -CH2N(R) 11 )-, substituted or unsubstituted alkylene groups (e.g., C1-C8, C1-C6, C1-C4 or C1-C2), substituted or unsubstituted alkenyl groups (e.g., C2-C8, C2-C6 or C2-C4), substituted or unsubstituted ynynyl groups (e.g., C2-C8, C2-C6 or C2-C4), substituted or unsubstituted heteroalkyl groups (e.g., 2- to 8-membered, 2- to 6-membered, 4- to 6-membered or 2- to 3-membered), substituted or unsubstituted alkenyl groups (e.g., 3- to 8-membered, 3- to 6-membered or 4- to 6-membered), or substituted or unsubstituted heteroynyl groups (e.g., 3- to 8-membered, 3- to 6-membered or 4- to 6-membered).

[0190] Y is a substituted or unsubstituted alkylene group (e.g., C1-C8, C1-C6, C1-C4 or C1-C2), a substituted or unsubstituted alkenyl group (e.g., C2-C8, C2-C6 or C2-C4), or a substituted or unsubstituted heteroalkylene group (e.g., 2- to 8-membered, 2- to 6-membered, 4- to 6-membered or 2- to 3-membered).

[0191] R 1 for Wherein ring A is optionally substituted with the following heteroaryl ring or heterocyclic alkyl ring: hydroxyl, halogen, cyano, -N(R) 14 (R) 15Substituted or unsubstituted alkyl groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted alkoxy groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted haloalkyl groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted haloalkoxy groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted cycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, or C1-C2). C5-C6), substituted or unsubstituted cycloalkoxy groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted halocycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted halocycloalkoxy groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyl groups (e.g., ternary to octyl, ternary to septary, quaternary to septary, quaternary to quinary, or quinary to septary), substituted or unsubstituted aryl groups (e.g., C6-C6). 10 (or phenyl), substituted or unsubstituted heteroaryl groups (e.g., 5 to 10, 5 to 9, or 5 to 6), -S(O) n (R 16 ) or -SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S;

[0192] R 2The following are considered as hydrogen, deuterium, halogen, hydroxyl, substituted or unsubstituted alkyl groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted alkoxy groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted haloalkyl groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted haloalkoxy groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted cycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted... Cycloalkoxy groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted halocycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted halocycloalkoxy groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted alkylhydroxy groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted heterocycloalkyl groups (e.g., 3- to 8-membered, 3- to 6-membered, 4- to 6-membered, 4- to 5-membered, or 5- to 6-membered), substituted or unsubstituted aryl groups (e.g., C6-C6). 10 (or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5 to 10 yuan, 5 to 9 yuan or 5 to 6 yuan);

[0193] R 3Halogen, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted alkoxy (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted haloalkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted haloalkoxy (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted cycloalkoxy (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted halocycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted halocycloalkoxy groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted alkylhydroxy groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted heterocycloalkyl groups (e.g., 3- to 8-membered, 3- to 6-membered, 4- to 6-membered, 4- to 5-membered, or 5- to 6-membered), substituted or unsubstituted aryl groups (e.g., C6-C...). 10 (or phenyl) or substituted or unsubstituted heteroaryl groups (e.g., 5 to 10, 5 to 9, or 5 to 6); or R 2 and R 3 Combining to form a cycloalkyl (e.g., C3-C8, C3-C6, C4-C6 or C5-C6) or heterocycloalkyl (e.g., 3- to 8-membered, 3- to 6-membered, 4- to 6-membered, 4- to 5-membered or 5- to 6-membered) ring optionally substituted with: halogen, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4 or C1-C2) or substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6 or C5-C6);

[0194] R 4 and R 5 Independently selected from hydrogen, deuterium, halogens, and substituted or unsubstituted alkyl groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2); or R 3 and R 4Combining to form a cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6) or heterocycloalkyl (e.g., ternary to octyl, ternary to septary, quaternary to septary, quaternary to quinary, or quinary to septary) ring optionally substituted with: halogen, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2) or substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6); or R 4 and R 5 Combining to form a cycloalkyl (e.g., C3-C8, C3-C6, C4-C6 or C5-C6) or heterocycloalkyl (e.g., 3- to 8-membered, 3- to 6-membered, 4- to 6-membered, 4- to 5-membered or 5- to 6-membered) ring optionally substituted with: halogen, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4 or C1-C2) or substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6 or C5-C6);

[0195] R 6 and R 7 Independently selected from hydrogen, deuterium, halogens, and substituted or unsubstituted alkyl groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2); or R 3 and R 7 Combining to form a cycloalkyl (e.g., C4-C8, C4-C6, or C5-C6) or heterocycloalkyl (e.g., 4- to 8-membered, 4- to 6-membered, 4- to 5-membered, or 5- to 6-membered) ring optionally substituted with: halogen, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2) or substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6); or R 4 and R 6 Combining to form a cycloalkyl (e.g., C4-C8, C4-C6, or C5-C6) or heterocycloalkyl (e.g., 4- to 8-membered, 4- to 6-membered, 4- to 5-membered, or 5- to 6-membered) ring optionally substituted with: halogen, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2) or substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6); or R 5 and R 7 Combining to form bonds;

[0196] R 8 for

[0197] R 9 and R10 Independently selected from hydrogen, deuterium, halogen, substituted or unsubstituted alkyl groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted alkoxy groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted haloalkyl groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted haloalkoxy groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted cycloalkyl groups (e.g., C3-C8, C3-C6, C1-C4, C1-C2), and substituted or unsubstituted cycloalkyl groups (e.g., C3-C8, C3-C6, C1-C4, C1-C2). 4-C6 or C5-C6), substituted or unsubstituted cycloalkoxy groups (e.g., C3-C8, C3-C6, C4-C6 or C5-C6), substituted or unsubstituted halocycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6 or C5-C6), substituted or unsubstituted halocycloalkoxy groups (e.g., C3-C8, C3-C6, C4-C6 or C5-C6), substituted or unsubstituted heterocycloalkyl groups (e.g., 3- to 8-membered, 3- to 6-membered, 4- to 6-membered, 4- to 5-membered or 5- to 6-membered), substituted or unsubstituted aryl groups (e.g., C6-C6 or C5-C6). 10 Or phenyl), or substituted or unsubstituted heteroaryl groups (e.g., 5 to 10, 5 to 9, or 5 to 6); or R 3 and R 10 Combining to form a cycloalkyl (e.g., C4-C8, C4-C6, or C5-C6) or heterocycloalkyl (e.g., 4- to 8-membered, 4- to 6-membered, 4- to 5-membered, or 5- to 6-membered) ring optionally substituted with: halogen, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2) or substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6); or R 4 and R 10 Combining to form a cycloalkyl (e.g., C4-C8, C4-C6, or C5-C6) or heterocycloalkyl (e.g., 4- to 8-membered, 4- to 6-membered, 4- to 5-membered, or 5- to 6-membered) ring optionally substituted with: halogen, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2) or substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6); or R 6 and R 10Combining to form a cycloalkyl (e.g., C4-C8, C4-C6, or C5-C6) or heterocycloalkyl (e.g., 4- to 8-membered, 4- to 6-membered, 4- to 5-membered, or 5- to 6-membered) ring optionally substituted with: halogen, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2) or substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6); or R 9 and R 10 Combining to form a cycloalkyl (e.g., C3-C8, C3-C6, C4-C6 or C5-C6) or heterocycloalkyl (e.g., 3- to 8-membered, 3- to 6-membered, 4- to 6-membered, 4- to 5-membered or 5- to 6-membered) ring optionally substituted with: halogen, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4 or C1-C2) or substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6 or C5-C6);

[0198] R 11 Hydrogen, substituted or unsubstituted alkyl groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted haloalkyl groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted cycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted halocycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyl groups (e.g., 3- to 8-membered, 3- to 6-membered, 4- to 6-membered, 4- to 5-membered, or 5- to 6-membered), substituted or unsubstituted aryl groups (e.g., C6-C...). 10 (or phenyl) or substituted or unsubstituted heteroaryl groups (e.g., 5 to 10, 5 to 9, or 5 to 6); or R 3 and R 11 Combining to form a heterocyclic alkyl group optionally substituted with the following (e.g., 3- to 8-membered, 3- to 6-membered, 4- to 6-membered, 4- to 5-membered, or 5- to 6-membered) ring: halogen, substituted or unsubstituted alkyl group (e.g., C1-C8, C1-C6, C1-C4, or C1-C2) or substituted or unsubstituted cycloalkyl group (e.g., C3-C8, C3-C6, C4-C6, or C5-C6); or R 4 and R 11Combining to form a heterocyclic alkyl group optionally substituted with the following (e.g., 3- to 8-membered, 3- to 6-membered, 4- to 6-membered, 4- to 5-membered, or 5- to 6-membered) ring: halogen, substituted or unsubstituted alkyl group (e.g., C1-C8, C1-C6, C1-C4, or C1-C2) or substituted or unsubstituted cycloalkyl group (e.g., C3-C8, C3-C6, C4-C6, or C5-C6); or R 6 and R 11 Combining to form heterocyclic alkyl (e.g., 3- to 8-membered, 3- to 6-membered, 4- to 6-membered, 4- to 5-membered or 5- to 6-membered) rings optionally substituted with: halogen, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4 or C1-C2) or substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6 or C5-C6);

[0199] Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 Substituted or unsubstituted alkyl groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted alkoxy groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted haloalkyl groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted haloalkoxy groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted cycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted cycloalkoxy groups ( For example, C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted halocycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted halocycloalkoxy groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted alkylhydroxy groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted heterocycloalkyl groups (e.g., 3- to 8-membered, 3- to 6-membered, 4- to 6-membered, 4- to 5-membered, or 5- to 6-membered), substituted or unsubstituted aryl groups (e.g., C6-C...). 10 (or phenyl) or substituted or unsubstituted heteroaryl groups (e.g., 5 to 10, 5 to 9, or 5 to 6), -S(O) n (R 16 ) or -SF5; or R 3 And an R 12Combining to form a cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6) or heterocycloalkyl (e.g., ternary to octyl, ternary to septary, quaternary to septary, quaternary to quinary, or quinary to septary) ring optionally substituted with: halogen, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2) or substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6); or R 10 And an R 12 Combining to form a cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6) or heterocycloalkyl (e.g., ternary to octyl, ternary to septary, quaternary to septary, quaternary to quinary, or quinary to septary) ring optionally substituted with: halogen, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2) or substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6); or R 11 And an R 12 Combining to form heterocyclic alkyl (e.g., 3- to 8-membered, 3- to 6-membered, 4- to 6-membered, 4- to 5-membered or 5- to 6-membered) rings optionally substituted with: halogen, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4 or C1-C2) or substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6 or C5-C6);

[0200] R 13 Hydrogen, substituted or unsubstituted alkyl groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted haloalkyl groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted cycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted halocycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyl groups (e.g., 3- to 8-membered, 3- to 6-membered, 4- to 6-membered, 4- to 5-membered, or 5- to 6-membered), substituted or unsubstituted aryl groups (e.g., C6-C...). 10 (or phenyl) or substituted or unsubstituted heteroaryl (e.g., 5 to 10, 5 to 9 or 5 to 6);

[0201] R 14 and R 15Independently selected from hydrogen, substituted or unsubstituted alkyl groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted haloalkyl groups (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted cycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted halocycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyl groups (e.g., 3- to 8-membered, 3- to 6-membered, 4- to 6-membered, 4- to 5-membered, or 5- to 6-membered), and substituted or unsubstituted aryl groups (e.g., C6-C4). 10 (or phenyl) or substituted or unsubstituted heteroaryl groups (e.g., 5 to 10, 5 to 9, or 5 to 6); or R 14 and R 15 Combining to form heterocyclic alkyl (e.g., 3- to 8-membered, 3- to 6-membered, 4- to 6-membered, 4- to 5-membered or 5- to 6-membered) rings optionally substituted with: halogen, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4 or C1-C2) or substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6 or C5-C6);

[0202] R 16 The substituted or unsubstituted alkyl group (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), the substituted or unsubstituted haloalkyl group (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), the substituted or unsubstituted cycloalkyl group (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), the substituted or unsubstituted halocycloalkyl group (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), the substituted or unsubstituted heterocycloalkyl group (e.g., 3- to 8-membered, 3- to 6-membered, 4- to 6-membered, 4- to 5-membered, or 5- to 6-membered), and the substituted or unsubstituted aryl group (e.g., C6-C4, C5-C6, C6-C6, C7-C6, C7-C6, C7-C7-C6, C7-C8, C7-C6 ... 10 (or phenyl) or substituted or unsubstituted heteroaryl (e.g., 5 to 10, 5 to 9 or 5 to 6);

[0203] m is 0 or 1;

[0204] n is 0, 1, or 2;

[0205] o is 0, 1, 2, or 3; and

[0206] p is 0 or 1.

[0207] One aspect provides a compound of formula (IA) or (IB):

[0208]

[0209] in:

[0210] X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 )-、-O-、-S(O) n -, -CH2N(R) 11 - or -CH2O-;

[0211] Y is -CH2-, -CH2CH2-, -CH=CH-, or -CH2OCH2-;

[0212] R 1 for Wherein ring A is optionally substituted with a 5- or 6-membered heteroaryl ring or a 5- or 6-membered heterocyclic alkyl ring: halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S;

[0213] R 2 Hydrogen, deuterium, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl;

[0214] R 3 Halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; or R 2 and R 3 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0215] R 4 and R 5 Independently selected from hydrogen, deuterium, halogens and C 1-3 Alkyl; or R 3 and R 4 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 5 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0216] R 6 and R 7 Independently selected from hydrogen, deuterium, halogens and C 1-3 Alkyl; or R 3 and R 7 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 6 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 5 and R 7 Combining to form bonds;

[0217] R 8 for

[0218] R 9 and R 10 Independently selected from hydrogen, deuterium, halogens, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl or heteroaryl; or R 3 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 6 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 9 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0219] R 11 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 3 and R 11 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 11 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 6 and R 11 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0220] Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5; or R 3 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 10 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 11 And an R 12 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0221] R 13 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0222] R 14 and R 15 Independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 14 and R 15 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0223] R 16 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0224] m is 0 or 1;

[0225] n is 0, 1, or 2; and

[0226] o can be 0, 1, 2, or 3;

[0227] Or a pharmaceutically acceptable salt or solvate thereof, provided that the above combination does not violate the rules of value known to those skilled in the art.

[0228] One aspect provides a compound of formula (IIA) or (IIB):

[0229]

[0230] in:

[0231] X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 )-、-O-、-S(O) n -, -CH2N(R) 11 - or -CH2O-;

[0232] Y is -CH2-, -CH2CH2-, -CH=CH-, or -CH2OCH2-;

[0233] R 1 for Wherein ring A is optionally substituted with a 5- or 6-membered heteroaryl ring or a 5- or 6-membered heterocyclic alkyl ring: halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S;

[0234] R 2 Hydrogen, deuterium, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl;

[0235] R 3 Halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; or R 2 and R 3 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0236] R 8 for

[0237] R 9 and R 10 Independently selected from hydrogen, deuterium, halogens, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl or heteroaryl; or R 3 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 9 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0238] R 11 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 3 and R11 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0239] Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5; or R 3 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 10 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 11 And an R 12 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0240] R 13 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0241] R 14 and R 15 Independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 14 and R 15 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C1-6 Alkyl or C 3-6 cycloalkyl;

[0242] R 16 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0243] m is 0 or 1;

[0244] n is 0, 1, or 2; and

[0245] o can be 0, 1, 2, or 3;

[0246] Or a pharmaceutically acceptable salt or solvate thereof, provided that the above combination does not violate the rules of value known to those skilled in the art.

[0247] On the other hand, a compound of formula (III) is provided:

[0248]

[0249] in:

[0250] X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 )-、-O-、-S(O) n -, -CH2N(R) 11 - or -CH2O-;

[0251] R 1 for Wherein ring A is optionally substituted with a 5- or 6-membered heteroaryl ring or a 5- or 6-membered heterocyclic alkyl ring: halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S;

[0252] R 2 Hydrogen, deuterium, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl;

[0253] R 3 Halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; or R 2 and R 3 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0254] R 8 for

[0255] R 9 and R 10 Independently selected from hydrogen, deuterium, halogens, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl or heteroaryl; or R 3 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 9 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6cycloalkyl;

[0256] R 11 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 3 and R 11 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0257] Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5; or R 3 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 10 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 11 And an R 12 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0258] R 13 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0259] R 14 and R 15Independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 14 and R 15 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0260] R 16 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0261] m is 0 or 1;

[0262] n is 0, 1, or 2; and

[0263] o can be 0, 1, 2, or 3;

[0264] Or a pharmaceutically acceptable salt or solvate thereof, provided that the above combination does not violate the rules of value known to those skilled in the art.

[0265] In embodiments of the compounds described herein (e.g., compounds of formula (IA-1), (IB-1), (IA), (IB), (IIA), (IIB), or (III)) or their pharmaceutically acceptable salts or solvates, X is a bond, -C(R 9 (R) 10 )-、-N(R 11 - or -O-. In some embodiments, X is a key, -N(R) 11 )- or -O-.

[0266] In some embodiments of compounds of formula (IA), (IB), (IIA), (IIB), or (III) or their pharmaceutically acceptable salts or solvates, X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 - or -O-. In some embodiments, X is a key, -N(R) 11 )- or -O-.

[0267] In embodiments, the substituted X (e.g., a substituted alkylene group, a substituted alkenylene group, a substituted ynynylene group, a substituted heteroalkylene group, a substituted alkenylene group, and / or a substituted heteroynylene group) is substituted with at least one substituent, a size-restricted substituent, or a lower substituent; wherein if the substituted X is substituted with a plurality of groups selected from substituents, size-restricted substituents, and lower substituents, each substituent, size-restricted substituent, and / or lower substituent may optionally be different. In embodiments, when X is substituted, it is substituted with at least one substituent. In embodiments, when X is substituted, it is substituted with at least one size-restricted substituent. In embodiments, when X is substituted, it is substituted with at least one lower substituent.

[0268] In embodiments, the substituted Y (e.g., a substituted alkylene, a substituted alkenylene, and / or a substituted heteroalkylene) is substituted with at least one substituent, a size-restricted substituent, or a lower substituent; wherein if the substituted Y is substituted with a plurality of groups selected from substituents, size-restricted substituents, and lower substituents, each substituent, size-restricted substituent, and / or lower substituent may optionally be different. In embodiments, when Y is substituted, it is substituted with at least one substituent. In embodiments, when Y is substituted, it is substituted with at least one size-restricted substituent. In embodiments, when Y is substituted, it is substituted with at least one lower substituent.

[0269] In the embodiments, ring A may be substituted with a hydroxyl group in addition to the substituents listed.

[0270] In embodiments of the compounds described herein (e.g., compounds of formula (IA-1), (IB-1), (IA), (IB), (IIA), (IIB), or (III)) or their pharmaceutically acceptable salts or solvates, R 1 for In some embodiments, R 1 for

[0271] In some embodiments of compounds of formula (IA), (IB), (IIA), (IIB), or (III) or their pharmaceutically acceptable salts or solvates, R 1 for In some embodiments, R 1 for

[0272] In the embodiment, R 2Hydrogen, deuterium, halogen, hydroxyl group, substituted or unsubstituted C 1-6 Alkyl, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Halogenated alkyl, substituted or unsubstituted C 1-6 Haloalkoxy, substituted or unsubstituted C 3-6 Cycloalkyl, substituted or unsubstituted C 3-6 Cycloalkoxy, substituted or unsubstituted C 3-6 Halogenated cycloalkyl, substituted or unsubstituted C 3-6 Halogenated cycloalkoxy, substituted or unsubstituted C 1-6 Alkyl hydroxyl, substituted or unsubstituted heterocyclic alkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.

[0273] In the embodiments, the replaced R 2 (For example, a substituted alkyl group, a substituted alkoxy group, a substituted haloalkyl group, a substituted haloalkoxy group, a substituted cycloalkyl group, a substituted cycloalkoxy group, a substituted halocycloalkyl group, a substituted halocycloalkoxy group, a substituted alkylhydroxy group, a substituted heterocycloalkyl group, a substituted aryl group, and / or a substituted heteroaryl group) is substituted by at least one substituent, a size-restricted substituent, or a lower substituent; wherein if the substituted R 2 The substituent is selected from a plurality of groups chosen from substituents, size-restricted substituents, and lower substituents, wherein each substituent, size-restricted substituent, and / or lower substituent may optionally be different. In an embodiment, when R 2 When substituted, it is replaced by at least one substituent. In an embodiment, when R 2 When substituted, it is replaced by at least one size-restricted substituent. In an embodiment, when R 2 When substituted, it is replaced by at least one lower substituent.

[0274] In the embodiments, the replaced R 3 (For example, a substituted alkyl group, a substituted alkoxy group, a substituted haloalkyl group, a substituted haloalkoxy group, a substituted cycloalkyl group, a substituted cycloalkoxy group, a substituted halocycloalkyl group, a substituted halocycloalkoxy group, a substituted alkylhydroxy group, a substituted heterocycloalkyl group, a substituted aryl group, and / or a substituted heteroaryl group) is substituted by at least one substituent, a size-restricted substituent, or a lower substituent; wherein if the substituted R 3 The substituent is selected from a plurality of groups chosen from substituents, size-restricted substituents, and lower substituents, wherein each substituent, size-restricted substituent, and / or lower substituent may optionally be different. In an embodiment, when R 3When substituted, it is replaced by at least one substituent. In an embodiment, when R 3 When substituted, it is replaced by at least one size-restricted substituent. In an embodiment, when R 3 When substituted, it is replaced by at least one lower substituent.

[0275] In the embodiments, the replaced R 4 (For example, a substituted alkyl group) is substituted by at least one substituent, a size-restricted substituent, or a lower substituent; wherein if the substituted R 4 The substituent is selected from a plurality of groups chosen from substituents, size-restricted substituents, and lower substituents, wherein each substituent, size-restricted substituent, and / or lower substituent may optionally be different. In an embodiment, when R 4 When substituted, it is replaced by at least one substituent. In an embodiment, when R 4 When substituted, it is replaced by at least one size-restricted substituent. In an embodiment, when R 4 When substituted, it is replaced by at least one lower substituent.

[0276] In the embodiments, the replaced R 5 (For example, a substituted alkyl group) is substituted by at least one substituent, a size-restricted substituent, or a lower substituent; wherein if the substituted R 5 The substituent is selected from a plurality of groups chosen from substituents, size-restricted substituents, and lower substituents, wherein each substituent, size-restricted substituent, and / or lower substituent may optionally be different. In an embodiment, when R 5 When substituted, it is replaced by at least one substituent. In an embodiment, when R 5 When substituted, it is replaced by at least one size-restricted substituent. In an embodiment, when R 5 When substituted, it is replaced by at least one lower substituent.

[0277] In the embodiments, the replaced R 6 (For example, a substituted alkyl group) is substituted by at least one substituent, a size-restricted substituent, or a lower substituent; wherein if the substituted R 6 The substituent is selected from a plurality of groups chosen from substituents, size-restricted substituents, and lower substituents, wherein each substituent, size-restricted substituent, and / or lower substituent may optionally be different. In an embodiment, when R 6 When substituted, it is replaced by at least one substituent. In an embodiment, when R 6 When substituted, it is replaced by at least one size-restricted substituent. In an embodiment, when R 6 When substituted, it is replaced by at least one lower substituent.

[0278] In the embodiments, the replaced R 7 (For example, a substituted alkyl group) is substituted by at least one substituent, a size-restricted substituent, or a lower substituent; wherein if the substituted R 7 The substituent is selected from a plurality of groups chosen from substituents, size-restricted substituents, and lower substituents, wherein each substituent, size-restricted substituent, and / or lower substituent may optionally be different. In an embodiment, when R 7 When substituted, it is replaced by at least one substituent. In an embodiment, when R 7 When substituted, it is replaced by at least one size-restricted substituent. In an embodiment, when R 7 When substituted, it is replaced by at least one lower substituent.

[0279] In embodiments of the compounds described herein (e.g., compounds of formula (IA-1), (IB-1), (IA), (IB), (IIA), (IIB), or (III)) or their pharmaceutically acceptable salts or solvates, R 8 for In some embodiments, R 8 for

[0280] In some embodiments of compounds of formula (IA), (IB), (IIA), (IIB), or (III) or their pharmaceutically acceptable salts or solvates, R 8 for In some embodiments, R 8 for

[0281] In the embodiments, the replaced R 9 (For example, a substituted alkyl group, a substituted alkoxy group, a substituted haloalkyl group, a substituted haloalkoxy group, a substituted cycloalkyl group, a substituted cycloalkoxy group, a substituted halocycloalkyl group, a substituted halocycloalkoxy group, a substituted heterocycloalkyl group, a substituted aryl group, and / or a substituted heteroaryl group) is substituted by at least one substituent, a size-restricted substituent, or a lower substituent; wherein if the substituted R 9 The substituent is selected from a plurality of groups chosen from substituents, size-restricted substituents, and lower substituents, wherein each substituent, size-restricted substituent, and / or lower substituent may optionally be different. In an embodiment, when R 9 When substituted, it is replaced by at least one substituent. In an embodiment, when R 9 When substituted, it is replaced by at least one size-restricted substituent. In an embodiment, when R 9 When substituted, it is replaced by at least one lower substituent.

[0282] In the embodiments, the replaced R10 (For example, a substituted alkyl group, a substituted alkoxy group, a substituted haloalkyl group, a substituted haloalkoxy group, a substituted cycloalkyl group, a substituted cycloalkoxy group, a substituted halocycloalkyl group, a substituted halocycloalkoxy group, a substituted heterocycloalkyl group, a substituted aryl group, and / or a substituted heteroaryl group) is substituted by at least one substituent, a size-restricted substituent, or a lower substituent; wherein if the substituted R 10 The substituent is selected from a plurality of groups chosen from substituents, size-restricted substituents, and lower substituents, wherein each substituent, size-restricted substituent, and / or lower substituent may optionally be different. In an embodiment, when R 10 When substituted, it is replaced by at least one substituent. In an embodiment, when R 10 When substituted, it is replaced by at least one size-restricted substituent. In an embodiment, when R 10 When substituted, it is replaced by at least one lower substituent.

[0283] In the embodiments, the replaced R 11 (For example, a substituted alkyl group, a substituted haloalkyl group, a substituted cycloalkyl group, a substituted halocycloalkyl group, a substituted heterocycloalkyl group, a substituted aryl group, and / or a substituted heteroaryl group) is substituted by at least one substituent, a size-restricted substituent, or a lower substituent; wherein if the substituted R 11 The substituent is selected from a plurality of groups chosen from substituents, size-restricted substituents, and lower substituents, wherein each substituent, size-restricted substituent, and / or lower substituent may optionally be different. In an embodiment, when R 11 When substituted, it is replaced by at least one substituent. In an embodiment, when R 11 When substituted, it is replaced by at least one size-restricted substituent. In an embodiment, when R 11 When substituted, it is replaced by at least one lower substituent.

[0284] In the embodiments, the replaced R 12 (For example, a substituted alkyl group, a substituted alkoxy group, a substituted haloalkyl group, a substituted haloalkoxy group, a substituted cycloalkyl group, a substituted cycloalkoxy group, a substituted halocycloalkyl group, a substituted halocycloalkoxy group, a substituted alkylhydroxy group, a substituted heterocycloalkyl group, a substituted aryl group, and / or a substituted heteroaryl group) is substituted by at least one substituent, a size-restricted substituent, or a lower substituent; wherein if the substituted R 12 The substituent is selected from a plurality of groups chosen from substituents, size-restricted substituents, and lower substituents, wherein each substituent, size-restricted substituent, and / or lower substituent may optionally be different. In an embodiment, when R 12 When substituted, it is replaced by at least one substituent. In an embodiment, when R12 When substituted, it is replaced by at least one size-restricted substituent. In an embodiment, when R 12 When substituted, it is replaced by at least one lower substituent.

[0285] In the embodiments, the replaced R 13 (For example, a substituted alkyl group, a substituted haloalkyl group, a substituted cycloalkyl group, a substituted halocycloalkyl group, a substituted heterocycloalkyl group, a substituted aryl group, and / or a substituted heteroaryl group) is substituted by at least one substituent, a size-restricted substituent, or a lower substituent; wherein if the substituted R 13 The substituent is selected from a plurality of groups chosen from substituents, size-restricted substituents, and lower substituents, wherein each substituent, size-restricted substituent, and / or lower substituent may optionally be different. In an embodiment, when R 13 When substituted, it is replaced by at least one substituent. In an embodiment, when R 13 When substituted, it is replaced by at least one size-restricted substituent. In an embodiment, when R 13 When substituted, it is replaced by at least one lower substituent.

[0286] In the embodiments, the replaced R 14 (For example, a substituted alkyl group, a substituted haloalkyl group, a substituted cycloalkyl group, a substituted halocycloalkyl group, a substituted heterocycloalkyl group, a substituted aryl group, and / or a substituted heteroaryl group) is substituted by at least one substituent, a size-restricted substituent, or a lower substituent; wherein if the substituted R 14 The substituent is selected from a plurality of groups chosen from substituents, size-restricted substituents, and lower substituents, wherein each substituent, size-restricted substituent, and / or lower substituent may optionally be different. In an embodiment, when R 14 When substituted, it is replaced by at least one substituent. In an embodiment, when R 14 When substituted, it is replaced by at least one size-restricted substituent. In an embodiment, when R 14 When substituted, it is replaced by at least one lower substituent.

[0287] In the embodiments, the replaced R 15 (For example, a substituted alkyl group, a substituted haloalkyl group, a substituted cycloalkyl group, a substituted halocycloalkyl group, a substituted heterocycloalkyl group, a substituted aryl group, and / or a substituted heteroaryl group) is substituted by at least one substituent, a size-restricted substituent, or a lower substituent; wherein if the substituted R 15 The substituent is selected from a plurality of groups chosen from substituents, size-restricted substituents, and lower substituents, wherein each substituent, size-restricted substituent, and / or lower substituent may optionally be different. In an embodiment, when R 15When substituted, it is replaced by at least one substituent. In an embodiment, when R 15 When substituted, it is replaced by at least one size-restricted substituent. In an embodiment, when R 15 When substituted, it is replaced by at least one lower substituent.

[0288] In the embodiments, the replaced R 16 (For example, a substituted alkyl group, a substituted haloalkyl group, a substituted cycloalkyl group, a substituted halocycloalkyl group, a substituted heterocycloalkyl group, a substituted aryl group, and / or a substituted heteroaryl group) is substituted by at least one substituent, a size-restricted substituent, or a lower substituent; wherein if the substituted R 16 The substituent is selected from a plurality of groups chosen from substituents, size-restricted substituents, and lower substituents, wherein each substituent, size-restricted substituent, and / or lower substituent may optionally be different. In an embodiment, when R 16 When substituted, it is replaced by at least one substituent. In an embodiment, when R 16 When substituted, it is replaced by at least one size-restricted substituent. In an embodiment, when R 16 When substituted, it is replaced by at least one lower substituent.

[0289] This document envisions any combination of groups described above or below for various variables. Throughout the specification, those skilled in the art select groups and their substituents to provide stable moieties and compounds.

[0290] In some embodiments, the compounds are selected from the following:

[0291]

[0292]

[0293]

[0294]

[0295]

[0296]

[0297]

[0298]

[0299]

[0300]

[0301] Or its pharmaceutically acceptable salts or solvates. The list of compounds immediately preceding this sentence is referred to below as "Compound List 1".

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[0303] In the embodiments, the compound may be used as a comparative compound. In the embodiments, the comparative compound may be used to evaluate the activity of the test compound in an assay (e.g., as described herein, such as the assays in the Examples section or the table).

[0304] In the embodiments, the compound is a compound described herein (e.g., in the compound section, example section, method section, or claims and tables).

[0305] III. Other forms of compounds

[0306] Isomers

[0307] The compounds described herein comprise all possible tautomers within the formulas described herein. Furthermore, in some embodiments, the compounds described herein are present as geometric isomers. In some embodiments, the compounds described herein have one or more double bonds. The compounds provided herein comprise all cis, trans, syn, anti, engegen (E, opposite-side, trans), and zusammen (Z, same-side, cis) isomers and corresponding mixtures thereof. In some cases, the compounds are present as tautomers.

[0308] In some cases, the compounds described herein have one or more chiral centers, and each center exists in an (R)-configuration or (S)-configuration. The compounds described herein include all diastereomers, enantiomers, and epimers, as well as corresponding mixtures thereof. In further embodiments of the compounds and methods provided herein, mixtures of enantiomers and / or diastereomers produced by a single preparation step, combination, or tautomerization can be used for the applications described herein. In some embodiments, the compounds described herein are prepared as optically pure enantiomers by chiral chromatographic resolution of a racemic mixture. In some embodiments, the compounds described herein are prepared as a single stereoisomer by reacting a racemic mixture of the compounds with an optically active resolving agent to form a pair of diastereomers, separating the diastereomers, and recovering the optically pure enantiomer. In some embodiments, a dissociable complex (e.g., a crystalline diastereomer salt) is preferred. In some embodiments, the diastereomers have different physical properties (e.g., melting point, boiling point, solubility, reactivity, etc.) and are separated by utilizing these differences. In some embodiments, diastereomers are separated by chiral chromatography or preferably by a separation / resolution technique based on differences in solubility. In some embodiments, the optically pure enantiomers and the resolving agent are then recovered by any practical means that do not cause racemization.

[0309] The term "geometric isomer" refers to the E or Z geometric isomers of the double bond in an alkene (e.g., cis or trans). The term "positional isomer" refers to the structural isomers surrounding the central ring, such as the ortho, meta, and para isomers surrounding the benzene ring.

[0310] Labeled compounds

[0311] In some embodiments, the compounds disclosed herein are used in different enriched isotopic forms, for example, enriched in terms of content. 2 H, 3 H, 11 C 13 C and / or 14C. In one specific embodiment, the compound is deuterated at at least one position. Such a deuterated form can be prepared by the methods described in U.S. Patents 5,846,514 and 6,334,997. As described in U.S. Patents 5,846,514 and 6,334,997, deuteration can improve metabolic stability and / or efficacy, thereby prolonging the duration of drug action.

[0312] Unless otherwise stated, the structures described herein are intended to comprise compounds distinguished solely by the presence of one or more isotopically enriched atoms. For example, those having hydrogen replaced by deuterium or tritium, or those composed of... 13 C or 14 Compounds of the present invention with C-enriched carbon replacing carbon other than carbon are within the scope of this disclosure.

[0313] The compounds disclosed herein optionally contain atomic isotopes in non-natural proportions at one or more atoms constituting such compounds. For example, the compounds may use isotopes such as deuterium (… 2 H), tritium ( 3 H), Iodine-125 ( 125 I) or carbon-14 ( 14 C) Marking. It is envisioned that... 2 H, 11 C 13 C 14 C 15 C 12 N、 13 N、 15 N、 16 N、 17 O、 18 O、 14 F, 15 F, 16 F, 17 F, 18 F, 33 S, 34 S, 35 S, 36 S, 35 Cl、 37 Cl、 79 Br、 81 Br and 125 I undergoes isotopic substitution. All isotopic variations (whether radioactive or non-radioactive) of the compounds disclosed herein are covered within the scope of this disclosure.

[0314] In some embodiments, the compounds disclosed herein have been 2 H atoms replace some or all of them. 1H atom. The methods for synthesizing deuterium-containing compounds are known in the art. In some embodiments, deuterium-substituted compounds are synthesized using various methods described below: Dean, DC; “Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development”, Curr. Pharm. Des., 2000, 6(10); George W.; Varma, RS; “The Synthesis of Radiolabeled Compounds via Organometallic Intermediates”, Tetrahedron, 1989, 45(21), 6601-21; and Evans, EA; “Synthesis of Radiolabeled Compounds”, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

[0315] In some embodiments, the compounds described herein are labeled in other ways, including but not limited to the use of chromophores or fluorescent portions, bioluminescent labeling, or chemiluminescent labeling.

[0316] Pharmaceutically acceptable salts

[0317] In some embodiments, the compounds described herein are present in the form of their pharmaceutically acceptable salts. In some embodiments, the methods disclosed herein comprise a method of treating a disease by administering such pharmaceutically acceptable salts. In some embodiments, the methods disclosed herein comprise a method of treating a disease by administering such pharmaceutically acceptable salts as a pharmaceutical composition.

[0318] In some embodiments, the compounds described herein have acidic or basic groups and thus react with any of a number of inorganic or organic bases and inorganic and organic acids to form pharmaceutically acceptable salts. In some embodiments, these salts are prepared in situ during the final isolation and purification of the compounds disclosed herein, or by reacting a purified compound in its free form with a suitable acid or base alone and isolating the resulting salt.

[0319] solvates

[0320] In some embodiments, the compounds described herein are present in the form of solvates. This disclosure provides a method of treating a disease by applying such solvates. This disclosure further provides a method of treating a disease by applying such solvates in the form of pharmaceutical compositions.

[0321] The solvates contain stoichiometric or non-stoichiometric amounts of solvent and, in some embodiments, are formed during a crystallization process using a pharmaceutically acceptable solvent such as water or ethanol. When the solvent is water, hydrates are formed, or when the solvent is an alcohol, alcohols are formed. The solvates of the compounds described herein are conveniently prepared or formed in the methods described herein. By way of example only, hydrates of the compounds described herein are conveniently prepared by recrystallization from a water / organic solvent mixture using an organic solvent comprising, but not limited to, dioxane, tetrahydrofuran, or methanol. Furthermore, the compounds provided herein exist in both unsolvated and solvated forms. Generally, for the purposes of the compounds and methods provided herein, the solvated form is considered equivalent to the unsolvated form.

[0322] prodrug

[0323] In some embodiments, the compounds described herein are in the form of a prodrug. This disclosure provides a method of treating a disease by administering such a prodrug. This disclosure further provides a method of treating a disease by administering such a prodrug in the form of a pharmaceutical composition.

[0324] In some embodiments, the prodrug comprises a compound in which an amino acid residue or a polypeptide chain consisting of two or more (e.g., two, three, or four) amino acid residues is covalently linked to a free amino, hydroxy, or formic acid group of the disclosed compound via an amide or ester bond. The amino acid residues include, but are not limited to, 20 naturally occurring amino acids, and also include 4-hydroxyproline, hydroxylysine, chain-locked lysine, isochain-locked lysine, 3-methylhistidine, valine, β-alanine, γ-aminobutyric acid, citrulline, homocysteine, homoserine, ornithine, and methionine sulfone. In other embodiments, the prodrug comprises a compound in which a nucleic acid residue or an oligonucleotide consisting of two or more (e.g., two, three, or four) nucleic acid residues is covalently linked to a compound of the disclosed compound.

[0325] Pharmaceutically acceptable prodrugs of the compounds described herein also include, but are not limited to, esters, carbonates, thiocarbonates, N-acyl derivatives, N-acyloxyalkyl derivatives, quaternary derivatives of tertiary amines, N-Mannichbases, Schiffbases, amino acid conjugates, phosphate esters, metal salts, and sulfonates. In some embodiments, compounds having a free amino, amide, hydroxyl, or carboxyl group are converted into prodrugs. For example, a free carboxyl group is derived into an amide or alkyl ester. In some cases, all of these prodrug moieties incorporate groups comprising, but are not limited to, ether, amine, and formic acid functional groups.

[0326] Hydroxyl prodrugs include esters, such as, but not limited to, acyloxyalkyl (e.g., acyloxymethyl, acyloxyethyl) esters, alkoxycarbonyloxyalkyl esters, alkyl esters, aryl esters, phosphate esters, sulfonates, sulfate esters, and disulfide-containing esters; ethers, amides, carbamates, hemisuccinates, dimethylaminoacetate, and phosphoryloxymethoxycarbonyl, as outlined in Fleisher, D. et al., “Improved oral drug delivery: solubility limitations overcome by the use of prodrugs”, Advanced Drug Delivery Reviews, 1996, 19, 115-130.

[0327] Amine-derived prodrugs include, but are not limited to, the following groups and combinations of groups:

[0328]

[0329] And sulfonamides and phosphonamides.

[0330] IV. Pharmaceutical Compositions

[0331] In the embodiments, the compounds described herein (e.g., compounds of formula (IA-1), (IB-1), (IA), (IB), (IIA), (IIB), or (III)) are administered in pure chemical form. In the embodiments, the compounds described herein (e.g., compounds of formula (IA-1), (IB-1), (IA), (IB), (IIA), (IIB), or (III)) are combined with pharmaceutically suitable or acceptable carriers (also referred to herein as pharmaceutically suitable (or acceptable) excipients, physiologically suitable (or acceptable) excipients, or physiologically suitable (or acceptable) carriers) selected based on the chosen route of administration and, for example, standard pharmaceutical practices as described below: Gennaro, AR, "Remington: The Science and Practice of Pharmacy," 21st edition, Easton: Lippincott Williams & Wilkins, 2005.

[0332] In some embodiments, compounds of formula (IA), (IB), (IIA), (IIB), or (III) as described herein are administered in pure chemical form. In some embodiments, compounds of formula (IA), (IB), (IIA), (IIB), or (III) as described herein are combined with pharmaceutically suitable or acceptable carriers (also referred to herein as pharmaceutically suitable (or acceptable) excipients, physiologically suitable (or acceptable) excipients, or physiologically suitable (or acceptable) carriers) selected based on the chosen route of administration and, for example, standard pharmaceutical practices as described below: Gennaro, AR, "Remington: The Science and Practice of Pharmaceuticals," 21st edition, Easton: Lippincott Williams Wilkins Publishing Company, 2005.

[0333] Therefore, this document provides a pharmaceutical composition comprising at least one compound of formula (IA-1), (IB-1), (IA), (IB), (IIA), (IIB), or (III) described herein, or a pharmaceutically acceptable salt or solvate thereof, together with one or more pharmaceutically acceptable carriers. The carrier (or excipient) is acceptable or suitable if it is compatible with the other components of the composition and is harmless to the recipient of the composition (i.e., the subject).

[0334] Therefore, this document provides a pharmaceutical composition comprising at least one compound of formula (IA), (IB), (IIA), (IIB), or (III) described herein, or a pharmaceutically acceptable salt or solvate thereof, together with one or more pharmaceutically acceptable carriers. The carrier (or excipient) is acceptable or suitable if it is compatible with the other components of the composition and is harmless to the recipient of the composition (i.e., the subject).

[0335] One embodiment provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof.

[0336] One embodiment provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof.

[0337] One embodiment provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula (IA) or a pharmaceutically acceptable salt thereof.

[0338] One embodiment provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula (IB) or a pharmaceutically acceptable salt thereof.

[0339] One embodiment provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula (IIA) or a pharmaceutically acceptable salt thereof.

[0340] One embodiment provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula (IIB) or a pharmaceutically acceptable salt thereof.

[0341] One embodiment provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula (III) or a pharmaceutically acceptable salt thereof.

[0342] In the embodiments, the pharmaceutical composition comprises a compound selected from the list of compounds 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.

[0343] In the embodiments, the compounds described herein (e.g., compounds of formula (IA-1), (IB-1), (IA), (IB), (IIA), (IIB), or (III)) are substantially pure because they contain less than about 5%, or less than about 1%, or less than about 0.1% of other small organic molecules, such as contaminating intermediates or byproducts generated in one or more steps of the synthetic method.

[0344] In some embodiments, the compounds of formula (IA), (IB), (IIA), (IIB), or (III) described herein are substantially pure because they contain less than about 5%, or less than about 1%, or less than about 0.1% of other small organic molecules, such as contaminating intermediates or byproducts generated in one or more steps of the synthetic method.

[0345] These pharmaceutical compositions comprise those suitable for oral, rectal, topical, oral, parenteral (e.g., subcutaneous, intramuscular, intradermal, or intravenous), vaginal, ocular, or aerosol administration.

[0346] Exemplary pharmaceutical compositions are used in the form of pharmaceutical preparations, such as solid, semi-solid, or liquid forms, comprising one or more of the disclosed compounds in the form of an active ingredient, in the form of a mixture with an organic or inorganic carrier or excipient suitable for external, enteral, or parenteral application. In some instances, the active ingredient is mixed with a generally non-toxic, pharmaceutically acceptable carrier, for example, for tablets, pills, capsules, suppositories, solutions, emulsions, suspensions, and any other suitable form. The active compound is included in the pharmaceutical composition in an amount sufficient to produce the desired effect on the course or condition of the disease.

[0347] In some embodiments used to prepare solid compositions such as tablets, the primary active ingredient is mixed with a pharmaceutical carrier, such as conventional tableting ingredients like corn starch, lactose, sucrose, sorbitol, talc, stearic acid, magnesium stearate, dicalcium phosphate, or gum, and other pharmaceutical diluents (e.g., water) to form a solid preformed composition containing a homogeneous mixture of the disclosed compound or a non-toxic, pharmaceutically acceptable salt. When these preformed compositions are referred to as homogeneous, it means that the active ingredient is uniformly dispersed throughout the composition, making it readily reproducible into equally effective unit dosage forms, such as tablets, pills, and capsules.

[0348] In solid dosage forms (capsules, tablets, pills, sugar-coated pills, powders, granules, etc.) intended for oral administration, the subject composition is mixed with one or more pharmaceutically acceptable carriers such as sodium citrate or dicalcium phosphate and / or one or more of the following: (1) fillers or extenders such as starch, cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, lactose, sucrose, glucose, mannitol, and / or silicic acid; (2) binders such as carboxymethyl cellulose, hydroxypropyl methylcellulose, alginate, gelatin, polyvinylpyrrolidone, sucrose, and / or gum arabic; (3) wet... (3) Humectants, such as glycerin; (4) Disintegrants, such as crospovidone, croscarmellose sodium, carboxymethyl starch sodium, agar, calcium carbonate, potato or cassava starch, alginate, certain silicates and sodium carbonate; (5) Solution blockers, such as paraffin; (6) Absorption accelerators, such as quaternary ammonium compounds; (7) Wetting agents, such as sodium docusate, cetyl alcohol and glyceryl monostearate; (8) Absorbents, such as kaolin and bentonite; (9) Lubricants, such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate and mixtures thereof; and (10) Colorants. In the case of capsules, tablets and pills, in some embodiments, the composition contains a buffer. In some embodiments, similar type of solid composition is also used as a filler in soft and hard filled gelatin capsules using excipients such as lactose and high molecular weight polyethylene glycol.

[0349] In some embodiments, tablets are prepared by compression or molding, optionally together with one or more excipients. In some instances, binders (e.g., gelatin or hydroxypropyl methylcellulose), lubricants, inert diluents, preservatives, disintegrants (e.g., sodium starch-hydroxyacetate or croscarmellose sodium), surfactants, or dispersants are used to prepare compressed tablets. In some embodiments, molded tablets are prepared by molding a mixture of a subject composition wetted with an inert liquid diluent in a suitable machine. In some embodiments, tablets and other solid dosage forms such as sugar-coated pills, capsules, pellets, and granules are scored or prepared with coatings and shells, such as enteric coatings and other coatings.

[0350] Compositions for inhalation or inhalation comprise solutions and suspensions in the form of pharmaceutically acceptable aqueous or organic solvents or mixtures thereof, as well as powders. Liquid dosage forms for oral administration comprise pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and elixirs. In addition to the subject composition, in some instances, liquid dosage forms contain inert diluents such as, for example, water or other solvents, solubilizers, and emulsifiers such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butanediol, oils (particularly cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil, and sesame oil), glycerin, tetrahydrofuranol, fatty acid esters of polyethylene glycol and sorbitol, cyclodextrins, and mixtures thereof.

[0351] In some embodiments, in addition to the subject composition, the suspension contains suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitol esters, microcrystalline cellulose, aluminum hydroxide, bentonite, agar and tragacanth gum, and mixtures thereof.

[0352] In some instances, formulations for rectal or vaginal application are presented in suppository form, which are prepared by mixing a subject composition with one or more suitable non-irritating excipients or carriers, including, for example, cocoa butter, polyethylene glycol, suppository wax, or salicylate, and are solid at room temperature but liquid at body temperature, and thus melt in the body cavity and release the active agent.

[0353] Dosage forms for transdermal application of the subject composition include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches, and inhalants. In some embodiments, the active ingredient is mixed under sterile conditions with a pharmaceutically acceptable carrier and, where appropriate, with any preservative, buffer, or propellant.

[0354] In some embodiments, in addition to the subject composition, ointments, pastes, creams, and gels contain excipients such as animal and vegetable fats, oils, waxes, paraffin wax, starch, tragacanth gum, cellulose derivatives, polyethylene glycol, silicone, bentonite, silicic acid, talc, and zinc oxide, or mixtures thereof.

[0355] In some embodiments, in addition to the subject composition, the powder and spray also contain excipients such as lactose, talc, silica, aluminum hydroxide, calcium silicate, and polyamide powder or mixtures thereof. In some embodiments, the spray further contains conventional propellants such as chlorofluorocarbons and volatile unsubstituted hydrocarbons such as butane and propane.

[0356] In some embodiments, the compounds described herein are formulated as eye drops for ocular application.

[0357] The compositions and compounds disclosed herein can alternatively be administered via aerosols. This is achieved by preparing aqueous aerosols, liposomal formulations, or solid particles containing said compounds. In some embodiments, non-aqueous suspensions (e.g., fluorocarbon propellants) are used. In some embodiments, sonic nebulizers are used because they minimize exposure of the drug to shear, which can lead to degradation of the compounds contained in the subject composition. Typically, aqueous aerosols are prepared by formulating an aqueous solution or suspension of the subject composition with conventionally pharmaceutically acceptable carriers and stabilizers. The carriers and stabilizers vary depending on the specific subject composition required but typically include nonionic surfactants (e.g., Tweens, Pluronics, or polyethylene glycol), harmless proteins such as serum albumin, sorbitol esters, oleic acid, lecithin, amino acids such as glycine, buffers, salts, sugars, or sugar alcohols. Aerosols are typically prepared from isotonic solutions.

[0358] Pharmaceutical compositions suitable for parenteral administration include a subject composition combined with one or more pharmaceutically acceptable sterile isotonic or non-aqueous solutions, dispersions, suspensions or emulsions, or sterile powders reconstituted into sterile injectable solutions or dispersions prior to use. In some embodiments, the combination contains antioxidants, buffers, antibacterial agents, solutes or suspending agents or thickeners that make the formulation isotonic with the blood of the intended recipient.

[0359] Examples of suitable aqueous and non-aqueous carriers for pharmaceutical compositions include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, etc.) and suitable mixtures thereof, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate and cyclodextrin. For example, in the case of dispersions, by using coating materials (such as lecithin), the desired particle size is maintained and appropriate flowability is maintained by using surfactants.

[0360] Enteric drug formulations comprising the disclosed compounds and enteric-coating materials, as well as pharmaceutically acceptable carriers or excipients thereof, are also envisioned. Enteric-coating materials are polymers that are substantially insoluble in the acidic environment of the stomach and primarily soluble in intestinal fluid at a specific pH. The small intestine is part of the gastrointestinal tract (intestine) between the stomach and large intestine, comprising the duodenum, jejunum, and ileum. The pH of the duodenum is approximately 5.5, the jejunum approximately 6.5, and the distal ileum approximately 7.5. Therefore, enteric materials are insoluble up to, for example, the following pH values: 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, about 7.4, about 7.6, about 7.8, about 8.0, about 8.2, about 8.4, about 8.6, about 8.8, about 9.0, about 9.2, about 9.4, about 9.6, about 9.8, or about 10.0. Exemplary enteric-coated materials include cellulose acetate phthalate (CAP), hydroxypropyl methylcellulose phthalate (HPMCP), polyvinyl acetate phthalate (PVAP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), cellulose trimellitate, hydroxypropyl methylcellulose succinate, cellulose acetate succinate, cellulose hexahydrophthalate, cellulose propionate, cellulose maleate, cellulose butyrate, cellulose propionate, copolymers of methyl methacrylate and methyl methacrylate, methyl acrylate, copolymers of methyl methacrylate and methacrylic acid, copolymers of methyl vinyl ether and maleic anhydride (Gantrez ES series), ethyl methacrylate-methyl methacrylate-trimethylammonium chloride ethyl acrylate copolymers, and natural resins such as zein, shellac, and copal. The materials include collophorium and several commercially available enteric dispersion systems (e.g., Eudragit L30D55, Eudragit FS30D, Eudragit L100, Eudragit S100, Kollicoat EMM30D, Estacryl 30D, Coateric, and Aquateric). The solubility of each of the above materials is known or readily determined in vitro.

[0361] The dosage of compositions comprising at least one compound described herein (e.g., compounds of formula (IA-1), (IB-1), (IA), (IB), (IIA), (IIB), or (III)) varies depending on the patient's (e.g., human) condition, i.e., the stage of the disease, overall health status, age, and other factors.

[0362] The dosage of compositions comprising at least one compound of formula (IA), (IB), (IIA), (IIB) or (III) described herein varies depending on the patient's (e.g., human) condition, i.e., the stage of the disease, overall health status, age and other factors.

[0363] The pharmaceutical composition is administered in a manner suitable for the disease to be treated (or prevented). The appropriate dosage and the appropriate duration and frequency of administration will be determined by factors such as the patient's condition, the type and severity of the patient's disease, the specific form of the active ingredient, and the method of administration. Generally, the appropriate dosage and treatment regimen are to provide the composition in an amount sufficient to provide therapeutic and / or preventive benefits (e.g., improved clinical outcomes, such as more frequent complete or partial remissions, or longer disease-free and / or overall survival, or reduced symptom severity). The optimal dosage is typically determined using experimental models and / or clinical trials. In some embodiments, the optimal dosage depends on the patient's body mass, weight, or blood volume.

[0364] The oral dosage typically ranges from about 1.0 mg to about 1000 mg per day, once or four times or more.

[0365] The disclosed compounds are administered to subjects or patients (animals and humans) requiring such treatment at a dose that provides optimal pharmaceutical efficacy. It should be understood that the dose required for any particular application will vary from patient to patient, depending not only on the specific compound or composition chosen, but also on the route of administration, the nature of the condition being treated, the patient's age and condition, any concurrent medications or special diets the patient subsequently follows, and other factors, with the appropriate dose ultimately determined by the attending physician. For the treatment of the aforementioned clinical conditions and diseases, the intended compounds disclosed herein are administered orally, subcutaneously, topically, parenterally, via inhalation spray, or rectally in dosage unit formulations containing conventional, non-toxic, and pharmaceutically acceptable carriers, adjuvants, and mediators. Parenterally administration includes subcutaneous injection, intravenous or intramuscular injection, or infusion techniques.

[0366] V. Methods using compounds and compositions

[0367] antagonists of mAChRM1

[0368] Muscarinic acetylcholine receptor M1 (mAChRM1) is present in both the central and peripheral nervous systems, specifically in the cerebral cortex and sympathetic ganglia. Notably, M1 is expressed on oligodendrocyte precursor cells (OPCs) in the central nervous system. Over time, OPCs differentiate into myelin-producing oligodendrocytes. Myelin is essential for action potential conduction along axons, and its loss is attributed to neurodegenerative diseases, particularly multiple sclerosis. In some embodiments, selective mAChRM1 antagonists accelerate OPC differentiation into oligodendrocytes. In some embodiments, selective mAChRM1 antagonists can be used to treat demyelinating diseases such as multiple sclerosis. In some embodiments, selective mAChRM1 antagonists can be used to treat epileptic disorders and certain movement disorders, including Parkinson's disease, dystonia, and Fragile X syndrome.

[0369] In one aspect, the compounds disclosed herein are selective antagonists of the muscarinic acetylcholine M1 receptor (mAChRM1). In some embodiments, the compounds disclosed herein are selective antagonists of the muscarinic acetylcholine M1 receptor (mAChRM1) that are superior to one or more of the mAChRM2, M3, M4, or M5 receptors. In some embodiments, the compounds disclosed herein exhibit an IC50 response to mAChRM1. 50 The IC50 values ​​of the compounds disclosed in this paper against mAChRM2 are shown. 50 Approximately 1 / 5, approximately 1 / 10, approximately 1 / 20, approximately 1 / 30, approximately 1 / 50, approximately 1 / 100, or <1 / 100. In some embodiments, the compounds disclosed herein exhibit an IC50 response to mAChRM1. 50 The IC50 values ​​of the compounds disclosed in this paper against mAChRM3 are shown. 50 Approximately 1 / 5, approximately 1 / 10, approximately 1 / 20, approximately 1 / 30, approximately 1 / 50, approximately 1 / 100, or <1 / 100. In some embodiments, the compounds disclosed herein exhibit an IC50 response to mAChRM1. 50 The IC50 values ​​of the compounds disclosed in this paper against mAChRM4 are shown. 50 Approximately 1 / 5, 1 / 10, 1 / 20, 1 / 30, 1 / 50, 1 / 100, or <1 / 100. In some embodiments, the compounds disclosed herein exhibit an IC50 response to mAChR M1. 50 The IC50 values ​​of the compounds disclosed in this paper against mAChR M5 are shown. 50Approximately 1 / 5, 1 / 10, 1 / 20, 1 / 30, 1 / 50, 1 / 100, or <1 / 100. In some embodiments, the compounds disclosed herein exhibit an IC50 response to mAChR M1. 50 The IC50 values ​​of the compounds disclosed herein against mAChR M2, M3, M4, or M5, or combinations thereof. 50 Approximately 1 / 5, 1 / 10, 1 / 20, 1 / 30, 1 / 50, 1 / 100, or <1 / 100.

[0370] Treatment

[0371] The compounds disclosed herein can be used to treat, prevent, improve, control, or reduce the risk of various diseases, in which patients or subjects will benefit from the antagonistic effect of muscarinic acetylcholine M1 receptors.

[0372] In one aspect, treatment may include selective M1 receptor antagonism to the extent that it effectively affects cholinergic activity. Therefore, the compounds disclosed herein may be used for conditions associated with cholinergic activity, such as hypercholinergic dysfunction. In some embodiments, this document provides a method for treating or preventing a condition in a subject, comprising administering to the subject a compound disclosed herein, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein, at a dose and amount effective in treating the subject's condition.

[0373] This document provides a method for treating a subject for one or more conditions, for which inhibition of muscarinic acetylcholine receptors is predicted to be beneficial, the method comprising the steps of administering to the subject a compound disclosed herein or a pharmaceutically acceptable salt or solvate thereof or a pharmaceutical composition described herein at a dose and amount effective in treating the subject's condition.

[0374] In some embodiments, this document provides a method for treating a subject with neurodegenerative disease, the method comprising administering to the subject a therapeutically effective amount of a compound described herein (e.g., a compound of formula (IA-1), (IB-1), (IA), (IB), (IIA), (IIB), or (III)) or a pharmaceutically acceptable salt or solvation thereof.

[0375] In some embodiments, this document provides a method for treating a subject with neurodegenerative disease, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (IA), (IB), (IIA), (IIB), or (III) or a pharmaceutically acceptable salt or solvate thereof.

[0376] In an embodiment, a method of treating a subject with neurodegenerative disease in need comprises administering an effective amount of a compound selected from the list of compounds 1 or a pharmaceutically acceptable salt or solvate thereof.

[0377] In some embodiments, this document provides a method for treating neuropathy in a subject in need, the method comprising administering to the subject a therapeutically effective amount of a compound described herein (e.g., a compound of formula (IA-1), (IB-1), (IA), (IB), (IIA), (IIB), or (III)) or a pharmaceutically acceptable salt or solvation thereof. In some embodiments, this document provides a method for treating neuropathy in a subject in need, the method comprising administering to the subject a therapeutically effective amount of a compound described herein (e.g., a compound of formula (IA-1), (IB-1), (IA), (IB), (IIA), (IIB), or (III)) or a pharmaceutically acceptable salt or solvation thereof, wherein the neuropathy is a peripheral neuropathy. In some embodiments, this document provides a method for treating neuropathy in a subject in need, the method comprising administering to the subject a therapeutically effective amount of a compound described herein (e.g., a compound of formula (IA-1), (IB-1), (IA), (IB), (IIA), (IIB), or (III)) or a pharmaceutically acceptable salt or solvation thereof, wherein the neuropathy is diabetic neuropathy.

[0378] In some embodiments, this document provides a method for treating neuropathy in a subject in need, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (IA), (IB), (IIA), (IIB), or (III) or a pharmaceutically acceptable salt or solvation thereof. In some embodiments, this document provides a method for treating neuropathy in a subject in need, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (IA), (IB), (IIA), (IIB), or (III) or a pharmaceutically acceptable salt or solvation thereof, wherein the neuropathy is a peripheral neuropathy. In some embodiments, this document provides a method for treating neuropathy in a subject in need, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (IA), (IB), (IIA), (IIB), or (III) or a pharmaceutically acceptable salt or solvation thereof, wherein the neuropathy is diabetic neuropathy.

[0379] In an embodiment, a method of treating neuropathy in a subject in need comprises administering an effective amount of a compound selected from the list of compounds 1 or a pharmaceutically acceptable salt or solvation thereof.

[0380] In some embodiments, a method for treating a subject with a demyelinating disease includes administering to the subject a therapeutically effective amount of a compound described herein (e.g., a compound of formula (IA-1), (IB-1), (IA), (IB), (IIA), (IIB), or (III)) or a pharmaceutically acceptable salt or solvation thereof. In some embodiments, a method for treating a subject with a demyelinating disease includes administering to the subject a therapeutically effective amount of a compound described herein (e.g., a compound of formula (IA-1), (IB-1), (IA), (IB), (IIA), (IIB), or (III)) or a pharmaceutically acceptable salt or solvation thereof, wherein the demyelinating disease is a demyelinating disease of the central nervous system. In some embodiments, a method for treating a subject with a demyelinating disease includes administering to the subject a therapeutically effective amount of a compound described herein (e.g., a compound of formula (IA-1), (IB-1), (IA), (IB), (IIA), (IIB), or (III)) or a pharmaceutically acceptable salt or solvation thereof, wherein the demyelinating disease is multiple sclerosis. In some embodiments, a method of treating a subject with a demyelinating disease includes administering to the subject a therapeutically effective amount of a compound described herein (e.g., a compound of formula (IA-1), (IB-1), (IA), (IB), (IIA), (IIB), or (III)) or a pharmaceutically acceptable salt or solvate thereof, wherein the demyelinating disease is a demyelinating disease of the peripheral nervous system.

[0381] In some embodiments, a method for treating a demyelinating disease in a subject of need includes administering to the subject a therapeutically effective amount of a compound of formula (IA), (IB), (IIA), (IIB), or (III) or a pharmaceutically acceptable salt or solvation thereof. In some embodiments, a method for treating a demyelinating disease in a subject of need includes administering to the subject a therapeutically effective amount of a compound of formula (IA), (IB), (IIA), (IIB), or (III) or a pharmaceutically acceptable salt or solvation thereof, wherein the demyelinating disease is a central nervous system demyelinating disease. In some embodiments, a method for treating a demyelinating disease in a subject of need includes administering to the subject a therapeutically effective amount of a compound of formula (IA), (IB), (IIA), (IIB), or (III) or a pharmaceutically acceptable salt or solvation thereof, wherein the demyelinating disease is multiple sclerosis. In some embodiments, a method for treating a subject with a demyelinating disease includes administering to the subject a therapeutically effective amount of a compound of formula (IA), (IB), (IIA), (IIB), or (III) or a pharmaceutically acceptable salt or solvate thereof, wherein the demyelinating disease is a demyelinating disease of the peripheral nervous system.

[0382] In an embodiment, a method of treating a subject with demyelinating disease comprises administering an effective amount of a compound selected from the list of compounds 1 or a pharmaceutically acceptable salt or solvation thereof.

[0383] In some embodiments, a method for modulating the activity of muscarinic acetylcholine receptor M1 in a subject is provided, the method comprising administering to the subject a compound described herein (e.g., a compound of formula (IA-1), (IB-1), (IA), (IB), (IIA), (IIB), or (III)) or a pharmaceutically acceptable salt or solvation thereof. In some embodiments, the compound described herein (e.g., a compound of formula (IA-1), (IB-1), (IA), (IB), (IIA), (IIB), or (III)) or a pharmaceutically acceptable salt or solvation thereof acts as a selective M1 antagonist.

[0384] In some embodiments, a method for modulating the activity of muscarinic acetylcholine receptor M1 in a subject is provided, the method comprising administering to the subject a compound of formula (IA), (IB), (IIA), (IIB), or (III), or a pharmaceutically acceptable salt or solvate thereof. In some embodiments, the compound of formula (IA), (IB), (IIA), (IIB), or (III), or a pharmaceutically acceptable salt or solvate thereof, acts as a selective M1 antagonist.

[0385] In an embodiment, a method for modulating the activity of muscarinic acetylcholine receptor M1 in a subject comprises administering a compound selected from the list of compounds 1 or a pharmaceutically acceptable salt or solvate thereof.

[0386] VI. Combination therapy

[0387] This document also envisions combination therapies, such as co-administration of the disclosed compounds and additional active agents, as part of a specific treatment regimen designed to provide a beneficial effect through the combined action of these therapeutic agents. In some embodiments, the compounds described herein are administered in combination with one or more immunomodulators. In some embodiments, the compounds described herein are administered in combination with one or more immunomodulators selected from: IFN-β1 molecules; corticosteroids; polymers of glutamate, lysine, alanine, and tyrosine, or glatiramer; antibodies or fragments thereof against α-4 integrin or natamizumab; anthraquinone molecules or mitoxantrone; fingolimod or other S1P1 modulators; dimethyl fumarate or other NRF2 modulators; antibodies against the T-cell IL-2 receptor α subunit (CD25) or dacrolimus; antibodies against CD52 or alenzab; antibodies against CD20 or oligrin; inhibitors of dihydroorotate dehydrogenase or teriflunomide. In some embodiments, the immunomodulator is an IFN-β1 molecule. In some embodiments, the immunomodulator is a corticosteroid. In some embodiments, the immunomodulator is a polymer of glutamate, lysine, alanine, and tyrosine, or glatiramer. In some embodiments, the immunomodulator is an antibody or fragment thereof targeting α-4 integrin, or natamizumab. In some embodiments, the immunomodulator is an anthrone molecule or mitoxantrone. In some embodiments, the immunomodulator is fingolimod or other S1P1 modulators. In some embodiments, the immunomodulator is dimethyl fumarate or other NRF2 modulators. In some embodiments, the immunomodulator is an antibody against the T-cell IL-2 receptor α subunit (CD25) or dacrolimus. In some embodiments, the immunomodulator is an antibody against CD52 or alenmab. In some embodiments, the immunomodulator is an antibody against CD20 or olizumab. In some embodiments, the immunomodulator is an inhibitor of dihydroorotate dehydrogenase or teriflunomide.

[0388] The beneficial effects of a combination include, but are not limited to, the combined pharmacokinetic or pharmacodynamic effects of the combination of therapeutic agents. These combined administrations of therapeutic agents are typically carried out over a defined time period (usually weeks, months, or years, depending on the chosen combination). Combination therapy is intended to include the sequential administration of multiple therapeutic agents, i.e., each therapeutic agent is given at different times, and the administration of these therapeutic agents or at least two therapeutic agents in a substantially simultaneous manner.

[0389] Substantial simultaneous administration is achieved, for example, by administering a single formulation or composition to the subject (e.g., tablets or capsules in the form of multiple single formulations (e.g., capsules) for each therapeutic agent in a fixed ratio). Each therapeutic agent is administered sequentially or substantially simultaneously via any suitable route, including but not limited to oral, intravenous, intramuscular, and direct absorption through mucosal tissue. The therapeutic agents may be administered via the same or different routes. For example, the first therapeutic agent in a selected combination may be administered intravenously, while the other therapeutic agents in the combination may be administered orally. Alternatively, for example, all therapeutic agents may be administered orally or via intravenous injection.

[0390] Combination therapy also includes the further administration of the aforementioned therapeutic agents in combination with other bioactive ingredients and non-pharmacological therapies. When combination therapy further includes non-pharmacological treatment, the non-pharmacological treatment is administered at any appropriate time, as long as the combined beneficial effects of the therapeutic agent and non-pharmacological treatment are achieved. For example, in appropriate circumstances, beneficial effects may still be achieved when non-pharmacological treatment is temporarily removed (potentially for several days or even weeks) without the application of the therapeutic agent.

[0391] The combined components are administered to the patient simultaneously or sequentially. It should be understood that the components are contained in the same pharmaceutically acceptable carrier and are therefore administered simultaneously. Alternatively, the active ingredient may be contained in separate drug carriers, such as conventional oral dosage forms administered simultaneously or sequentially.

[0392] The following examples are provided only as illustrations and should not be construed as limiting the invention in any way.

[0393] It should be understood that the examples and embodiments described herein are for illustrative purposes only, and various modifications or changes made thereto will inspire those skilled in the art and will be included within the spirit and scope of this application and the appended claims. All publications, patents and patent applications cited herein are incorporated herein by reference in their entirety for all purposes.

[0394] VII. Preparation of Compounds

[0395] The compounds used in the reactions described herein are prepared from commercially available chemicals and / or compounds described in chemical literature, according to known organic synthesis techniques. “Commercially available chemicals” are obtained from standard commercial sources, including AcrosOrganics (Geel, Belgium), Aldrich Chemical (Milwaukee, WI, including Sigma Chemical and Fluka), Apin Chemicals Ltd. (Milton Park, UK), ArkPharm, Inc. (Libertyville, IL), and Avocado Research (UK). Lancashire (UK), BDH Inc. (Toronto, Canada), Bionet (Cornwall, UK), Chemservice Inc. (West Chester, PA), Combi-blocks (San Diego, CA), Crescent Chemical Co. (Hauppauge, NY), eMolecules (San Diego, California), Fisher Scientific Co. (Pittsburgh, PA), Fisons Chemicals (Leicestershire, UK), Frontier Scientific (Logan, Utah), and ICN Biomedicals, Inc.(Costa Mesa, CA) , Key Organics (Cormwick, UK) , Lancaster Synthesis (Windham, NH, New Hampshire) , Matrix Scientific (Columbia, SC, South Carolina) , Maybridge Chemicals (Cormwick, UK) , Parish Chemical Co. (Orem, Utah) , Pfaltz & Bauer, Inc. (Waterbury, CN, Connecticut) , Polyorganix (Houston, TX, Texas) , Pierce Chemical Co. (Rockford, IL, Illinois) , Riedel de Haen Haen AG (Hanover, Germany), Ryan Scientific, Inc. (Mount Pleasant, SC, South Carolina), Spectrum Chemicals (Gardena, CA), Sundia Meditech (Shanghai, China), TCI America (Portland, OR), Trans World Chemicals, Inc. (Rockville, MD, Maryland), and WuXi (Shanghai, China).

[0396] Suitable reference books and papers that detail the synthesis of reactants used to prepare the compounds described herein or that provide reference to articles describing the preparations include, for example, *Synthetic Organic Chemistry*, New York: John Wiley & Sons, Inc., 1982; Sandler SR et al., *Organic Functional Group Preparations*, 2nd ed., New York: Academic Press, 1983; House, HO, *Modern Synthetic Reactions*, 2nd ed., Menlo Park: WA Benjamin, Inc., 1972; Gilchrist, TL, *Heterocyclic Chemistry*. 2nd edition of *Advanced Organic Chemistry*, New York: Wiley & Co., 1992; March, J., 4th edition of *Advanced Organic Chemistry: Reactions, Mechanisms and Structure*, New York: Wiley & Co., 1992.Further suitable references and papers that detail the synthesis of reactants used to prepare the compounds described herein or that provide reference to articles describing the preparations include, for example, Fuhrhop, J. and Penzlin, G., *Organic Synthesis: Concepts, Methods, Starting Materials*, 2nd ed., New York: Wiley & Co., 1994; Hoffman, RV, *Organic Chemistry: An Intermediate Text*, Oxford: Oxford University Press, 1996; and Larock, RC, *Comprehensive Organic Transformation: A Guide to the Preparation of Functional Groups*. Transformations: A Guide to Functional Group Preparations, 2nd ed., New York: Willie Company, 1999; Otera, J., Modern Carbonyl Chemistry, New York: Willie Company, 2000; Solomons, TWG, Organic Chemistry, 7th ed., New York: Willie Company, 2000; Stowell, JC, Intermediate Organic Chemistry, 2nd ed., New York: Willie Company, 1993; Industrial Organic Chemicals: Starting Materials and Intermediates: An Ullmann's Encyclopedia, New York: Willie Company, 8 volumes; Organic Reactions "Reactions", New York: Wiley & Co., 55 volumes; and "Chemistry of Functional Groups", New York: Wiley & Co., 73 volumes.

[0397] Specific and similar reactants can also be found through an index of known chemicals produced by the Chemical Abstracts Service of the American Chemical Society (available in most public and university libraries) and through online databases (contact the American Chemical Society, Washington, DC for more details). Chemicals known but not commercially available in the catalogue are optionally prepared by custom chemical synthesis companies, many of which offer custom synthesis services to standard chemical suppliers (such as those listed above). References for the pharmaceutical salts used in the preparation and selection of the compounds described herein are Stahl, PH, and Wermuth, CG, *Handbook of Pharmaceutical Salts*, Zurich: Verlag Helvetica Chimica Acta, 2002.

[0398] List of abbreviations

[0399] As used above, and throughout this disclosure, unless otherwise indicated, the following abbreviations shall be understood to have the following meanings:

[0400] ACN or MeCN acetonitrile

[0401] aq water-based

[0402] Bn benzyl

[0403] Bu Butyl

[0404] BOC or Boc tert-butyl carbamate

[0405] BrettPhos 2-(dicyclohexylphosphino)-3,6-dimethoxy-2'4'6'-triisopropyl-1,1'-biphenyl

[0406] BSA (Bovine Serum Albumin)

[0407] CDI 1,1'-carbonyldiimidazole

[0408] CHO Chinese hamster ovary

[0409] Cyclohexyl

[0410] dba dibenzylidene acetone

[0411] DAST diethylaminosulfur trifluoride

[0412] DCC N,N'-Dicyclohexylcarbodiimide

[0413] DCE (dichloroethane) (ClCH2CH2Cl)

[0414] DCM (dichloromethane (CH2Cl2))

[0415] DIPEA or DIEA (diisopropylethylamine)

[0416] DMAP 4-(N,N-dimethylamino)pyridine

[0417] DME 1,2-dimethoxyethane

[0418] DMEM (Dürbeco Modified Eagle Medium)

[0419] DMF N,N-dimethylformamide

[0420] DMA N,N-dimethylacetamide

[0421] DMSO (dimethyl sulfoxide)

[0422] EDC N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide

[0423] equivalent

[0424] Et Ethyl

[0425] EtOH (ethanol)

[0426] EtOAc (ethyl acetate)

[0427] FBS Fetal Bovine Serum

[0428] h hours

[0429] HATU 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridine-3-hexafluorophosphate oxide

[0430] HEPES 4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid

[0431] Hexane

[0432] HPLC (High Performance Liquid Chromatography)

[0433] LAH Lithium Aluminum Hydrogen

[0434] LCMS or LC-MS liquid chromatography-mass spectrometry

[0435] LG leaving group

[0436] M Moore

[0437] mCPBA (m-chloroperoxybenzoic acid)

[0438] Me methyl

[0439] MeOH (methanol)

[0440] min minutes

[0441] MS mass spectrometry

[0442] NMM N-methylmorpholine

[0443] NMP (N-methyl-2-pyrrolidone)

[0444] NMR (Nuclear Magnetic Resonance)

[0445] Pd / C Palladium on Carbon

[0446] PG protecting group

[0447] PMB p-methoxybenzyl

[0448] RT room temperature

[0449] RuPhos Pd G3 (2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II)methanesulfonate

[0450] sec seconds

[0451] T3P Propionic Anhydride

[0452] t BuXPhos Pd G3 [(2-di-tert-butylphosphino-2',4'6'-triisopropyl-1,1'-biphenyl)-2-(2'-amino-1,1'-biphenyl)]palladium(II)methanesulfonate

[0453] TBAF Tetrabutylammonium Fluoride

[0454] TEA Triethylamine

[0455] TFA (trifluoroacetic acid)

[0456] THF Tetrahydrofuran

[0457] TLC (Thin Layer Chromatography)

[0458] XantPhos 4,5-bis(diphenylphosphino)-9,9-dimethylxanthine

[0459] XPhos 2-Dicyclohexylphosphino-2'4'6'-triisopropylbiphenyl

[0460] (diethylamino)difluorosulfonium tetrafluoroborate

[0461] General synthesis scheme

[0462] The compounds of formula (IA) or (IB) disclosed herein can be prepared, for example, from an amine (1a) or (1b) or its corresponding ammonium salt and formic acid (2) in the presence of a suitable coupling agent such as HATU, CDI, T3P and a suitable base such as TEA, DIEA (Scheme 1). Alternatively, the acid can be preactivated by converting it to the corresponding acyl chloride using a reagent such as thionyl chloride, oxalyl chloride, etc. The resulting amide (3a) or (3b), which itself may be a compound of formula (IA) or (IB), can be further functionalized using synthetic methods known to those skilled in the art to deliver another compound of formula (IA) or (IB). Examples of such conversions include, but are not limited to:

[0463] (a) Reduction of alkenes or alkynes in the presence of catalysts such as Pd / C or Pd(OH)2 and reducing agents such as hydrogen or deuterium.

[0464] (b) Cyclopropanization of olefins in the presence of methylene sources such as trimethylsulfonium iodide and diazomethane and promoters such as potassium tert-butoxide and palladium(II) acetate.

[0465] (c) Oxidation of sulfides in the presence of oxidants such as oxone or mCPBA.

[0466] (d) In the presence of a methyl source such as iodomethane or dimethyl sulfate and an accelerator such as sodium iodide or potassium iodide, appropriately functionalized 2- or 4-methoxypyridine is converted into its corresponding 1-methylpyridin-2(1H)-one or 1-methylpyridin-4(1H)-one.

[0467] (e) In the presence of zinc cyanide in the form of a suitable palladium ligand complex in the form of a catalyst and a cyanide source, a suitable functionalized (hetero)aryl halide is converted into its corresponding (hetero)aryl cyanide.

[0468] (f) Using appropriate chiral columns, such as ChiralPAKOD and ChiralPAKAD, to separate mixtures of stereoisomers into their stereochemically enriched components.

[0469] Option 1

[0470]

[0471] Alternatively, it may be more advantageous to prepare compounds of formula (IA) or (IB) by means of the following three-step sequence (Scheme 2): initially coupling a suitably protected amine (4a) or (4b) with formic acid (2), then removing the protecting group in the amide (5a) or (5b) using conditions known to those skilled in the art (i.e., by treatment with HCl, TFA, etc. when N-PG is tert-butyl carbamate), and finally reacting the resulting amine (6a) or (6b) with a suitably functionalized (hetero)aryl halide using, for example, standard nucleophilic aromatic substitution conditions (i.e., by heating the reactants in a polar aprotic solvent in the presence of a suitable base) or Buchwald-Hartwig coupling conditions (i.e., by coupling in the presence of a suitable palladium ligand complex in the form of a catalyst and a metal alkoxide in the form of a base).

[0472] Option 2

[0473]

[0474] In some embodiments, those skilled in the art may also obtain compounds of formula (IA) or (IB) by directly nucleophilically substituting the leaving group (LG) in the electrophile (8a) or (8b) using the conditions described in the previously highlighted references and papers (Scheme 3). In some cases, especially when the nucleophile (9) is an amine, it may be advantageous to first activate (9) by pretreatment with a reagent such as a lithium chloride complex of isopropyl magnesium chloride. The electrophile (8a) or (8b) itself can be readily synthesized, for example, in the presence of a suitable base such as TEA, DIEA, etc., from the amine (1a) or (1b) and an acidic halide (7).

[0475] Option 3

[0476]

[0477] In some embodiments, the aforementioned direct nucleophilic substitution can be best achieved by using an amide (11a) or (11b) as the affinity and a suitable functionalization (12) as the electrophile (Scheme 4), wherein the amide itself is readily prepared by an amine (1a) or (1b) and an acid (10) via, for example, a two-step amide coupling deprotection sequence.

[0478] Option 4

[0479]

[0480] In some embodiments, where X in formula (IA) or (IB) is NH, it may prove more advantageous to use ketone (14) and amine (13a) or (13b) to form the necessary bond under dehydration conditions known to those skilled in the art (Scheme 5). The resulting Schiff base (15a) or (15b) can be reduced using reagents such as lithium borohydride or sodium cyanoborohydride, or captured using organometallic compounds such as Grignard reagents or (hetero)aryl lithium reagents. In the case where the organometallic compound is an organosilicon reagent, it may be advantageous to add a fluoride activator such as TBAF or cesium fluoride.

[0481] Option 5

[0482]

[0483] The general synthetic schemes described above have been presented in an illustrative manner and are intended to be descriptive rather than limiting. It should also be understood that many of the reagents provided in the examples below can be substituted with other suitable reagents (see, for example, Fieser, L. et al., Encyclopedia of Reagents for Organic Synthesis, 2nd ed., New York: Wiley & Co., 2009). Furthermore, it should be understood that conditions such as the choice of solvent, reaction temperature, volume, and reaction time can be varied while still producing the desired compound. Such changes and modifications can be made without departing from the spirit and scope of this work, including but not limited to those relating to the chemical structures, substituents, derivatives, intermediates, and / or synthesis provided herein.

[0484] VIII. Examples

[0485] Example P1. A compound or a pharmaceutically acceptable salt or solvate thereof having the structure of formula (IA) or (IB):

[0486]

[0487] in:

[0488] X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 )-、-O-、-S(O) n -, -CH2N(R) 11 - or -CH2O-;

[0489] Y is -CH2-, -CH2CH2-, -CH=CH-, or -CH2OCH2-;

[0490] R1 for Wherein ring A is optionally substituted with a 5- or 6-membered heteroaryl ring or a 5- or 6-membered heterocyclic alkyl ring: halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl,

[0491] C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S;

[0492] R 2 Hydrogen, deuterium, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl;

[0493] R 3 Halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; or R 2 and R 3 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0494] R 4 and R 5Independently selected from hydrogen, deuterium, halogens and C 1-3 Alkyl; or R 3 and R 4 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 5 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0495] R 6 and R 7 Independently selected from hydrogen, deuterium, halogens and C 1-3 Alkyl; or R 3 and R 7 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 6 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 5 and R 7 Combining to form bonds;

[0496] R 8 for

[0497] R 9 and R 10 Independently selected from hydrogen, deuterium, halogens, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl or heteroaryl; or R 3 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6cycloalkyl; or R 6 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 9 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0498] R 11 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 3 and R 11 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 11 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 6 and R 11 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0499] Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5; or R 3 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R10 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 11 And an R 12 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0500] R 13 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0501] R 14 and R 15 Independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 14 and R 15 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0502] R 16 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0503] m is 0 or 1;

[0504] n is 0, 1, or 2; and

[0505] o can be 0, 1, 2, or 3.

[0506] Example P2. The compound or its pharmaceutically acceptable salt or solvate according to Example P1, having a structure of formula (IIA) or (IIB):

[0507]

[0508] in:

[0509] X is a bond, -C(R) 9 (R) 10 )-、-N(R11 )-、-O-、-S(O) n -, -CH2N(R) 11 - or -CH2O-;

[0510] Y is -CH2-, -CH2CH2-, -CH=CH-, or -CH2OCH2-;

[0511] R 1 for Wherein ring A is optionally substituted with a 5- or 6-membered heteroaryl ring or a 5- or 6-membered heterocyclic alkyl ring: halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S;

[0512] R 2 Hydrogen, deuterium, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl;

[0513] R 3 Halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; or R 2 and R3 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0514] R 8 for

[0515] R 9 and R 10 Independently selected from hydrogen, deuterium, halogens, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl or heteroaryl; or R 3 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 9 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0516] R 11 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 3 and R 11 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0517] Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5; or R 3 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 10 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 11 And an R 12 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0518] R 13 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0519] R 14 and R 15 Independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 14 and R 15 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0520] R 16 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0521] m is 0 or 1;

[0522] n is 0, 1, or 2; and

[0523] o can be 0, 1, 2, or 3.

[0524] Example P3. The compound according to Example P1, or a pharmaceutically acceptable salt or solvate thereof, has the structure of formula (III):

[0525]

[0526] in:

[0527] X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 )-、-O-、-S(O) n -, -CH2N(R) 11 - or -CH2O-;

[0528] R 1 for Wherein ring A is optionally substituted with a 5- or 6-membered heteroaryl ring or a 5- or 6-membered heterocyclic alkyl ring: halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S;

[0529] R 2 Hydrogen, deuterium, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl;

[0530] R 3 Halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; or R 2 and R 3 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0531] R 8 for

[0532] R 9 and R 10 Independently selected from hydrogen, deuterium, halogens, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl or heteroaryl; or R 3 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 9 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0533] R 11 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 3 and R 11 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0534] Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5; or R 3 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 10 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 11 And an R 12 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0535] R 13 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0536] R 14 and R 15 Independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 14 and R 15 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0537] R 16 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0538] m is 0 or 1;

[0539] n is 0, 1, or 2; and

[0540] o can be 0, 1, 2, or 3.

[0541] Example P4. A compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples P1-P3, wherein X is a bond.

[0542] Example P5. A compound according to any one of Examples P1-P3, or a pharmaceutically acceptable salt or solvation thereof, wherein X is -C(R 9 (R) 10 )-.

[0543] Example P6. A compound according to any one of Examples P1-P3, or a pharmaceutically acceptable salt or solvation thereof, wherein X is -N(R 11 )-.

[0544] Example P7. A compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples P1-P3, wherein X is -O-.

[0545] Example P8. A compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples P1-P3, wherein X is -S-.

[0546] Example P9. A compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples P1-P3, wherein X is -S(O)-.

[0547] Example P10. A compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples P1-P3, wherein X is -S(O)2-.

[0548] Example P11. The compound according to any one of Examples P1-P10, or a pharmaceutically acceptable salt or solvation thereof, wherein R 1 for

[0549] Example P12. The compound according to any one of Examples P1-P11, wherein R 2 It can be hydrogen, -F, -CH3, -CH2CH3, -CF2H, -CF3, -CH2OH, -C(CH3)2OH, phenyl, or cyclopropyl.

[0550] Example P13. The compound according to any one of Examples P1-P12, wherein R 3It can be -F, -CH3, -CH2CH3, -CF2H, -CF3, -CH2OH, -C(CH3)2OH, phenyl, or cyclopropyl.

[0551] Example P14. The compound according to any one of Examples P1-P11, wherein R 2 and R 3 Combining to form cyclopropyl rings, cyclobutyl rings, or cyclopentyl rings.

[0552] Example P15. The compound according to any one of Examples P1-P11, wherein R 2 and R 3 Combining them to form oxetanyl rings or tetrahydrofuranyl rings.

[0553] Example P16. The compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples P1-P15, wherein m is 0.

[0554] Example P17. A compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples P1-P15, wherein m is 1.

[0555] Example P18. A compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples P1-P17, wherein o is 0.

[0556] Example P19. A compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples P1-P17, wherein o is 1.

[0557] Example P20. The compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples P1-P17, wherein o is 2.

[0558] Example P21. The compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples P1-P17, wherein o is 3.

[0559] Example P22. The compound or its pharmaceutically acceptable salt or solvation according to any one of Examples P1-P21, wherein R 8 for

[0560] Example P23. A compound selected from the list of compounds 1 or a pharmaceutically acceptable salt thereof.

[0561] Example P24. A pharmaceutical composition comprising a compound according to any one of Examples P1-P23 or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.

[0562] Example P25. A method for treating neurodegenerative diseases in a subject in need, the method comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples P1-P23.

[0563] Example P26. A method for treating a subject with demyelinating disease, the method comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples P1-P23.

[0564] Example P27. The method according to Example P26, wherein the demyelinating disease is a demyelinating disease of the central nervous system.

[0565] Example P28. The method according to Example P27, wherein the disease is multiple sclerosis.

[0566] Example P29. The method according to Example P26, wherein the demyelinating disease is a demyelinating disease of the peripheral nervous system.

[0567] Example P30. A method for treating a neurological disease, optionally peripheral neuropathy, in a subject in need, the method comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples P1-P23.

[0568] Example P31. The method according to Example P30, wherein the neurological disease is diabetic neuropathy.

[0569] Example P32. The method according to any one of Examples P25-P31, further comprising administering one or more immunomodulators.

[0570] Example P33. The method according to Example P32, wherein the one or more immunomodulators are selected from: IFN-β1 molecules; corticosteroids; polymers of glutamate, lysine, alanine, and tyrosine or glatiramer; antibodies or fragments thereof against α-4 integrin or natamizumab; anthraquinone molecules or mitoxantrone; fingolimod or FTY720 or other S1P1 modulators; dimethyl fumarate or other NRF2 modulators; antibodies against the T-cell IL-2 receptor α subunit (CD25) or dacrolimus; antibodies against CD52 or alenzab; antibodies against CD20 or oliguriab; inhibitors of dihydroorotate dehydrogenase or teriflunomide.

[0571] Example P34. A method for modulating the activity of muscarinic acetylcholine receptor M1 in a subject, the method comprising administering to the subject a compound according to any one of Examples P1-P23 or a pharmaceutically acceptable salt or solvate thereof.

[0572] Example P35. The method according to Example P34, wherein the compound acts as a selective M1 antagonist.

[0573] IX. Additional Examples

[0574] Example PP1. A compound or a pharmaceutically acceptable salt or solvate thereof having the structure of formula (IA-1) or (IB-1):

[0575]

[0576] in:

[0577] X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 )-、-O-、-S(O) n -, -CH2N(R) 11 )-, substituted or unsubstituted alkylene, substituted or unsubstituted alkenyl, substituted or unsubstituted ynylene, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroalkenyl or substituted or unsubstituted heteroalkenyl;

[0578] Y is a substituted or unsubstituted alkylene group, a substituted or unsubstituted alkenyl group, or a substituted or unsubstituted heteroalkylene group;

[0579] R 1 for Wherein ring A is optionally substituted with the following heteroaryl ring or heterocyclic alkyl ring: hydroxyl, halogen, cyano, -N(R) 14 (R) 15 ), substituted or unsubstituted alkyl groups, substituted or unsubstituted alkoxy groups, substituted or unsubstituted haloalkyl groups, substituted or unsubstituted haloalkoxy groups, substituted or unsubstituted cycloalkyl groups, substituted or unsubstituted cycloalkoxy groups, substituted or unsubstituted halocycloalkyl groups, substituted or unsubstituted halocycloalkoxy groups, substituted or unsubstituted heterocycloalkyl groups, substituted or unsubstituted aryl groups, substituted or unsubstituted heteroaryl groups, -S(O) n (R 16) or -SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S;

[0580] R 2 It can be hydrogen, deuterium, halogen, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted haloalkyl, substituted or unsubstituted haloalkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted halocycloalkyl, substituted or unsubstituted halocycloalkoxy, substituted or unsubstituted alkylhydroxy, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;

[0581] R 3 Halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted haloalkyl, substituted or unsubstituted haloalkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted halocycloalkyl, substituted or unsubstituted halocycloalkoxy, substituted or unsubstituted alkylhydroxy, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or R 2 and R 3 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl;

[0582] R 4 and R 5 Independently selected from hydrogen, deuterium, halogens, and substituted or unsubstituted alkyl groups; or R 3 and R 4 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 4 and R 5 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl;

[0583] R 6 and R 7 Independently selected from hydrogen, deuterium, halogens, and substituted or unsubstituted alkyl groups; or R 3 and R 7Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 4 and R 6 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 5 and R 7 Combining to form bonds;

[0584] R 8 for

[0585] R 9 and R 10 Independently selected from hydrogen, deuterium, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted haloalkyl, substituted or unsubstituted haloalkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkoxy, substituted or unsubstituted halocycloalkyl, substituted or unsubstituted halocycloalkoxy, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or R 3 and R 10 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 4 and R 10 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 6 and R 10 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 9 and R 10 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl;

[0586] R 11 It is hydrogen, a substituted or unsubstituted alkyl group, a substituted or unsubstituted haloalkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted halocycloalkyl group, a substituted or unsubstituted heterocycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group; or R 3 and R 11Combining to form a heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 4 and R 11 Combining to form a heterocyclic alkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 6 and R 11 Combining to form a heterocyclic alkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl;

[0587] Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 ), substituted or unsubstituted alkyl groups, substituted or unsubstituted alkoxy groups, substituted or unsubstituted haloalkyl groups, substituted or unsubstituted haloalkoxy groups, substituted or unsubstituted cycloalkyl groups, substituted or unsubstituted cycloalkoxy groups, substituted or unsubstituted halocycloalkyl groups, substituted or unsubstituted halocycloalkoxy groups, substituted or unsubstituted alkylhydroxy groups, substituted or unsubstituted heterocycloalkyl groups, substituted or unsubstituted aryl groups, substituted or unsubstituted heteroaryl groups, -S(O) n (R 16 ) or -SF5; or R 3 And an R 12 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 10 And an R 12 Combining to form a cycloalkyl ring or heteroalkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl; or R 11 And an R 12 Combining to form a heterocyclic alkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl;

[0588] R 13 It is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted halocycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;

[0589] R 14 and R 15Independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted halocycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; or R 14 and R 15 Combining to form a heterocyclic alkyl ring optionally substituted with: halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted cycloalkyl;

[0590] R 16 It can be a substituted or unsubstituted alkyl group, a substituted or unsubstituted haloalkyl group, a substituted or unsubstituted cycloalkyl group, a halocycloalkyl group, a substituted or unsubstituted heterocycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group.

[0591] m is 0 or 1;

[0592] n is 0, 1, or 2;

[0593] o is 0, 1, 2, or 3; and

[0594] p is 0 or 1.

[0595] Example PP2. The compound or its pharmaceutically acceptable salt or solvate according to Example PP1 has a structure of formula (IA) or (IB):

[0596]

[0597] in:

[0598] X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 )-、-O-、-S(O) n -, -CH2N(R) 11 - or -CH2O-;

[0599] Y is -CH2-, -CH2CH2-, -CH=CH-, or -CH2OCH2-;

[0600] R 1 for Wherein ring A is optionally substituted with a 5- or 6-membered heteroaryl ring or a 5- or 6-membered heterocyclic alkyl ring: halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S;

[0601] R 2 Hydrogen, deuterium, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl;

[0602] R 3 Halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; or R 2 and R 3 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0603] R 4 and R 5 Independently selected from hydrogen, deuterium, halogens and C 1-3 Alkyl; or R 3 and R 4 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 5 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6Alkyl or C 3-6 cycloalkyl;

[0604] R 6 and R 7 Independently selected from hydrogen, deuterium, halogens and C 1-3 Alkyl; or R 3 and R 7 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 6 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 5 and R 7 Combining to form bonds;

[0605] R 8 for

[0606] R 9 and R 10 Independently selected from hydrogen, deuterium, halogens, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl or heteroaryl; or R 3 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 6 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 9 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0607] R 11 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 3 and R 11 Combining to form heteroalkyl rings optionally substituted with: halogens, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 11 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 6 and R 11 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0608] Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5; or R 3 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 10 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 11 And an R 12 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0609] R 13 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0610] R 14 and R 15 Independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 14 and R 15 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0611] R 16 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0612] m is 0 or 1;

[0613] n is 0, 1, or 2; and

[0614] o can be 0, 1, 2, or 3.

[0615] Example PP3. The compound or its pharmaceutically acceptable salt or solvate according to any one of Examples PP1-PP2, having a structure of formula (IIA) or (IIB):

[0616]

[0617] in:

[0618] X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 )-、-O-、-S(O) n -, -CH2N(R) 11 - or -CH2O-;

[0619] Y is -CH2-, -CH2CH2-, -CH=CH-, or -CH2OCH2-;

[0620] R 1 for Wherein ring A is optionally substituted with a 5- or 6-membered heteroaryl ring or a 5- or 6-membered heterocyclic alkyl ring: halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S;

[0621] R 2 Hydrogen, deuterium, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl;

[0622] R 3 Halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; or R 2 and R 3 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0623] R 8 for

[0624] R 9 and R 10Independently selected from hydrogen, deuterium, halogens, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl or heteroaryl; or R 3 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 9 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0625] R 11 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 3 and R 11 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0626] Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5; or R 3 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R10 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 11 And an R 12 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0627] R 13 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0628] R 14 and R 15 Independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 14 and R 15 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0629] R 16 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0630] m is 0 or 1;

[0631] n is 0, 1, or 2; and

[0632] o can be 0, 1, 2, or 3.

[0633] Example PP4. The compound or its pharmaceutically acceptable salt or solvate according to any one of Examples PP1-PP2, having the structure of formula (III):

[0634]

[0635] in:

[0636] X is a bond, -C(R) 9 (R) 10 )-、-N(R11 )-、-O-、-S(O) n -, -CH2N(R) 11 - or -CH2O-;

[0637] R 1 for Wherein ring A is optionally substituted with a 5- or 6-membered heteroaryl ring or a 5- or 6-membered heterocyclic alkyl ring: halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S;

[0638] R 2 Hydrogen, deuterium, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl;

[0639] R 3 Halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; or R 2 and R 3 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C3-6 cycloalkyl;

[0640] R 8 for

[0641] R 9 and R 10 Independently selected from hydrogen, deuterium, halogens, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl or heteroaryl; or R 3 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 9 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0642] R 11 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 3 and R 11 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0643] Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R16 ) or SF5; or R 3 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 10 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 11 And an R 12 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0644] R 13 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0645] R 14 and R 15 Independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 14 and R 15 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0646] R 16 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0647] m is 0 or 1;

[0648] n is 0, 1, or 2; and

[0649] o can be 0, 1, 2, or 3.

[0650] Example PP5. A compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples PP1-PP4, wherein X is a bond.

[0651] Example PP6. A compound according to any one of Examples PP1-PP4, or a pharmaceutically acceptable salt or solvation thereof, wherein X is -C(R 9 (R) 10 )-.

[0652] Example PP7. A compound according to any one of Examples PP1-PP4, or a pharmaceutically acceptable salt or solvate thereof, wherein X is -N(R 11 )-.

[0653] Example PP8. A compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples PP1-PP4, wherein X is -O-.

[0654] Example PP9. A compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples PP1-PP4, wherein X is -S-.

[0655] Example PP10. A compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples PP1-PP4, wherein X is -S(O)-.

[0656] Example PP11. A compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples PP1-PP4, wherein X is -S(O)2-.

[0657] Example PP12. The compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples PP1-PP11, wherein R 1 for

[0658] Example PP13. The compound according to any one of Examples PP1-PP12, wherein R 2 It can be hydrogen, -F, -CH3, -CH2CH3, -CF2H, -CF3, -CH2OH, -C(CH3)2OH, phenyl, or cyclopropyl.

[0659] Example PP14. The compound according to any one of Examples PP1-PP13, wherein R 3 It can be -F, -CH3, -CH2CH3, -CF2H, -CF3, -CH2OH, -C(CH3)2OH, phenyl, or cyclopropyl.

[0660] Example PP15. The compound according to any one of Examples PP1-PP12, wherein R 2 and R 3 Combining to form cyclopropyl rings, cyclobutyl rings, or cyclopentyl rings.

[0661] Example PP16. The compound according to any one of Examples PP1-PP12, wherein R 2 and R 3 Combining them to form oxocyclic butyl rings or tetrahydrofuranyl rings.

[0662] Example PP17. The compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples PP1-PP16, wherein m is 0.

[0663] Example PP18. A compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples PP1-PP16, wherein m is 1.

[0664] Example PP19. The compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples PP1-PP18, wherein o is 0.

[0665] Example PP20. The compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples PP1-PP18, wherein o is 1.

[0666] Example PP21. The compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples PP1-PP18, wherein o is 2.

[0667] Example PP22. The compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples PP1-PP18, wherein o is 3.

[0668] Example PP23. The compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples PP1-PP22, wherein R 8 for

[0669] Example PP24. A compound selected from the list of compounds 1 or a pharmaceutically acceptable salt thereof.

[0670] Example PP25. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples PP1-PP24, and at least one pharmaceutically acceptable excipient.

[0671] Example PP26. A method for treating a subject with neurodegenerative disease, the method comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples PP1-PP24.

[0672] Example PP27. A method of treating a subject with a demyelinating disease, the method comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples PP1-PP24.

[0673] Example PP28. The method according to Example PP27, wherein the demyelinating disease is a demyelinating disease of the central nervous system.

[0674] Example PP29. The method according to Example PP28, wherein the disease is multiple sclerosis.

[0675] Example PP30. The method according to Example PP27, wherein the demyelinating disease is a demyelinating disease of the peripheral nervous system.

[0676] Example PP31. A method for treating a neurological disease, optionally peripheral neuropathy, in a subject in need, the method comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or solvate thereof according to any one of Examples PP1-PP24.

[0677] Example PP32. The method according to Example PP31, wherein the neurological disease is diabetic neuropathy.

[0678] Example PP33. The method according to any one of Examples PP26-PP32 further includes the administration of one or more immunomodulators.

[0679] Example PP34. The method according to Example PP33, wherein the one or more immunomodulators are selected from: IFN-β1 molecules; corticosteroids; polymers of glutamate, lysine, alanine, and tyrosine or glatiramer; antibodies or fragments thereof against α-4 integrin or natamizumab; anthraquinone molecules or mitoxantrone; fingolimod or FTY720 or other S1P1 modulators; dimethyl fumarate or other NRF2 modulators; antibodies against the T-cell IL-2 receptor α subunit (CD25) or dacrolimus; antibodies against CD52 or alenzab; antibodies against CD20 or oliguriab; inhibitors of dihydroorotate dehydrogenase or teriflunomide.

[0680] Example PP35. A method for modulating the activity of muscarinic acetylcholine receptor M1 in a subject, the method comprising administering to the subject a compound according to any one of Examples PP1-PP24 or a pharmaceutically acceptable salt or solvate thereof.

[0681] Example PP36. The method according to Example PP35, wherein the compound acts as a selective M1 antagonist.

[0682] X. Other embodiments

[0683] Example 1. A compound or a pharmaceutically acceptable salt or solvate thereof having the structure of formula (IA) or (IB):

[0684]

[0685] in:

[0686] X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 )-、-O-、-S(O) n -, -CH2N(R) 11 - or -CH2O-;

[0687] Y is -CH2-, -CH2CH2-, -CH=CH-, or -CH2OCH2-;

[0688] R 1 for Wherein ring A is optionally substituted with a 5- or 6-membered heteroaryl ring or a 5- or 6-membered heterocyclic alkyl ring: halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy groups, heterocyclic alkyl groups, aryl groups, heteroaryl groups, -S(O) n (R 16 ) or -SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S;

[0689] R 2 Hydrogen, deuterium, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl;

[0690] R 3 Halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; or R 2 and R 3 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0691] R 4 and R 5 Independently selected from hydrogen, deuterium, halogens and C 1-3 Alkyl; or R 3 and R 4 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 5 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0692] R 6 and R 7 Independently selected from hydrogen, deuterium, halogens and C 1-3 Alkyl; or R 3 and R 7 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 6 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 5 and R 7 Combining to form bonds;

[0693] R 8 for

[0694] R 9 and R 10 Independently selected from hydrogen, deuterium, halogens, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl or heteroaryl; or R 3 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 6 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 9 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0695] R 11 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 3 and R 11 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 11 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 6 and R 11 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0696] Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl, heteroaryl, -S(O) n (R 16 ) or -SF5; or R 3 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 10 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 11 And an R 12 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0697] R 13 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0698] R 14 and R 15 Independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 14 and R 15 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0699] R 16C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0700] m is 0 or 1;

[0701] n is 0, 1, or 2; and

[0702] o can be 0, 1, 2, or 3.

[0703] Example 2. The compound according to Example 1, or a pharmaceutically acceptable salt or solvate thereof, having a structure of formula (IIA) or (IIB):

[0704]

[0705] in:

[0706] X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 )-、-O-、-S(O) n -, -CH2N(R) 11 - or -CH2O-;

[0707] Y is -CH2-, -CH2CH2-, -CH=CH-, or -CH2OCH2-;

[0708] R 1 for Wherein ring A is optionally substituted with a 5- or 6-membered heteroaryl ring or a 5- or 6-membered heterocyclic alkyl ring: halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy groups, heterocyclic alkyl groups, aryl groups, heteroaryl groups, -S(O) n (R 16 ) or -SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S;

[0709] R 2 Hydrogen, deuterium, halogen, hydroxyl, C 1-6 Alkyl, C1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl;

[0710] R 3 Halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; or R 2 and R 3 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0711] R 8 for

[0712] R 9 and R 10 Independently selected from hydrogen, deuterium, halogens, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl or heteroaryl; or R 3 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 9 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0713] R 11 For hydrogen, C1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 3 and R 11 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0714] Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl, heteroaryl, -S(O) n (R 16 ) or -SF5; or R 3 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 10 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 11 And an R 12 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0715] R 13 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0716] R 14 and R 15 Independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 14 and R 15 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0717] R 16 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0718] m is 0 or 1;

[0719] n is 0, 1, or 2; and

[0720] o can be 0, 1, 2, or 3.

[0721] Example 3. The compound according to Example 1, or its pharmaceutically acceptable salt or solvate, has the structure of formula (III):

[0722]

[0723] in:

[0724] X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 )-、-O-、-S(O) n -, -CH2N(R) 11 - or -CH2O-;

[0725] R 1 for Wherein ring A is optionally substituted with a 5- or 6-membered heteroaryl ring or a 5- or 6-membered heterocyclic alkyl ring: halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy groups, heterocyclic alkyl groups, aryl groups, heteroaryl groups, -S(O) n (R 16) or -SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S;

[0726] R 2 Hydrogen, deuterium, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl;

[0727] R 3 Halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; or R 2 and R 3 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0728] R 8 for

[0729] R 9 and R 10 Independently selected from hydrogen, deuterium, halogens, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl or heteroaryl; or R 3 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 9and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0730] R 11 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 3 and R 11 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0731] Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl, heteroaryl, -S(O) n (R 16 ) or -SF5; or R 3 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 10 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 11 And an R 12 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0732] R 13 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0733] R 14 and R 15 Independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 14 and R 15 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl;

[0734] R 16 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0735] m is 0 or 1;

[0736] n is 0, 1, or 2; and

[0737] o can be 0, 1, 2, or 3.

[0738] Example 4. The compound according to any one of Examples 1-3 or a pharmaceutically acceptable salt or solvate thereof, wherein X is a bond.

[0739] Example 5. A compound according to any one of Examples 1-3, or a pharmaceutically acceptable salt or solvation thereof, wherein X is -C(R 9 (R) 10 )-.

[0740] Example 6. A compound according to any one of Examples 1-3, or a pharmaceutically acceptable salt or solvate thereof, wherein X is -N(R 11 )-.

[0741] Example 7. The compound according to any one of Examples 1-3 or a pharmaceutically acceptable salt or solvation thereof, wherein X is -O-.

[0742] Example 8. The compound according to any one of Examples 1-3 or a pharmaceutically acceptable salt or solvation thereof, wherein X is -S-.

[0743] Example 9. The compound according to any one of Examples 1-3 or a pharmaceutically acceptable salt or solvation thereof, wherein X is -S(O)-.

[0744] Example 10. The compound according to any one of Examples 1-3 or a pharmaceutically acceptable salt or solvate thereof, wherein X is -S(O)2-.

[0745] Example 11. The compound according to any one of Examples 1-10, or a pharmaceutically acceptable salt or solvation thereof, wherein R 1 for

[0746] Example 12. The compound according to any one of Examples 1-11, or a pharmaceutically acceptable salt or solvation thereof, wherein R 2 It can be hydrogen, -F, -CH3, -CH2CH3, -CF2H, -CF3, -CH2OH, -C(CH3)2OH, phenyl, or cyclopropyl.

[0747] Example 13. The compound according to any one of Examples 1-12, or a pharmaceutically acceptable salt or solvate thereof, wherein R 3 It can be -F, -CH3, -CH2CH3, -CF2H, -CF3, -CH2OH, -C(CH3)2OH, phenyl, or cyclopropyl.

[0748] Example 14. The compound according to any one of Examples 1-11, or a pharmaceutically acceptable salt or solvation thereof, wherein R 2 and R 3 Combining to form cyclopropyl rings, cyclobutyl rings, or cyclopentyl rings.

[0749] Example 15. The compound according to any one of Examples 1-11, or a pharmaceutically acceptable salt or solvation thereof, wherein R 2 and R 3 Combining them to form oxocyclic butyl rings or tetrahydrofuranyl rings.

[0750] Example 16. The compound according to any one of Examples 1-15, or a pharmaceutically acceptable salt or solvation thereof, wherein m is 0.

[0751] Example 17. The compound according to any one of Examples 1-15 or a pharmaceutically acceptable salt or solvation thereof, wherein m is 1.

[0752] Example 18. The compound according to any one of Examples 1-17 or a pharmaceutically acceptable salt or solvation thereof, wherein o is 0.

[0753] Example 19. The compound according to any one of Examples 1-17 or a pharmaceutically acceptable salt or solvation thereof, wherein o is 1.

[0754] Example 20. The compound according to any one of Examples 1-17 or a pharmaceutically acceptable salt or solvate thereof, wherein o is 2.

[0755] Example 21. The compound according to any one of Examples 1-17 or a pharmaceutically acceptable salt or solvation thereof, wherein o is 3.

[0756] Example 22. The compound according to any one of Examples 1-21, or a pharmaceutically acceptable salt or solvation thereof, wherein R 8 for

[0757] Example 23. A compound selected from the list of compounds 1 or a pharmaceutically acceptable salt thereof.

[0758] Example 24. A pharmaceutical composition comprising a compound according to any one of Examples 1-23 or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.

[0759] Example 25. A method for treating neurodegenerative diseases in a subject in need, the method comprising administering to the subject a therapeutically effective amount of a compound according to any one of Examples 1-23 or a pharmaceutically acceptable salt or solvate thereof.

[0760] Example 26. A method for treating a subject with demyelinating disease, the method comprising administering to the subject a therapeutically effective amount of a compound according to any one of Examples 1-23 or a pharmaceutically acceptable salt or solvate thereof.

[0761] Example 27. The method according to Example 26, wherein the demyelinating disease is a demyelinating disease of the central nervous system.

[0762] Example 28. The method according to Example 27, wherein the demyelinating disease is multiple sclerosis.

[0763] Example 29. The method according to Example 26, wherein the demyelinating disease is a demyelinating disease of the peripheral nervous system.

[0764] Example 30. A method for treating a neurological disease, optionally peripheral neuropathy, in a subject in need, the method comprising administering to the subject a therapeutically effective amount of a compound according to any one of Examples 1-23 or a pharmaceutically acceptable salt or solvate thereof.

[0765] Example 31. The method according to Example 30, wherein the neurological disease is diabetic neuropathy.

[0766] Example 32. The method according to any one of Examples 25-31, further comprising administering one or more immunomodulators.

[0767] Example 33. The method according to Example 32, wherein the one or more immunomodulators are selected from: IFN-β1 molecules; corticosteroids; polymers of glutamate, lysine, alanine, and tyrosine or glatiramer; antibodies or fragments thereof against α-4 integrin or natamizumab; anthraquinone molecules or mitoxantrone; fingolimod or FTY720 or other S1P1 modulators; dimethyl fumarate or other NRF2 modulators; antibodies against the T-cell IL-2 receptor α subunit (CD25) or dacrolimus; antibodies against CD52 or alenzab; antibodies against CD20 or olizumab; inhibitors of dihydroorotate dehydrogenase or teriflunomide.

[0768] Example 34. A method for modulating the activity of muscarinic acetylcholine receptor M1 in a subject, the method comprising administering to the subject a compound according to any one of Examples 1-23 or a pharmaceutically acceptable salt or solvate thereof.

[0769] Example 35. The method according to Example 34, wherein the compound acts as a selective M1 antagonist.

[0770] Example

[0771] Unless otherwise specified, reagents and solvents received from commercial suppliers were used. Anhydrous solvents and dried glassware were used for synthetic transformations sensitive to moisture and / or oxygen. Yields were not optimized. Reaction times were approximate and not optimized. Unless otherwise specified, column chromatography and thin-layer chromatography (TLC) were performed on silica gel.

[0772] Intermediate Amine 1: Preparation of 1-(quinolin-5-yl)cyclopropane-1-amine

[0773]

[0774] In a dry round-bottom flask equipped with a magnetic stirrer, quinoline-5-carboxynitrile (1 equivalent, Combi-Blocks) and titanium isopropoxide (IV) (1.1 equivalent, Combi-Blocks) were dissolved in diethyl ether (0.2 M). Ethyl magnesium bromide (2 equivalents, 3 M solution / ether, Sigma-Aldrich) was then added dropwise to this product at -78 °C over 5-minute intervals. The resulting brown suspension was stirred at -78 °C for more than 10 minutes, allowing the suspension to warm to RT over 1 hour. Finally, purified boron trifluoride diethyl ether compound (2 equivalents, Sigma-Aldrich) was added dropwise to the reaction mixture over 5-minute intervals. The now dark brown suspension was allowed to stir at RT for an additional 2 hours. The reaction was then quenched by adding 1 M HCl aqueous solution, and the resulting biphase mixture was poured into a separatory funnel. The golden aqueous layer was separated, further washed with diethyl ether (3×), and carefully alkalized by adding 1M NaOH aqueous solution. The resulting suspension was then extracted with EtOAc (3×). The combined EtOAc extracts were further washed with water and brine, dried over MgSO4, filtered, and the filtrate was concentrated under vacuum to give a viscous golden oil. Purification of the crude product thus obtained by column chromatography (SiO2, gradient elution: EtOAc → 9:1 (v / v) EtOAc:MeOH) gave the title compound as a yellow oil, which solidified upon standing (44% yield).

[0775] The following amines are prepared in a similar manner to intermediate amine 1, but with the desired formonitrile substituted for quinoline-5-formonitrile:

[0776]

[0777] Intermediate Amine 17: Preparation of 1-(2-methoxypyridin-4-yl)cyclopropane-1-amine

[0778]

[0779] In a dry round-bottom flask equipped with a magnetic stirrer, a combination of lithium isopropoxide (2.5 equivalents, 3M solution / THF, Sigma-Aldrich) and lithium iodide (2.5 equivalents, Sigma-Aldrich) was dissolved in THF (0.31M). Triisopropoxide methyltitanium (IV) (1.2 equivalents, 1M solution / THF, Sigma-Aldrich) and 4-cyano-2-methoxypyridine (1 equivalent, 1.9M solution / THF, Combi-Blocks) were then carefully added dropwise to this product over a 15-minute period. Finally, diethylzinc (1.2 equivalents, 1M solution / toluene, Sigma-Aldrich) was added dropwise over a 60-minute period. The resulting mixture was stirred at RT for 16 hours, after which the reaction was quenched by careful addition of water. The resulting slurry was stirred until it turned yellow, and the precipitate was removed by filtration. Insoluble matter was further washed with diethyl ether. The combined filtrates were washed sequentially with water and brine, dried over Na2SO4, filtered, and concentrated under vacuum. The filtrates were then analyzed by reversed-phase column chromatography (C1000-C1000). 18 Gradient elution: 9:1 (v / v) H2O: MeCN + 0.1% formic acid → MeCN + 0.1% formic acid) Purification of the crude product obtained therefrom followed by free basification yielded the title compound (14% yield).

[0780] The following amines are prepared in a similar manner to intermediate amine 17, but with the desired formonitrile substituted for 4-cyano-2-methoxypyridine:

[0781]

[0782] Intermediate amine 24: Preparation of 1-(3-methoxyphenyl)cyclobutane-1-amine

[0783]

[0784] Step 1:In a dry round-bottom flask equipped with a magnetic stirrer, cyclobutanone (1.2 equivalents, Combi-Blocks) was dissolved in THF (0.5 M). Tetraethanolamine (IV) (1.8 equivalents, Acros) and 2-methylpropane-2-sulfinamide (1 equivalent, Combi-Blocks) were then added sequentially to the product. The mixture was allowed to be stirred at RT for 16 hours. The volatiles were then removed under vacuum, and the resulting residue was partitioned between EtOAc and a saturated aqueous solution of NaHCO3. The resulting suspension was then filtered through a diatomaceous earth mat, and the insoluble matter was further washed with EtOAc. The filtrate was then poured into a separatory funnel. The organic layer was separated, further washed with brine, dried over MgSO4, filtered, and the filtrate concentrated under vacuum. The crude product obtained was purified by column chromatography (SiO2, gradient elution: Hex→EtOAc) to give N-cyclobutenyl-2-methylpropane-2-sulfinamide in the form of a yellow oil (64% yield).

[0785] Step 2: In a dry round-bottom flask equipped with a magnetic stirrer, 1-iodo-3-methoxybenzene (1 equivalent, Acros) was dissolved in diethyl ether (0.43 M). The resulting solution was then cooled to -78°C, and the solution was added dropwise over 5 minutes. n BuLi (1.1 equivalents, 2.5 M solution / hexane, Sigma-Aldrich) was used to give a bright yellow solution. After stirring at -78 °C for 30 min, N-cyclobutenyl-2-methylpropane-2-sulfinamide (1.1 equivalents) from the previous step was added. The resulting mixture was allowed to be heated to RT over 30 min, and the reaction was then quenched by adding a saturated aqueous solution of NH4Cl. The aqueous phase was separated and back-extracted with EtOAc. The combined organic extracts were further washed with water and brine, dried over MgSO4, filtered, and the filtrate was concentrated under vacuum. Purification of the crude product thus obtained by column chromatography (SiO2, gradient elution: Hex → EtOAc) gave N-(1-(3-methoxyphenyl)cyclobutyl)-2-methylpropane-2-sulfinamide as a colorless oil (39% yield).

[0786] Step 3:In a dry round-bottom flask equipped with a magnetic stirrer, N-(1-(3-methoxyphenyl)cyclobutyl)-2-methylpropane-2-sulfinamide (1 equivalent) from the previous step was dissolved in methanol (0.83 M). HCl (3 equivalents, 4 M solution / dioxane, Sigma-Aldrich) was then added to this product, and the resulting solution was allowed to be stirred at RT for 30 minutes. The reaction was then quenched with a saturated aqueous solution of NaHCO3 and extracted with EtOAc. The combined organic extracts were further washed with brine, dried over Na2SO4, and filtered. The filtrate was concentrated under vacuum to give the title compound (45% crude product yield).

[0787] The following amines are prepared in a similar manner to intermediate amine 24, but with the desired (hetero)aryl halide from step 2 substituted for 1-iodo-3-methoxybenzene:

[0788]

[0789] Intermediate amine 31: Preparation of 7-methoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline

[0790]

[0791] Step 1: In a dry round-bottom flask equipped with a magnetic stirrer, 4-methoxyphenylethylamine (1 equivalent, Combi-Blocks) and pyridine (2.5 equivalents, Sigma-Aldrich) were combined in dichloromethane (0.34 M). Pure acetyl chloride (2 equivalents, Sigma-Aldrich) was then added dropwise to this product over a 5-minute interval. The resulting mixture was allowed to be stirred at RT for 3 hours. The volatiles were then removed under vacuum, and the resulting residue was directly purified by column chromatography (SiO2, gradient elution: Hex → EtOAc) to give N-(4-methoxyphenylethyl)acetamide (63% yield) as a yellow oil.

[0792] Step 2: In a dry round-bottom flask equipped with a magnetic stirrer, N-(4-methoxyphenylethyl)acetamide (1 equivalent), phosphorus pentoxide (2 equivalents, Sigma-Aldrich), and phosphorus oxychloride (V) (2 equivalents, Sigma-Aldrich) from the previous step were combined in toluene (0.21 M). The resulting solution was heated at 110 °C for 2 hours. The volatiles were then removed under vacuum, and the resulting residue was subjected directly to reversed-phase column chromatography (C2C10). 18 Purification was carried out by gradient elution: 10:1 (v / v) H2O:MeCN→MeCN to give 7-methoxy-1-methyl-3,4-dihydroisoquinoline in yellow oil form (77% yield).

[0793] Step 3: In a dry round-bottom flask equipped with a magnetic stirrer, 7-methoxy-1-methyl-3,4-dihydroisoquinoline (1 equivalent) from the previous step was combined in methanol (0.32 M). Sodium borohydride (4 equivalents, Sigma-Aldrich) was then added fractionally to this product at 0 °C, and the resulting solution was stirred at 0 °C for 2 hours. The reaction was then quenched with water and extracted with DCM. The combined organic extracts were further washed with brine, dried over Na₂SO₄, filtered, and the filtrate concentrated under vacuum. The solution was then analyzed by reversed-phase column chromatography (C₂). 18 Gradient elution: 10:1 (v / v) H2O:MeCN → MeCN) The crude product obtained was purified to give the title compound in pale yellow oil form (74% yield).

[0794] The following amines were prepared in a similar manner to intermediate amine 31, but with 2-(2-methoxyphenyl)ethylamine (TCI) replacing 4-methoxyphenylethylamine in step 1:

[0795]

[0796] Intermediate amine 33: Preparation of 6-(3,8-diazabicyclo[3.2.1]octane-8-yl)nicotinonitrile dihydrochloride

[0797]

[0798] Step 1:In a dry round-bottom flask equipped with a magnetic stirrer and a reflux condenser, tert-butyl 3,8-diazabicyclo[3.2.1]octane-3-carboxylate (1 equivalent, PharmaBlock, Inc.) and 5-cyano-2-fluoropyridine (1.2 equivalent, Combi-Blocks) were dissolved in acetonitrile...

Claims

1. A compound or a pharmaceutically acceptable salt or solvate thereof having the structure of formula (IA) or (IB): in: X is a bond, -C(R 9 )(R 10 )-, -N(R 11 )-, -O-, -S(O) n -, -CH2N(R 11 )- or -CH2O-; Y is -CH2-, -CH2CH2-, -CH=CH-, or -CH2OCH2-; R 1 for wherein ring A is a 5- or 6-membered heteroaryl ring or a 5- or 6-membered heterocycloalkyl ring optionally substituted with halogen, cyano, -N(R 14 )(R 15 ), C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 3-6 cycloalkyl, C 3-6 cycloalkoxy, C 3-6 halocycloalkyl, C 3-6 halocycloalkoxy, heterocycloalkyl, aryl, heteroaryl, -S(O) n (R 16 ) or -SF5, wherein said heteroaryl ring or said heterocycloalkyl ring contains 1, 2 or 3 heteroatoms selected from the group consisting of O, N or S; R 2 halogen, hydroxyl, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 3-6 cycloalkyl, C 3-6 cycloalkoxy, C 3-6 halocycloalkyl, C 3-6 halocycloalkoxy, C 1-6 alkylhydroxyl, heterocycloalkyl, aryl, or heteroaryl; R 3 Halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; or R 2 and R 3 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; R 4 and R 5 Independently selected from hydrogen, deuterium, halogens and C 1-3 Alkyl; or R 3 and R 4 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 5 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; R 6 and R 7 Independently selected from hydrogen, deuterium, halogens and C 1-3 Alkyl; or R 3 and R 7 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 6 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 5 and R 7 Combining to form bonds; R 8 for R 9 and R 10 Independently selected from hydrogen, deuterium, halogens, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl or heteroaryl; or R 3 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 6 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 9 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; R 11 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 3 and R 11 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 4 and R 11 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 6 and R 11 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or -SF5; or R 3 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 10 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 11 And an R 12 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; R 13 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; R 14 and R 15 Independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 14 and R 15 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; R 16 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; m is 0 or 1; n is 0, 1, or 2; and o can be 0, 1, 2, or 3.

2. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, having a structure of formula (IIA) or (IIB): in: X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 )-、-O-、-S(O) n -, -CH2N(R) 11 - or -CH2O-; Y is -CH2-, -CH2CH2-, -CH=CH-, or -CH2OCH2-; R 1 for Wherein ring A is optionally substituted with a 5- or 6-membered heteroaryl ring or a 5- or 6-membered heterocyclic alkyl ring: halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy groups, heterocyclic alkyl groups, aryl groups, heteroaryl groups, -S(O) n (R 16 ) or -SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S; R 2 Hydrogen, deuterium, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; R 3 Halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; or R 2 and R 3 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; R 8 for R 9 and R 10 Independently selected from hydrogen, deuterium, halogens, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl or heteroaryl; or R 3 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 9 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; R 11 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 3 and R 11 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or -SF5; or R 3 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 10 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 11 And an R 12 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; R 13 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; R 14 and R 15 Independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 14 and R 15 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; R 16 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; m is 0 or 1; n is 0, 1, or 2; and o can be 0, 1, 2, or 3.

3. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, having the structure of formula (III): in: X is a bond, -C(R) 9 (R) 10 )-、-N(R 11 )-、-O-、-S(O) n -, -CH2N(R) 11 - or -CH2O-; R 1 for Wherein ring A is optionally substituted with a 5- or 6-membered heteroaryl ring or a 5- or 6-membered heterocyclic alkyl ring: halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy groups, heterocyclic alkyl groups, aryl groups, heteroaryl groups, -S(O) n (R 16 ) or -SF5, wherein the heteroaryl ring or the heterocyclic alkyl ring contains one, two or three heteroatoms selected from the group consisting of O, N or S; R 2 Hydrogen, deuterium, halogen, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; R 3 Halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl or heteroaryl; or R 2 and R 3 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; R 8 for R 9 and R 10 Independently selected from hydrogen, deuterium, halogens, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, heterocyclic alkyl, aryl or heteroaryl; or R 3 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 9 and R 10 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; R 11 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 3 and R 11 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; Each R 12 Independently selected from hydroxyl, halogen, cyano, -N(R) 14 (R) 15 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Halogenated cycloalkyl, C 3-6 Halogenated cycloalkoxy, C 1-6 Alkyl hydroxyl, heterocyclic alkyl, aryl, heteroaryl, S(O) n (R 16 ) or -SF5; or R 3 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 10 And an R 12 Combining to form cycloalkyl or heteroalkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; or R 11 And an R 12 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; R 13 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; R 14 and R 15 Independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or R 14 and R 15 Combining to form heterocyclic alkyl rings optionally substituted with: halogen, C 1-6 Alkyl or C 3-6 cycloalkyl; R 16 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 3-6 Halogenated cycloalkyl, heterocycloalkyl, aryl or heteroaryl; m is 0 or 1; n is 0, 1, or 2; and o can be 0, 1, 2, or 3.

4. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein X is a bond.

5. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein X is -C(R) 9 (R) 10 )-.

6. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein X is -N(R 11 )-.

7. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein X is -O-.

8. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein X is -S-.

9. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein X is -S(O)-.

10. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein X is -S(O)2-.

11. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 for 12. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 It can be hydrogen, -F, -CH3, -CH2CH3, -CF2H, -CF3, -CH2OH, -C(CH3)2OH, phenyl, or cyclopropyl.

13. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein R 3 It can be -F, -CH3, -CH2CH3, -CF2H, -CF3, -CH2OH, -C(CH3)2OH, phenyl, or cyclopropyl.

14. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 and R 3 Combining to form cyclopropyl rings, cyclobutyl rings, or cyclopentyl rings.

15. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 and R 3 Combining them to form oxetanyl rings or tetrahydrofuranyl rings.

16. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein m is 0.

17. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein m is 1.

18. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein o is 0.

19. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein o is 1.

20. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein o is 2.

21. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein o is 3.

22. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein R 8 for 23. A compound selected from the following: Or its pharmaceutically acceptable salt.

24. The compound of claim 23 or a pharmaceutically acceptable salt thereof, wherein the compound has the following formula:

25. The compound of claim 23 or a pharmaceutically acceptable salt thereof, wherein the compound has the following formula:

26. The compound of claim 23 or a pharmaceutically acceptable salt thereof, wherein the compound has the following formula:

27. The compound of claim 23 or a pharmaceutically acceptable salt thereof, wherein the compound has the following formula:

28. The compound of claim 23 or a pharmaceutically acceptable salt thereof, wherein the compound has the following formula:

29. The compound of claim 23 or a pharmaceutically acceptable salt thereof, wherein the compound has the following formula:

30. The compound of claim 23 or a pharmaceutically acceptable salt thereof, wherein the compound has the following formula:

31. The compound of claim 23 or a pharmaceutically acceptable salt thereof, wherein the compound has the following formula:

32. The compound of claim 23 or a pharmaceutically acceptable salt thereof, wherein the compound has the following formula:

33. The compound of claim 23 or a pharmaceutically acceptable salt thereof, wherein the compound has the following formula:

34. A pharmaceutical composition comprising a compound according to any one of claims 1 to 33 or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.

35. Use of the compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 33 in the preparation of a medicament for treating neurodegenerative diseases in a subject in need.

36. The use according to claim 35, wherein the medicament further comprises administration of one or more immunomodulators.

37. The use according to claim 36, wherein the one or more immunomodulators are selected from: IFN-β1 molecules; corticosteroids; polymers of glutamate, lysine, alanine, and tyrosine or glatiramer; antibodies or fragments thereof against α-4 integrin or natalizumab; anthraquinone molecules or mitoxantrone; fingolimod or FTY720 or other S1P1 modulators; dimethyl fumarate or other NRF2 modulators; antibodies against the T-cell IL-2 receptor α subunit (CD25) or daclizumab; antibodies against CD52 or alemtuzumab; antibodies against CD20 or ocrelizumab; inhibitors of dihydroorotate dehydrogenase or teriflunomide.

38. Use of the compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 33 in the preparation of a medicament for treating demyelinating diseases in a subject of need.

39. The use according to claim 38, wherein the demyelinating disease is a demyelinating disease of the central nervous system.

40. The use according to claim 39, wherein the demyelinating disease is multiple sclerosis.

41. The use according to claim 38, wherein the demyelinating disease is a demyelinating disease of the peripheral nervous system.

42. The use according to claim 38, wherein the medicament further comprises administration of one or more immunomodulators.

43. The use according to claim 42, wherein the one or more immunomodulators are selected from: IFN-β1 molecules; corticosteroids; polymers of glutamate, lysine, alanine, and tyrosine or glatiramer; antibodies or fragments thereof against α-4 integrin or natamizumab; anthraquinone molecules or mitoxantrone; fingolimod or FTY720 or other S1P1 modulators; dimethyl fumarate or other NRF2 modulators; antibodies against the T-cell IL-2 receptor α subunit (CD25) or dacrolimus; antibodies against CD52 or alenzab; antibodies against CD20 or olizumab; inhibitors of dihydroorotate dehydrogenase or teriflunomide.

44. Use of the compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 33 in the preparation of a medicament for treating a neurological disorder in a subject in need.

45. The use according to claim 44, wherein the neurological disease is a peripheral neuropathy.

46. ​​The use according to claim 44, wherein the neurological disease is diabetic neuropathy.

47. The use according to claim 44, wherein the medicament further comprises one or more immunomodulators.

48. The use according to claim 47, wherein the one or more immunomodulators are selected from: IFN-β1 molecules; corticosteroids; polymers of glutamate, lysine, alanine, and tyrosine or glatiramer; antibodies or fragments thereof against α-4 integrin or natamizumab; anthraquinone molecules or mitoxantrone; fingolimod or FTY720 or other S1P1 modulators; dimethyl fumarate or other NRF2 modulators; antibodies against the T-cell IL-2 receptor α subunit (CD25) or dacrolimus; antibodies against CD52 or alenzab; antibodies against CD20 or oliguriab; inhibitors of dihydroorotate dehydrogenase or teriflunomide.

49. A method for preparing a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 33 for modulating the activity of muscarinic acetylcholine receptor M1 in a subject in need.

50. The use according to claim 49, wherein the compound acts as a selective M1 antagonist.

51. A method for preparing a compound of formula (IA) or (IB) according to any one of claims 1 to 33, or a pharmaceutically acceptable form thereof, said compound having formula (IA-1) or (IB-1). Where p is 1, The method includes: (a) The step of reacting a compound of formula (1a) or (1b) or its corresponding ammonium salt with a carboxylic acid of formula (2) in the presence of a suitable coupling agent and a base. or (b) the following steps (i) The step of reacting a compound of formula (1a) or (1b) with a carboxylic acid of formula (2) that has been previously preactivated to the corresponding acyl chloride to produce an amide of formula (3a) or (3b). and optional, (ii) the step of further functionalizing into another compound of formula (IA-1) or (IB-1); or (c) The following steps (i) Coupling a compound of formula (4a) or (4b) with a carboxylic acid of formula (2) to generate a compound of formula (5a) or (5b). PG is a protecting group. (ii) Removing the protecting group (PG) to generate a compound of formula (6a) or (6b). and (iii) React the resulting amine (6a) or (6b) with a suitably functionalized (hetero)aryl halide to generate a compound of formula (IA-1) or (IB-1); or (d) The following steps (i) Reacting the compound of formula (9) with the compound of formula (8a) or (8b) via a direct nucleophilic substitution reaction of the leaving group (LG). Where LG is a leaving group; and optional, (ii) includes a prior step of activating the compound of formula (9), when the compound is an amine; or (e) The steps of reacting the compound of formula (11a) or (11b) with the compound of formula (12). Where LG is a leaving group; or (f) Reduce compound of formula (15a) or (15b) with a suitable reagent or with formula R 2 -M organometallic compound trapping steps of compound (15a) or (15b) 52. The method of claim 51, wherein the method comprises the following steps: (i) Reacting the compound of formula (9) with the compound of formula (8a) or (8b) via a direct nucleophilic substitution reaction of the leaving group (LG). Where LG is a leaving group; and optionally includes a prior step of activating the compound of formula (9), when the compound is an amine; and (ii) Optionally, it further includes the step of preparing a compound of formula (8a) or (8b). Wherein LG is a leaving group, and the step includes reacting a compound of formula (1a) or (1b) with a compound of formula (7) in the presence of a suitable base.

53. The method of claim 51, wherein the method comprises the following steps: (i) Reacting compound of formula (11a) or (11b) with compound of formula (12). Where LG is a leaving group; and (ii) Optionally, it also includes the step of preparing compound (11a) or (11b). The steps include reacting a compound of formula (1a) or (1b) with a compound of formula (10) and subsequently removing the protecting group (PG).

54. The method of claim 51, wherein the method comprises the following steps: (i) Reduce compound of formula (15a) or (15b) with a suitable reagent or with formula R 2 -M organometallic compounds capturing compounds of formula (15a) or (15b) and (ii) Optionally, it also includes the step of preparing a compound of formula (15a) or (15b). The step includes reacting compound (13a) or (13b) with compound (14) under dehydration conditions.

55. A compound of formula (2), wherein the compound of formula (2) is a compound Or its salt.

56. The following compound, Or its salt.

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