LPAR1 antagonists and uses thereof

Abstract

Among other things, LPAR1 antagonists and uses thereof are described herein.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Provisional Application No. 63 / 229,858, filed August 5, 2021, which is incorporated herein by reference in its entirety and for all purposes. [Background technology]

[0002] Lysophosphatidic acid (LPA) is a family of bioactive phospholipids associated with multiple cellular functions. Although family members differ in the length and degree of saturation of their respective long-chain fatty acid backbones (Fujiwara et al., J. Biol. Chem., 2005, 280, 35038-35050), they are all capped with a glycerol-phosphate group via an ester bond. LPA is biologically produced from membrane phospholipids through a multistep cascade mediated by enzymes including lysophospholipase D (lysoPLD), autotaxin (ATX), phospholipase A1 (PLA1), phospholipase A2 (PLA2), and acylglycerol kinase (AGK) (Mutoh et al., British J. Pharmacol., 2012, 165, 829-844). Once formed, LPA can regulate numerous cell signaling pathways by binding to a class of seven membrane-domain G protein-coupled receptors (GPCRs) collectively known as LPA receptors (LPARs), six of which have been characterized as LPAR1, LPAR2, LPAR3, LPAR4, LPAR5, and LPAR6 (Choi, JW, Annu. Rev. Pharmacol. Toxicol., 2010, 50, 157-186). The biological responses elicited by LPA binding to LPARs are broad and context-dependent (Yung et al., J. Lipid Res. 2014, 55, 1192-1214; Yung et al., Neuron 2015, 85, 669-682).These may include inducing cell proliferation, stimulating cell migration and contraction, promoting axonal retraction, inhibiting apoptosis, initiating chemotaxis, closing gap junctions, and others (Chun et al., Editors, Lysophospholipid Receptors: Signaling and Biochemistry, 2013, Wiley, ISBN: 978-0-470-56905-4). Furthermore, abnormal upregulation of the LPA pathway has been implicated in multiple diseases, including cancer, inflammatory diseases, infertility, neuropathic pain, psychotic and neurodegenerative disorders, atherosclerosis, and fibrosis of the skin, kidney, lung, and liver (Choi, JW, Annu. Rev. Pharmacol. Toxicol., 2010, 50, 157-186; Noguchi et al., Curr. Opin Pharmacol., 2009, 9, 15-23; Yanagida et al., J. Biochem., 2011, 150, 223-232). As a result, targeting the LPA receptor has been and continues to be an area of ​​intense interest in identifying potential treatments for these disorders. Specifically, solutions to these and other problems in the art are disclosed herein. [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] Fujiwara et al.,J.Biol.Chem.,2005,280,35038-35050 [Non-patent document 2] Mutoh et al.,British J.Pharmacol.,2012,165,829-844 [Non-patent document 3] Choi, JW, Annu. Rev. Pharmacol. Toxicol., 2010, 50, 157-186 [Non-patent document 4] Yung et al.,J.Lipid Res.2014,55,1192-1214 [Non-patent document 5] Yung et al.,Neuron 2015,85,669-682 [Non-patent document 6] Chun et al.,Editors,Lysophospholipid Receptors:Signaling and Biochemistry,2013,Wiley,ISBN:978-0-470-56905-4 [Non-Patent Document 7] Noguchi et al.,Curr.Opin Pharmacol.,2009,9,15-23 [Non-patent document 8] Yanagida et al.,J.Biochem.,2011,150,223-232 Summary of the Invention

[0004] In one aspect, a compound is provided having the formula:

[0005] [ka]

[0006] L 1 is a bond or a substituted or unsubstituted C1 to C5 alkylene.

[0007] R 1 is an unsubstituted C2-C5 alkyl.

[0008] W 2 is N or C(R 2 )

[0009] R 2 is hydrogen, halogen, -CX 2 3. -CHX 2 2. -CH2X 2 , -OCX 2 3. -OCH2X 2 , -OCHX 2 2, -CN, -SOn2 R 2D , -SO v2 NR 2A R 2B , -NR 2C NR 2A R 2B , -ONR 2A R 2B , -NHC(O)NR 2C NR 2A R 2B , -NHC(O)NR 2A R 2B , -N(O) m2 , -NR 2A R 2B , -C(O)R 2C , -C(O)OR 2C , -C(O)NR 2A R 2B , -OR 2D , -SR 2D , -NR 2A SO2R 2D , -NR 2A C(O)R 2C , -NR 2A C(O)OR 2C , -NR 2A OR 2C , -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0010] R 3 However, hydrogen, halogen, -CX 3 3. -CHX 3 2. -CH2X 3 , -OCX 3 3. -OCH2X 3 , -OCHX 3 2, -CN, -SO n3 R 3D , -SO v3 NR 3A R 3B , -NR 3C NR 3A R 3B , -ONR 3A R 3B , -NHC(O)NR3C NR 3A R 3B , -NHC(O)NR 3A R 3B , -N(O) m3 , -NR 3A R 3B , -C(O)R 3C , -C(O)OR 3C , -C(O)NR 3A R 3B , -OR 3D , -SR 3D , -NR 3A SO2R 3D , -NR 3A C(O)R 3C , -NR 3A C(O)OR 3C , -NR 3A OR 3C , -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0011] W 4 is N or C(R 4 )

[0012] R 4 is hydrogen, halogen, -CX 4 3. -CHX 4 2. -CH2X 4 , -OCX 4 3. -OCH2X 4 , -OCHX 4 2, -CN, -SO n4 R 4D , -SO v4 NR 4A R 4B , -NR 4C NR 4A R 4B , -ONR 4A R 4B , -NHC(O)NR 4C NR 4A R 4B , -NHC(O)NR 4A R 4B , -N(O)m4 , -NR 4A R 4B , -C(O)R 4C , -C(O)OR 4C , -C(O)NR 4A R 4B , -OR 4D , -SR 4D , -NR 4A SO2R 4D , -NR 4A C(O)R 4C , -NR 4A C(O)OR 4C , -NR 4A OR 4C , -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0013] W 5 is N or C(R 5 )

[0014] R 5 is hydrogen, halogen, -CX 5 3. -CHX 5 2. -CH2X 5 , -OCX 5 3. -OCH2X 5 , -OCHX 5 2, -CN, -SO n5 R 5D , -SO v5 NR 5A R 5B , -NR 5C NR 5A R 5B , -ONR 5A R 5B , -NHC(O)NR 5C NR 5A R 5B , -NHC(O)NR 5A R 5B , -N(O) m5 , -NR 5A R 5B , -C(O)R 5C , -C(O)OR 5C, -C(O)NR 5A R 5B , -OR 5D , -SR 5D , -NR 5A SO2R 5D , -NR 5A C(O)R 5C , -NR 5A C(O)OR 5C , -NR 5A OR 5C , -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0015] R 2 and R 3 The substituents may optionally be linked to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0016] R 3 and R 4 The substituents may optionally be linked to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0017] R 4 and R 5 The substituents may optionally be linked to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0018] W 6 is N or C(R 6 )

[0019] R 6 is hydrogen, halogen, -CX 6 3. -CHX 6 2. -CH2X 6 , -OCX6 3. -OCH2X 6 , -OCHX 6 2, -CN, -SO n6 R 6D , -SO v6 NR 6A R 6B , -NR 6C NR 6A R 6B , -ONR 6A R 6B , -NHC(O)NR 6C NR 6A R 6B , -NHC(O)NR 6A R 6B , -N(O) m6 , -NR 6A R 6B , -C(O)R 6C , -C(O)OR 6C , -C(O)NR 6A R 6B , -OR 6D , -SR 6D , -NR 6A SO2R 6D , -NR 6A C(O)R 6C , -NR 6A C(O)OR 6C , -NR 6A OR 6C , -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0020] W 7 is N, N + -O - , or C(R 7 )

[0021] R 7 is hydrogen, halogen, -CX 7 3. -CHX 7 2. -CH2X 7 , -OCX 7 3. -OCH2X 7 , -OCHX 72, -CN, -SO n7 R 7D , -SO v7 NR 7A R 7B , -NR 7C NR 7A R 7B , -ONR 7A R 7B , -NHC(O)NR 7C NR 7A R 7B , -NHC(O)NR 7A R 7B , -N(O) m7 , -NR 7A R 7B , -C(O)R 7C , -C(O)OR 7C , -C(O)NR 7A R 7B , -OR 7D , -SR 7D , -NR 7A SO2R 7D , -NR 7A C(O)R 7C , -NR 7A C(O)OR 7C , -NR 7A OR 7C , -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0022] R 8 are independently halogen, -CX 8 3. -CHX 8 2. -CH2X 8 , -OCX 8 3. -OCH2X 8 , -OCHX 8 2, -CN, -SO n8 R 8D , -SO v8 NR 8A R 8B , -NR 8C NR 8A R 8B , -ONR 8A R 8B, -NHC(O)NR 8C NR 8A R 8B , -NHC(O)NR 8A R 8B , -N(O) m8 , -NR 8A R 8B , -C(O)R 8C , -C(O)OR 8C , -C(O)NR 8A R 8B , -OR 8D , -SR 8D , -NR 8A SO2R 8D , -NR 8A C(O)R 8C , -NR 8A C(O)OR 8C , -NR 8A OR 8C , -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. 8 The substituents may optionally be linked to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0023] R 9 is a substituted or unsubstituted cycloalkyl, or a substituted or unsubstituted heterocycloalkyl.

[0024] R 2A , R 2B , R 2C , R 2D , R 3A , R 3B , R 3C , R 3D , R 4A , R 4B , R 4C , R 4D , R 5A , R 5B , R 5C , R 5D , R 6A , R6B , R 6C , R 6D , R 7A , R 7B , R 7C , R 7D , R 8A , R 8B , R 8C and R 8D are independently hydrogen, —CCl3, —CBr3, —CF3, —CI3, —CHCl2, —CHBr2, —CHF2, —CHI2, —CH2Cl, —CH2Br, —CH2F, —CH2I, —CN, —OH, —NH2, —COOH, —CONH2, —OCCl3, —OCF3, —OCBr3, —OCI3, —OCHCl2, —OCHBr2, —OCHI2, —OCHF2, —OCH2Cl, —OCH2Br, —OCH2I, —OCH2F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and R attached to the same nitrogen atom are independently substituted or unsubstituted. 2A and R 2B The substituents may be optionally linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R 3A and R 3B The substituents may be optionally linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R 4A and R 4B The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R 5A and R 5B The substituents may be optionally linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R 6A and R 6B The substituents may be optionally linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R 7A and R 7BThe substituents may be optionally linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R 8A and R 8B The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.

[0025] X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , and X 8 is independently -F, -Cl, -Br, or -I.

[0026] The symbols n2, n3, n4, n5, n6, n7, and n8 are independently integers of 0 to 4. The symbols m2, m3, m4, m5, m6, m7, m8, v2, v3, v4, v5, v6, v7, and v8 are independently 1 or 2. The symbol z8 is an integer of 0 to 3.

[0027] In one aspect, a compound is provided having the formula:

[0028] [ka] L 1 , R 2 , R 3 , R 4 , R 5 , W 6 , W 7 , R 8 , z8, and R 9 is as described herein, including embodiments. 6 or W 7 At least one of the W is N. 6 is C(R 6 ) or W 7 is C(R 7 ), then R 10 is not hydrogen. W 6 and W7 If both are N, then R 3 is not -S(O)2CH3. W 6 is CH and W 7 If is N, then -L 1 -R 9 teeth,

[0029] [ka] isn't it.

[0030] R 10 is hydrogen, halogen, -CX 10 3. -CHX 10 2. -CH2X 10 , -OCX 10 3. -OCH2X 10 , -OCHX 10 2, -CN, -SO n10 R 10D , -SO v10 NR 10A R 10B , -NR 10C NR 10A R 10B , -ONR 10A R 10B , -NHC(O)NR 10C NR 10A R 10B , -NHC(O)NR 10A R 10B , -N(O) m10 , -NR 10A R 10B , -C(O)R 10C , -C(O)OR 10C , -C(O)NR 10A R 10B , -OR 10D , -SR 10D , -NR 10A SO2R 10D , -NR 10A C(O)R 10C , -NR 10A C(O)OR 10C , -NR 10A OR 10C, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0031] R 10 and R 2 The substituents may optionally be linked to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0032] R 10A , R 10B , R 10C , and R 10D are independently hydrogen, —CCl3, —CBr3, —CF3, —CI3, —CHCl2, —CHBr2, —CHF2, —CHI2, —CH2Cl, —CH2Br, —CH2F, —CH2I, —CN, —OH, —NH2, —COOH, —CONH2, —OCCl3, —OCF3, —OCBr3, —OCI3, —OCHCl2, —OCHBr2, —OCHI2, —OCHF2, —OCH2Cl, —OCH2Br, —OCH2I, —OCH2F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and R attached to the same nitrogen atom are independently substituted or unsubstituted; 10A and R 10B The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.

[0033] X 10 is independently -F, -Cl, -Br, or -I.

[0034] The symbol n10 is an integer of 0 to 4. The symbols m10 and v10 are each independently 1 or 2.

[0035] In one aspect, a pharmaceutical composition is provided comprising a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

[0036] In one aspect, provided is a method of treating a neurodegenerative disorder in a subject in need thereof, comprising administering to a subject in need thereof a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof.

[0037] In one aspect, provided is a method of treating an inflammatory disease in a subject in need thereof, comprising administering to a subject in need thereof a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof.

[0038] In one aspect, provided is a method of treating a demyelinating disease in a subject in need thereof, comprising administering to a subject in need thereof a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof.

[0039] In one aspect, there is provided a method of treating a fibrotic disorder in a subject in need thereof, comprising administering to a subject in need thereof a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof.

[0040] In one aspect, provided is a method of treating cancer in a subject in need thereof, comprising administering to a subject in need thereof a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof.

[0041] In one aspect, a method is provided for treating an LPAR1-associated disease in a subject in need thereof, the method comprising administering to the subject in need thereof a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof.

[0042] In one aspect, a method of modulating LPAR1 activity in a subject is provided, comprising administering to the subject a compound described herein, or a pharmaceutically acceptable salt or solvate thereof. DETAILED DESCRIPTION OF THE INVENTION

[0043] I. Definition The abbreviations used herein have their conventional meaning within the chemical and biological arts. The chemical structures and formulas set forth herein are constructed according to the standard rules of chemical valency known to the chemical arts.

[0044] Substituent groups, when specified by their conventional chemical formula written from left to right, equally encompass the chemically identical substitutes that would result from writing the structure from right to left, e.g., -CHO- is equivalent to -OCH-.

[0045] The term "alkyl," by itself or as part of another substituent, means, unless otherwise stated, linear (i.e., unbranched) or branched carbon chains (or carbons), or combinations thereof, which may be fully saturated, monounsaturated, or polyunsaturated, and which may include monovalent, divalent, and polyvalent radicals. An alkyl may contain the specified number of carbons (e.g., C1 to C6). 10means 1 to 10 carbons). In embodiments, the alkyl is fully saturated. In embodiments, the alkyl is monounsaturated. In embodiments, the alkyl is polyunsaturated. The alkyl is a non-cyclized chain. Examples of saturated hydrocarbon radicals include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, methyl, and homologs and isomers of, for example, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like. Unsaturated alkyl groups are those having one or more double or triple bonds. Examples of unsaturated alkyl groups include, but are not limited to, vinyl, 2-propenyl, crotyl, 2-isopentenyl, 2-(butadienyl), 2,4-pentadienyl, 3-(1,4-pentadienyl), ethynyl, 1- and 3-propynyl, 3-butynyl, and higher homologs and isomers. Alkoxy is an alkyl attached to the rest of the molecule via an oxygen linker (-O-). The alkyl moiety can be an alkenyl moiety. The alkyl moiety can be an alkynyl moiety. An alkenyl contains one or more double bonds. An alkynyl contains one or more triple bonds.

[0046] The term "alkylene," by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from alkyl, exemplified by, but not limited to, -CH2CH2CH2CH2-. Typically, an alkyl (or alkylene) group will have from 1 to 24 carbon atoms, with groups having 10 or fewer carbon atoms being preferred herein. A "lower alkyl" or "lower alkylene" is a shorter chain alkyl or alkylene group, generally having 8 or fewer carbon atoms. The term "alkenylene," by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from an alkene. The term "alkynylene," by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from an alkyne. In embodiments, an alkylene is fully saturated. In embodiments, an alkylene is monounsaturated. In embodiments, an alkylene is polyunsaturated. An alkenylene contains one or more double bonds. An alkynylene contains one or more triple bonds.

[0047] The term "heteroalkyl," by itself or in combination with another term, means, unless otherwise specified, a stable linear or branched chain, or combination thereof, containing 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 be optionally oxidized, and the nitrogen heteroatom may be optionally quaternized. The heteroatom (e.g., N, S, Si, or P) may be placed at any interior position of the heteroalkyl group or at the position at which the alkyl group is attached to the remainder of the molecule. Heteroalkyl groups are non-cyclizing chains. Examples include, but are not limited to, -CH2-CH2-O-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -S-CH2-CH2, -S(O)-CH3, -CH2-CH2-S(O)-CH3, -CH=CH-O-CH3, -Si(CH3)3, -CH2-CH=N-OCH3, -CH=CH-N(CH3)-CH3, -O-CH3, -O-CH2-CH3, and -CN. Up to two or three heteroatoms may be consecutive, such as, for example, -CH2-NH-OCH3 and -CH2-O-Si(CH3)3. The heteroalkyl moiety may contain one heteroatom (e.g., O, N, S, Si, or P). A heteroalkyl moiety can contain two, optionally different heteroatoms (e.g., O, N, S, Si, or P). A heteroalkyl moiety can contain three, optionally different heteroatoms (e.g., O, N, S, Si, or P). A heteroalkyl moiety can contain four, optionally different heteroatoms (e.g., O, N, S, Si, or P). A heteroalkyl moiety can contain five, optionally different heteroatoms (e.g., O, N, S, Si, or P). A heteroalkyl moiety can contain up to eight, optionally different heteroatoms (e.g., O, N, S, Si, or P). The term "heteroalkenyl," alone or in combination with another term, means, unless otherwise stated, a heteroalkyl containing at least one double bond. A heteroalkenyl can optionally contain, in addition to one or more double bonds, two or more double bonds and / or one or more triple bonds.The term "heteroalkynyl," alone or in combination with another term, means, unless otherwise stated, a heteroalkynyl containing at least one triple bond. A heteroalkynyl can optionally contain, in addition to one or more triple bonds, two or more triple bonds and / or one or more double bonds. In embodiments, a heteroalkyl is fully saturated. In embodiments, a heteroalkyl is monounsaturated. In embodiments, a heteroalkyl is polyunsaturated.

[0048] Similarly, the term "heteroalkylene," by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from heteroalkyl, exemplified by, but not limited to, -CH-CH-S-CH-CH- and -CH-S-CH-CH-NH-CH-. For heteroalkylene groups, heteroatoms can also occupy either or both of the chain termini (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, etc.). Still further, for alkylene and heteroalkylene linking groups, no orientation of the linking group is implied by the direction in which the formula of the linking group is written. For example, the formula -C(O)R'- represents both -C(O)R'- and -R'C(O)-. As noted above, heteroalkyl groups, as used herein, include groups attached to the remainder of the molecule via a heteroatom, such as -C(O)R', -C(O)NR', ​​-NR'R'', -OR', -SR', and / or -S02R'. When "heteroalkyl" is recited followed by a specific heteroalkyl group, such as -NR'R'', it is understood that the terms heteroalkyl and -NR'R'' are not redundant or mutually exclusive. Rather, the specific heteroalkyl group is recited for clarity. Thus, the term "heteroalkyl" should not be interpreted herein as excluding specific heteroalkyl groups, such as -NR'R''. The term "heteroalkenylene," by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from a heteroalkene. The term "heteroalkynylene," by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from a heteroalkyne. In embodiments, a heteroalkylene is fully saturated. In embodiments, a heteroalkylene is monounsaturated. In embodiments, heteroalkylene is polyunsaturated. Heteroalkenylene contains one or more double bonds. Heteroalkynylene contains one or more triple bonds.

[0049] The terms "cycloalkyl" and "heterocycloalkyl," by themselves or in combination with other terms, mean, unless otherwise stated, cyclic versions of "alkyl" and "heteroalkyl," respectively. Cycloalkyl and heterocycloalkyl are not aromatic. Additionally, for heterocycloalkyl, a heteroatom can occupy the position at which the heterocycle is attached to the remainder of the molecule. Examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-cyclohexenyl, 3-cyclohexenyl, cycloheptyl, and the like. Examples of heterocycloalkyl include, but are not limited to, 1-(1,2,5,6-tetrahydropyridyl), 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-morpholinyl, 3-morpholinyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, 1-piperazinyl, 2-piperazinyl, and the like. A "cycloalkylene" and a "heterocycloalkylene," alone or as part of another substituent, mean a divalent radical derived from a cycloalkyl and a heterocycloalkyl, respectively. In embodiments, the cycloalkyl is fully saturated. In embodiments, the cycloalkyl is monounsaturated. In embodiments, the cycloalkyl is polyunsaturated. In embodiments, the heterocycloalkyl is fully saturated. In embodiments, the heterocycloalkyl is monounsaturated. In embodiments, the heterocycloalkyl is polyunsaturated.

[0050] In embodiments, the term "cycloalkyl" refers to a monocyclic, bicyclic, or polycyclic cycloalkyl ring system. In embodiments, a monocyclic ring system is a cyclic hydrocarbon group containing 3 to 8 carbon atoms; such groups can be saturated or unsaturated, but are not aromatic. In embodiments, a cycloalkyl group is fully saturated. A bicyclic or polycyclic cycloalkyl ring system refers to multiple rings fused together, at least one of the fused rings being a cycloalkyl ring, and the multiple rings being connected to the parent molecular moiety through any carbon atom contained within the cycloalkyl ring of the multiple rings.

[0051] In embodiments, cycloalkyl is cycloalkenyl. The term "cycloalkenyl" is used according to its plain and ordinary meaning. In embodiments, cycloalkenyl is a monocyclic, bicyclic, or polycyclic cycloalkenyl ring system. A bicyclic or polycyclic cycloalkenyl ring system refers to multiple rings fused together, at least one of which is a cycloalkenyl ring, and the multiple rings are bonded to the parent molecular moiety through any carbon atom contained within the cycloalkenyl ring of the multiple rings.

[0052] In embodiments, the term "heterocycloalkyl" refers to a monocyclic, bicyclic, or polycyclic heterocycloalkyl ring system. In embodiments, the heterocycloalkyl group is fully saturated. A bicyclic or polycyclic heterocycloalkyl ring system refers to multiple rings fused together, where at least one of the fused rings is a heterocycloalkyl ring, and the rings are attached to the parent molecular moiety through any atom contained within the heterocycloalkyl ring of the multiple rings.

[0053] The terms "halo" or "halogen," by themselves or as part of another substituent, mean, unless otherwise stated, a fluorine, chlorine, bromine, or iodine atom. Additionally, terms such as "haloalkyl" are meant to include monohaloalkyl and polyhaloalkyl. For example, the term "halo(C1-C4)alkyl" includes, but is not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 4-chlorobutyl, and 3-bromopropyl.

[0054] The term "acyl," unless otherwise specified, means -C(O)R, where R is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0055] The term "aryl," unless otherwise specified, refers to a polyunsaturated, aromatic, hydrocarbon substituent, which may be a single ring or multiple rings (preferably 1 to 3 rings) fused together (i.e., fused-ring aryl) or covalently linked together. Fused-ring aryl refers to multiple rings fused together, at least one of which is an aryl ring, and the multiple rings are bonded to the parent molecular moiety through any carbon atom contained within the aryl ring of the multiple rings. The term "heteroaryl" refers to an aryl group (or ring) containing at least one heteroatom, such as N, O, or S, wherein the nitrogen and sulfur atoms are optionally oxidized and the nitrogen atom is optionally quaternized. Thus, the term "heteroaryl" includes fused-ring heteroaryl groups (i.e., multiple rings fused together, at least one of which is a heteroaromatic ring, and the multiple rings are bonded to the parent molecular moiety through any atom contained within the heteroaromatic ring of the multiple rings). A 5,6-fused ring heteroarylene refers to two rings fused together, one ring having 5 members and the other ring having 6 members, and at least one ring being a heteroaryl ring. Similarly, a 6,6-fused ring heteroarylene refers to two rings fused together, one ring having 6 members and the other ring having 6 members, and at least one ring being a heteroaryl ring. Also, a 6,5-fused ring heteroarylene refers to two rings fused together, one ring having 6 members and the other ring having 5 members, and at least one ring being a heteroaryl ring. A heteroaryl group can be attached to the rest of the molecule through a carbon atom or a heteroatom.Non-limiting examples of aryl and heteroaryl groups include phenyl, naphthyl, pyrrolyl, pyrazolyl, pyridazinyl, triazinyl, pyrimidinyl, imidazolyl, pyrazinyl, purinyl, oxazolyl, isoxazolyl, thiazolyl, furyl, thienyl, pyridyl, pyrimidyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzofuran, isobenzofuranyl, indolyl, isoindolyl, benzothiophenyl, isoquinolyl, quinoxalinyl, quinolyl, 1-naphthyl, 2-naphthyl, 4-biphenyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 2-imidazolyl, and the like. aryl, 4-imidazolyl, pyrazinyl, 2-oxazolyl, 4-oxazolyl, 2-phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-benzothiazolyl, purinyl, 2-benzimidazolyl, 5-indolyl, 1-isoquinolyl, 5-isoquinolyl, 2-quinoxalinyl, 5-quinoxalinyl, 3-quinolyl, and 6-quinolyl. Substituents for each of the above noted aryl and heteroaryl ring systems are selected from the group of acceptable substituents described below. An "arylene" and a "heteroarylene," alone or as part of another substituent, mean a divalent radical derived from an aryl and heteroaryl, respectively. The heteroaryl group substituent may be -O-bonded to a ring heteroatom nitrogen.

[0056] Spirocyclic rings are two or more rings in which adjacent rings are connected via a single atom. The individual rings within a spirocyclic ring can be the same or different. The individual rings within a spirocyclic ring can be substituted or unsubstituted and can have different substituents than the other individual rings within a set of spirocyclic rings. The possible substituents for the individual rings within a spirocyclic ring are the possible substituents for the same ring (e.g., the substituents for a cycloalkyl ring or heterocycloalkyl ring) when not part of a spirocyclic ring. The spirocyclic ring can be a substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heterocycloalkylene, and the individual rings within a spirocyclic ring group can be any of the rings in the list immediately above, including all rings of one type (e.g., all rings can be substituted heterocycloalkylene, and each ring can be the same or different substituted heterocycloalkylene). When referring to a spirocyclic ring system, a heterocyclic spirocyclic ring means a spirocyclic ring in which at least one ring is heterocyclic, and each ring may be a different ring. When referring to a spirocyclic ring system, a substituted spirocyclic ring means that at least one ring is substituted, and each substituent may optionally be different.

[0057] A bridged ring is two or more rings that share three or more atoms, with a bridge containing at least one atom separating the two bridgehead atoms. Each ring within a bridged ring may be substituted or unsubstituted and may have different substituents than the other individual rings within a set of bridged rings. The possible substituents for each ring within a bridged ring, when not part of a bridged ring, are the possible substituents for the same ring (e.g., substituents for a cycloalkyl ring or heterocycloalkyl ring). The bridged ring may be a substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heterocycloalkylene, and the individual rings within the bridged ring may be any of those listed immediately above, including when all rings are of the same type (e.g., all rings may be substituted heterocycloalkylene, and each ring may be the same or different substituted heterocycloalkylene). When referring to a bridged ring system, a heterocyclic bridged ring refers to a bridged ring in which at least one ring is a heterocyclic ring, and each ring may be a different ring. When referring to a bridged ring system, a substituted bridged ring means that at least one ring is substituted, and each substituent may optionally be different.

[0058] symbol

[0059] [ka] indicates the point of attachment of the chemical moiety to the rest of the molecule or chemical formula.

[0060] The term "oxo" as used herein means an oxygen that is double bonded to a carbon atom.

[0061] The term "alkylarylene" as an arylene moiety covalently linked to an alkylene moiety (also referred to herein as an alkylene linker). In embodiments, the alkylarylene group has the formula:

[0062] [ka] It has.

[0063] The alkylarylene moiety can be substituted (e.g., by a substituent) at the alkylene portion or in the arylene linker (e.g., at carbons 2, 3, 4, or 6) with halogen, oxo, -N, -CF, -CCl, -CBr, -CI, -CN, -CHO, -OH, -NH, -COOH, -CONH, -NO, -SH, -SOCH, -SOH, -OSOH, -SONH, -NHNH, -ONH, -NHC(O)NHNH, substituted or unsubstituted C-C alkyl, or substituted or unsubstituted 2-5 membered heteroalkyl. In embodiments, the alkylarylene is unsubstituted.

[0064] Each of the above terms (e.g., "alkyl," "heteroalkyl," "cycloalkyl," "heterocycloalkyl," "aryl," and "heteroaryl") includes both substituted and unsubstituted forms of the indicated radical. Preferred substituents for each type of radical are provided below.

[0065] Substituents for alkyl and heteroalkyl radicals (including groups often referred to as alkylene, alkenyl, heteroalkylene, heteroalkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, and heterocycloalkenyl) range in number from zero to (2m'+1), where m' is the total number of carbon atoms in such radical, and include -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', halogen, -SiR'R''R''', -OC(O)R', -C(O)R', -COR', -CONR'R'', -OC(O)NR'R ", -NR"C(O)R', -NR'C(O)NR"R'", -NR"C(O)R', -NRC(NR'R"R'")=NR"", -NRC(NR'R")=NR'", -S(O)R', -S(O)R', -S(O)NR'R", -NRSO2R', -NR'NR"R'", -ONR'R", -NR'C(O)NR"NR"'R"", -CN, -NO2, -NR'S02R", -NR'C(O)R", -NR'C(O)OR", -NR'OR". R, R', R'', R''', and R'''' each preferably independently refer to hydrogen, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl (e.g., aryl substituted with 1 to 3 halogens), substituted or unsubstituted heteroaryl, substituted or unsubstituted alkyl, alkoxy, or thioalkoxy group, or arylalkyl group. When the compounds described herein include more than one R group, for example, each of the R groups is independently selected as each R', R'', R''', and R'''' group when more than one of these groups is present. When R' and R'' are attached to the same nitrogen atom, they can be combined with the nitrogen atom to form a 4-, 5-, 6-, or 7-membered ring. For example, -NR'R'' includes, but is not limited to, 1-pyrrolidinyl and 4-morpholinyl.From the above discussion of substituents, one of skill in the art will understand that the term "alkyl" is intended to include groups that contain carbon atoms bonded to groups other than hydrogen groups, such as haloalkyl (e.g., -CF and -CHCF) and acyl (e.g., -C(O)CH, -C(O)CF, -C(O)CHOCH, etc.).

[0066] Similar to the substituents described for the alkyl radical, substituents for the aryl and heteroaryl groups vary and include, for example, —OR′, —NR′R″, —SR′, -halogen, —SiR′R″R′′, —OC(O)R′, —C(O)R′, —COR′, —CONR′R″, —OC(O)NR′R″, —NR″C(O)R′, —NR′C(O)NR″R′′′, —NR″C(O)R′, —NR—C(NR′R″R′′)═NR′″, —NR—C(NR′R″)═NR′″, —S(O)R′, —S(O)R′, —S(O)NR′R″, —NRSOR′, —NR′N and R', R''', -ONR'R'', -NR'C(O)NR''NR'''R'''', -CN, -NO2, -R', -N3, -CH(Ph)2, fluoro(C1-C4)alkoxy, fluoro(C1-C4)alkyl, -NR'S02R'', -NR'C(O)R'', -NR'C(O)-OR'', -NR'OR'', where R', R'', R''', and R'''' are preferably independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. When the compounds described herein include more than one R group, for example, each of the R groups is independently selected for each R', R'', R''', and R'''' group when more than one of these groups is present.

[0067] Substituents for a ring (e.g., cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylene, heterocycloalkylene, arylene, or heteroarylene) may be designated as substituents on the ring (commonly referred to as floating substituents) rather than on a specific atom of the ring. In such cases, the substituent may be attached to any of the ring atoms (according to the rules of chemical valence), and in the case of a fused or spirocyclic ring, a substituent shown as attached to one member of the fused or spirocyclic ring (a floating substituent on a single ring) may also be a substituent on either the fused or spirocyclic ring (a floating substituent on a polycyclic ring). When a substituent is attached to a ring rather than to a specific atom (a floating substituent), and the substituent subscript is an integer greater than 1, multiple substituents may be on the same atom, the same ring, different atoms, different fused rings, or different spirocyclic rings, and each substituent may optionally be different. When the point of attachment of a ring to the rest of the molecule is not limited to a single atom (a floating substituent), the point of attachment may be any atom of the ring, or, in the case of a fused or spirocyclic ring, any atom of the fused or spirocyclic ring, according to the rules of chemical valence. When a ring, fused ring, or spirocyclic ring contains one or more ring heteroatoms and the ring, fused ring, or spirocyclic ring is shown with another floating substituent (including, but not limited to, the point of attachment to the rest of the molecule), the floating substituent may be attached to the heteroatom. When a ring heteroatom is shown to be attached to one hydrogen in a structure or formula with a floating substituent (e.g., a ring nitrogen with two bonds to ring atoms and a third bond to a hydrogen), it will be understood that when the heteroatom is attached to the floating substituent, the substituent replaces the hydrogen, according to the rules of chemical valence.

[0068] Two or more substituents may optionally be linked to form an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group. These so-called ring-forming substituents are typically, but not necessarily, found attached to a cyclic base structure. In one embodiment, the ring-forming substituents are attached to adjacent members of the base structure. For example, two ring-forming substituents attached to adjacent members of a cyclic base structure form a fused ring structure. In another embodiment, the ring-forming substituents are attached to a single member of the base structure. For example, two ring-forming substituents attached to a single member of a cyclic base structure create a spirocyclic structure. In yet another embodiment, the ring-forming substituents are attached to non-adjacent members of the base structure.

[0069] Two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be of the formula -TC(O)-(CRR') q -U-, where T and U are independently -NR-, -O-, -CRR'-, or a single bond, and q is an integer from 0 to 3. Alternatively, two of the substituents on adjacent atoms of the aryl or heteroaryl ring can form a ring of the formula -A-(CH2) r -B- (wherein A and B are independently -CRR'-, -O-, -NR-, -S-, -S(O)-, -S(O)2-, -S(O)2NR'-, or a single bond, and r is an integer from 1 to 4). One of the single bonds in the new ring so formed may optionally be replaced with a double bond. Alternatively, two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be replaced with a substituent of the formula -(CRR') s -X'-(C''R''R'') dwherein s and d are independently integers from 0 to 3, and X' is -O-, -NR'-, -S-, -S(O)-, -S(O)2-, or -S(O)2NR'-. The substituents R, R', R", and R'" are preferably independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.

[0070] As used herein, the term "heteroatom" or "ring heteroatom" is meant to include oxygen (O), nitrogen (N), sulfur (S), phosphorus (P), selenium (Se), and silicon (Si). In embodiments, "heteroatom" or "ring heteroatom" is meant to include oxygen (O), nitrogen (N), sulfur (S), phosphorus (P), and silicon (Si).

[0071] As used herein, a "substituent" means a group selected from the following moieties: (A) Oxo, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2 , -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO 2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, -SF5, unsubstituted alkyl (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), unsubstituted heteroalkyl (e.g., 2-8 membered heteroalkyl, 2-6 membered heteroalkyl, or 2-4 membered heteroalkyl), unsubstituted cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), unsubstituted heterocycloalkyl (e.g., 3-8 membered heterocycloalkyl, 3-6 membered heterocycloalkyl, or 5-6 membered heterocycloalkyl), 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 (B) alkyl (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), heteroalkyl (e.g., 2-8 membered heteroalkyl, 2-6 membered heteroalkyl, or 2-4 membered heteroalkyl), cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), heterocycloalkyl (e.g., 3-8 membered heterocycloalkyl, 3-6 membered heterocycloalkyl, or 5-6 membered heterocycloalkyl), aryl (e.g., C6-C 10 Aryl, C 10aryl, or phenyl), heteroaryl (e.g., 5- to 10-membered heteroaryl, 5- to 9-membered heteroaryl, or 5- to 6-membered heteroaryl), each of which is substituted with at least one substituent selected from the following: alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl: (i) Oxo, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2 , -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO 2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, -SF5, unsubstituted alkyl (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), unsubstituted heteroalkyl (e.g., 2-8 membered heteroalkyl, 2-6 membered heteroalkyl, or 2-4 membered heteroalkyl), unsubstituted cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), unsubstituted heterocycloalkyl (e.g., 3-8 membered heterocycloalkyl, 3-6 membered heterocycloalkyl, or 5-6 membered heterocycloalkyl), 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 (ii) alkyl (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), heteroalkyl (e.g., 2-8 membered heteroalkyl, 2-6 membered heteroalkyl, or 2-4 membered heteroalkyl), cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), heterocycloalkyl (e.g., 3-8 membered heterocycloalkyl, 3-6 membered heterocycloalkyl, or 5-6 membered heterocycloalkyl), aryl (e.g., C6-C 10 Aryl, C 10 aryl, or phenyl), heteroaryl (e.g., 5- to 10-membered heteroaryl, 5- to 9-membered heteroaryl, or 5- to 6-membered heteroaryl), each of which is substituted with at least one substituent selected from the following: alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl: (a) Oxo, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2 , -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO 2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, -SF5, unsubstituted alkyl (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), unsubstituted heteroalkyl (e.g., 2-8 membered heteroalkyl, 2-6 membered heteroalkyl, or 2-4 membered heteroalkyl), unsubstituted cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), unsubstituted heterocycloalkyl (e.g., 3-8 membered heterocycloalkyl, 3-6 membered heterocycloalkyl, or 5-6 membered heterocycloalkyl), unsubstituted aryl (e.g., C6-C10 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 (b) Oxo, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2 , -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO 2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, -SF5, unsubstituted alkyl (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), unsubstituted heteroalkyl (e.g., 2-8 membered heteroalkyl, 2-6 membered heteroalkyl, or 2-4 membered heteroalkyl), unsubstituted cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), unsubstituted heterocycloalkyl (e.g., 3-8 membered heterocycloalkyl, 3-6 membered heterocycloalkyl, or 5-6 membered heterocycloalkyl), unsubstituted aryl (e.g., C6-C 10 Aryl, C 10alkyl (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), heteroalkyl (e.g., 2-8 membered heteroalkyl, 2-6 membered heteroalkyl, or 2-4 membered heteroalkyl), cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), heterocycloalkyl (e.g., 3-8 membered heterocycloalkyl, 3-6 membered heterocycloalkyl, or 5-6 membered heterocycloalkyl), aryl (e.g., C6-C 10 Aryl, C 10 aryl, or phenyl), heteroaryl (for example, 5- to 10-membered heteroaryl, 5- to 9-membered heteroaryl, or 5- to 6-membered heteroaryl).

[0072] As used herein, a "size-limited substituent" or "size-limited substituent group" refers to a group selected from all of the substituents described above for "substituent group," and each substituted or unsubstituted alkyl is a substituted or unsubstituted C1-C 20 each substituted or unsubstituted heteroalkyl is a substituted or unsubstituted 2- to 20-membered heteroalkyl; each substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C3-C8 cycloalkyl; each substituted or unsubstituted heterocycloalkyl is a substituted or unsubstituted 3- to 8-membered heterocycloalkyl; and each substituted or unsubstituted aryl is a substituted or unsubstituted C6-C8 10 aryl, and each substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5- to 10-membered heteroaryl.

[0073] As used herein, a "lower substituent" or "lower substituent group" means a group selected from all of the substituents described above for a "substituent group," wherein each substituted or unsubstituted alkyl is a substituted or unsubstituted C1-C8 alkyl, each substituted or unsubstituted heteroalkyl is a substituted or unsubstituted 2- to 8-membered heteroalkyl, each substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C3-C7 cycloalkyl, each substituted or unsubstituted heterocycloalkyl is a substituted or unsubstituted 3- to 7-membered heterocycloalkyl, each substituted or unsubstituted aryl is a substituted or unsubstituted phenyl, and each substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5- to 6-membered heteroaryl.

[0074] In some embodiments, each substituent described in the compounds herein is substituted with at least one substituent. More specifically, in some embodiments, each substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and / or substituted heteroarylene described in the compounds herein 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-limited substituent. In other embodiments, at least one or all of these groups are substituted with at least one lower substituent.

[0075] In other embodiments of the compounds herein, each substituted or unsubstituted alkyl is a substituted or unsubstituted C1-C 20each substituted or unsubstituted heteroalkyl is a substituted or unsubstituted 2- to 20-membered heteroalkyl; each substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C3-C8 cycloalkyl; each substituted or unsubstituted heterocycloalkyl is a substituted or unsubstituted 3- to 8-membered heterocycloalkyl; and each substituted or unsubstituted aryl is a substituted or unsubstituted C6-C8 10 aryl, and / or each substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5-10 membered heteroaryl. In some embodiments of the compounds herein, each substituted or unsubstituted alkylene is a substituted or unsubstituted C1-C 20 each substituted or unsubstituted heteroalkylene is a substituted or unsubstituted 2- to 20-membered heteroalkylene; each substituted or unsubstituted cycloalkylene is a substituted or unsubstituted C3-C8 cycloalkylene; each substituted or unsubstituted heterocycloalkylene is a substituted or unsubstituted 3- to 8-membered heterocycloalkylene; and each substituted or unsubstituted arylene is a substituted or unsubstituted C6-C8 10 arylene, and / or each substituted or unsubstituted heteroarylene is a substituted or unsubstituted 5- to 10-membered heteroarylene.

[0076] In some embodiments, each substituted or unsubstituted alkyl is a substituted or unsubstituted C1-C8 alkyl, each substituted or unsubstituted heteroalkyl is a substituted or unsubstituted 2-8 membered heteroalkyl, each substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C3-C7 cycloalkyl, each substituted or unsubstituted heterocycloalkyl is a substituted or unsubstituted 3-7 membered heterocycloalkyl, and each substituted or unsubstituted aryl is a substituted or unsubstituted C6-C8 10In some embodiments, each substituted or unsubstituted alkylene is a substituted or unsubstituted C1-C8 alkylene, each substituted or unsubstituted heteroalkylene is a substituted or unsubstituted 2-8 membered heteroalkylene, each substituted or unsubstituted cycloalkylene is a substituted or unsubstituted C3-C7 cycloalkylene, each substituted or unsubstituted heterocycloalkylene is a substituted or unsubstituted 3-7 membered heterocycloalkylene, and each substituted or unsubstituted arylene is a substituted or unsubstituted C6-C8 10 and / or each substituted or unsubstituted heteroarylene is a substituted or unsubstituted 5- to 9-membered heteroarylene. In some embodiments, the compound is a species described in the Examples section, Figures, or Tables below.

[0077] In embodiments, a substituted or unsubstituted moiety (e.g., substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, and / or substituted or unsubstituted heteroarylene) is unsubstituted (e.g., unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, unsubstituted heteroaryl, unsubstituted alkylene, unsubstituted heteroalkylene, unsubstituted cycloalkylene, unsubstituted heterocycloalkylene, unsubstituted arylene, and / or unsubstituted heteroarylene, respectively). In embodiments, a substituted or unsubstituted moiety (e.g., substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, and / or substituted or unsubstituted heteroarylene) is substituted (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and / or substituted heteroarylene, respectively).

[0078] In embodiments, a substituted moiety (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and / or substituted heteroarylene) is substituted with at least one substituent, and when a substituted moiety is substituted with multiple substituents, each substituent can optionally be different. In embodiments, when a substituted moiety is substituted with multiple substituents, each substituent is different.

[0079] In embodiments, a substituted moiety (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and / or substituted heteroarylene) is substituted with at least one size-limiting substituent, and when a substituted moiety is substituted with multiple substituents, each size-limiting substituent can optionally be different. In embodiments, when a substituted moiety is substituted with multiple size-limiting substituents, each size-limiting substituent is different.

[0080] In embodiments, a substituted moiety (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and / or substituted heteroarylene) is substituted with at least one lower substituent, and when a substituted moiety is substituted with multiple lower substituents, each lower substituent may optionally be different. In embodiments, when a substituted moiety is substituted with multiple lower substituents, each lower substituent is different.

[0081] In embodiments, a substituted moiety (e.g., a substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and / or substituted heteroarylene) is substituted with at least one substituent, size-limiting substituent, or lower substituent; when a substituted moiety is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent can optionally be different. In embodiments, when a substituted moiety is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent is different.

[0082] In any cited claim or formula description herein, each R substituent or L linker described as "substituted" (also referred to herein as an "open substitution" or "openly substituted" R substituent or L linker for an "open" R substituent or L linker), without reference to the identity of any chemical moieties that make up the "substituted" group, the recited R substituent or L linker may, in embodiments, be substituted with one or more first substituents, as defined below.

[0083] The first substituent can be, for example, R 1 But R 1.1 and R 2 But R 2.1 and R 3 But R 3.1 and R 4 But R 4.1 and R 5 But R 5.1 and may be substituted with one or more first substituents represented by the formula: 100 But R 100.1As a further example, R 1A But R 1A.1 and R 2A But R 2A.1 and R 3A But R 3A.1 and R 4A But R 4A.1 and R 5A But R 5A.1 and may be substituted with one or more first substituents represented by the formula: 100A But R 100A.1 As a further example, L 1 But R L1.1 and L may be substituted with one or more first substituents represented by 2 But R L2.1 and L may be substituted with one or more first substituents represented by 3 But R L3.1 and L may be substituted with one or more first substituents represented by 4 But R L4.1 and L may be substituted with one or more first substituents represented by 5 But R L5.1 and may be substituted with one or more first substituents represented by the formula: 100 But R L100.1 Thus, each numbered R or L group described herein (alternatively, R WW or L WW and "WW" represents the listed superscript number of the subject R or L group) are generally referred to herein as R WW.1 or R LWW.1 Each first substituent (e.g., R 1.1 , R 2.1 , R 3.1 , R4.1 , R 5.1 ...R 100.1 , R 1A.1 , R 2A.1 , R 3A.1 , R 4A.1 , R 5A.1 ...R 100A.1 R L1.1 , R L2.1 , R L3.1 , R L4.1 , R L5.1 ...R L100.1 ) may be substituted with one or more second substituents (e.g., R 1.2 , R 2.2 , R 3.2 , R 4.2 , R 5.2 ...R 100.2 , R 1A.2 , R 2A.2 , R 3A.2 , R 4A.2 , R 5A.2 ...R 100A.2 R L1.2 , R L2.2 , R L3.2 , R L4.2 , R L5.2 ...R L100.2 ) may be further substituted. Therefore, as used herein, R WW.1 Each first substituent may alternatively be represented as R WW.2 The alkyl group may be further substituted with one or more second substituents, which may alternatively be represented as:

[0084] Finally, each second substituent (e.g., R 1.2 , R 2.2 , R 3.2 , R 4.2 , R 5.2 ...R 100.2 , R 1A.2 , R 2A.2 , R 3A.2 , R 4A.2 , R 5A.2 ...R 100A.2 R L1.2 , R L2.2 , R L3.2 , R L4.2 , R L5.2 ...R L100.2 ) may be one or more third substituents (e.g., R1.3 , R 2.3 , R 3.3 , R 4.3 , R 5.3 ...R 100.3 , R 1A.3 , R 2A.3 , R 3A.3 , R 4A.3 , R 5A.3 ...R 100A.3 R L1.3 , R L2.3 , R L3.3 , R L4.3 , R L5.3 ...R L100.3 ) may be further substituted. Therefore, as used herein, R WW.2 Each second substituent may alternatively be represented as R WW.3 Each of the first substituents may be optionally different. Each of the second substituents may be optionally different. Each of the third substituents may be optionally different.

[0085] Thus, as used herein, R WW represents an openly substituted substituent as listed in the claims or in the formula descriptions herein. "WW" represents the superscript number (1, 2, 3, 1A, 2A, 3A, 1B, 2B, 3B, etc.) of the R group in question. Similarly, L WW is an open-substituted linker as described in the claims or formula descriptions herein. Additionally, "WW" represents the superscript number (1, 2, 3, 1A, 2A, 3A, 1B, 2B, 3B, etc.) of the subject L group. As noted above, in embodiments, each R WW may be unsubstituted or may be defined herein as R WW.1 and each first substituent R WW.1 may be unsubstituted or may be defined herein as R WW.2 Each of the groups may be independently substituted with one or more second substituents, referred to herein as R WW.3Similarly, each L may be independently substituted with one or more third substituents, referred to as WW The linker may be unsubstituted or may be any of the groups defined herein as R LWW.1 and each first substituent R LWW.1 may be unsubstituted or may be defined herein as R LWW.2 Each of the groups may be independently substituted with one or more second substituents, referred to herein as R LWW.3 Each of the first substituents is optionally different. Each of the second substituents is optionally different. Each of the third substituents is optionally different. For example, R WW When is phenyl, the phenyl group may be one or more R WW.1 Optionally substituted by groups, such as R WW.1 R WW.2 In the case of substituted or unsubstituted alkyl, examples of the groups so formed include one or more R WW.2 and R itself optionally substituted with WW.2 is one or more R WW.3 For example, R WW R is a methyl group WW.1 When the methyl group is phenyl substituted by

[0086] [ka] It may form groups including, but not limited to:

[0087] R WW.1 are independently oxo, halogen, -CX WW.1 3. -CHX WW.1 2. -CH2X WW.1 , -OCX WW.1 3. -OCH2X WW.1 , -OCHX WW.12, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, R WW.2 substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), R WW.2 substituted or unsubstituted heteroalkyl (e.g., 2-8 membered, 2-6 membered, 4-6 membered, 2-3 membered, or 4-5 membered), R WW.2 substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, C5-C6), R WW.2 substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), R WW.2 Substituted or unsubstituted aryl (e.g., C6-C 12 , C6~C 10 , or phenyl), or R WW.2 In embodiments, R is a substituted or unsubstituted heteroaryl (e.g., 5-12 membered, 5-10 membered, 5-9 membered, or 5-6 membered). WW.1 are independently oxo, halogen, -CX WW.1 3. -CHX WW.1 2. -CH2X WW.1 , -OCX WW.1 3. -OCH2X WW.1 , -OCHX WW.12, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, unsubstituted alkyl (e.g., C1-C8, C C1-C6, C1-C4, C1-C2), unsubstituted heteroalkyl (e.g., 2-8 membered, 2-6 membered, 4-6 membered, 2-3 membered, or 4-5 membered), unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, C5-C6), unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), unsubstituted aryl (e.g., C6-C 12 , C6~C 10 , or phenyl), or unsubstituted heteroaryl (e.g., 5 to 12-membered, 5 to 10-membered, 5 to 9-membered, or 5 to 6-membered). WW.1 is independently -F, -Cl, -Br, or -I.

[0088] R WW.2 are independently oxo, halogen, -CX WW.2 3. -CHX WW.2 2. -CH2X WW.2 , -OCX WW.2 3. -OCH2X WW.2 , -OCHX WW.2 2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, R WW.3 substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, C1-C2), R WW.3 substituted or unsubstituted heteroalkyl (e.g., 2-8 membered, 2-6 membered, 4-6 membered, 2-3 membered, or 4-5 membered), R WW.3 substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, C5-C6), R WW.3substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), R WW.3 Substituted or unsubstituted aryl (e.g., C6-C 12 , C6~C 10 , or phenyl), or R WW.3 In embodiments, R is a substituted or unsubstituted heteroaryl (e.g., 5-12 membered, 5-10 membered, 5-9 membered, or 5-6 membered). WW.2 are independently oxo, halogen, -CX WW.2 3. -CHX WW.2 2. -CH2X WW.2 , -OCX WW.2 3. -OCH2X WW.2 , -OCHX WW.2 2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, unsubstituted alkyl (e.g., C1-C8, C C1-C6, C1-C4, C1-C2), unsubstituted heteroalkyl (e.g., 2-8 membered, 2-6 membered, 4-6 membered, 2-3 membered, or 4-5 membered), unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, C5-C6), unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), unsubstituted aryl (e.g., C6-C 12 , C6~C 10 , or phenyl), or unsubstituted heteroaryl (e.g., 5 to 12-membered, 5 to 10-membered, 5 to 9-membered, or 5 to 6-membered). WW.2 is independently -F, -Cl, -Br, or -I.

[0089] R WW.3 are independently oxo, halogen, -CX WW.3 3. -CHX WW.3 2. -CH2X WW.3 , -OCX WW.3 3. -OCH2X WW.3 , -OCHX WW.32, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, unsubstituted alkyl (e.g., C1-C8, C C1-C6, C1-C4, C1-C2), unsubstituted heteroalkyl (e.g., 2-8 membered, 2-6 membered, 4-6 membered, 2-3 membered, or 4-5 membered), unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, C5-C6), unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), unsubstituted aryl (e.g., C6-C 12 , C6~C 10 , or phenyl), or unsubstituted heteroaryl (e.g., 5 to 12-membered, 5 to 10-membered, 5 to 9-membered, or 5 to 6-membered). WW.3 is independently -F, -Cl, -Br, or -I.

[0090] Two different R WW When substituents join together to form an openly substituted ring (e.g., substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, or substituted heteroaryl), in embodiments, the openly substituted ring is referred to herein as R WW.1 and each first substituent R WW.1 may be unsubstituted or may be defined herein as R WW.2 and each second substituent R WW.2 may be unsubstituted or may be defined herein as R WW.3 and each third substituent R WW.3 are unsubstituted. Each first substituent is optionally different. Each second substituent is optionally different. Each third substituent is optionally different. Two different R WWIn the context where the substituents are joined together to form an open substituted ring, R WW.1 , R WW.2 , and R WW.3 The "WW" symbol in WW Refers to a specified number of one of the substituents. For example, R 100A and R 100B are optionally linked together to form an open substituted ring, R WW.1 is R 100A.1 and R WW.2 is R 100A.2 and R WW.3 is R 100A.3 Alternatively, R 100A and R 100B are optionally linked together to form an open substituted ring, R WW.1 is R 100B.1 and R WW.2 is R 100B.2 and R WW.3 is R 100B.3 R in this paragraph WW.1 , R WW.2 , and R WW.3 is as defined in the previous paragraph.

[0091] R LWW.1 are independently oxo, halogen, -CX LWW.1 3. -CHX LWW.1 2. -CH2X LWW.1 , -OCX LWW.1 3. -OCH2X LWW.1 , -OCHX LWW.1 2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, R LWW.2 substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), R LWW.2 substituted or unsubstituted heteroalkyl (e.g., 2-8 membered, 2-6 membered, 4-6 membered, 2-3 membered, or 4-5 membered), R LWW.2substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, C5-C6), R LWW.2 substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), R LWW.2 Substituted or unsubstituted aryl (e.g., C6-C 12 , C6~C 10 , or phenyl), or R LWW.2 In embodiments, R is a substituted or unsubstituted heteroaryl (e.g., 5-12 membered, 5-10 membered, 5-9 membered, or 5-6 membered). LWW.1 are independently oxo, halogen, -CX LWW.1 3. -CHX LWW.1 2. -CH2X LWW.1 , -OCX LWW.1 3. -OCH2X LWW.1 , -OCHX LWW.1 2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, unsubstituted alkyl (e.g., C1-C8, C C1-C6, C1-C4, C1-C2), unsubstituted heteroalkyl (e.g., 2-8 membered, 2-6 membered, 4-6 membered, 2-3 membered, or 4-5 membered), unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, C5-C6), unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), unsubstituted aryl (e.g., C6-C 12 , C6~C 10 , or phenyl), or unsubstituted heteroaryl (e.g., 5 to 12-membered, 5 to 10-membered, 5 to 9-membered, or 5 to 6-membered). LWW.1 is independently -F, -Cl, -Br, or -I.

[0092] R LWW.2 are independently oxo, halogen, -CX LWW.2 3. -CHX LWW.2 2. -CH2X LWW.2 , -OCX LWW.23. -OCH2X LWW.2 , -OCHX LWW.2 2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, R LWW.3 substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, C1-C2), R LWW.3 substituted or unsubstituted heteroalkyl (e.g., 2-8 membered, 2-6 membered, 4-6 membered, 2-3 membered, or 4-5 membered), R WW.3 substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, C5-C6), R LWW.3 substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), R LWW.3 Substituted or unsubstituted aryl (e.g., C6-C 12 , C6~C 10 , or phenyl), or R LWW.3 In embodiments, R is a substituted or unsubstituted heteroaryl (e.g., 5-12 membered, 5-10 membered, 5-9 membered, or 5-6 membered). LWW.2 are independently oxo, halogen, -CX LWW.2 3. -CHX LWW.2 2. -CH2X LWW.2 , -OCX LWW.2 3. -OCH2X LWW.2 , -OCHX LWW.22, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, unsubstituted alkyl (e.g., C1-C8, C C1-C6, C1-C4, C1-C2), unsubstituted heteroalkyl (e.g., 2-8 membered, 2-6 membered, 4-6 membered, 2-3 membered, or 4-5 membered), unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, C5-C6), unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), unsubstituted aryl (e.g., C6-C 12 , C6~C 10 , or phenyl), or unsubstituted heteroaryl (e.g., 5 to 12-membered, 5 to 10-membered, 5 to 9-membered, or 5 to 6-membered). LWW.2 is independently -F, -Cl, -Br, or -I.

[0093] R LWW.3 are independently oxo, halogen, -CX LWW.3 3. -CHX LWW.3 2. -CH2X LWW.3 , -OCX LWW.3 3. -OCH2X LWW.3 , -OCHX LWW.3 2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, unsubstituted alkyl (e.g., C1-C8, C C1-C6, C1-C4, C1-C2), unsubstituted heteroalkyl (e.g., 2-8 membered, 2-6 membered, 4-6 membered, 2-3 membered, or 4-5 membered), unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, C5-C6), unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), unsubstituted aryl (e.g., C6-C 12 , C6~C 10, or phenyl), or unsubstituted heteroaryl (e.g., 5 to 12-membered, 5 to 10-membered, 5 to 9-membered, or 5 to 6-membered). LWW.3 is independently -F, -Cl, -Br, or -I.

[0094] Any R group (R WW If an R group (R WW The groups) are independently oxo, halogen, -CX WW 3. -CHX WW 2. -CH2X WW , -OCX WW 3. -OCH2X WW , -OCHX WW 2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, R WW.1 substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, C1-C2), R WW.1 substituted or unsubstituted heteroalkyl (e.g., 2-8 membered, 2-6 membered, 4-6 membered, 2-3 membered, or 4-5 membered), R WW.1 substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, C5-C6), R WW.1 substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), R WW.1 Substituted or unsubstituted aryl (e.g., C6-C 12 , C6~C 10 , or phenyl), or R WW.1 X is defined herein as substituted or unsubstituted heteroaryl (e.g., 5-12 membered, 5-10 membered, 5-9 membered, or 5-6 membered). WW are independently -F, -Cl, -Br, -I. Additionally, "WW" represents the superscript number of the R group in question (e.g., 1, 2, 3, 1A, 2A, 3A, 1B, 2B, 3B, etc.). RWW.1 , R WW.2 , and R WW.3 is as defined above.

[0095] Any L linker group (i.e., L) listed in the chain or formula descriptions herein WW If the L group (L WW groups) are independently a bond, -O-, -NH-, -C(O)-, -C(O)NH-, -NHC(O)-, -NHC(O)NH-, -NHC(NH)NH-, -C(O)O-, -OC(O)-, -S-, -SO2-, -SO2NH-, R LWW.1 substituted or unsubstituted alkylene (e.g., C1-C8, C1-C6, C1-C4, C1-C2), R LWW.1 substituted or unsubstituted heteroalkylene (e.g., 2-8 membered, 2-6 membered, 4-6 membered, 2-3 membered, or 4-5 membered), R LWW.1 Substituted or unsubstituted cycloalkylene (e.g., C3-C8, C3-C6, C4-C6, C5-C6), R LWW.1 substituted or unsubstituted heterocycloalkylene (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), R LWW.1 Substituted or unsubstituted arylene (e.g., C6-C 12 , C6~C 10 , or phenyl), or R LWW.1 R is defined herein as a substituted or unsubstituted heteroarylene (e.g., 5-12 membered, 5-10 membered, 5-9 membered, or 5-6 membered). Additionally, "WW" represents the listed superscript numbers (1, 2, 3, 1A, 2A, 3A, 1B, 2B, 3B, etc.) of the subject L group. LWW.1 , and R LWW.2 and R LWW.3 is as defined above.

[0096] Certain compounds of the present disclosure possess asymmetric carbon atoms (optical or chiral centers) or double bonds, which may be defined in terms of absolute stereochemistry as (R)- or (S)- or (D)- or (L)- for amino acids. Enantiomers, racemates, diastereomers, tautomers, geometric isomers, stereoisomeric forms, and individual isomers are encompassed within the scope of the present disclosure. The compounds of the present disclosure do not include compounds known in the art to be too unstable to synthesize and / or isolate. The present disclosure is intended to include compounds in racemic and optically pure form. Optically active (R)- and (S)- or (D)- and (L)-isomers may be prepared using chiral synthons or chiral reagents or resolved using conventional techniques. When the compounds described herein contain olefinic bonds or other centers of geometric asymmetry, unless otherwise specified, it is intended that the compounds include both E and Z geometric isomers.

[0097] As used herein, the term "isomers" refers to compounds that have the same number and kind of atoms, and therefore the same molecular weight, but differ with regard to the structural arrangement or configuration of the atoms.

[0098] The term "tautomer," as used herein, refers to one of two or more structural isomers that exist in equilibrium and are readily converted from one isomeric form to another.

[0099] It will be apparent to one of ordinary skill in the art that certain compounds of the present disclosure may exist in tautomeric forms, all such tautomeric forms of the compounds being within the scope of the disclosure.

[0100] Unless otherwise stated, structures depicted herein are also meant to include all stereochemical forms of the structure, i.e., the R and S configurations for each asymmetric center. Therefore, single stereochemical isomers as well as enantiomeric and diastereomeric mixtures of the present compounds are within the scope of the disclosure.

[0101] Unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms, for example, the replacement of a hydrogen by deuterium or tritium, or 13 C or 14 Compounds having this structure, except for the replacement of a carbon with a C-enriched carbon, are within the scope of this disclosure.

[0102] The compounds of the present disclosure may also contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. For example, the compounds may contain unnatural proportions of atomic isotopes, such as tritium ( 3 H), iodine-125( 125 I), or carbon-14 ( 14 C). All isotopic variations of the compounds of the present disclosure, whether radioactive or not, are encompassed within the scope of the present disclosure.

[0103] It should be noted that throughout this application, alternatives, e.g., each amino acid position containing more than one possible amino acid, are described in terms of a Markush group. It is specifically contemplated that each member of a Markush group should be considered separately, thereby including alternative embodiments, and that a Markush group should not be read as a single unit.

[0104] As used herein, the terms "bioconjugate" and "bioconjugate linker" refer to the resulting association between atoms or molecules of a bioconjugate reactive group or bioconjugate reactive moiety. The association can be direct or indirect. For example, provided herein, a conjugate between a first bioconjugate reactive group (e.g., -NH, -COOH, -N-hydroxysuccinimide, or -maleimide) and a second bioconjugate reactive group (e.g., sulfhydryl, sulfur-containing amino acid, amine, amine side chain-containing amino acid, or carboxylate) can be direct, e.g., via a covalent bond or linker (e.g., a first linker to a second linker), or indirect, e.g., via a non-covalent bond (e.g., electrostatic interactions (e.g., ionic bonds, hydrogen bonds, halogen bonds), van der Waals interactions (e.g., dipole-dipole, dipole-induced dipole, London dispersion), ring stacking (pi effect), hydrophobic interactions), etc. In embodiments, bioconjugates or bioconjugate linkers are formed using bioconjugate chemistry (i.e., the association of two bioconjugate reactive groups), including, but not limited to, nucleophilic substitution (e.g., reaction of amines and alcohols with acyl halides, activated esters), electrophilic substitution (e.g., enamine reaction), and addition across carbon-carbon and carbon-heteroatom multiple bonds (e.g., Michael reaction, Diels-Alder addition). These and other useful reactions are discussed, for example, in March, ADVANCED ORGANIC CHEMISTRY, 3rd Ed., John Wiley & Sons, New York, 1985; Hermanson, BIOCONJUGATE TECHNIQUES, Academic Press, San Diego, 1996; and Feeney et al., MODIFICATION OF PROTEINS; Advances in Chemistry Series, Vol. 198, American Chemical Society, Washington, DC, 1982.In embodiments, a first bioconjugate reactive group (e.g., a maleimide moiety) is covalently linked to a second bioconjugate reactive group (e.g., a sulfhydryl). In embodiments, a first bioconjugate reactive group (e.g., a haloacetyl moiety) is covalently linked to a second bioconjugate reactive group (e.g., a sulfhydryl). In embodiments, a first bioconjugate reactive group (e.g., a pyridyl moiety) is covalently linked to a second bioconjugate reactive group (e.g., a sulfhydryl). In embodiments, a first bioconjugate reactive group (e.g., an -N-hydroxysuccinimide moiety) is covalently linked to a second bioconjugate reactive group (e.g., an amine). In embodiments, a first bioconjugate reactive group (e.g., a maleimide moiety) is covalently linked to a second bioconjugate reactive group (e.g., a sulfhydryl). In embodiments, a first bioconjugate reactive group (eg, a -sulfo-N-hydroxysuccinimide moiety) is covalently attached to a second bioconjugate reactive group (eg, an amine).

[0105] Useful bioconjugate reactive groups for use in the bioconjugate chemistry herein include: (a) carboxyl groups and their various derivatives, including, but not limited to, N-hydroxysuccinimide esters, N-hydroxybenzotriazole esters, acid halides, acylimidazoles, thioesters, p-nitrophenyl esters, alkyl, alkenyl, alkynyl, and aromatic esters; (b) hydroxyl groups, which can be converted to esters, ethers, aldehydes, etc.; (c) haloalkyl groups, where the halide can be subsequently displaced with a nucleophilic group, such as an amine, carboxylate anion, thiol anion, carbanion, or alkoxide ion, resulting in the covalent attachment of a new group at the halogen atom; (d) dienophile groups, such as maleimide or maleimide groups, that can participate in Diels-Alder reactions; and (e) subsequent cleavage reactions, such as via the formation of carbonyl derivatives, such as imines, hydrazones, semicarbazones, or oximes, or via mechanisms such as Grignard addition or alkyllithium addition. (f) sulfonyl halide groups, e.g., for subsequent reaction with amines to form sulfonamides; (g) thiol groups, which can be converted to disulfides, reacted with acyl halides, attached to metals such as gold, or reacted with maleimides; (h) amine or sulfhydryl groups (e.g., those present in cysteine), which can be acylated, alkylated, or oxidized; (i) alkenes, which can undergo, e.g., cycloaddition, acylation, Michael addition, etc.; (j) amines, e.g., amines, and hydroxyl compounds, (k) phosphoramidites and other standard functional groups useful in nucleic acid synthesis, (l) metal-silicon oxide linkages, (m) metal linkages to reactive phosphorus groups (e.g., phosphines) to form, for example, phosphodiester bonds, (n) azides coupled to alkynes using copper-catalyzed cycloaddition click chemistry, and (o) biotin conjugates that can react with avidin or streptavidin to form avidin-biotin or streptavidin-biotin complexes.

[0106] Bioconjugate reactive groups can be selected so that they do not contribute to or interfere with the chemical stability of the conjugates described herein. Alternatively, reactive functional groups can be protected from participating in crosslinking reactions by the presence of protecting groups. In embodiments, bioconjugates include molecular entities resulting from the reaction of an unsaturated bond, such as a maleimide, with a sulfhydryl group.

[0107] The terms "analog," "analogue," or "derivative" are used according to their plain and ordinary meaning within chemistry and biology to refer to a compound that is structurally similar to another compound (i.e., a so-called "reference" compound) but differs in composition, e.g., the substitution of one atom with an atom of a different element, or the presence of a particular functional group, or the substitution of one functional group with another functional group, or the absolute stereochemistry of one or more chiral centers of the reference compound. Thus, an analog is a compound that is similar or equivalent in function and appearance to the reference compound, but differs in structure or origin.

[0108] As used herein, the terms "a" or "an" mean one or more. Additionally, as used herein, the phrase "substituted with a[n]" means that the specified group can be substituted with one or more of any or all of the specified substituents. For example, when a group such as an alkyl group or heteroaryl group is referred to as an "unsubstituted C1-C 20 When "substituted with alkyl or unsubstituted 2-20 membered heteroalkyl," the group is substituted with one or more unsubstituted C1-C 20 It may contain alkyl and / or one or more unsubstituted 2-20 membered heteroalkyl.

[0109] Furthermore, when a moiety is substituted with an R substituent, the group may be referred to as "R-substituted." When a moiety is R-substituted, the moiety is substituted with at least one R substituent, and each R substituent is optionally different. When a particular R group occurs in a description of a chemical species (such as formula (I)), Roman alphabet symbols may be used to distinguish between each occurrence of that particular R group. For example, multiple R 13When substituents are present, each R 13 The substituents are R 13.A , R 13.B , R 13.C , R 13.D can be distinguished from R 13.A , R 13.B , R 13.C , R 13.D Each of these is R 13 Within the definition of , it may be defined differently at will.

[0110] The description of the compounds of the present disclosure is limited by the principles of chemical bonding known to those skilled in the art.Therefore, when a group can be substituted with one or more of several substituents, such substitutions are selected to comply with the principles of chemical bonding and to bring about a compound known to those skilled in the art that is not inherently unstable and / or is likely to be unstable under ambient conditions, such as aqueous, neutral, and some known physiological conditions.For example, heterocycloalkyl or heteroaryl is bonded to the rest of the molecule through ring heteroatom according to the principles of chemical bonding known to those skilled in the art, thereby avoiding inherently unstable compounds.

[0111] The term "protecting group" is used according to its ordinary meaning in organic chemistry to refer to a moiety covalently attached to a heteroatom, heterocycloalkyl, or heteroaryl to prevent reactivity of the heteroatom, heterocycloalkyl, or heteroaryl during one or more chemical reactions performed prior to removal of the protecting group. Typically, a protecting group is attached to a heteroatom (e.g., O) during a part of a multi-part synthesis where it is undesirable to react the heteroatom with a reagent (e.g., chemical reduction). After protection, the protecting group can be removed (e.g., by adjusting the pH). In embodiments, the protecting group is an alcohol protecting group. Non-limiting examples of alcohol protecting groups include acetyl, benzoyl, benzyl, methoxymethyl ether (MOM), tetrahydropyranyl (THP), and silyl ethers (e.g., trimethylsilyl (TMS), tert-butyldimethylsilyl (TBS)). In embodiments, the protecting group is an amine protecting group. Non-limiting examples of amine protecting groups include carbobenzyloxy (Cbz), tert-butyloxycarbonyl (BOC), 9-fluorenylmethyloxycarbonyl (FMOC), acetyl, benzoyl, benzyl, carbamate, p-methoxybenzyl ether (PMB), and tosyl (Ts).

[0112] The term "pharmaceutically acceptable salts" is intended to include salts of active compounds prepared using relatively non-toxic acids or bases, depending on the specific substituents found in the compounds described herein. When a compound of the present disclosure contains a relatively acidic functional group, a base addition salt can be obtained by contacting the neutral form of such a compound with a sufficient amount of the desired base, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salts, or similar salts. When a compound of the present disclosure contains a relatively basic functional group, an acid addition salt can be obtained by contacting the neutral form of such a compound with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include salts derived from inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, carbonic acid, monohydrogencarbonic acid, phosphoric acid, monohydrogenphosphate, dihydrogenphosphate, sulfuric acid, monohydrogensulfuric acid, hydroiodic acid, or phosphorous acid, as well as salts derived from relatively non-toxic organic acids such as acetic acid, propionic acid, isobutyric acid, maleic acid, malonic acid, benzoic acid, succinic acid, suberic acid, fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-tolylsulfonic acid, citric acid, tartaric acid, oxalic acid, and methanesulfonic acid. Also included are salts of amino acids such as argininate, and salts of organic acids such as glucuronic acid or galactunoric acid (see, e.g., Berge et al., "Pharmaceutical Salts," Journal of Pharmaceutical Science, 1977, 66, 1-19). Certain specific compounds of the present disclosure contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts.

[0113] Therefore, the compounds of the present disclosure may exist as salts with pharmaceutically acceptable acids, etc. The present disclosure includes such salts. Non-limiting examples of such salts include hydrochloride, hydrobromide, phosphate, sulfate, methanesulfonate, nitrate, maleate, acetate, citrate, fumarate, propionate, tartrate (e.g., (+)-tartrate, (-)-tartrate, or a mixture thereof, including a racemic mixture), succinate, benzoate, and salts with amino acids, such as glutamic acid, and quaternary ammonium salts (e.g., methyl iodide, ethyl iodide, etc.). These salts can be prepared by methods known to those skilled in the art.

[0114] The neutral forms of the compounds are preferably regenerated by contacting the salt with a base or acid and isolating the parent compound in the conventional manner. The parent form of the compound may differ from the various salt forms in certain physical properties, such as solubility in polar solvents.

[0115] In addition to salt forms, the present disclosure provides compounds in prodrug form. Prodrugs of the compounds described herein are compounds that readily undergo chemical changes under physiological conditions to yield the compounds of the present disclosure. Prodrugs of the compounds described herein can be converted in vivo after administration. Furthermore, prodrugs can be converted to the compounds of the present invention by chemical or biochemical methods in an ex vivo environment, for example, when contacted with a suitable enzyme or chemical reagent.

[0116] Certain compounds of the present disclosure may exist in unsolvated forms and solvated forms, including hydrated forms. Generally, solvated forms are equivalent to unsolvated forms and are included within the scope of the present disclosure. Certain compounds of the present disclosure may exist in polycrystalline or amorphous forms. Generally, all physical forms are equivalent for the uses contemplated by the present disclosure and are intended to be within the scope of the present disclosure.

[0117] A polypeptide or cell is "recombinant" if it is artificially or engineered, or if it is derived from or contains an artificially or engineered protein or nucleic acid (e.g., non-naturally occurring or non-wild-type). For example, a polynucleotide that is inserted into a vector or any other heterologous location, e.g., in the genome of a recombinant organism, so that it is not associated with nucleotide sequences that normally flank the polynucleotide as found in nature is a recombinant polynucleotide. A protein expressed in vitro or in vivo from a recombinant polynucleotide is an example of a recombinant polypeptide. Similarly, a polynucleotide sequence not found in nature, e.g., a variant of a naturally occurring gene, is recombinant.

[0118] As used herein, a "cell" refers to a cell that performs metabolic or other functions sufficient to preserve or replicate its genomic DNA. Cells can be identified by methods well known in the art, including, for example, the presence of an intact membrane, staining with certain dyes, the ability to produce progeny, or, in the case of gametes, the ability to combine with a second gamete to produce viable progeny. Cells may include prokaryotic and eukaryotic cells. Prokaryotic cells include, but are not limited to, bacteria. Eukaryotic cells include, but are not limited to, yeast cells and cells derived from plants and animals, such as mammalian cells, insect (e.g., Spodoptera) cells, and human cells. Cells may be useful if they are naturally non-adherent or have been treated to prevent them from adhering to surfaces, for example, by trypsinization.

[0119] The term "treating" or "treatment" refers to any indication of success in treatment or improvement of an injury, disease, condition, or state, including any objective or subjective parameter, such as relief, remission, reduction in symptoms, or making the injury, condition, or state more tolerable to the patient, slowing the rate of degeneration or decline, making the end point of degeneration less debilitating, or improving the patient's physical or mental health. The treatment or improvement of symptoms can be based on objective or subjective parameters, including the results of a physical examination, neuropsychiatric examination, and / or psychiatric evaluation. For example, certain methods provided herein successfully treat cancer by reducing the incidence of cancer and / or by causing remission of cancer. In some embodiments of the compositions or methods described herein, treating cancer includes slowing the rate of growth or spread of cancer cells, reducing metastasis, or reducing the growth of metastatic tumors. The term "treating" and its conjugations includes prevention of an injury, lesion, condition, or disease. In embodiments, treating is preventing. In embodiments, treating does not include preventing. In some embodiments, the treating or treatment is not a prophylactic treatment.

[0120] An "effective amount" is an amount sufficient for a compound to achieve a predetermined purpose (e.g., achieve the effect of being administered, treat a disease, reduce enzyme activity, increase enzyme activity, reduce a signal transduction pathway, or reduce one or more symptoms of a disease or condition) compared to the absence of the compound. An example of an "effective amount" is an amount sufficient to contribute to the treatment, prevention, or alleviation of a symptom or symptoms of a disease, which may also be referred to as a "therapeutically effective amount" when referred to in this context. A "reduction" of a symptom(s) (and grammatical equivalents of this phrase) means a decrease in the severity or frequency of the symptom, or the elimination of the symptom. A "prophylactically effective amount" of a drug is an amount of a drug that, when administered to a subject, will have an intended prophylactic effect, for example, an amount of a drug that prevents or delays the onset (or recurrence) of an injury, disease, pathology, or condition, or reduces the likelihood of the onset (or recurrence) of an injury, disease, pathology, or condition, or a symptom thereof. A complete prophylactic effect does not necessarily occur by administration of a single dose, but may occur only after administration of a series of doses. Thus, a prophylactically effective amount may be administered in one or more administrations. As used herein, an "activity-reducing amount" refers to the amount of antagonist required to reduce the activity of an enzyme compared to the absence of the antagonist. As used herein, a "function-interfering amount" refers to the amount of antagonist required to interfere with the function of an enzyme or protein compared to the absence of the antagonist. As used herein, an "activity-increasing amount" refers to the amount of agonist required to increase the activity of an enzyme compared to the absence of the agonist. As used herein, a "function-increasing amount" refers to the amount of agonist required to increase the function of an enzyme or protein compared to the absence of the agonist.The exact amount will depend on the purpose of the treatment and will be ascertainable by one of ordinary skill in the art using known techniques (see, e.g., Lieberman, Pharmaceutical Dosage Forms (vols. 1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Pickar, Dosage Calculations (1999); and Remington: The Science and Practice of Pharmacy, 20th Edition, 2003, Gennaro, Ed., Lippincott, Williams & Wilkins).

[0121] "Control" or "control experiment" is used according to its plain and ordinary meaning to refer to an experiment in which the experimental subject or reagent is treated the same as in a parallel experiment except for the omission of the experimental procedure, reagent, or variable. In some instances, a control is used as a standard of comparison in evaluating experimental efficacy. In some embodiments, a control is a measurement of a protein activity (e.g., a signaling pathway) in the absence of a compound described herein (including in any embodiment, example, figure, or table).

[0122] "Contacting" is used according to its plain and ordinary meaning to refer to a process that allows at least two distinct species (e.g., chemical compounds, including biomolecules or cells) to come into sufficient proximity to react, interact, or physically contact each other. However, it should be understood that the resulting reaction product may be produced directly from the reaction between the added reagents, or may be produced from an intermediate from one or more of the added reagents that may be produced in the reaction mixture.

[0123] The term "contacting" can include allowing two species to react, interact, or come into physical contact, where the two species can be a compound described herein and a cellular component (e.g., a protein, ion, lipid, nucleic acid, nucleotide, amino acid, protein, particle, organelle, subcellular compartment, microorganism, virus, lipid droplet, vesicle, small molecule, protein complex, protein aggregate, or macromolecule). In some embodiments, contacting includes allowing a compound described herein to interact with a cellular component (e.g., a protein, ion, lipid, nucleic acid, nucleotide, amino acid, protein, particle, virus, lipid droplet, organelle, subcellular compartment, microorganism, vesicle, small molecule, protein complex, protein aggregate, or macromolecule) involved in a signaling pathway.

[0124] As defined herein, the terms "activation," "activate," "activating," and the like, with respect to proteins, refer to the conversion of a protein from an initial, inactive, or inactivated state to a biologically active derivative. These terms refer to activating, or activating, sensitizing, or upregulating signal transduction or enzymatic activity or the amount of a protein that is decreased in a disease.

[0125] The terms "agonist," "activator," "up-regulator," and the like refer to a substance capable of detectably increasing the expression or activity of a given gene or protein. An agonist can increase expression or activity by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% compared to a control in the absence of the agonist. In certain cases, expression or activity is 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, or more, greater than expression or activity in the absence of the agonist.

[0126] As defined herein, the terms "inhibition," "inhibit," "inhibiting," and the like, with respect to cellular component-inhibitor interactions, mean to adversely affect (e.g., reduce) the activity or function of the cellular component (e.g., reduce a signal transduction pathway stimulated by the cellular component (e.g., a protein, ion, lipid, virus, lipid droplet, nucleic acid, nucleotide, amino acid, protein, particle, organelle, subcellular compartment, microorganism, vesicle, small molecule, protein complex, protein aggregate, or macromolecule)) compared to the activity or function of the cellular component in the absence of the inhibitor. In embodiments, inhibition means adversely affecting (e.g., reducing) the concentration or level of the cellular component compared to the concentration or level of the cellular component in the absence of the inhibitor. In embodiments, inhibition refers to a reduction in a disease or disease symptom. In some embodiments, inhibition refers to a decrease in the activity of a signal transduction or signal transduction pathway (e.g., a decrease in a pathway in which the cellular component is involved). Thus, inhibiting includes at least partially, partially or completely blocking a stimulus, reducing, preventing, or delaying activation, or inactivating, desensitizing, or downregulating a signaling pathway or enzymatic activity or amount of a protein.

[0127] The terms "inhibitor," "suppressor," "antagonist," or "down-regulator" refer interchangeably to a substance capable of detectably reducing the expression or activity of a given gene or protein. An antagonist can reduce expression or activity by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% compared to a control in the absence of the antagonist. In certain cases, expression or activity is 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, or more lower than the expression or activity in the absence of the antagonist.

[0128] The term "lysophosphatidic acid receptor 1 antagonist" or "LPAR1 antagonist" refers to any exogenously administered compound or agent that can partially or completely inhibit or reverse the effect of an agonist (e.g., lysophosphatidic acid) on the LPAR1 receptor. This term includes compounds or agents characterized or described as antagonists, partial antagonists, and negative allosteric modulators.

[0129] The term "modulator" refers to a composition that increases or decreases the level of a target molecule or the function of a target molecule or the physical state of a target of the molecule relative to the absence of the composition (e.g., the target may be a cellular component (e.g., a protein, ion, lipid, virus, lipid droplet, nucleic acid, nucleotide, amino acid, protein, particle, organelle, subcellular compartment, microorganism, vesicle, small molecule, protein complex, protein aggregate, or macromolecule)).

[0130] The term "expression" includes 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 detecting proteins (e.g., ELISA, Western blotting, flow cytometry, immunofluorescence, immunohistochemistry, etc.).

[0131] The term "modulate" is used according to its plain and ordinary meaning to refer to the act of changing or varying one or more properties. "Modulation" refers to the process of changing or varying one or more properties. For example, as applied to the effect of a modulator on a target protein, modulating means altering by increasing or decreasing the property or function of the target molecule or the amount of the target molecule.

[0132] A "patient" or "subject in need of treatment" refers to an organism suffering from or susceptible to a disease or condition that can be treated by administration of a pharmaceutical composition as provided herein. Non-limiting examples include humans, other mammals, cows, rats, mice, dogs, monkeys, goats, sheep, cattle, deer, and other non-mammals. In some embodiments, the patient is a human.

[0133] "Disease" or "condition" refers to a state of existence or health of a patient or subject that can be treated with the compounds or methods provided herein. In some embodiments, the disease is a disease associated with (e.g., caused by) a cellular component (e.g., a protein, ion, lipid, nucleic acid, nucleotide, amino acid, protein, particle, organelle, subcellular compartment, microorganism, vesicle, small molecule, protein complex, protein aggregate, or macromolecule). In embodiments, the disease is a neurodegenerative disease. In embodiments, the disease is an inflammatory disease. In embodiments, the disease is post-hemorrhagic encephalitis. In embodiments, the disease is a demyelinating disease. In embodiments, the disease is multiple sclerosis. In embodiments, the disease is a fibrotic disease. In embodiments, the disease is pulmonary fibrosis. In embodiments, the disease is idiopathic pulmonary fibrosis. In embodiments, the disease is cancer. In embodiments, the disease is glioblastoma.

[0134] As used herein, the term "neurodegenerative disease" refers to a disease or condition in which the function of a subject's nervous system is impaired. Examples of neurodegenerative diseases that may be treated with the compounds, pharmaceutical compositions, or methods described herein include Alexander disease, Alper's disease, Alzheimer's disease, amyotrophic lateral sclerosis, ataxia-telangiectasia, Batten disease (also known as Spielmeyer-Vogt-Sjogren-Batten disease), bovine spongiform encephalopathy, and cerebrospinal fluid disorders. encephalopathy, BSE), Canavan disease, Cockayne syndrome, corticobasal degeneration, Creutzfeldt-Jakob disease, frontotemporal dementia, Gerstmann-Straussler-Scheinker syndrome, Huntington's disease, HIV-related disorders, Kennedy disease, Krave disease, Kuhl, dementia with Lewy bodies, Machado-Joseph disease (spinocerebellar ataxia type 3), multiple sclerosis, multiple system atrophy, narcolepsy, neuroborreliosis, Parkinson's disease, Pelizaeus-Merzbach disease, Pick's disease, primary lateral sclerosis, prion diseases, Refsum disease, Sandhoff disease, Schilder's disease, subacute combined degeneration of the spinal cord secondary to pernicious anemia, schizophrenia, spinocerebellar ataxia (various types with varying features), spinal muscular atrophy, Steele-Richardson-Olszewski disease, or tabes dorsalis.

[0135] As used herein, the term "inflammatory disease" refers to a disease or condition characterized by abnormal inflammation (e.g., increased levels of inflammation compared to a control, such as a healthy individual not afflicted with the disease). Examples of inflammatory diseases include autoimmune diseases, arthritis, rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis, multiple sclerosis, systemic lupus erythematosus (SLE), myasthenia gravis, juvenile-onset diabetes, type 1 diabetes mellitus, Guillain-Barré syndrome, Hashimoto's encephalopathy, Hashimoto's thyroiditis, ankylosing spondylitis, psoriasis, Sjogren's syndrome, vasculitis, glomerulonephritis, autoimmune thyroiditis, Behcet's disease, Crohn's disease, ulcerative colitis, bullous pemphigoid, sarcoidosis, ichthyosis, Graves' ophthalmopathy, inflammatory bowel disease, Addison's disease, vitiligo, asthma, allergic asthma, acne vulgaris, celiac disease, chronic prostatitis, inflammatory bowel disease, pelvic inflammatory disease, reperfusion injury, sarcoidosis, transplant rejection, interstitial cystitis, atherosclerosis, scleroderma, and atopic dermatitis.

[0136] As used herein, the term "demyelinating disease" refers to any disease or condition characterized by damage to the protective covering (e.g., myelin sheath) surrounding nerve fibers (e.g., in the brain, optic nerve, or spinal cord). In embodiments, the demyelinating disease is a demyelinating disease of the central nervous system. In embodiments, the demyelinating disease is multiple sclerosis. In embodiments, the demyelinating disease is a demyelinating disease of the peripheral nervous system.

[0137] As used herein, the terms "fibrotic disease" and "fibrosis" refer to any disease or condition characterized by the formation of excess fibrous connective tissue. The formation of excess fibrous connective tissue may be responsive to a repair or reactive process. Fibrotic diseases include, but are not limited to, pulmonary fibrosis (e.g., idiopathic pulmonary fibrosis (IPF)), liver fibrosis (e.g., nonalcoholic steatohepatitis (NASH)), myelofibrosis, skin fibrosis (e.g., scleroderma), ocular fibrosis, mediastinal fibrosis, cardiac fibrosis, renal fibrosis, interstitial fibrosis, epidural fibrosis, epithelial fibrosis, or idiopathic fibrosis.

[0138] As used herein, the term "cardiovascular disorder" or "cardiovascular disease" is used according to its plain and ordinary meaning. In embodiments, cardiovascular diseases that may be treated with the compounds, pharmaceutical compositions, or methods described herein include, but are not limited to, stroke, heart failure, hypertension, hypertensive heart disease, myocardial infarction, angina pectoris, tachycardia, cardiomyopathy, rheumatic heart disease, cardiomyopathies, cardiac arrhythmias, congenital heart disease, valvular heart disease, carditis, aortic aneurysm, peripheral arterial disease, thromboembolism, and venous thrombosis.

[0139] As used herein, the term "cancer" refers to all types of cancers, neoplasms, or malignant tumors found in mammals (e.g., humans), including leukemia, lymphoma, carcinoma, and sarcoma. Exemplary cancers that may be treated with the compounds or methods provided herein include thyroid cancer, endocrine system cancer, brain cancer, breast cancer, cervical cancer, colon cancer, head and neck cancer, liver cancer, kidney cancer, lung cancer, non-small cell lung cancer, melanoma, mesothelioma, ovarian cancer, sarcoma, gastric cancer, uterine cancer, medulloblastoma, colorectal cancer, or pancreatic cancer. Further examples may include Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, neuroblastoma, glioma, glioblastoma multiforme, ovarian cancer, rhabdomyosarcoma, primary thrombocythemia, primary macroglobulinemia, primary brain tumor, cancer, malignant pancreatic insulanoma, malignant carcinoid, bladder cancer, premalignant skin lesions, testicular cancer, lymphoma, thyroid cancer, esophageal cancer, genitourinary cancer, malignant hypercalcemia, endometrial cancer, adrenocortical carcinoma, endocrine or exocrine pancreatic neoplasms, medullary thyroid cancer, medullary thyroid carcinoma, melanoma, colorectal cancer, papillary thyroid cancer, hepatocellular carcinoma, or prostate cancer.

[0140] The term "leukemia" broadly refers to progressive, malignant diseases of the blood-forming organs and is generally characterized by the distorted proliferation and development of white blood cells and their precursor cells in the blood and bone marrow. Leukemias are generally classified clinically based on: (1) the duration and character of the disease—acute or chronic; (2) the type of cell involved—myeloid (myeloid), lymphatic (lymphoid), or monocytic; and (3) the increased or non-increasing number of abnormal cells in the blood—leukemia or non-leukemia (subleukemia). Exemplary leukemias that may be treated with the compounds or methods provided herein include, for example, acute nonlymphocytic leukemia, chronic lymphocytic leukemia, acute granulocytic leukemia, chronic granulocytic leukemia, acute promyelocytic leukemia, adult T-cell leukemia, and non-leukemia. leukemia), leukemic leukemia, basophilic leukemia, blast cell leukemia, bovine leukemia, chronic myelocytic leukemia, leukemia cutis, fetal leukemia, eosinophilic leukemia, gross leukemia, hairy cell leukemia, hemoblastic leukemia, hemoblastic leukemia, histiocytic leukemia, stem cell leukemia, acute monocytic leukemia, leukopenic leukemia, lymphocytic leukemia, lymphoblastic leukemia, lymphocytic leukemia, lymphoid leukemia, lymphoid leukemia, lymphoid leukemia, Examples of leukemia include lymphocytic leukemia, lymphosarcoma cell leukemia, mast cell leukemia, megakaryocytic leukemia, small myeloblastic leukemia, monocytic leukemia, myeloblastic leukemia, myelocytic leukemia, myelogranulocytic leukemia, myelomonocytic leukemia, Naegeli leukemia, plasma cell leukemia, multiple myeloma, plasma cell leukemia, promyelocytic leukemia, Leder cell leukemia, Schilling leukemia, stem cell leukemia, subleukemic leukemia, and anaplastic cell leukemia.

[0141] As used herein, the term "lymphoma" refers to a group of cancers affecting hematopoietic and lymphatic tissues. It develops primarily in lymphocytes, which are blood cells found in lymph nodes, spleen, thymus, and bone marrow. The two main types of lymphoma are non-Hodgkin's lymphoma and Hodgkin's disease. Hodgkin's disease accounts for approximately 15% of all diagnosed lymphomas. It is a cancer associated with Reed-Sternberg malignant B lymphocytes. Non-Hodgkin's lymphoma (NHL) can be classified based on the rate at which the cancer grows and the type of cell involved. NHL includes aggressive (high-grade) and indolent (low-grade) types. Based on the type of cell involved, there are B-cell and T-cell NHL. Exemplary B-cell lymphomas that may be treated with the compounds or methods provided herein include, but are not limited to, small lymphocytic lymphoma, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, extranodal (MALT) lymphoma, nodal (monocytic B-cell) lymphoma, splenic lymphoma, diffuse large B-cell lymphoma, Burkitt's lymphoma, lymphoblastic lymphoma, immunoblastic large cell lymphoma, or precursor B-lymphoblastic lymphoma. Exemplary T-cell lymphomas that may be treated with the compounds or methods provided herein include, but are not limited to, cutaneous T-cell lymphoma, peripheral T-cell lymphoma, anaplastic large cell lymphoma, mycosis fungoides, and precursor T-lymphoblastic lymphoma.

[0142] The term "sarcoma" generally refers to a tumor composed of closely packed cells that are composed of a substance like embryonic connective tissue and that is generally composed of tightly packed cells embedded in a fibrous or homogeneous substance. Sarcomas that may be treated with the compounds or methods provided herein include chondrosarcoma, fibrosarcoma, lymphosarcoma, melanosarcoma, myxosarcoma, osteosarcoma, Abemethy's sarcoma, liposarcoma, liposarcoma, alveolar soft part sarcoma, ameloblastic sarcoma, botryoid sarcoma, green sarcoma, choriocarcinoma, embryonal sarcoma, Wilms' tumor sarcoma, endometrial sarcoma, stromal sarcoma, Ewing's sarcoma, fascial sarcoma, fibroblastic sarcoma, and fibroblastic sarcoma. These include alveolar sarcoma, giant cell sarcoma, granulocytic sarcoma, Hodgkin's sarcoma, idiopathic multiple pigmented hemorrhagic sarcoma, B-cell immunoblastic sarcoma, lymphoma, T-cell immunoblastic sarcoma, Jensen's sarcoma, Kaposi's sarcoma, Kupffer cell sarcoma, angiosarcoma, leukemia sarcoma, malignant mesenchymal sarcoma, parosteal osteosarcoma, reticulocytic sarcoma, Rous sarcoma, serous cystic sarcoma, synovial sarcoma, and telangiectatic sarcoma.

[0143] The term "melanoma" is intended to mean a tumor arising from the melanocytic system of the skin and other organs. Melanomas that may be treated with the compounds or methods provided herein include, for example, acral lentiginous melanoma, amelanotic melanoma, benign juvenile melanoma, Cloudman's melanoma, S91 melanoma, Harding-Passey melanoma, juvenile melanoma, lentigo maligna melanoma, malignant melanoma, nodular melanoma, subungual melanoma, or superficial spreading melanoma.

[0144] The term "carcinoma" refers to a malignant new growth composed of epithelial cells that tend to infiltrate surrounding tissues and give rise to metastases. Exemplary carcinomas that may be treated with the compounds or methods provided herein include, for example, medullary thyroid carcinoma, familial medullary thyroid carcinoma, lobular cell carcinoma, acinic cell carcinoma, adenocell carcinoma, adenoid cystic carcinoma, carcinoma adenomatous, adrenocortical carcinoma, alveolar carcinoma, alveolar cell carcinoma, basal cell carcinoma, carcinoma basocellulare, basaloid cell carcinoma, basosquamous cell carcinoma, bronchioloalveolar carcinoma, bronchiolocarcinoma, bronchogenic carcinoma, cerebriform carcinoma, cholangiocarcinoma, choriocarcinoma, colloid carcinoma, comedocarcinoma, corpus carcinoma, cribriform carcinoma, armored carcinoma, skin carcinoma, cylindrical carcinoma, cylindrical cell carcinoma, ductal carcinoma, and compact carcinoma. durum, embryonal carcinoma, encephalomyocellular carcinoma, epidermoid carcinoma, epidermoid carcinoma, tonsillar carcinoma, exophytic carcinoma, ulcer carcinoma, fibrous carcinoma, gelatinous carcinoma, colloid adenocarcinoma, giant cell carcinoma, adenocarcinoma, granulosa cell carcinoma, hair matrix carcinoma, hematoid carcinoma, hepatocellular carcinoma, Hürthle cell carcinoma, glassy carcinoma, adrenal carcinoma, infantile embryonal carcinoma, carcinoma in situ, carcinoma in situ, carcinoma in epidermis, carcinoma in situ, Krompecher's carcinoma, Kulchitzky cell carcinoma, large cell carcinoma, lenticular carcinoma, lipomatous carcinoma, lymphoepithelial carcinoma, medullary carcinoma, melanoma, carcinoma molle, mucinous carcinoma, mucinous secreting carcinoma muciparum, mucous cell carcinoma, mucoepidermoid carcinoma, mucous carcinoma (carcinoma mucosum), mucosal carcinoma, myxomatous carcinoma, nasopharyngeal carcinoma, oat cell carcinoma, ossifying carcinoma, osteoid carcinoma, papillary carcinoma, periportal carcinoma, preinvasive carcinoma, squamous cell carcinoma, pasty carcinoma, renal cell carcinoma of the kidney, storage cell carcinoma, sarcomatoid carcinoma, Schneiderian carcinoma, scirrhous carcinoma, scrotal carcinoma, signet ring cell carcinoma, simplex carcinoma, small cell carcinoma, solanoid carcinomacarcinoma, globular cell carcinoma, spindle cell carcinoma, porocytic carcinoma, squamous cell carcinoma, squamous cell carcinoma, string carcinoma, telangiectatic carcinoma, telangiectasia-like carcinoma, transitional cell carcinoma, carcinoma tuberosum, nodular carcinoma, verrucous carcinoma, or choriocarcinoma.

[0145] As used herein, the terms "metastasis," "metastatic," and "metastatic cancer" can be used interchangeably and refer to the spread of a proliferative disease or disorder, e.g., cancer, from one organ or another non-adjacent organ or part of the body. "Metastatic cancer" is also referred to as "stage IV cancer." Cancer begins at a site of origin, e.g., the breast, called a primary tumor, e.g., primary breast cancer. Some cancer cells in the primary tumor or site of origin acquire the ability to penetrate and invade surrounding normal tissue in the local area and / or penetrate the walls of the lymphatic or vascular system and circulate through the system to other parts and tissues of the body. Clinically detectable secondary tumors formed from cancer cells of the primary tumor are called metastatic or secondary tumors. When cancer cells metastasize, the metastatic tumor and its cells are presumed to be similar to those of the original tumor. Thus, if lung cancer metastasizes to the breast, the secondary tumor in the breast site will consist of abnormal lung cells, not abnormal breast cells. The secondary tumor in the breast is called metastatic lung cancer. Therefore, the term metastatic cancer refers to a disease in which a subject has or has had a primary tumor, and has one or more secondary tumors.The term non-metastatic cancer or a subject with non-metastatic cancer refers to a disease in which a subject has a primary tumor but does not have one or more secondary tumors.For example, metastatic lung cancer refers to a disease in a subject who has or has had a history of a primary lung tumor, and has one or more secondary tumors, for example, in a second location or multiple locations in the breast.

[0146] The term "skin metastasis" or "skin metastasis" refers to secondary malignant cell growth in the skin, where the malignant cells originate from a primary cancer site (e.g., breast). In skin metastasis, cancerous cells from the primary cancer site migrate to the skin, where they can divide and cause lesions. Skin metastasis can result from the migration of cancer cells from a breast cancer tumor to the skin.

[0147] The term "visceral metastasis" refers to secondary malignant cell growth in an internal organ (e.g., heart, lung, liver, pancreas, intestine) or body cavity (e.g., pleura, peritoneum), where the malignant cells originate from the primary cancer site (e.g., head and neck, liver, breast). In visceral metastasis, cancerous cells from the primary cancer site migrate to an internal organ, where they may divide and cause lesions. Visceral metastasis can result from the migration of cancer cells from a liver cancer tumor or a head and neck tumor to an internal organ.

[0148] As used herein, the term "LPAR1-associated disease" refers to any disease or condition caused by aberrant activity or signaling of LPAR1. In embodiments, the LPAR1-associated disease is a neurodegenerative disease. In embodiments, the LPAR1-associated disease is an inflammatory disease. In embodiments, the LPAR1-associated disease is post-hemorrhagic encephalitis. In embodiments, the LPAR1-associated disease is a demyelinating disease. In embodiments, the LPAR1-associated disease is multiple sclerosis. In embodiments, the LPAR1-associated disease is a fibrotic disease. In embodiments, the LPAR1-associated disease is pulmonary fibrosis. In embodiments, the LPAR1-associated disease is idiopathic pulmonary fibrosis. In embodiments, the LPAR1-associated disease is cancer. In embodiments, the LPAR1-associated disease is glioblastoma.

[0149] The term "drug" is used according to its ordinary meaning to refer to a substance that has a physiological effect (e.g., a beneficial effect, useful for treating a subject) when introduced into or onto a subject (e.g., into or onto the body of a subject or patient). The drug moiety is the radical of the drug.

[0150] A "detectable agent," "detectable compound," "detectable label," or "detectable moiety" is a substance (e.g., an element), molecule, or composition detectable by spectroscopic, photochemical, biochemical, immunochemical, chemical, magnetic resonance imaging, or other physical means. For example, detectable agents include: 18 F, 32 P, 33 P, 45 Ti, 47 Sc, 52 Fe, 59 Fe, 62 Cu, 64 Cu, 67 Cu, 67 Ga, 68 Ga, 77 As, 86 Y, 90 Y, 89 Sr, 89 Zr, 94 Tc, 94 Tc, 99m Tc, 99 Mo, 105 Pd, 105 Rh, 111 Ag, 111 In, 123 I, 124 I, 125 I, 131 I, 142 Pr, 143 Pr, 149 Pm, 153 Sm, 154-1581 Gd, 161 Tb, 166 Dy, 166 Ho, 169 Er, 175 Lu, 177 Lu, 186 Re, 188 Re, 189 Re, 194 Ir, 198 Au, 199 Au, 211 At, 211 Pb, 212 Bi, 212 Pb, 213 Bi, 223 Ra, 225Ac, Cr, V, Mn, Fe, Co, Ni, Cu, La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, 32 P, fluorophores (e.g., fluorescent dyes), modified oligonucleotides (e.g., portions described in PCT / US2015 / 022063, incorporated herein by reference), electron-dense reagents, enzymes (e.g., commonly used in ELISA), biotin, digoxigenin, paramagnetic molecules, paramagnetic nanoparticles, ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, USPIO nanoparticle aggregates, superparamagnetic iron oxide ("superparamagnetic iron oxide (SPIO") nanoparticles, SPIO nanoparticle aggregates, single-crystal iron oxide nanoparticles, single-crystal iron oxide, nanoparticle contrast agents, liposomes, or other delivery vehicles containing gadolinium chelate ("Gd-chelate") molecules, gadolinium, radioisotopes, radionuclides (e.g., carbon-11, nitrogen-13, oxygen-15, fluorine-18, rubidium-82), fluorodeoxyglucose (e.g., fluorine-18 labeled), any gamma-emitting radionuclide, positron-emitting radionuclide, radiolabeled glucose, radiolabeled water, radiolabeled ammonia, biocolloids, microbubbles (e.g., microbubble shells comprising albumin, galactose, lipids, and / or polymers; air, These include heavy gases, perfluorocarbons, nitrogen, octafluoropropane, perflexane lipid microspheres, microbubble gas cores including perflutren, etc., iodinated contrast agents (e.g., iohexol, iodixanol, ioversol, iopamidol, ioxilan, iopromide, diatrizoate, metrizoate, ioxaglate), barium sulfate, thorium dioxide, gold, gold nanoparticles, gold nanoparticle aggregates, fluorophores, two-photon fluorophores, or haptens, and proteins or other entities that can be made detectable by, for example, incorporating a radioactive label into a peptide or an antibody that specifically reacts with a target peptide.

[0151] Radioactive substances (e.g., radioisotopes) that may be used as imaging and / or labeling agents according to embodiments of the present disclosure include: 18 F, 32 P, 33 P, 45 Ti, 47 Sc, 52 Fe, 59 Fe, 62 Cu, 64 Cu, 67 Cu, 67 Ga, 68 Ga, 77 As, 86 Y, 90 Y, 89 Sr, 89 Zr, 94 Tc, 94 Tc, 99m Tc, 99 Mo, 105 Pd, 105 Rh, 111 Ag, 111 In, 123 I, 124 I, 125 I, 131 I, 142 Pr, 143 Pr, 149 Pm, 153 Sm, 154-1581 Gd, 161 Tb, 166 Dy, 166 Ho, 169 Er, 175 Lu, 177 Lu, 186 Re, 188 Re, 189 Re, 194 Ir, 198 Au, 199 Au, 211 At, 211 Pb, 212 Bi, 212 Pb, 213 Bi, 223 Ra, and 225Paramagnetic ions that can be used as additional imaging agents in accordance with embodiments of the present disclosure include, but are not limited to, ions of transition metals and lanthanide metals (e.g., metals with atomic numbers 21-29, 42, 43, 44, or 57-71). These metals include ions of Cr, V, Mn, Fe, Co, Ni, Cu, La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu.

[0152] "Pharmaceutically acceptable excipients" and "pharmaceutically acceptable carriers" refer to substances that aid in the administration and absorption of an active agent by a subject and can be included in the compositions of the present invention without causing significant adverse toxic effects to the patient. Non-limiting examples of pharmaceutically acceptable excipients include water, NaCl, normal saline, lactated Ringer's solution, normal sucrose, normal glucose, binders, fillers, disintegrants, lubricants, coating agents, sweeteners, flavoring agents, saline (such as Ringer's solution), alcohol, oils, gelatin, carbohydrates such as lactose, amylose, or starch, fatty acid esters, hydroxymethylcellulose, polyvinylpyrrolidine, and coloring agents. Such preparations can be sterilized and, if desired, mixed with auxiliary substances such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring agents, and / or aromatic substances that do not adversely react with the compounds of the present invention. Those skilled in the art will recognize that other pharmaceutical excipients are useful in the present invention.

[0153] The term "preparation" is intended to include formulations of an active compound with an encapsulating material as a carrier to provide a capsule in which the active ingredient, with or without other carriers, is surrounded by the carrier and is therefore associated with the carrier. Also included are cachets and lozenges. Tablets, powders, capsules, pills, cachets, and lozenges can be used as solid dosage forms suitable for oral administration.

[0154] As used herein, the term "about" refers to a range of values ​​that includes the particular value and that one of ordinary skill in the art would consider reasonably similar to the particular value. In embodiments, about refers to within a standard deviation using measurements generally accepted in the art. In embodiments, about refers to a range that covers + / - 10% of the particular value. In embodiments, about includes the particular value.

[0155] As used herein, the term "administering" is used according to its simple and ordinary meaning and refers to oral administration, administration as a suppository, topical contact, intravenous, intraperitoneal, intramuscular, intralesional, intrathecal, intranasal, or subcutaneous administration, or implantation of a sustained-release device, e.g., a mini-osmotic pump, to a subject. Administration is by any route, including parenteral and transmucosal (e.g., buccal, sublingual, palatal, gingival, nasal, vaginal, rectal, or transdermal). Parenteral administration includes, for example, intravenous, intramuscular, intraarteriolar, intradermal, subcutaneous, intraperitoneal, intraventricular, and intracranial administration. Other modes of delivery include, but are not limited to, the use of liposomal formulations, intravenous infusion, transdermal patches, and the like. "Coadministration" means that the compositions described herein are administered simultaneously with, immediately before, or immediately after the administration of one or more additional therapies, e.g., cancer therapies such as chemotherapy, hormonal therapy, radiation therapy, or immunotherapy. The compounds of the present invention can be administered alone or simultaneously to a patient. Co-administration is intended to include simultaneous or sequential administration of compounds (more than one compound) individually or in combination. Thus, the preparations can also be combined with other active agents, if desired (e.g., to reduce metabolic degradation). The compositions of the present invention can be delivered transdermally or topically, and can be formulated as applicator sticks, solutions, suspensions, emulsions, gels, creams, ointments, nanoparticles, pastes, jellies, paints, powders, and aerosols.

[0156] The compounds described herein can be used in combination with each other, in combination with other active agents known to be useful in treating diseases associated with cells expressing disease-associated cellular components, or in combination with adjunct agents that may not be effective alone but may contribute to the effectiveness of the active agent.

[0157] In some embodiments, co-administration includes administering one active agent within 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, or 24 hours of a second active agent. Co-administration includes administering two active agents simultaneously, near simultaneously (e.g., within about 1, 5, 10, 15, 20, or 30 minutes of each other), or sequentially in any order. In some embodiments, co-administration can be achieved by co-formulation, i.e., preparing a single pharmaceutical composition containing both active agents. In other embodiments, the active agents can be formulated separately. In another embodiment, the active agent and / or adjunct agent may be linked or conjugated to each other.

[0158] In therapeutic use for the treatment of disease, the compounds utilized in the pharmaceutical compositions of the present invention may be administered at an initial dosage of about 0.001 mg / kg to about 1000 mg / kg daily. Daily dose ranges of about 0.01 mg / kg to about 500 mg / kg, or about 0.1 mg / kg to about 200 mg / kg, or about 1 mg / kg to about 100 mg / kg, or about 10 mg / kg to about 50 mg / kg can be used. However, dosages may vary depending on the requirements of the patient, the severity of the condition being treated, and the compound or drug being used. For example, dosages can be empirically determined taking into account the type and stage of disease (e.g., multiple sclerosis, fibrotic disease, encephalitis, or cancer) diagnosed in a particular patient. In accordance with the present invention, the dose administered to a patient should be sufficient to effect a beneficial therapeutic response in the patient over time. The size of the dose will also be determined by the existence, nature, and extent of any adverse side effects associated with the administration of the compound in a particular patient. The determination of suitable dosage for specific situation is within the ability of those skilled in the art.Generally, treatment is started with a smaller dosage that is less than the optimal dose of compound.Then, dosage is gradually increased until it reaches the optimal effect under the circumstances.For convenience, if desired, total daily dosage can be divided and administered in portions throughout the day.

[0159] In the context of a substance or substance activity or function related to a disease (e.g., a protein-related disease, a disease associated with a cellular component), the term "related to" or "associated with" means that the substance or substance activity or function causes (in whole or in part) the disease (e.g., multiple sclerosis, a fibrotic disease, encephalitis, or cancer) or causes (in whole or in part) a symptom of the disease, or that a symptom of the disease can be treated by modulating (e.g., inhibiting or activating) the substance (e.g., a cellular component). As used herein, something that is described as associated with a disease, if it is a causative agent, can be a target for treating the disease.

[0160] As used herein, the term "aberrant" refers to something that is different from normal. When used to describe enzyme activity, abnormal refers to activity that is greater than or less than the average of a normal control or normal, non-disease control sample. Abnormal activity can also refer to an amount of activity that results in disease, and restoring the abnormal activity to a normal or non-disease-associated amount (e.g., by administering a compound or using the methods described herein) results in a reduction of the disease or one or more symptoms.

[0161] The term "isolated," when applied to a nucleic acid or protein, means that the nucleic acid or protein is essentially free from other cellular components with which it is associated in its natural state. It can be, for example, in a homogeneous state, either a dry or aqueous solution. Purity and homogeneity are typically determined using analytical chemistry techniques such as polyacrylamide gel electrophoresis or high performance liquid chromatography. A protein present as the predominant species in a preparation is substantially purified.

[0162] The term "amino acid" refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function similarly to naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those that are later modified, such as hydroxyproline, γ-carboxyglutamate, and O-phosphoserine. Amino acid analogs refer to compounds that have the same basic chemical structure as a naturally occurring amino acid, i.e., an α-carbon bonded to a hydrogen, a carboxyl group, an amino group, and an R group, such as homoserine, norleucine, methionine sulfoxide, and methionine methylsulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refer to compounds that have a structure that differs from the general chemical structure of an amino acid, but that function similarly to a naturally occurring amino acid. The terms "non-naturally occurring amino acid" and "unnatural amino acid" refer to amino acid analogs, synthetic amino acids, and amino acid mimetics that are not found in nature.

[0163] Amino acids may be referred to herein by either their commonly known three letter symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Similarly, nucleotides may be referred to by their commonly accepted single-letter codes.

[0164] The terms "polypeptide," "peptide," and "protein" are used interchangeably herein to refer to a polymer of amino acid residues, which may, in embodiments, be conjugated to moieties not composed of amino acids. The term applies to amino acid polymers in which one or more amino acid residues are artificial chemical mimetics of corresponding naturally occurring amino acids, as well as to naturally occurring and non-naturally occurring amino acid polymers.

[0165] The "position" of an amino acid or nucleotide base is indicated by a number sequentially identifying each amino acid (or nucleotide base) in a reference sequence based on its position relative to the N-terminus (or 5'-terminus). Due to deletions, insertions, truncations, fusions, etc., which must be considered when determining optimal alignment, the number of amino acid residues in a test sequence, determined simply by counting from the N-terminus, is generally not necessarily the same as the number of corresponding positions in the reference sequence. For example, if a variant has a deletion compared to the aligned reference sequence, there will be no amino acid in the variant corresponding to a position in the reference sequence at the site of the deletion. If there is an insertion in the aligned reference sequence, the insertion will not correspond to a numbered amino acid position in the reference sequence. In the case of a truncation or fusion, there may be a stretch of amino acids in either the reference sequence or the aligned sequence that does not correspond to any amino acid in the corresponding sequence.

[0166] When used in the context of the numbering of a given amino acid or polynucleotide sequence, the term "numbered with reference to" or "corresponding to" refers to the numbering of residues in a particular reference sequence when the given amino acid or polynucleotide sequence is compared to the reference sequence.

[0167] The term "protein complex" is used according to its plain and ordinary meaning and refers to a protein associated with an additional substance (e.g., another protein, a protein subunit, or a compound). A protein complex typically has a defined quaternary structure. The association between the protein and the additional substance may be a covalent bond. In embodiments, the association between the protein and the additional substance (e.g., a compound) is via a non-covalent interaction. In embodiments, a protein complex refers to a group of two or more polypeptide chains. The proteins in a protein complex are linked by non-covalent protein-protein interactions. A non-limiting example of a protein complex is the proteasome.

[0168] The term "lysophosphatidic acid receptor" or "LPAR" refers to one or more of a family of G protein-coupled receptors for lysophosphatidic acid (LPA). In embodiments, LPARs include LPAR1, LPAR2, LPAR3, LPAR4, LPAR5, and LPAR6.

[0169] The term "lysophosphatidic acid receptor 1" or "LPAR1" refers to a G protein-coupled receptor (including homologs, isoforms, and functional fragments thereof) that binds the lipid signaling molecule lysophosphatidic acid (LPA). This term includes any recombinant or native form of an LPAR1 variant thereof that maintains LPAR1 activity (e.g., within the range of at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 100% activity compared to wild-type LPAR1). In embodiments, the LPAR1 protein encoded by the LPAR1 gene has an amino acid sequence set forth in or corresponding to Entrez 1902, UniProt Q92633, RefSeq(protein) NP_001392.2, or RefSeq(protein) NP_476500.1. In an embodiment, the LPAR1 gene has the nucleic acid sequence set forth in RefSeq(mRNA)NM_001401.3 or RefSeq(mRNA)NM_057159.2. In an embodiment, the amino acid sequence or nucleic acid sequence is a sequence known at the time of filing this application.

[0170] "Selective" or "selectivity," etc., with respect to a compound or agent, refers to the ability of a compound or agent to preferentially increase or decrease the activity of a particular molecular target (e.g., a protein, enzyme, etc.) over one or more different molecular targets (e.g., a compound having selectivity for lysophosphatidic acid receptor 1 (LPAR1) preferentially inhibits LPAR1 over other lysophosphatidic acid receptors). In embodiments, a "lysophosphatidic acid receptor 1-selective compound" or an "LPAR1-selective compound" refers to a compound (e.g., a compound described herein) that has selectivity for lysophosphatidic acid receptor 1 (LPAR1). In embodiments, a compound (e.g., a compound described herein) is about 5-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, or about 100-fold selective for lysophosphatidic acid receptor 1 (LPAR1) over one or more of LPAR2, LPAR3, LPAR4, LPAR5, or LPAR6. In embodiments, a compound (e.g., a compound described herein) is at least 5-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, or at least 100-fold selective for lysophosphatidic acid receptor 1 (LPAR1) over one or more of LPAR2, LPAR3, LPAR4, LPAR5, or LPAR6.

[0171] II. Compounds In one aspect, a compound is provided having the formula:

[0172] [ka]

[0173] L 1 is a bond or a substituted or unsubstituted alkylene (e.g., C1-C8, C1-C6, C1-C4, or C1-C2).

[0174] R 1 is substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2).

[0175] W 2 is N or C(R 2 )

[0176] R 2 is hydrogen, halogen, -CX 2 3. -CHX 2 2. -CH2X 2 , -OCX 2 3. -OCH2X 2 , -OCHX 2 2, -CN, -SO n2 R 2D , -SO v2 NR 2A R 2B , -NR 2C NR 2A R 2B , -ONR 2A R 2B , -NHC(O)NR 2C NR 2A R 2B , -NHC(O)NR 2A R 2B , -N(O) m2 , -NR 2A R 2B , -C(O)R 2C , -C(O)OR 2C , -C(O)NR 2A R 2B , -OR 2D , -SR 2D , -NR 2A SO2R 2D , -NR 2A C(O)R 2C , -NR 2A C(O)OR 2C , -NR 2A OR 2C , -SF5, -N3, substituted or unsubstituted alkyl (e.g., C1 to C8, C1 to C6, C1 to C4, or C1 to C2), substituted or unsubstituted heteroalkyl (e.g., 2 to 8 members, 2 to 6 members, 4 to 6 members, 2 to 3 members, or 4 to 5 members), substituted or unsubstituted cycloalkyl (e.g., C3 to C8, C3 to C6, C4 to C6, or C5 to C6), substituted or unsubstituted heterocycloalkyl (e.g., 3 to 8 members, 3 to 6 members, 4 to 6 members, 4 to 5 members, or 5 to 6 members), substituted or unsubstituted aryl (e.g., C6 to C10 or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered).

[0177] R 3 is hydrogen, halogen, -CX 3 3. -CHX 3 2. -CH2X 3 , -OCX 3 3. -OCH2X 3 , -OCHX 3 2, -CN, -SO n3 R 3D , -SO v3 NR 3A R 3B , -NR 3C NR 3A R 3B , -ONR 3A R 3B , -NHC(O)NR 3C NR 3A R 3B , -NHC(O)NR 3A R 3B , -N(O) m3 , -NR 3A R 3B , -C(O)R 3C , -C(O)OR 3C , -C(O)NR 3A R 3B , -OR 3D , -SR 3D , -NR 3A SO2R 3D , -NR 3A C(O)R 3C , -NR 3A C(O)OR 3C , -NR 3A OR 3C, -SF5, -N3, substituted or unsubstituted alkyl (e.g., C1 to C8, C1 to C6, C1 to C4, or C1 to C2), substituted or unsubstituted heteroalkyl (e.g., 2 to 8 members, 2 to 6 members, 4 to 6 members, 2 to 3 members, or 4 to 5 members), substituted or unsubstituted cycloalkyl (e.g., C3 to C8, C3 to C6, C4 to C6, or C5 to C6), substituted or unsubstituted heterocycloalkyl (e.g., 3 to 8 members, 3 to 6 members, 4 to 6 members, 4 to 5 members, or 5 to 6 members), substituted or unsubstituted aryl (e.g., C6 to C 10 or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered).

[0178] W 4 is N or C(R 4 )

[0179] R 4 is hydrogen, halogen, -CX 4 3. -CHX 4 2. -CH2X 4 , -OCX 4 3. -OCH2X 4 , -OCHX 4 2, -CN, -SO n4 R 4D , -SO v4 NR 4A R 4B , -NR 4C NR 4A R 4B , -ONR 4A R 4B , -NHC(O)NR 4C NR 4A R 4B , -NHC(O)NR 4A R 4B , -N(O) m4 , -NR 4A R 4B , -C(O)R 4C , -C(O)OR 4C , -C(O)NR 4A R 4B , -OR 4D , -SR 4D , -NR 4A SO2R 4D, -NR 4A C(O)R 4C , -NR 4A C(O)OR 4C , -NR 4A OR 4C , -SF5, -N3, substituted or unsubstituted alkyl (e.g., C1 to C8, C1 to C6, C1 to C4, or C1 to C2), substituted or unsubstituted heteroalkyl (e.g., 2 to 8 members, 2 to 6 members, 4 to 6 members, 2 to 3 members, or 4 to 5 members), substituted or unsubstituted cycloalkyl (e.g., C3 to C8, C3 to C6, C4 to C6, or C5 to C6), substituted or unsubstituted heterocycloalkyl (e.g., 3 to 8 members, 3 to 6 members, 4 to 6 members, 4 to 5 members, or 5 to 6 members), substituted or unsubstituted aryl (e.g., C6 to C 10 or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered).

[0180] W 5 is N or C(R 5 )

[0181] R 5 is hydrogen, halogen, -CX 5 3. -CHX 5 2. -CH2X 5 , -OCX 5 3. -OCH2X 5 , -OCHX 5 2, -CN, -SO n5 R 5D , -SO v5 NR 5A R 5B , -NR 5C NR 5A R 5B , -ONR 5A R 5B , -NHC(O)NR 5C NR 5A R 5B , -NHC(O)NR 5A R 5B , -N(O) m5 , -NR 5A R 5B , -C(O)R 5C , -C(O)OR 5C, -C(O)NR 5A R 5B , -OR 5D , -SR 5D , -NR 5A SO2R 5D , -NR 5A C(O)R 5C , -NR 5A C(O)OR 5C , -NR 5A OR 5C , -SF5, -N3, substituted or unsubstituted alkyl (e.g., C1 to C8, C1 to C6, C1 to C4, or C1 to C2), substituted or unsubstituted heteroalkyl (e.g., 2 to 8 members, 2 to 6 members, 4 to 6 members, 2 to 3 members, or 4 to 5 members), substituted or unsubstituted cycloalkyl (e.g., C3 to C8, C3 to C6, C4 to C6, or C5 to C6), substituted or unsubstituted heterocycloalkyl (e.g., 3 to 8 members, 3 to 6 members, 4 to 6 members, 4 to 5 members, or 5 to 6 members), substituted or unsubstituted aryl (e.g., C6 to C 10 or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered).

[0182] R 2 and R 3 The substituents may be optionally linked to form a substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), a substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), a substituted or unsubstituted aryl (e.g., C6-C 10 or phenyl), or substituted or unsubstituted heteroaryl (eg, 5-10 membered, 5-9 membered, or 5-6 membered).

[0183] R 3 and R 4 The substituents may be optionally linked to form a substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), a substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), a substituted or unsubstituted aryl (e.g., C6-C10 or phenyl), or substituted or unsubstituted heteroaryl (eg, 5-10 membered, 5-9 membered, or 5-6 membered).

[0184] R 4 and R 5 The substituents may be optionally linked to form a substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), a substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), a substituted or unsubstituted aryl (e.g., C6-C 10 or phenyl), or substituted or unsubstituted heteroaryl (eg, 5-10 membered, 5-9 membered, or 5-6 membered).

[0185] W 6 is N or C(R 6 )

[0186] R 6 is hydrogen, halogen, -CX 6 3. -CHX 6 2. -CH2X 6 , -OCX 6 3. -OCH2X 6 , -OCHX 6 2, -CN, -SO n6 R 6D , -SO v6 NR 6A R 6B , -NR 6C NR 6A R 6B , -ONR 6A R 6B , -NHC(O)NR 6C NR 6A R 6B , -NHC(O)NR 6A R 6B , -N(O) m6 , -NR 6A R 6B , -C(O)R 6C , -C(O)OR 6C , -C(O)NR 6A R 6B , -OR 6D , -SR6D , -NR 6A SO2R 6D , -NR 6A C(O)R 6C , -NR 6A C(O)OR 6C , -NR 6A OR 6C , -SF5, -N3, substituted or unsubstituted alkyl (e.g., C1 to C8, C1 to C6, C1 to C4, or C1 to C2), substituted or unsubstituted heteroalkyl (e.g., 2 to 8 members, 2 to 6 members, 4 to 6 members, 2 to 3 members, or 4 to 5 members), substituted or unsubstituted cycloalkyl (e.g., C3 to C8, C3 to C6, C4 to C6, or C5 to C6), substituted or unsubstituted heterocycloalkyl (e.g., 3 to 8 members, 3 to 6 members, 4 to 6 members, 4 to 5 members, or 5 to 6 members), substituted or unsubstituted aryl (e.g., C6 to C 10 or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered).

[0187] W 7 is N, N + -O - , or C(R 7 )

[0188] R 7 is hydrogen, halogen, -CX 7 3. -CHX 7 2. -CH2X 7 , -OCX 7 3. -OCH2X 7 , -OCHX 7 2, -CN, -SO n7 R 7D , -SO v7 NR 7A R 7B , -NR 7C NR 7A R 7B , -ONR 7A R 7B , -NHC(O)NR 7C NR 7A R 7B , -NHC(O)NR 7A R 7B , -N(O)m7 , -NR 7A R 7B , -C(O)R 7C , -C(O)OR 7C , -C(O)NR 7A R 7B , -OR 7D , -SR 7D , -NR 7A SO2R 7D , -NR 7A C(O)R 7C , -NR 7A C(O)OR 7C , -NR 7A OR 7C , -SF5, -N3, substituted or unsubstituted alkyl (e.g., C1 to C8, C1 to C6, C1 to C4, or C1 to C2), substituted or unsubstituted heteroalkyl (e.g., 2 to 8 members, 2 to 6 members, 4 to 6 members, 2 to 3 members, or 4 to 5 members), substituted or unsubstituted cycloalkyl (e.g., C3 to C8, C3 to C6, C4 to C6, or C5 to C6), substituted or unsubstituted heterocycloalkyl (e.g., 3 to 8 members, 3 to 6 members, 4 to 6 members, 4 to 5 members, or 5 to 6 members), substituted or unsubstituted aryl (e.g., C6 to C 10 or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered).

[0189] R 8 are independently halogen, -CX 8 3. -CHX 8 2. -CH2X 8 , -OCX 8 3. -OCH2X 8 , -OCHX 8 2, -CN, -SO n8 R 8D , -SO v8 NR 8A R 8B , -NR 8C NR 8A R 8B , -ONR 8A R 8B , -NHC(O)NR 8C NR 8A R 8B , -NHC(O)NR8A R 8B , -N(O) m8 , -NR 8A R 8B , -C(O)R 8C , -C(O)OR 8C , -C(O)NR 8A R 8B , -OR 8D , -SR 8D , -NR 8A SO2R 8D , -NR 8A C(O)R 8C , -NR 8A C(O)OR 8C , -NR 8A OR 8C , -SF5, -N3, substituted or unsubstituted alkyl (e.g., C1 to C8, C1 to C6, C1 to C4, or C1 to C2), substituted or unsubstituted heteroalkyl (e.g., 2 to 8 members, 2 to 6 members, 4 to 6 members, 2 to 3 members, or 4 to 5 members), substituted or unsubstituted cycloalkyl (e.g., C3 to C8, C3 to C6, C4 to C6, or C5 to C6), substituted or unsubstituted heterocycloalkyl (e.g., 3 to 8 members, 3 to 6 members, 4 to 6 members, 4 to 5 members, or 5 to 6 members), substituted or unsubstituted aryl (e.g., C6 to C 10 or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered), and two R 8 The substituents may be optionally linked to form a substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), a substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), a substituted or unsubstituted aryl (e.g., C6-C 10 or phenyl), or substituted or unsubstituted heteroaryl (eg, 5-10 membered, 5-9 membered, or 5-6 membered).

[0190] R 9is a substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6) or a substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered).

[0191] R 2A , R 2B , R 2C , R 2D , R 3A , R 3B , R 3C , R 3D , R 4A , R 4B , R 4C , R 4D , R 5A , R 5B , R 5C , R 5D , R 6A , R 6B , R 6C , R 6D , R 7A , R 7B , R 7C , R 7D , R 8A , R 8B , R 8C , and R 8D are independently hydrogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl( For example, C1 to C8, C1 to C6, C1 to C4, or C1 to C2), substituted or unsubstituted heteroalkyl (for example, 2 to 8 members, 2 to 6 members, 4 to 6 members, 2 to 3 members, or 4 to 5 members), substituted or unsubstituted cycloalkyl (for example, C3 to C8, C3 to C6, C4 to C6, or C5 to C6), substituted or unsubstituted heterocycloalkyl (for example, 3 to 8 members, 3 to 6 members, 4 to 6 members, 4 to 5 members, or 5 to 6 members), substituted or unsubstituted aryl (for example, C6 to C 10or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered), and R 2A and R 2B The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered) or a substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered), and R 3A and R 3B The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered) or a substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered), and R 4A and R 4B The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered) or a substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered), and R 5A and R 5B The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered) or a substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered), and R 6A and R 6B The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered) or a substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered), and R 7A and R 7BThe substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered) or a substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered), and R 8A and R 8B The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered) or a substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered).

[0192] X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , and X 8 is independently -F, -Cl, -Br, or -I.

[0193] The symbols n2, n3, n4, n5, n6, n7, and n8 are independently integers of 0 to 4.

[0194] The symbols m2, m3, m4, m5, m6, m7, m8, v2, v3, v4, v5, v6, v7, and v8 are independently 1 or 2.

[0195] The symbol z8 is an integer of 0 to 3.

[0196] In embodiments, the compound has the formula:

[0197] [ka] L 1 , R 1 , R 6 , R 8 , z8, and R 9 as described herein, including the embodiments.

[0198] In embodiments, the compound has the formula:

[0199] [ka] L 1 , R 1 , R 6 , R 8 , z8, and R 9 as described herein, including the embodiments.

[0200] In embodiments, the compound has the formula:

[0201] [ka] L 1 , R 1 , R 6 , R 8 , z8, and R 9 as described herein, including the embodiments.

[0202] In embodiments, the compound has the formula:

[0203] [ka] L 1 , R 1 , R 6 , R 8 , z8, and R 9 as described herein, including the embodiments.

[0204] In embodiments, the compound has the formula:

[0205] [ka] L 1 , R 1 , R 7 , R 8 , z8, and R 9 as described herein, including the embodiments.

[0206] In embodiments, the compound has the formula:

[0207] [ka] L 1 , R 1 , R 7 , R 8 , z8, and R 9 as described herein, including the embodiments.

[0208] In embodiments, the compound has the formula:

[0209] [ka] L 1 , R 1 , R 7 , R 8 , z8, and R 9 as described herein, including the embodiments.

[0210] In embodiments, the compound has the formula:

[0211] [ka] L 1 , R 1 , R 6 , R 7 , z8, and R 9 as described herein, including the embodiments.

[0212] In embodiments, the compound has the formula:

[0213] [ka] L 1 , R 1 , R 8 , z8, and R 9as described herein, including the embodiments.

[0214] In embodiments, the compound has the formula:

[0215] [ka] L 1 , R 1 , R 8 , z8, and R 9 as described herein, including the embodiments.

[0216] In embodiments, the compound has the formula:

[0217] [ka] L 1 , R 1 , R 8 , z8, and R 9 as described herein, including the embodiments.

[0218] In embodiments, the compound has the formula:

[0219] [ka] L 1 , R 1 , R 8 , z8, and R 9 as described herein, including the embodiments.

[0220] In embodiments, the compound has the formula:

[0221] [ka] L 1 , R 1 , R 6 , R 7 , R 8 , z8, and R9 as described herein, including the embodiments.

[0222] In embodiments, the compound has the formula:

[0223] [ka] L 1 , R 1 , R 6 , R 7 , R 8 , z8, and R 9 as described herein, including the embodiments.

[0224] In embodiments, the compound has the formula:

[0225] [ka] L 1 , R 1 , R 6 , R 7 , R 8 , z8, and R 9 as described herein, including the embodiments.

[0226] In embodiments, the compound has the formula:

[0227] [ka] L 1 , R 1 , R 6 , R 7 , R 8 , z8, and R 9 as described herein, including the embodiments.

[0228] In embodiments, the substitution R 1 (e.g., substituted alkyl) is substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 1When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 1 When substituted, R is substituted with at least one substituent. 1 When substituted, R is substituted with at least one size-limited substituent. 1 When substituted, it is substituted with at least one lower substituent.

[0229] In embodiments, R 1 is unsubstituted alkyl. In embodiments, R 1 is an unsubstituted C2-C5 alkyl. In embodiments, R 1 is an unsubstituted C alkyl. In embodiments, R 1 is unsubstituted ethyl. In embodiments, R 1 is an unsubstituted C alkyl. In embodiments, R 1 is unsubstituted propyl. In embodiments, R 1 is unsubstituted n-propyl. In embodiments, R 1 is unsubstituted isopropyl (i.e., isopropyl). In embodiments, R 1 is an unsubstituted C4 alkyl. In embodiments, R 1 is unsubstituted butyl. In embodiments, R 1 is unsubstituted n-butyl. In embodiments, R 1 is unsubstituted isobutyl. In embodiments, R 1 is unsubstituted tert-butyl. In embodiments, R 1 is an unsubstituted C alkyl. In embodiments, R 1 is unsubstituted pentyl. In embodiments, R 1 is unsubstituted n-pentyl. In embodiments, R 1 is unsubstituted tert-pentyl. In embodiments, R 1 is unsubstituted neopentyl. In embodiments, R 1 is unsubstituted isopentyl. In embodiments, R 1is unsubstituted sec-pentyl. In embodiments, R 1 is unsubstituted 3-pentyl. In embodiments, R 1 is unsubstituted sec-isopentyl. In embodiments, R 1 is unsubstituted 2-methylbutyl.

[0230] In an embodiment, W 2 is N. In an embodiment, W 2 is C(R 2 In an embodiment, W 2 is CH.

[0231] In an embodiment, W 4 is N. In an embodiment, W 4 is C(R 4 In an embodiment, W 4 is CH.

[0232] In an embodiment, W 5 is N. In an embodiment, W 5 is C(R 5 In an embodiment, W 5 is CH.

[0233] In one aspect, a compound is provided having the formula:

[0234] [ka] L 1 , R 2 , R 3 , R 4 , R 5 , W 6 , W 7 , R 8 , z8, and R 9 is as described herein, including embodiments. 6 or W 7 At least one of the W is N. 6 is C(R 6 ) or W 7is C(R 7 ), then R 10 is not hydrogen. W 6 and W 7 If both are N, then R 3 is not -S(O)2CH3. W 6 is CH and W 7 If is N, then -L 1 -R 9 teeth,

[0235] [ka] isn't it.

[0236] R 10 is hydrogen, halogen, -CX 10 3. -CHX 10 2. -CH2X 10 , -OCX 10 3. -OCH2X 10 , -OCHX 10 2, -CN, -SO n10 R 10D , -SO v10 NR 10A R 10B , -NR 10C NR 10A R 10B , -ONR 10A R 10B , -NHC(O)NR 10C NR 10A R 10B , -NHC(O)NR 10A R 10B , -N(O) m10 , -NR 10A R 10B , -C(O)R 10C , -C(O)OR 10C , -C(O)NR 10A R 10B , -OR 10D , -SR 10D , -NR 10A SO2R 10D , -NR 10A C(O)R 10C , -NR 10A C(O)OR 10C , -NR 10AOR 10C , -SF5, -N3, substituted or unsubstituted alkyl (e.g., C1 to C8, C1 to C6, C1 to C4, or C1 to C2), substituted or unsubstituted heteroalkyl (e.g., 2 to 8 members, 2 to 6 members, 4 to 6 members, 2 to 3 members, or 4 to 5 members), substituted or unsubstituted cycloalkyl (e.g., C3 to C8, C3 to C6, C4 to C6, or C5 to C6), substituted or unsubstituted heterocycloalkyl (e.g., 3 to 8 members, 3 to 6 members, 4 to 6 members, 4 to 5 members, or 5 to 6 members), substituted or unsubstituted aryl (e.g., C6 to C 10 or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered).

[0237] R 10 and R 2 The substituents may be optionally linked to form a substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), a substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), a substituted or unsubstituted aryl (e.g., C6-C 10 or phenyl), or substituted or unsubstituted heteroaryl (eg, 5-10 membered, 5-9 membered, or 5-6 membered).

[0238] R 10A , R 10B , R 10C , and R 10Dare independently hydrogen, -CCl3, -CBr3, -CF3, -CI3, CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl( For example, C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted heteroalkyl (for example, 2-8 membered, 2-6 membered, 4-6 membered, 2-3 membered, or 4-5 membered), substituted or unsubstituted cycloalkyl (for example, C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyl (for example, 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), substituted or unsubstituted aryl (for example, C6-C 10 or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered), and R 10A and R 10B The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered) or a substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered).

[0239] X 10 is independently -F, -Cl, -Br, or -I.

[0240] The symbol n10 is an integer of 0-4.

[0241] The symbols m10 and v10 are independently 1 or 2.

[0242] In embodiments, the compound has the formula:

[0243] [ka] L1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 8 , z8, R 9 , and R 10 as described herein, including the embodiments.

[0244] In embodiments, the compound has the formula:

[0245] [ka] L 1 , R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , z8, R 9 , and R 10 as described herein, including the embodiments.

[0246] In embodiments, the compound has the formula:

[0247] [ka] L 1 , R 2 , R 3 , R 4 , R 5 , R 8 , z8, R 9 , and R 10 as described herein, including the embodiments.

[0248] In embodiments, the compound has the formula:

[0249] [ka] L 1 , R 6 , R 8 , z8, R 9, and R 10 as described herein, including the embodiments.

[0250] In embodiments, the compound has the formula:

[0251] [ka] L 1 , R 7 , R 8 , z8, R 9 , and R 10 as described herein, including the embodiments.

[0252] In embodiments, the compound has the formula:

[0253] [ka] L 1 , R 8 , z8, R 9 , and R 10 as described herein, including the embodiments.

[0254] In embodiments, the substitution R 10 (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 10 When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 10 When substituted, R is substituted with at least one substituent. 10 When substituted, R is substituted with at least one size-limited substituent. 10 When substituted, it is substituted with at least one lower substituent.

[0255] In embodiments, the substitution R 10A (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 10A When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 10A When R is substituted, it is substituted with at least one substituent. 10A When R is substituted, it is substituted with at least one size-limited substituent. 10A When is substituted, it is substituted with at least one lower substituent.

[0256] In embodiments, the substitution R 10B (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 10B When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 10B When substituted, R is substituted with at least one substituent. 10B When substituted, R is substituted with at least one size-limited substituent. 10B When is substituted, it is substituted with at least one lower substituent.

[0257] In embodiments, R 10A and R 10BIf the substituted ring formed when the substituents are linked is substituted, it is substituted with at least one substituent group, size-limited substituent group, or lower substituent group, and R 10A and R 10B When the substituted ring formed when the substituents are linked is substituted with multiple groups selected from a substituent group, a size-limited substituent group, and a lower substituent group, each substituent, size-limited substituent, and / or lower substituent may optionally be different. In embodiments, R 10A and R 10B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one substituent group. In embodiments, R 10A and R 10B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one size-limited substituent group. In embodiments, R 10A and R 10B The substituted ring formed when the substitutes are linked, if substituted, is substituted with at least one lower substitute group.

[0258] In embodiments, the substitution R 10C (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 10CWhen R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 10C When substituted, R is substituted with at least one substituent. 10C When substituted, R is substituted with at least one size-limited substituent. 10C When substituted, it is substituted with at least one lower substituent.

[0259] In embodiments, the substitution R 10D (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 10D When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 10D When substituted, R is substituted with at least one substituent. 10D When substituted, R is substituted with at least one size-limited substituent. 10D When substituted, it is substituted with at least one lower substituent.

[0260] In embodiments, R 10are hydrogen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, - NHC(O)NHNH2, -NHC(O)NH2, -NO2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0261] In embodiments, R 10 is hydrogen, —CHF2, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted 2-6 membered heteroalkyl, or substituted or unsubstituted C3-C8 cycloalkyl. 10 is hydrogen, —CHF, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted 2-6 membered heteroalkyl. 10 is hydrogen or unsubstituted C1-C6 alkyl. In an embodiment, R 10 is hydrogen. In embodiments, R 10 is an unsubstituted C alkyl. In embodiments, R 10 is unsubstituted methyl. In embodiments, R 10 is an unsubstituted C alkyl. In embodiments, R 10 is unsubstituted ethyl. In embodiments, R 10 is an unsubstituted C alkyl. In embodiments, R 10 is unsubstituted propyl. In embodiments, R 10 is unsubstituted n-propyl. In embodiments, R 10is unsubstituted isopropyl (i.e., isopropyl). In embodiments, R 10 is —CH(CD3)2. In embodiments, R 10 teeth,

[0262] [ka] In an embodiment, R 10 is an unsubstituted C4 alkyl. In embodiments, R 10 is unsubstituted butyl. In embodiments, R 10 is unsubstituted n-butyl. In embodiments, R 10 is unsubstituted isobutyl. In embodiments, R 10 is unsubstituted tert-butyl. In embodiments, R 10 is an unsubstituted C alkyl. In embodiments, R 10 is unsubstituted pentyl. In embodiments, R 10 is unsubstituted n-pentyl. In embodiments, R 10 is unsubstituted tert-pentyl. In embodiments, R 10 is unsubstituted neopentyl. In embodiments, R 10 is unsubstituted isopentyl. In embodiments, R 10 is unsubstituted sec-pentyl. In embodiments, R 10 is unsubstituted 3-pentyl. In embodiments, R 10 is unsubstituted sec-isopentyl. In embodiments, R 10 is unsubstituted 2-methylbutyl. In embodiments, R 10 is an unsubstituted C alkyl. In embodiments, R 10 is unsubstituted hexyl. In embodiments, R 10 is a substituted C1-C6 alkyl. In an embodiment, R 10 is a substituted 2-6 membered heteroalkyl. In embodiments, R 10 is —CH(CH)OCH. In embodiments, R 10 is —CF(CH). In embodiments, R 10 is —C(CH)(OH). In embodiments, R10 is —CH(CH)(CHOH). In embodiments, R 10 is -CHF2. In an embodiment, R 10 is unsubstituted C3-C8 cycloalkyl. In embodiments, R 10 is unsubstituted cyclopropyl. In embodiments, R 10 is unsubstituted cyclobutyl. In embodiments, R 10 is unsubstituted cyclopentyl. In embodiments, R 10 is unsubstituted cyclohexyl. In embodiments, R 10 is unsubstituted cycloheptyl. In embodiments, R 10 is unsubstituted cyclooctyl.

[0263] In embodiments, the substitution R 2 (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 2 When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 2 When substituted, R is substituted with at least one substituent. 2 When substituted, R is substituted with at least one size-limited substituent. 2 When substituted, it is substituted with at least one lower substituent.

[0264] In embodiments, the substitution R 2A (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 2AWhen R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 2A When substituted, R is substituted with at least one substituent. 2A When substituted, R is substituted with at least one size-limited substituent. 2A When substituted, it is substituted with at least one lower substituent.

[0265] In embodiments, the substitution R 2B (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 2B When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 2B When substituted, R is substituted with at least one substituent. 2B When substituted, R is substituted with at least one size-limited substituent. 2B When substituted, it is substituted with at least one lower substituent.

[0266] In embodiments, R 2A and R 2B The substituted ring formed when the substituents are linked (e.g., substituted heterocycloalkyl and / or substituted heteroaryl) is substituted with at least one substituent group, size-limited substituent group, or lower substituent group, and R 2A and R 2BWhen the substituted ring formed when the substituents are linked is substituted with multiple groups selected from a substituent group, a size-limited substituent group, and a lower substituent group, each substituent, size-limited substituent, and / or lower substituent may optionally be different. In embodiments, R 2A and R 2B The substituted ring formed when the substituents are joined, if substituted, is substituted with at least one substituent group. In embodiments, R 2A and R 2B The substituted ring formed when the substituents are joined, if substituted, is substituted with at least one size-limited substituent group. In embodiments, R 2A and R 2B The substituted ring formed when the substituents are joined, if substituted, is substituted with at least one lower substituent group.

[0267] In embodiments, the substitution R 2C (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 2C When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 2C When substituted, R is substituted with at least one substituent. 2C When substituted, R is substituted with at least one size-limited substituent.2C When substituted, it is substituted with at least one lower substituent.

[0268] In embodiments, the substitution R 2D (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 2D When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 2D When substituted, R is substituted with at least one substituent. 2D When substituted, R is substituted with at least one size-limited substituent. 2D When substituted, it is substituted with at least one lower substituent.

[0269] In embodiments, R 2 is hydrogen, halogen, -CX 2 3. -CHX 2 2. -CH2X 2 , -OCX 2 3. -OCH2X 2 , -OCHX 2 2, -CN, -SO n2 R 2D , -SO v2 NR 2A R 2B , -NHC(O)NR 2A R 2B , -NR 2A R 2B , -C(O)R 2C , -C(O)OR 2C , -C(O)NR 2A R 2B , -OR 2D , -SR 2D , -NR 2A SO2R 2D , -NR 2A C(O)R 2C , -NR2A C(O)OR 2C , -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0270] In embodiments, R 2 are hydrogen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, - NHC(O)NHNH2, -NHC(O)NH2, -NO2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0271] In embodiments, R 2represents hydrogen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -SO 2NH2, -NHC(O)NH2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHSO2H, -NHC(O)H, -NHC(O)OH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0272] In embodiments, R 2 is hydrogen or unsubstituted C1-C6 alkyl. In an embodiment, R 2 is hydrogen. In embodiments, R 2 is unsubstituted methyl. In embodiments, R 2 is unsubstituted ethyl. In embodiments, R 2 is unsubstituted propyl. In embodiments, R 2 is unsubstituted n-propyl. In embodiments, R 2 is unsubstituted isopropyl. In embodiments, R 2 is unsubstituted butyl. In embodiments, R 2 is unsubstituted n-butyl. In embodiments, R 2 is unsubstituted isobutyl. In embodiments, R 2 is unsubstituted tert-butyl. In embodiments, R 2 is unsubstituted pentyl. In embodiments, R 2 is unsubstituted hexyl.

[0273] In embodiments, R 10 and R 2The substituted ring formed when the substituents are linked (e.g., substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) is substituted with at least one substituent group, size-limited substituent group, or lower substituent group; R 10 and R 2 When the substituted ring formed when the substituents are linked is substituted with multiple groups selected from a substituent group, a size-limited substituent group, and a lower substituent group, each substituent, size-limited substituent, and / or lower substituent may optionally be different. 10 and R 2 The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one size-limited substituent group. 10 and R 2 The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one size-limited substituent group. 10 and R 2 The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one lower substituent group.

[0274] In embodiments, R 10 and R 2 The substituents may optionally be linked to form a substituted or unsubstituted heteroaryl. In embodiments, R 10 and R 2The substituents may optionally be linked to form a substituted or unsubstituted 5-6 membered heteroaryl. In embodiments, R 10 and R 2 The substituents may optionally be linked to form a methyl-substituted 5-6 membered heteroaryl. In embodiments, R 10 and R 2 The substituents are optionally linked to

[0275] [ka] can be formed.

[0276] In embodiments, the substitution R 3 (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 3 When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 3 When substituted, R is substituted with at least one substituent. 3 When substituted, R is substituted with at least one size-limited substituent. 3 When substituted, it is substituted with at least one lower substituent.

[0277] In embodiments, the substitution R 3A (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 3A When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 3AWhen substituted, R is substituted with at least one substituent. 3A When substituted, R is substituted with at least one size-limited substituent. 3A When substituted, it is substituted with at least one lower substituent.

[0278] In embodiments, the substitution R 3B (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 3B When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 3B When substituted, R is substituted with at least one substituent. 3B When substituted, R is substituted with at least one size-limited substituent. 3B When substituted, it is substituted with at least one lower substituent.

[0279] In embodiments, R 3A and R 3B The substituted ring formed when the substituents are linked (e.g., substituted heterocycloalkyl and / or substituted heteroaryl) is substituted with at least one substituent group, size-limited substituent group, or lower substituent group, and R 3A and R 3BWhen the substituted ring formed when the substituents are linked is substituted with multiple groups selected from a substituent group, a size-limited substituent group, and a lower substituent group, each substituent, size-limited substituent, and / or lower substituent may optionally be different. In embodiments, R 3A and R 3B The substituted ring formed when the substituents are joined, if substituted, is substituted with at least one substituent group. In embodiments, R 3A and R 3B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one size-limited substituent group. In embodiments, R 3A and R 3B The substituted ring formed when the substituents are joined, if substituted, is substituted with at least one lower substituent group.

[0280] In embodiments, the substitution R 3C (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 3C When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 3C When substituted, R is substituted with at least one substituent. 3C When substituted, R is substituted with at least one size-limited substituent.3C When substituted, it is substituted with at least one lower substituent.

[0281] In embodiments, the substitution R 3D (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 3D When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 3D When substituted, R is substituted with at least one substituent. 3D When substituted, R is substituted with at least one size-limited substituent. 3D When substituted, it is substituted with at least one lower substituent.

[0282] In embodiments, R 3 is hydrogen, halogen, -CX 3 3. -CHX 3 2. -CH2X 3 , -OCX 3 3. -OCH2X 3 , -OCHX 3 2, -CN, -SO n3 R 3D , -SO v3 NR 3A R 3B , -NHC(O)NR 3A R 3B , -NR 3A R 3B , -C(O)R 3C , -C(O)OR 3C , -C(O)NR 3A R 3B , -OR 3D , -SR 3D , -NR 3A SO2R 3D , -NR 3A C(O)R 3C , -NR3A C(O)OR 3C , -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0283] In embodiments, R 3 are hydrogen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, - NHC(O)NHNH2, -NHC(O)NH2, -NO2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0284] In embodiments, R 3represents hydrogen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -SO 2NH2, -NHC(O)NH2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHSO2H, -NHC(O)H, -NHC(O)OH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0285] In embodiments, R 3 is hydrogen or unsubstituted C1-C6 alkyl. In an embodiment, R 3 is hydrogen. In embodiments, R 3 is unsubstituted methyl. In embodiments, R 3 is unsubstituted ethyl. In embodiments, R 3 is unsubstituted propyl. In embodiments, R 3 is unsubstituted n-propyl. In embodiments, R 3 is unsubstituted isopropyl. In embodiments, R 3 is unsubstituted butyl. In embodiments, R 3 is unsubstituted n-butyl. In embodiments, R 3 is unsubstituted isobutyl. In embodiments, R 3 is unsubstituted tert-butyl. In embodiments, R 3 is unsubstituted pentyl. In embodiments, R 3 is unsubstituted hexyl.

[0286] In embodiments, R 2 and R 3The substituted ring formed when the substituents are linked (e.g., substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) is substituted with at least one substituent group, size-limited substituent group, or lower substituent group; R 2 and R 3 When the substituted ring formed when the substituents are linked is substituted with multiple groups selected from a substituent group, a size-limited substituent group, and a lower substituent group, each substituent, size-limited substituent, and / or lower substituent may optionally be different. 2 and R 3 The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one size-limited substituent group. 2 and R 3 The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one size-limited substituent group. 2 and R 3 The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one lower substituent group.

[0287] In embodiments, the substitution R 4 (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R4 When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 4 When substituted, R is substituted with at least one substituent. 4 When substituted, R is substituted with at least one size-limited substituent. 4 When substituted, it is substituted with at least one lower substituent.

[0288] In embodiments, the substitution R 4A (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 4A When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 4A When substituted, R is substituted with at least one substituent. 4A When substituted, R is substituted with at least one size-limited substituent. 4A When substituted, it is substituted with at least one lower substituent.

[0289] In embodiments, the substitution R 4B (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 4B When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 4BWhen substituted, R is substituted with at least one substituent. 4B When substituted, R is substituted with at least one size-limited substituent. 4B When substituted, it is substituted with at least one lower substituent.

[0290] In embodiments, R 4A and R 4B If the substituted ring formed when the substituents are linked is substituted, it is substituted with at least one substituent group, size-limited substituent group, or lower substituent group, and R 4A and R 4B When the substituted ring formed when the substituents are linked is substituted with multiple groups selected from a substituent group, a size-limited substituent group, and a lower substituent group, each substituent, size-limited substituent, and / or lower substituent may optionally be different. In embodiments, R 4A and R 4B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one substituent group. In embodiments, R 4A and R 4B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one size-limited substituent group. In embodiments, R 4A and R 4BThe substituted ring formed when the substituents are linked, if substituted, is substituted with at least one lower substituent group.

[0291] In embodiments, the substitution R 4C (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 4C When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 4C When substituted, R is substituted with at least one substituent. 4C When substituted, R is substituted with at least one size-limited substituent. 4C When substituted, it is substituted with at least one lower substituent.

[0292] In embodiments, the substitution R 4D (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 4D When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 4D When substituted, R is substituted with at least one substituent. 4D When substituted, R is substituted with at least one size-limited substituent. 4D When substituted, it is substituted with at least one lower substituent.

[0293] In embodiments, R4 is hydrogen, halogen, -CX 4 3. -CHX 4 2. -CH2X 4 , -OCX 4 3. -OCH2X 4 , -OCHX 4 2, -CN, -SO n4 R 4D , -SO v4 NR 4A R 4B , -NHC(O)NR 4A R 4B , -NR 4A R 4B , -C(O)R 4C , -C(O)OR 4C , -C(O)NR 4A R 4B , -OR 4D , -SR 4D , -NR 4A SO2R 4D , -NR 4A C(O)R 4C , -NR 4A C(O)OR 4C , -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0294] In embodiments, R 4are hydrogen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, - NHC(O)NHNH2, -NHC(O)NH2, -NO2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0295] In embodiments, R 4 represents hydrogen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -SO 2NH2, -NHC(O)NH2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHSO2H, -NHC(O)H, -NHC(O)OH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0296] In embodiments, R 4 is hydrogen or unsubstituted C1-C6 alkyl. In an embodiment, R 4 is hydrogen. In embodiments, R 4is unsubstituted methyl. In embodiments, R 4 is unsubstituted ethyl. In embodiments, R 4 is unsubstituted propyl. In embodiments, R 4 is unsubstituted n-propyl. In embodiments, R 4 is unsubstituted isopropyl. In embodiments, R 4 is unsubstituted butyl. In embodiments, R 4 is unsubstituted n-butyl. In embodiments, R 4 is unsubstituted isobutyl. In embodiments, R 4 is unsubstituted tert-butyl. In embodiments, R 4 is unsubstituted pentyl. In embodiments, R 4 is unsubstituted hexyl.

[0297] In embodiments, R 3 and R 4 The substituted ring formed when the substituents are linked (e.g., substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) is substituted with at least one substituent group, size-limited substituent group, or lower substituent group; R 3 and R 4 When the substituted ring formed when the substituents are linked is substituted with multiple groups selected from a substituent group, a size-limited substituent group, and a lower substituent group, each substituent, size-limited substituent, and / or lower substituent may optionally be different. 3 and R 4 The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one size-limited substituent group.3 and R 4 The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one size-limited substituent group. 3 and R 4 The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one lower substituent group.

[0298] In embodiments, the substitution R 5 (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 5 When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 5 When substituted, R is substituted with at least one substituent. 5 When substituted, R is substituted with at least one size-limited substituent. 5 When substituted, it is substituted with at least one lower substituent.

[0299] In embodiments, the substitution R 5A (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 5A When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 5AWhen substituted, R is substituted with at least one substituent. 5A When substituted, R is substituted with at least one size-limited substituent. 5A When substituted, it is substituted with at least one lower substituent.

[0300] In embodiments, the substitution R 5B (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 5B When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 5B When substituted, R is substituted with at least one substituent. 5B When substituted, R is substituted with at least one size-limited substituent. 5B When substituted, it is substituted with at least one lower substituent.

[0301] In embodiments, R 5A and R 5B If the substituted ring formed when the substituents are linked is substituted, it is substituted with at least one substituent group, size-limited substituent group, or lower substituent group, and R 5A and R 5BWhen the substituted ring formed when the substituents are linked is substituted with multiple groups selected from a substituent group, a size-limited substituent group, and a lower substituent group, each substituent, size-limited substituent, and / or lower substituent may optionally be different. In embodiments, R 5A and R 5B The substituted ring formed when the substituents are attached, if substituted, is substituted with at least one substituent group. In embodiments, R 5A and R 5B The substituted ring formed when the substituents are attached, if substituted, is substituted with at least one size-limited substituent group. In embodiments, R 5A and R 5B The substituted ring formed when the substituents are attached, if substituted, is substituted with at least one lower substituent group.

[0302] In embodiments, the substitution R 5C (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 5C When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 5C When substituted, R is substituted with at least one substituent. 5C When substituted, R is substituted with at least one size-limited substituent.5C When substituted, it is substituted with at least one lower substituent.

[0303] In embodiments, the substitution R 5D (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 5D When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 5D When substituted, R is substituted with at least one substituent. 5D When substituted, R is substituted with at least one size-limited substituent. 5D When substituted, it is substituted with at least one lower substituent.

[0304] In embodiments, R 5 is hydrogen, halogen, -CX 5 3. -CHX 5 2. -CH2X 5 , -OCX 5 3. -OCH2X 5 , -OCHX 5 2, -CN, -SO n5 R 5D , -SO v5 NR 5A R 5B , -NHC(O)NR 5A R 5B , -NR 5A R 5B , -C(O)R 5C , -C(O)OR 5C , -C(O)NR 5A R 5B , -OR 5D , -SR 5D , -NR 5A SO2R 5D , -NR 5A C(O)R 5C , -NR5A C(O)OR 5C , -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0305] In embodiments, R 5 are hydrogen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, - NHC(O)NHNH2, -NHC(O)NH2, -NO2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0306] In embodiments, R 5represents hydrogen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -SO 2NH2, -NHC(O)NH2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHSO2H, -NHC(O)H, -NHC(O)OH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0307] In embodiments, R 5 is hydrogen or unsubstituted C1-C6 alkyl. In an embodiment, R 5 is hydrogen. In embodiments, R 5 is unsubstituted methyl. In embodiments, R 5 is unsubstituted ethyl. In embodiments, R 5 is unsubstituted propyl. In embodiments, R 5 is unsubstituted n-propyl. In embodiments, R 5 is unsubstituted isopropyl. In embodiments, R 5 is unsubstituted butyl. In embodiments, R 5 is unsubstituted n-butyl. In embodiments, R 5 is unsubstituted isobutyl. In embodiments, R 5 is unsubstituted tert-butyl. In embodiments, R 5 is unsubstituted pentyl. In embodiments, R 5 is unsubstituted hexyl.

[0308] In embodiments, R 4 and R 5The substituted ring formed when the substituents are linked (e.g., substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) is substituted with at least one substituent group, size-limited substituent group, or lower substituent group; R 4 and R 5 When the substituted ring formed when the substituents are linked is substituted with multiple groups selected from a substituent group, a size-limited substituent group, and a lower substituent, each substituent, size-limited substituent, and / or lower substituent may optionally be different. 4 and R 5 The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one size-limited substituent group. In embodiments, two R 4 and R 5 The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one size-limited substituent group. 4 and R 5 The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one lower substituent group.

[0309] In an embodiment, W 6 is N. In an embodiment, W 6 is C(R 6 In an embodiment, W 6 is CH.

[0310] In embodiments, the substitution R 6(e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 6 When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 6 When substituted, R is substituted with at least one substituent. 6 When substituted, R is substituted with at least one size-limited substituent. 6 When substituted, it is substituted with at least one lower substituent.

[0311] In embodiments, the substitution R 6A (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 6A When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 6A When substituted, R is substituted with at least one substituent. 6A When substituted, R is substituted with at least one size-limited substituent. 6A When substituted, it is substituted with at least one lower substituent.

[0312] In embodiments, the substitution R 6B (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 6BWhen R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 6B When substituted, R is substituted with at least one substituent. 6B When substituted, R is substituted with at least one size-limited substituent. 6B When substituted, it is substituted with at least one lower substituent.

[0313] In embodiments, R 6A and R 6B If the substituted ring formed when the substituents are linked is substituted, it is substituted with at least one substituent group, size-limited substituent group, or lower substituent group, and R 6A and R 6B When the substituted ring formed when the substituents are linked is substituted with multiple groups selected from a substituent group, a size-limited substituent group, and a lower substituent group, each substituent, size-limited substituent, and / or lower substituent may optionally be different. In embodiments, R 6A and R 6B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one substituent group. In embodiments, R 6A and R 6BThe substituted ring formed when the substituents are linked, if substituted, is substituted with at least one size-limited substituent group. In embodiments, R 6A and R 6B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one lower substituent group.

[0314] In embodiments, the substitution R 6C (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 6C When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 6C When substituted, R is substituted with at least one substituent. 6C When substituted, R is substituted with at least one size-limited substituent. 6C When substituted, it is substituted with at least one lower substituent.

[0315] In embodiments, the substitution R 6D (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 6D When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 6D When substituted, R is substituted with at least one substituent.6D When substituted, R is substituted with at least one size-limited substituent. 6D When substituted, it is substituted with at least one lower substituent.

[0316] In embodiments, R 6 is hydrogen, halogen, -CX 6 3. -CHX 6 2. -CH2X 6 , -OCX 6 3. -OCH2X 6 , -OCHX 6 2, -CN, -SO n6 R 6D , -SO v6 NR 6A R 6B , -NHC(O)NR 6A R 6B , -NR 6A R 6B , -C(O)R 6C , -C(O)OR 6C , -C(O)NR 6A R 6B , -OR 6D , -SR 6D , -NR 6A SO2R 6D , -NR 6A C(O)R 6C , -NR 6A C(O)OR 6C , -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0317] In embodiments, R 6are hydrogen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, - NHC(O)NHNH2, -NHC(O)NH2, -NO2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0318] In embodiments, R 6 represents hydrogen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -SO 2NH2, -NHC(O)NH2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHSO2H, -NHC(O)H, -NHC(O)OH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0319] In embodiments, R 6 is hydrogen, —OCHF, unsubstituted C1-C6 alkyl, or unsubstituted 2-6 membered heteroalkyl. 6 is hydrogen. In embodiments, R6 is -OCHF. In an embodiment, R 6 is unsubstituted methyl. In embodiments, R 6 is unsubstituted ethyl. In embodiments, R 6 is unsubstituted propyl. In embodiments, R 6 is unsubstituted n-propyl. In embodiments, R 6 is unsubstituted isopropyl. In embodiments, R 6 is unsubstituted butyl. In embodiments, R 6 is unsubstituted n-butyl. In embodiments, R 6 is unsubstituted isobutyl. In embodiments, R 6 is unsubstituted tert-butyl. In embodiments, R 6 is unsubstituted pentyl. In embodiments, R 6 is unsubstituted hexyl. In embodiments, R 6 is unsubstituted methoxy. In embodiments, R 6 is unsubstituted ethoxy. In embodiments, R 6 is unsubstituted propoxy. In embodiments, R 6 is unsubstituted n-propoxy. In embodiments, R 6 is unsubstituted isopropoxy. In embodiments, R 6 is -OCD3. In embodiments, R 6 is unsubstituted butoxy. In embodiments, R 6 teeth,

[0320] [ka] In an embodiment, R 6 teeth,

[0321] [ka] In an embodiment, R 6 teeth,

[0322] [ka] is.

[0323] In an embodiment, W 7 is N. In an embodiment, W 7 is N + -O - In an embodiment, W 7 is C(R 7 In an embodiment, W 7 is CH.

[0324] In embodiments, the substitution R 7 (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 7 When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 7 When substituted, R is substituted with at least one substituent. 7 When substituted, R is substituted with at least one size-limited substituent. 7 When substituted, it is substituted with at least one lower substituent.

[0325] In embodiments, the substitution R 7A (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 7A When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 7A When substituted, R is substituted with at least one substituent. 7AWhen substituted, R is substituted with at least one size-limited substituent. 7A When substituted, it is substituted with at least one lower substituent.

[0326] In embodiments, the substitution R 7B (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 7B When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 7B When substituted, R is substituted with at least one substituent. 7B When substituted, R is substituted with at least one size-limited substituent. 7B When substituted, it is substituted with at least one lower substituent.

[0327] In embodiments, R 7A and R 7B If the substituted ring formed when the substituents are linked is substituted, it is substituted with at least one substituent group, size-limited substituent group, or lower substituent group, and R 7A and R 7BWhen the substituted ring formed when the substituents are linked is substituted with multiple groups selected from a substituent group, a size-limited substituent group, and a lower substituent group, each substituent, size-limited substituent, and / or lower substituent may optionally be different. In embodiments, R 7A and R 7B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one substituent group. In embodiments, R 7A and R 7B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one size-limited substituent group. In embodiments, R 7A and R 7B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one lower substituent group.

[0328] In embodiments, the substitution R 7C (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 7C When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 7C When substituted, R is substituted with at least one substituent. 7C When substituted, R is substituted with at least one size-limited substituent.7C When substituted, it is substituted with at least one lower substituent.

[0329] In embodiments, the substitution R 7D (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 7D When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 7D When substituted, R is substituted with at least one substituent. 7D When substituted, R is substituted with at least one size-limited substituent. 7D When substituted, it is substituted with at least one lower substituent.

[0330] In embodiments, R 7 is hydrogen, halogen, -CX 7 3. -CHX 7 2. -CH2X 7 , -OCX 7 3. -OCH2X 7 , -OCHX 7 2, -CN, -SO n7 R 7D , -SO v7 NR 7A R 7B , -NHC(O)NR 7A R 7B , -NR 7A R 7B , -C(O)R 7C , -C(O)OR 7C , -C(O)NR 7A R 7B , -OR 7D , -SR 7D , -NR 7A SO2R 7D , -NR 7A C(O)R 7C , -NR7A C(O)OR 7C , -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0331] In embodiments, R 7 are hydrogen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, - NHC(O)NHNH2, -NHC(O)NH2, -NO2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0332] In embodiments, R 7represents hydrogen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -SO 2NH2, -NHC(O)NH2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHSO2H, -NHC(O)H, -NHC(O)OH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0333] In embodiments, R 7 is hydrogen, halogen, —OCHF, or unsubstituted C1-C6 alkyl. 7 is hydrogen. In embodiments, R 7 is halogen. In embodiments, R 7 is -F. In an embodiment, R 7 is —Cl. In embodiments, R 7 is -Br. In embodiments, R 7 is -OCHF. In an embodiment, R 7 is unsubstituted methyl. In embodiments, R 7 is unsubstituted ethyl. In embodiments, R 7 is unsubstituted propyl. In embodiments, R 7 is unsubstituted n-propyl. In embodiments, R 7 is unsubstituted isopropyl. In embodiments, R 7 is unsubstituted butyl. In embodiments, R 7 is unsubstituted n-butyl. In embodiments, R 7 is unsubstituted isobutyl. In embodiments, R 7 is unsubstituted tert-butyl. In embodiments, R 7is unsubstituted pentyl. In embodiments, R 7 is unsubstituted hexyl.

[0334] In embodiments, the substitution R 8 (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 8 When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 8 When substituted, R is substituted with at least one substituent. 8 When substituted, R is substituted with at least one size-limited substituent. 8 When substituted, it is substituted with at least one lower substituent.

[0335] In embodiments, the substitution R 8A (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 8A When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 8A When substituted, R is substituted with at least one substituent. 8A When substituted, R is substituted with at least one size-limited substituent. 8A When substituted, it is substituted with at least one lower substituent.

[0336] In embodiments, the substitution R 8B(e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 8B When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 8B When substituted, R is substituted with at least one substituent. 8B When substituted, R is substituted with at least one size-limited substituent. 8B When substituted, it is substituted with at least one lower substituent.

[0337] In embodiments, R 8A and R 8B If the substituted ring formed when the substituents are linked is substituted, it is substituted with at least one substituent group, size-limited substituent group, or lower substituent group, and R 8A and R 8B When the substituted ring formed when the substituents are linked is substituted with multiple groups selected from a substituent group, a size-limited substituent group, and a lower substituent group, each substituent, size-limited substituent, and / or lower substituent may optionally be different. In embodiments, R 8A and R 8B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one substituent group. In embodiments, R 8Aand R 8B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one size-limited substituent group. In embodiments, R 8A and R 8B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one lower substituent group.

[0338] In embodiments, the substitution R 8C (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 8C When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 8C When substituted, R is substituted with at least one substituent. 8C When substituted, R is substituted with at least one size-limited substituent. 8C When substituted, it is substituted with at least one lower substituent.

[0339] In embodiments, the substitution R 8D (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 8D When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 8DWhen substituted, R is substituted with at least one substituent. 8D When substituted, R is substituted with at least one size-limited substituent. 8D When substituted, it is substituted with at least one lower substituent.

[0340] In embodiments, R 8 are independently halogen, -CX 8 3. -CHX 8 2. -CH2X 8 , -OCX 8 3. -OCH2X 8 , -OCHX 8 2, -CN, -SO n8 R 8D , -SO v8 NR 8A R 8B , -NHC(O)NR 8A R 8B , -NR 8A R 8B , -C(O)R 8C , -C(O)OR 8C , -C(O)NR 8A R 8B , -OR 8D , -SR 8D , -NR 8A SO2R 8D , -NR 8A C(O)R 8C , -NR 8A C(O)OR 8C , -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and two R 8 The substituents may optionally be linked to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0341] In embodiments, R 8are independently halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NO2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0342] In embodiments, R 8 are independently halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -S O2NH2, -NHC(O)NH2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHS02H, -NHC(O)H, -NHC(O)OH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0343] In embodiments, R 8 are independently halogen, -CF3, -CHF2, -CN, -OCHF2, -C(O)R 8C , -C(O)OR 8C , -OR8D , unsubstituted C1-C6 alkyl, unsubstituted 2-8 membered heteroalkyl, unsubstituted C3-C8 cycloalkyl, or unsubstituted phenyl.

[0344] In embodiments, R 8C are independently hydrogen or unsubstituted C1-C6 alkyl. 8C are independently hydrogen. In embodiments, R 8C is independently unsubstituted methyl. In embodiments, R 8C is independently unsubstituted ethyl. In embodiments, R 8C is independently unsubstituted propyl. In embodiments, R 8C is independently unsubstituted n-propyl. In embodiments, R 8C is independently unsubstituted isopropyl. In embodiments, R 8C is independently unsubstituted butyl. In embodiments, R 8C is independently unsubstituted n-butyl. In embodiments, R 8C is independently unsubstituted isobutyl. In embodiments, R 8C is independently unsubstituted tert-butyl. In embodiments, R 8C is independently unsubstituted pentyl. In embodiments, R 8C is independently unsubstituted hexyl.

[0345] In embodiments, R 8D are independently hydrogen or unsubstituted C1-C6 alkyl. 8D are independently hydrogen. In embodiments, R 8D is independently unsubstituted methyl. In embodiments, R 8D is independently unsubstituted ethyl. In embodiments, R 8D is independently unsubstituted propyl. In embodiments, R 8D is independently unsubstituted n-propyl. In embodiments, R 8D is independently unsubstituted isopropyl. In embodiments, R 8D is independently unsubstituted butyl. In embodiments, R 8Dis independently unsubstituted n-butyl. In embodiments, R 8D is independently unsubstituted isobutyl. In embodiments, R 8D is independently unsubstituted tert-butyl. In embodiments, R 8D is independently unsubstituted pentyl. In embodiments, R 8D is independently unsubstituted hexyl.

[0346] In embodiments, R 8 are independently -F, -Cl, -Br, -CF, -CHF, -CN, -C(O)H, -OCHF, -OCH, -OCHCH, -OCHCF, -OCH(CH)CHOCH, -OCHCHF, unsubstituted methyl, unsubstituted cyclopropyl, or unsubstituted phenyl.

[0347] In embodiments, R 8 are independently -F, -Cl, -Br, -CF, -CHF, -OH, -CN, -C(O)H, -OCHF, -OCH, -OCHCH, -OCHCF, -OCH(CH)CHOCH, -OCHCHF, substituted or unsubstituted methyl, unsubstituted cyclopropyl, or unsubstituted phenyl.

[0348] In embodiments, R 8 is independently -F. In an embodiment, R 8 is independently -Cl. In an embodiment, R 8 is independently -Br. In an embodiment, R 8 is independently —CF. In an embodiment, R 8 is independently -CHF. In an embodiment, R 8 is independently —OH. In an embodiment, R 8 is independently —CN. In an embodiment, R 8 is independently —C(O)H. In embodiments, R 8 is independently —C(O)OCH. In embodiments, R 8 is independently -OCHF. In an embodiment, R 8is independently an unsubstituted C1-C6 alkyl. In an embodiment, R 8 is independently unsubstituted methyl. In embodiments, R 8 is independently unsubstituted ethyl. In embodiments, R 8 is independently unsubstituted propyl. In embodiments, R 8 is independently unsubstituted n-propyl. In embodiments, R 8 is independently unsubstituted isopropyl. In embodiments, R 8 is independently unsubstituted butyl. In embodiments, R 8 is independently unsubstituted n-butyl. In embodiments, R 8 is independently unsubstituted isobutyl. In embodiments, R 8 is independently unsubstituted tert-butyl. In embodiments, R 8 is independently unsubstituted pentyl. In embodiments, R 8 is independently unsubstituted hexyl. In embodiments, R 8 is independently a substituted C1-C6 alkyl. In an embodiment, R 8 is independently a substituted methyl. In embodiments, R 8 is independently substituted ethyl. In embodiments, R 8 is independently unsubstituted propyl. In embodiments, R 8 is independently unsubstituted n-propyl. In embodiments, R 8 is independently unsubstituted isopropyl. In embodiments, R 8 is independently unsubstituted butyl. In embodiments, R 8 is independently unsubstituted n-butyl. In embodiments, R 8 is independently unsubstituted isobutyl. In embodiments, R 8 is independently unsubstituted tert-butyl. In embodiments, R 8 is independently unsubstituted pentyl. In embodiments, R 8 is independently unsubstituted hexyl. In embodiments, R 8 is independently —CH—(unsubstituted phenyl). In embodiments, R 8is independently a substituted or unsubstituted 2-8 membered heteroalkyl. 8 is independently unsubstituted methoxy. In embodiments, R 8 is independently -OCD3. In embodiments, R 8 is independently unsubstituted ethoxy. In embodiments, R 8 is independently unsubstituted propoxy. In embodiments, R 8 is independently unsubstituted n-propoxy. In embodiments, R 8 is independently unsubstituted isopropoxy. In embodiments, R 8 is independently unsubstituted butoxy. In embodiments, R 8 is independently —CH2OCH3. In an embodiment, R 8 is independently —OCH2CF3. In embodiments, R 8 is independently —OCHCHF. In an embodiment, R 8 is independently —OCH2CH2F. In an embodiment, R 8 is, independently,

[0349] [ka] In an embodiment, R 8 is, independently,

[0350] [ka] In an embodiment, R 8 is, independently,

[0351] [ka] In an embodiment, R 8 is independently an unsubstituted C-C cycloalkyl. 8 is independently unsubstituted cyclopropyl. In embodiments, R 8 is independently unsubstituted cyclobutyl. In embodiments, R 8is independently unsubstituted cyclopentyl. In embodiments, R 8 is independently unsubstituted cyclohexyl. In embodiments, R 8 is independently unsubstituted phenyl.

[0352] In embodiments, two R 8 The substituents are linked to form an unsubstituted C-C cycloalkyl. In embodiments, two R 8 The substituents are linked to form an unsubstituted C cycloalkyl. In embodiments, two R 8 The substituents are linked to form an unsubstituted C4 cycloalkyl. In embodiments, two R 8 The substituents are linked to form an unsubstituted C5 cycloalkyl. In embodiments, two R 8 The substituents are linked to form an unsubstituted C6 cycloalkyl. In embodiments, two R 8 The substituents are linked to form an unsubstituted C7 cycloalkyl. In embodiments, two R 8 The substituents are linked to form an unsubstituted C8 cycloalkyl.

[0353] In an embodiment, z8 is 0. In an embodiment, z8 is 1. In an embodiment, z8 is 2. In an embodiment, z8 is 3.

[0354] In an embodiment,

[0355] [ka] where R 6 and R 7 is as described herein, including the embodiments. 8.1 , R 8.2 , and R 8.3 are independently hydrogen or any of the R 8 is any value of .

[0356] In an embodiment,

[0357] [ka] where R 6 and R 7 is as described herein, including embodiments. 8.1 , R 8.2 , and R 8.3 are independently hydrogen or any of the R 8 is any value of .

[0358] In an embodiment,

[0359] [ka] where R 6 and R 7 is as described herein, including embodiments. 8.1 , R 8.2 , and R 8.3 are independently hydrogen or any of the R 8 is any value of .

[0360] In embodiments, the substitution R 8.1 (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 8.1 When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 8.1 When substituted, R is substituted with at least one substituent. 8.1 When substituted, R is substituted with at least one size-limited substituent. 8.1 When substituted, it is substituted with at least one lower substituent.

[0361] In embodiments, the substitution R 8.2(e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 8.2 When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 8.2 When substituted, R is substituted with at least one substituent. 8.2 When substituted, R is substituted with at least one size-limited substituent. 8.2 When substituted, it is substituted with at least one lower substituent.

[0362] In embodiments, the substitution R 8.3 (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 8.3 When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 8.3 When substituted, R is substituted with at least one substituent. 8.3 When substituted, R is substituted with at least one size-limited substituent. 8.3 When substituted, it is substituted with at least one lower substituent.

[0363] In embodiments, R 8.2 and R 8.3The substituted ring formed when the substituents are linked (e.g., substituted cycloalkyl and / or substituted heterocycloalkyl) is substituted with at least one substituent group, size-limited substituent group, or lower substituent group; R 8.2 and R 8.3 When the substituted ring formed when the substituents are linked is substituted with multiple groups selected from a substituent group, a size-limited substituent group, and a lower substituent group, each substituent, size-limited substituent, and / or lower substituent may optionally be different. 8.2 and R 8.3 The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one substituent group. 8.2 and R 8.3 The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one size-limited substituent group. 8.2 and R 8.3 The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one lower substituent group.

[0364] In embodiments, R 8.1 , R 8.2 , and R 8.3 are independently hydrogen, halogen, -CX 8 3. -CHX 8 2. -CH2X 8 , -OCX 8 3. -OCH2X 8 , -OCHX8 2, -CN, -SO n8 R 8D , -SO v8 NR 8A R 8B , -NR 8C NR 8A R 8B , -ONR 8A R 8B , -NHC(O)NR 8C NR 8A R 8B , -NHC(O)NR 8A R 8B , -N(O) m8 , -NR 8A R 8B , -C(O)R 8C , -C(O)OR 8C , -C(O)NR 8A R 8B , -OR 8D , -SR 8D , -NR 8A SO2R 8D , -NR 8A C(O)R 8C , -NR 8A C(O)OR 8C , -NR 8A OR 8C , -SF5, -N3, substituted or unsubstituted alkyl (e.g., C1 to C8, C1 to C6, C1 to C4, or C1 to C2), substituted or unsubstituted heteroalkyl (e.g., 2 to 8 members, 2 to 6 members, 4 to 6 members, 2 to 3 members, or 4 to 5 members), substituted or unsubstituted cycloalkyl (e.g., C3 to C8, C3 to C6, C4 to C6, or C5 to C6), substituted or unsubstituted heterocycloalkyl (e.g., 3 to 8 members, 3 to 6 members, 4 to 6 members, 4 to 5 members, or 5 to 6 members), substituted or unsubstituted aryl (e.g., C6 to C 10 or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered), and R 8.2 and R 8.3The substituents may be optionally linked to form a substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), a substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), a substituted or unsubstituted aryl (e.g., C6-C 10 or phenyl), or substituted or unsubstituted heteroaryl (eg, 5-10 membered, 5-9 membered, or 5-6 membered).

[0365] In embodiments, R 8.1 , R 8.2 , and R 8.3 are independently hydrogen, halogen, -CX 8 3. -CHX 8 2. -CH2X 8 , -OCX 8 3. -OCH2X 8 , -OCHX 8 2, -CN, -SO n8 R 8D , -SO v8 NR 8A R 8B , -NHC(O)NR 8A R 8B , -NR 8A R 8B , -C(O)R 8C , -C(O)OR 8C , -C(O)NR 8A R 8B , -OR 8D , -SR 8D , -NR 8A SO2R 8D , -NR 8A C(O)R 8C , -NR 8A C(O)OR 8C , -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 8.2 and R 8.3The substituents may optionally be linked to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0366] In embodiments, R 8.1 , R 8.2 , and R 8.3 are independently hydrogen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH 2, -NHC(O)NHNH2, -NHC(O)NH2, -NO2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0367] In embodiments, R 8.1 , R 8.2 , and R 8.3are independently hydrogen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, - SO2NH2, -NHC(O)NH2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHSO2H, -NHC(O)H, -NHC(O)OH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0368] In embodiments, R 8.1 is -F. In an embodiment, R 8.1 is —Cl. In embodiments, R 8.1 is -Br. In embodiments, R 8.1 is —CF. In embodiments, R 8.1 is -CHF2. In an embodiment, R 8.1 is -CN. In embodiments, R 8.1 is —C(O)H. In embodiments, R 8.1 is —C(O)OCH. In embodiments, R 8.1 is -OCHF. In an embodiment, R 8.1 is an unsubstituted C1-C6 alkyl. In embodiments, R 8.1 is unsubstituted methyl. In embodiments, R 8.1 is unsubstituted ethyl. In embodiments, R 8.1 is unsubstituted propyl. In embodiments, R 8.1 is unsubstituted n-propyl. In embodiments, R 8.1 is unsubstituted isopropyl. In embodiments, R 8.1 is unsubstituted butyl. In embodiments, R 8.1 is unsubstituted n-butyl. In embodiments, R8.1 is unsubstituted isobutyl. In embodiments, R 8.1 is unsubstituted tert-butyl. In embodiments, R 8.1 is unsubstituted pentyl. In embodiments, R 8.1 is unsubstituted hexyl. In embodiments, R 8.1 is a substituted C1-C6 alkyl. In an embodiment, R 8.1 is a substituted methyl. In embodiments, R 8.1 is a substituted ethyl. In embodiments, R 8.1 is a substituted propyl. In embodiments, R 8.1 is unsubstituted n-propyl. In embodiments, R 8.1 is substituted isopropyl. In embodiments, R 8.1 is a substituted butyl. In embodiments, R 8.1 is a substituted n-butyl. In embodiments, R 8.1 is substituted isobutyl. In embodiments, R 8.1 is a substituted tert-butyl. In embodiments, R 8.1 is a substituted pentyl. In embodiments, R 8.1 is a substituted hexyl. In embodiments, R 8.1 is —CH—(unsubstituted phenyl). In embodiments, R 8.1 is a substituted or unsubstituted 2-8 membered heteroalkyl. In embodiments, R 8.1 is unsubstituted methoxy. In embodiments, R 8.1 is -OCD3. In embodiments, R 8.1 is unsubstituted ethoxy. In embodiments, R 8.1 is unsubstituted propoxy. In embodiments, R 8.1 is unsubstituted n-propoxy. In embodiments, R 8.1 is unsubstituted isopropoxy. In embodiments, R 8.1 is unsubstituted butoxy. In embodiments, R 8.1 is —CH2OCH3. In embodiments, R 8.1 is —OCH2CF3. In embodiments, R 8.1 is —OCH2CHF2. In an embodiment, R 8.1is —OCH2CH2F. In embodiments, R 8.1 teeth,

[0369] [ka] In an embodiment, R 8.1 teeth,

[0370] [ka] In an embodiment, R 8.1 teeth,

[0371] [ka] In an embodiment, R 8.1 is unsubstituted C3-C8 cycloalkyl. In embodiments, R 8.1 is unsubstituted cyclopropyl. In embodiments, R 8.1 is unsubstituted cyclobutyl. In embodiments, R 8.1 is unsubstituted cyclopentyl. In embodiments, R 8.1 is unsubstituted cyclohexyl. In embodiments, R 8.1 is unsubstituted phenyl.

[0372] In embodiments, R 8.2 is -F. In an embodiment, R 8.2 is —Cl. In embodiments, R 8.2 is -Br. In embodiments, R 8.2 is —CF. In embodiments, R 8.2 is -CHF2. In an embodiment, R 8.2 is -CN. In embodiments, R 8.2 is —C(O)H. In embodiments, R 8.2 is —C(O)OCH. In embodiments, R 8.2 is -OCHF. In an embodiment, R 8.2 is an unsubstituted C1-C6 alkyl. In embodiments, R 8.2is unsubstituted methyl. In embodiments, R 8.2 is unsubstituted ethyl. In embodiments, R 8.2 is unsubstituted propyl. In embodiments, R 8.2 is unsubstituted n-propyl. In embodiments, R 8.2 is unsubstituted isopropyl. In embodiments, R 8.2 is unsubstituted butyl. In embodiments, R 8.2 is unsubstituted n-butyl. In embodiments, R 8.2 is unsubstituted isobutyl. In embodiments, R 8.2 is unsubstituted tert-butyl. In embodiments, R 8.2 is unsubstituted pentyl. In embodiments, R 8.2 is unsubstituted hexyl. In embodiments, R 8.2 is a substituted C1-C6 alkyl. In an embodiment, R 8.2 is a substituted methyl. In embodiments, R 8.2 is a substituted ethyl. In embodiments, R 8.2 is a substituted propyl. In embodiments, R 8.2 is substituted n-propyl. In embodiments, R 8.2 is substituted isopropyl. In embodiments, R 8.2 is a substituted butyl. In embodiments, R 8.2 is a substituted n-butyl. In embodiments, R 8.2 is substituted isobutyl. In embodiments, R 8.2 is a substituted tert-butyl. In embodiments, R 8.2 is a substituted pentyl. In embodiments, R 8.2 is a substituted hexyl. In embodiments, R 8.2 is —CH—(unsubstituted phenyl). In embodiments, R 8.2 is a substituted or unsubstituted 2-8 membered heteroalkyl. In embodiments, R 8.2 is unsubstituted methoxy. In embodiments, R 8.2 is -OCD3. In embodiments, R 8.2 is unsubstituted ethoxy. In embodiments, R 8.2 is unsubstituted propoxy. In embodiments, R8.2 is unsubstituted n-propoxy. In embodiments, R 8.2 is unsubstituted isopropoxy. In embodiments, R 8.2 is unsubstituted butoxy. In embodiments, R 8.2 is —CH2OCH3. In embodiments, R 8.2 is —OCH2CF3. In embodiments, R 8.2 is —OCH2CHF2. In an embodiment, R 8.2 is —OCH2CH2F. In embodiments, R 8.2 teeth,

[0373] [ka] In an embodiment, R 8.2 teeth,

[0374] [ka] In an embodiment, R 8.2 teeth,

[0375] [ka] In an embodiment, R 8.2 is unsubstituted C3-C8 cycloalkyl. In embodiments, R 8.2 is unsubstituted cyclopropyl. In embodiments, R 8.2 is unsubstituted cyclobutyl. In embodiments, R 8.2 is unsubstituted cyclopentyl. In embodiments, R 8.2 is unsubstituted cyclohexyl. In embodiments, R 8.2 is unsubstituted phenyl.

[0376] In embodiments, R 8.3 is -F. In an embodiment, R 8.3 is —Cl. In embodiments, R 8.3 is -Br. In embodiments, R 8.3 is —CF. In embodiments, R8.3 is -CHF2. In an embodiment, R 8.3 is -CN. In embodiments, R 8.3 is —C(O)H. In embodiments, R 8.3 is —C(O)OCH. In embodiments, R 8.3 is -OCHF. In an embodiment, R 8.3 is an unsubstituted C1-C6 alkyl. In embodiments, R 8.3 is unsubstituted methyl. In embodiments, R 8.3 is unsubstituted ethyl. In embodiments, R 8.3 is unsubstituted propyl. In embodiments, R 8.3 is unsubstituted n-propyl. In embodiments, R 8.3 is unsubstituted isopropyl. In embodiments, R 8.3 is unsubstituted butyl. In embodiments, R 8.3 is unsubstituted n-butyl. In embodiments, R 8.3 is unsubstituted isobutyl. In embodiments, R 8.3 is unsubstituted tert-butyl. In embodiments, R 8.3 is unsubstituted cyclohexyl. In embodiments, R 8.3 is unsubstituted hexyl. In embodiments, R 8.3 is a substituted C1-C6 alkyl. In an embodiment, R 8.3 is a substituted methyl. In embodiments, R 8.3 is a substituted ethyl. In embodiments, R 8.3 is a substituted propyl. In embodiments, R 8.3 is substituted n-propyl. In embodiments, R 8.3 is substituted isopropyl. In embodiments, R 8.3 is a substituted butyl. In embodiments, R 8.3 is a substituted n-butyl. In embodiments, R 8.3 is substituted isobutyl. In embodiments, R 8.3 is a substituted tert-butyl. In embodiments, R 8.3 is a substituted pentyl. In embodiments, R 8.3 is a substituted hexyl. In embodiments, R8.3 is —CH—(unsubstituted phenyl). In embodiments, R 8.3 is a substituted or unsubstituted 2-8 membered heteroalkyl. In embodiments, R 8.3 is unsubstituted methoxy. In embodiments, R 8.3 is -OCD3. In embodiments, R 8.3 is unsubstituted ethoxy. In embodiments, R 8.3 is unsubstituted propoxy. In embodiments, R 8.3 is unsubstituted n-propoxy. In embodiments, R 8.3 is unsubstituted isopropoxy. In embodiments, R 8.3 is unsubstituted butoxy. In embodiments, R 8.3 is —CH2OCH3. In embodiments, R 8.3 is —OCH2CF3. In embodiments, R 8.3 is —OCH2CHF2. In an embodiment, R 8.3 is —OCH2CH2F. In embodiments, R 8.3 teeth,

[0377] [ka] In an embodiment, R 8.3 teeth,

[0378] [ka] In an embodiment, R 8.3 teeth,

[0379] [ka] In an embodiment, R 8.3 is unsubstituted C3-C8 cycloalkyl. In embodiments, R 8.3 is unsubstituted cyclopropyl. In embodiments, R 8.3 is unsubstituted cyclobutyl. In embodiments, R 8.3 is unsubstituted cyclopentyl. In embodiments, R 8.3is unsubstituted cyclohexyl. In embodiments, R 8.3 is unsubstituted phenyl.

[0380] In embodiments, R 8.2 and R 8.3 The substituents are linked to form an unsubstituted C3-C8 cycloalkyl. In embodiments, R 8.2 and R 8.3 The substituents are linked to form an unsubstituted C cycloalkyl. In embodiments, R 8.2 and R 8.3 The substituents are linked to form an unsubstituted C4 cycloalkyl. In embodiments, R 8.2 and R 8.3 The substituents are linked to form an unsubstituted C5 cycloalkyl. In embodiments, R 8.2 and R 8.3 The substituents are linked to form an unsubstituted C6 cycloalkyl. In embodiments, R 8.2 and R 8.3 The substituents are linked to form an unsubstituted C7 cycloalkyl. In embodiments, R 8.2 and R 8.3 The substituents are linked to form an unsubstituted C8 cycloalkyl.

[0381] In an embodiment,

[0382] [ka]

[0383] [ka] is.

[0384] In an embodiment,

[0385] [ka]

[0386] [ka]

[0387] [ka] is.

[0388] In an embodiment,

[0389] [ka] In an embodiment,

[0390] [ka] In an embodiment,

[0391] [ka] In an embodiment,

[0392] [ka] In an embodiment,

[0393] [ka] In an embodiment,

[0394] [ka] In an embodiment,

[0395] [ka] In an embodiment,

[0396] [ka] In an embodiment,

[0397] [ka] In an embodiment,

[0398] [ka] In an embodiment,

[0399] [ka] In an embodiment,

[0400] [ka] In an embodiment,

[0401] [ka] In an embodiment,

[0402] [ka] In an embodiment,

[0403] [ka] In an embodiment,

[0404] [ka] In an embodiment,

[0405] [ka] In an embodiment,

[0406] [ka] In an embodiment,

[0407] [ka] In an embodiment,

[0408] [ka] In an embodiment,

[0409] [ka] In an embodiment,

[0410] [ka] In an embodiment,

[0411] [ka] In an embodiment,

[0412] [ka] In an embodiment,

[0413] [ka] In an embodiment,

[0414] [ka] In an embodiment,

[0415] [ka] In an embodiment,

[0416] [ka] In an embodiment,

[0417] [ka] In an embodiment,

[0418] [ka] In an embodiment,

[0419] [ka] In an embodiment,

[0420] [ka] In an embodiment,

[0421] [ka] In an embodiment,

[0422] [ka] In an embodiment,

[0423] [ka] In an embodiment,

[0424] [ka] In an embodiment,

[0425] [ka] In an embodiment,

[0426] [ka] In an embodiment,

[0427] [ka] In an embodiment,

[0428] [ka] In an embodiment,

[0429] [ka] In an embodiment,

[0430] [ka] In an embodiment,

[0431] [ka] In an embodiment,

[0432] [ka] In an embodiment,

[0433] [ka] In an embodiment,

[0434] [ka] In an embodiment,

[0435] [ka] In an embodiment,

[0436] [ka] In an embodiment,

[0437] [ka] In an embodiment,

[0438] [ka] In an embodiment,

[0439] [ka] In an embodiment,

[0440] [ka] In an embodiment,

[0441] [ka] In an embodiment,

[0442] [ka] In an embodiment,

[0443] [ka] In an embodiment,

[0444] [ka] In an embodiment,

[0445] [ka] In an embodiment,

[0446] [ka] In an embodiment,

[0447] [ka] In an embodiment,

[0448] [ka] In an embodiment,

[0449] [ka] In an embodiment,

[0450] [ka] In an embodiment,

[0451] [ka] In an embodiment,

[0452] [ka] In an embodiment,

[0453] [ka] In an embodiment,

[0454] [ka] In an embodiment,

[0455] [ka] In an embodiment,

[0456] [ka] In an embodiment,

[0457] [ka] In an embodiment,

[0458] [ka] In an embodiment,

[0459] [ka] In an embodiment,

[0460] [ka] In an embodiment,

[0461] [ka] In an embodiment,

[0462] [ka] In an embodiment,

[0463] [ka] In an embodiment,

[0464] [ka] In an embodiment,

[0465] [ka] In an embodiment,

[0466] [ka] In an embodiment,

[0467] [ka] In an embodiment,

[0468] [ka] In an embodiment,

[0469] [ka] In an embodiment,

[0470] [ka] In an embodiment,

[0471] [ka] In an embodiment,

[0472] [ka] In an embodiment,

[0473] [ka] In an embodiment,

[0474] [ka] In an embodiment,

[0475] [ka] In an embodiment,

[0476] [ka] In an embodiment,

[0477] [ka] is.

[0478] In an embodiment, the substitution L 1 (e.g., substituted alkylene) is substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted L 1 When L is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 1 When substituted, L is substituted with at least one substituent. 1 When substituted, L is substituted with at least one size-limiting substituent. 1 When substituted, it is substituted with at least one lower substituent.

[0479] In an embodiment, L 1is a bond or a substituted or unsubstituted C1-C5 alkylene. 1 is a bond or unsubstituted C1-C5 alkylene. 1 is a bond. In embodiments, L 1 is unsubstituted methylene. In embodiments, L 1 is unsubstituted ethylene. In embodiments, L 1 is unsubstituted propylene. In embodiments, L 1 is unsubstituted butylene. In embodiments, L 1 is unsubstituted pentylene.

[0480] In embodiments, the substitution R 9 (e.g., substituted cycloalkylene and / or substituted heterocycloalkylene) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 9 When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 9 When substituted, R is substituted with at least one substituent. 9 When substituted, R is substituted with at least one size-limited substituent. 9 When substituted, it is substituted with at least one lower substituent.

[0481] In embodiments, R 9 is a substituted or unsubstituted C3-C8 cycloalkyl, or a substituted or unsubstituted 3- to 8-membered heterocycloalkyl.

[0482] In embodiments, R 9 is R 11 substituted or unsubstituted heteroalkyl, or R 11 It is a substituted or unsubstituted heterocycloalkyl.

[0483] R 11 are independently oxo, halogen, -CX 113. -CHX 11 2. -CH2X 11 , -OCX 11 3. -OCH2X 11 , -OCHX 11 2, -CN, -SO n11 R 11D , -SO v11 NR 11A R 11B , -NR 11C NR 11A R 11B , -ONR 11A R 11B , -NHC(O)NR 11C NR 11A R 11B , -NHC(O)NR 11A R 11B , -N(O) m11 , -NR 11A R 11B , -C(O)R 11C , -C(O)OR 11C , -C(O)NR 11A R 11B , -OR 11D , -SR 11D , -NR 11A SO2R 11D , -NR 11A C(O)R 11C , -NR 11A C(O)OR 11C , -NR 11A OR 11C , -SF5, -N3, substituted or unsubstituted alkyl (e.g., C1 to C8, C1 to C6, C1 to C4, or C1 to C2), substituted or unsubstituted heteroalkyl (e.g., 2 to 8 members, 2 to 6 members, 4 to 6 members, 2 to 3 members, or 4 to 5 members), substituted or unsubstituted cycloalkyl (e.g., C3 to C8, C3 to C6, C4 to C6, or C5 to C6), substituted or unsubstituted heterocycloalkyl (e.g., 3 to 8 members, 3 to 6 members, 4 to 6 members, 4 to 5 members, or 5 to 6 members), substituted or unsubstituted aryl (e.g., C6 to C 10 or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered), and two R 11The substituents may be optionally linked to form a substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), a substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), a substituted or unsubstituted aryl (e.g., C6-C 10 or phenyl), or substituted or unsubstituted heteroaryl (eg, 5-10 membered, 5-9 membered, or 5-6 membered).

[0484] R 11A , R 11B , R 11C , and R 11D are independently hydrogen, -CCl3, -CBr3, -CF3, -CI3, CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl( For example, C1 to C8, C1 to C6, C1 to C4, or C1 to C2), substituted or unsubstituted heteroalkyl (for example, 2 to 8 members, 2 to 6 members, 4 to 6 members, 2 to 3 members, or 4 to 5 members), substituted or unsubstituted cycloalkyl (for example, C3 to C8, C3 to C6, C4 to C6, or C5 to C6), substituted or unsubstituted heterocycloalkyl (for example, 3 to 8 members, 3 to 6 members, 4 to 6 members, 4 to 5 members, or 5 to 6 members), substituted or unsubstituted aryl (for example, C6 to C 10 or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered), and R 11A and R 11B The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered) or a substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered).

[0485] X11 is independently -F, -Cl, -Br, or -I.

[0486] The symbol n11 is independently an integer of 0 to 4.

[0487] The symbols m11 and v11 are independently 1 or 2.

[0488] In embodiments, R 9 is R 11 Substituted or unsubstituted C3-C8 cycloalkyl, or R 11 In one embodiment, R is a substituted or unsubstituted 3- to 8-membered heterocycloalkyl. 9 is R 11 substituted or unsubstituted spirocyclic cycloalkyl, or R 11 In embodiments, R is a substituted or unsubstituted spirocyclic heterocycloalkyl. 9 is R 11 Substituted or unsubstituted C6-C 12 Spirocyclic cycloalkyl or R 11 In one embodiment, R is a substituted or unsubstituted 6- to 12-membered spirocyclic heterocycloalkyl. 9 is R 11 substituted or unsubstituted bridged cycloalkyl, or R 11 In embodiments, R is a substituted or unsubstituted bridged heterocycloalkyl. 9 is R 11 Substituted or unsubstituted C5-C 12 Bridged cycloalkyl or R 11 It is a substituted or unsubstituted 5- to 12-membered spirocyclic heterocycloalkyl.

[0489] In embodiments, R 9 teeth,

[0490] [ka] R 11 is as described herein, including embodiments.

[0491] R 12is hydrogen, halogen, -CX 12 3. -CHX 12 2. -CH2X 12 , -OCX 12 3. -OCH2X 12 , -OCHX 12 2, -SO n12 R 12D , -SO v12 NR 12A R 12B , -C(O)R 12C , -C(O)OR 12C , -C(O)NR 12A R 12B , -OR 12D , substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted heteroalkyl (e.g., 2-8 membered, 2-6 membered, 4-6 membered, 2-3 membered, or 4-5 membered), substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyl (e.g., 3-8 membered, 3-6 membered, 4-6 membered, 4-5 membered, or 5-6 membered), substituted or unsubstituted aryl (e.g., C6-C 10 or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered).

[0492] R 12A , R 12B , R 12C , and R 12Dare independently hydrogen, -CCl3, -CBr3, -CF3, -CI3, CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl( For example, C1 to C8, C1 to C6, C1 to C4, or C1 to C2), substituted or unsubstituted heteroalkyl (for example, 2 to 8 members, 2 to 6 members, 4 to 6 members, 2 to 3 members, or 4 to 5 members), substituted or unsubstituted cycloalkyl (for example, C3 to C8, C3 to C6, C4 to C6, or C5 to C6), substituted or unsubstituted heterocycloalkyl (for example, 3 to 8 members, 3 to 6 members, 4 to 6 members, 4 to 5 members, or 5 to 6 members), substituted or unsubstituted aryl (for example, C6 to C 10 or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 membered, 5-9 membered, or 5-6 membered), and R 12A and R 12B The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl (e.g., 3 to 8 members, 3 to 6 members, 4 to 6 members, 4 to 5 members, or 5 to 6 members), or a substituted or unsubstituted heteroaryl (e.g., 5 to 10 members, 5 to 9 members, or 5 to 6 members).

[0493] X 12 is independently -F, -Cl, -Br, or -I.

[0494] The symbol n12 is independently an integer of 0 to 4.

[0495] The symbol v12 is independently 1 or 2.

[0496] The symbol z11 is an integer of 0-13.

[0497] In embodiments, R 9 teeth,

[0498] [ka] R 11 , z11, and R 12 as described herein, including the embodiments.

[0499] In embodiments, R 9 teeth,

[0500] [ka] R 11 , z11, and R 12 as described herein, including the embodiments.

[0501] In embodiments, the substitution R 11 (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 11 When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 11 When substituted, R is substituted with at least one substituent. 11 When substituted, R is substituted with at least one size-limited substituent. 11 When substituted, it is substituted with at least one lower substituent.

[0502] In embodiments, the substitution R 11A (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 11AWhen R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 11A When substituted, R is substituted with at least one substituent. 11A When substituted, R is substituted with at least one size-limited substituent. 11A When substituted, it is substituted with at least one lower substituent.

[0503] In embodiments, the substitution R 11B (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 11B When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 11B When substituted, R is substituted with at least one substituent. 11B When substituted, R is substituted with at least one size-limited substituent. 11B When substituted, it is substituted with at least one lower substituent.

[0504] In embodiments, R 11A and R 11B If the substituted ring formed when the substituents are linked is substituted, it is substituted with at least one substituent group, size-limited substituent group, or lower substituent group, and R 11A and R 11BWhen the substituted ring formed when the substituents are linked is substituted with multiple groups selected from a substituent group, a size-limited substituent group, and a lower substituent group, each substituent, size-limited substituent, and / or lower substituent may optionally be different. In embodiments, R 11A and R 11B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one substituent group. In embodiments, R 11A and R 11B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one size-limited substituent group. In embodiments, R 11A and R 11B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one lower substituent group.

[0505] In embodiments, the substitution R 11C (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 11C When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 11C When substituted, R is substituted with at least one substituent. 11C When substituted, R is substituted with at least one size-limited substituent.11C When substituted, it is substituted with at least one lower substituent.

[0506] In embodiments, the substitution R 11D (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 11D When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 11D When substituted, R is substituted with at least one substituent. 11D When substituted, R is substituted with at least one size-limited substituent. 11D When substituted, it is substituted with at least one lower substituent.

[0507] In embodiments, R 11 are independently oxo, halogen, -CX 11 3. -CHX 11 2. -CH2X 11 , -OCX 11 3. -OCH2X 11 , -OCHX 11 2, -CN, -SO n11 R 11D , -SO v11 NR 11A R 11B , -NHC(O)NR 11A R 11B , -NR 11A R 11B , -C(O)R 11C , -C(O)OR 11C , -C(O)NR 11A R 11B , -OR 11D , -SR 11D , -NR 11A SO2R 11D , -NR 11A C(O)R 11C , -NR11A C(O)OR 11C , -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0508] In embodiments, R 11 are independently oxo, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH 2, -NHC(O)NHNH2, -NHC(O)NH2, -NO2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0509] In embodiments, R 11are independently oxo, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -SONH, -NHC(O)NH, -NH, -C(O)H, -C(O)OH, -CONH, -OH, -SH, -NHSOH, -NHC(O)H, -NHC(O)OH, -SF, -N, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0510] In embodiments, R 11 are independently oxo, halogen, -CX 11 3. -CN, -C(O)OR 11C , -C(O)NR 11A R 11B , -C(O)R 11C , -OR 11D , substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted 2-5 membered heteroalkyl.

[0511] In embodiments, R 11 are independently oxo, halogen, -CX 11 3. -CHX 11 2, -CN, -SO n11 R 11D , -C(O)R 11C , -C(O)OR 11C , -C(O)NR 11A R 11B , -C(O)R 11C , -OR 11D , -NR 11A SO2R 11D , -NR 11A C(O)R 11C , -NR 11A C(O)OR 11C, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted 2- to 5-membered heteroalkyl, or substituted or unsubstituted 5- to 10-membered heteroaryl.

[0512] In embodiments, R 11A are independently hydrogen or unsubstituted C1-C6 alkyl, and R 11B are independently hydrogen. In embodiments, R 11A are independently hydrogen. In embodiments, R 11A is independently an unsubstituted C1-C6 alkyl. In an embodiment, R 11A is independently unsubstituted methyl. In embodiments, R 11A is independently unsubstituted ethyl. In embodiments, R 11A is independently unsubstituted propyl. In embodiments, R 11A is independently unsubstituted n-propyl. In embodiments, R 11A is independently unsubstituted isopropyl. In embodiments, R 11A is independently unsubstituted butyl. In embodiments, R 11A is independently unsubstituted n-butyl. In embodiments, R 11A is independently unsubstituted isobutyl. In embodiments, R 11A is independently unsubstituted tert-butyl. In embodiments, R 11A is independently unsubstituted pentyl. In embodiments, R 11A is independently unsubstituted hexyl. In embodiments, R 11A is independently —OH. In an embodiment, R 11A is independently —C(O)CH. In embodiments, R 11B are independently hydrogen.

[0513] In embodiments, R 11C are independently hydrogen or unsubstituted C1-C6 alkyl. 11C are independently hydrogen. In embodiments, R 11C is independently an unsubstituted C1-C6 alkyl. In an embodiment, R 11Cis independently unsubstituted methyl. In embodiments, R 11C is independently unsubstituted ethyl. In embodiments, R 11C is independently unsubstituted propyl. In embodiments, R 11C is independently unsubstituted n-propyl. In embodiments, R 11C is independently unsubstituted isopropyl. In embodiments, R 11C is independently unsubstituted butyl. In embodiments, R 11C is independently unsubstituted n-butyl. In embodiments, R 11C is independently unsubstituted isobutyl. In embodiments, R 11C is independently unsubstituted tert-butyl. In embodiments, R 11C is independently unsubstituted pentyl. In embodiments, R 11C is independently unsubstituted hexyl. In embodiments, R 11C is independently a substituted or unsubstituted 5-10 membered heteroaryl. 11C is independently unsubstituted thiazolyl. In embodiments, R 11C is, independently,

[0514] [ka] is.

[0515] In embodiments, R 11D are independently hydrogen or unsubstituted C1-C6 alkyl. 11D are independently hydrogen. In embodiments, R 11D is independently an unsubstituted C1-C6 alkyl. In an embodiment, R 11D is independently unsubstituted methyl. In embodiments, R 11D is independently unsubstituted ethyl. In embodiments, R 11D is independently unsubstituted propyl. In embodiments, R 11D is independently unsubstituted n-propyl. In embodiments, R 11Dis independently unsubstituted isopropyl. In embodiments, R 11D is independently unsubstituted butyl. In embodiments, R 11D is independently unsubstituted n-butyl. In embodiments, R 11D is independently unsubstituted isobutyl. In embodiments, R 11D is independently unsubstituted tert-butyl. In embodiments, R 11D is independently unsubstituted pentyl. In embodiments, R 11D is independently unsubstituted hexyl.

[0516] In embodiments, two R 11 The substituents may be linked to form a substituted or unsubstituted cycloalkyl. In embodiments, two R 11 The substituents may be linked to form a substituted or unsubstituted C3-C8 cycloalkyl. In embodiments, two R 11 The substituents are linked to form an unsubstituted cyclopropyl. In embodiments, two R 11 The substituents are linked to form an unsubstituted cyclobutyl. In embodiments, two R 11 The substituents are linked to form an unsubstituted cyclopentyl. In embodiments, two R 11 The substituents are linked to form an unsubstituted cyclohexyl. In embodiments, two R 11 The substituents are linked to form an unsubstituted cycloheptyl. In embodiments, two R 11 The substituents are linked to form an unsubstituted cyclooctyl.

[0517] In embodiments, R 11 is independently oxo. In embodiments, R 11 is independently halogen. In an embodiment, R 11 is -F. In an embodiment, R 11 is independently —CF. In an embodiment, R 11 is independently -CHF. In an embodiment, R 11 is independently —CN. In an embodiment, R 11 is independently —OH. In an embodiment, R11 is independently —C(O)OH. In embodiments, R 11 is independently —C(O)OCH. In embodiments, R 11 is independently —C(O)OCH2CH3. In embodiments, R 11 is independently —C(O)CH. In embodiments, R 11 is independently —C(O)NH. In embodiments, R 11 is independently —C(O)NHOH. In embodiments, R 11 is independently —S(O)2CH3. In an embodiment, R 11 is independently —NHC(O)CH. In embodiments, R 11 is independently —C(O)H. In embodiments, R 11 is independently —NHS(O)2CH3. In an embodiment, R 11 is independently —C(O)NHS(O)2CH3. In an embodiment, R 11 is independently an unsubstituted C1-C6 alkyl. In an embodiment, R 11 is independently unsubstituted methyl. In embodiments, R 11 is independently unsubstituted ethyl. In embodiments, R 11 is independently unsubstituted propyl. In embodiments, R 11 is independently unsubstituted n-propyl. In embodiments, R 11 is independently unsubstituted isopropyl. In embodiments, R 11 is independently unsubstituted butyl. In embodiments, R 11 is independently unsubstituted n-butyl. In embodiments, R 11 is independently unsubstituted isobutyl. In embodiments, R 11 is independently unsubstituted tert-butyl. In embodiments, R 11 is independently unsubstituted pentyl. In embodiments, R 11 is independently unsubstituted hexyl. In embodiments, R 11 is independently a substituted C1-C6 alkyl. In an embodiment, R 11is independently a substituted methyl. In embodiments, R 11 is independently substituted ethyl. In embodiments, R 11 is independently substituted propyl. In embodiments, R 11 is independently substituted n-propyl. In embodiments, R 11 is independently substituted isopropyl. In embodiments, R 11 is independently a substituted butyl. In an embodiment, R 11 is independently a substituted n-butyl. In an embodiment, R 11 is independently substituted isobutyl. In embodiments, R 11 is independently a substituted tert-butyl. In embodiments, R 11 is independently substituted pentyl. In embodiments, R 11 is independently a substituted hexyl. In embodiments, R 11 is independently a substituted or unsubstituted 2-6 membered heteroalkyl. 11 is independently unsubstituted methoxy. In embodiments, R 11 is independently unsubstituted ethoxy. In embodiments, R 11 is independently unsubstituted propoxy. In embodiments, R 11 is independently unsubstituted n-propoxy. In embodiments, R 11 is independently unsubstituted isopropoxy. In embodiments, R 11 is independently unsubstituted butoxy. In embodiments, R 11 is, independently,

[0518] [ka] In an embodiment, R 11 is, independently,

[0519] [ka] In an embodiment, R 11 is, independently,

[0520] [ka] In an embodiment, R 11 is, independently,

[0521] [ka] In an embodiment, R 11 is, independently,

[0522] [ka] In an embodiment, R 11 is, independently,

[0523] [ka] In an embodiment, R 11 is, independently,

[0524] [ka] In an embodiment, R 11 is, independently,

[0525] [ka] In an embodiment, R 11 is, independently,

[0526] [ka] In an embodiment, R 11 is, independently,

[0527] [ka] In an embodiment, R 11 is, independently,

[0528] [ka] In an embodiment, R 11 is, independently,

[0529] [ka] In an embodiment, R 11 is, independently,

[0530] [ka] In an embodiment, R 11 is, independently,

[0531] [ka] In an embodiment, R 11 is, independently,

[0532] [ka] In an embodiment, R 11 is, independently,

[0533] [ka] In an embodiment, R 11 is independently a substituted or unsubstituted 5-10 membered heteroaryl. 11 is independently unsubstituted pyridyl. In embodiments, R 11 is independently unsubstituted 2-pyridyl. In embodiments, R 11 is independently unsubstituted 3-pyridyl. In embodiments, R 11 is independently unsubstituted 4-pyridyl. In embodiments, R 11 is independently unsubstituted oxazolyl. In embodiments, R 11is independently unsubstituted isoxazolyl. In embodiments, R 11 is independently a substituted isoxazolyl. 11 is, independently,

[0534] [ka] In an embodiment, R 11 is independently unsubstituted tetrazolyl.

[0535] In an embodiment, z11 is 0. In an embodiment, z11 is 1. In an embodiment, z11 is 2. In an embodiment, z11 is 3. In an embodiment, z11 is 4. In an embodiment, z11 is 5. In an embodiment, z11 is 6. In an embodiment, z11 is 7. In an embodiment, z11 is 8. In an embodiment, z11 is 9. In an embodiment, z11 is 10. In an embodiment, z11 is 11. In an embodiment, z11 is 12. In an embodiment, z11 is 13.

[0536] In embodiments, the substitution R 12 (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 12 When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 12 When substituted, R is substituted with at least one substituent. 12 When substituted, R is substituted with at least one size-limited substituent. 12 When substituted, it is substituted with at least one lower substituent.

[0537] In embodiments, the substitution R12A (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 12A When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 12A When R is substituted, it is substituted with at least one substituent. 12A When R is substituted, it is substituted with at least one size-limited substituent. 12A When is substituted, it is substituted with at least one lower substituent.

[0538] In embodiments, the substitution R 12B (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 12B When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 12B When substituted, R is substituted with at least one substituent. 12B When substituted, R is substituted with at least one size-limited substituent. 12B When is substituted, it is substituted with at least one lower substituent.

[0539] In embodiments, R 12A and R 12BIf the substituted ring formed when the substituents are linked is substituted, it is substituted with at least one substituent group, size-limited substituent group, or lower substituent group, and R 12A and R 12B When the substituted ring formed when the substituents are linked is substituted with multiple groups selected from a substituent group, a size-limited substituent group, and a lower substituent group, each substituent, size-limited substituent, and / or lower substituent may optionally be different. In embodiments, R 12A and R 12B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one substituent group. In embodiments, R 12A and R 12B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one size-limited substituent group. In embodiments, R 12A and R 12B The substituted ring formed when the substituents are linked, if substituted, is substituted with at least one lower substituent group.

[0540] In embodiments, the substitution R 12C (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 12CWhen R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 12C When substituted, R is substituted with at least one substituent. 12C When substituted, R is substituted with at least one size-limited substituent. 12C When substituted, it is substituted with at least one lower substituent.

[0541] In embodiments, the substitution R 12D (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and the substituted R 12D When R is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may optionally be different. 12D When substituted, R is substituted with at least one substituent. 12D When substituted, R is substituted with at least one size-limited substituent. 12D When substituted, it is substituted with at least one lower substituent.

[0542] In embodiments, R 12 is hydrogen, halogen, -CX 12 3. -CHX 12 2. -CH2X 12 , -OCX 12 3. -OCH2X 12 , -OCHX 12 2, -CN, -SO n12 R 12D , -SO v12 NR 12A R 12B , -NHC(O)NR 12A R 12B , -NR 12A R12B , -C(O)R 12C , -C(O)OR 12C , -C(O)NR 12A R 12B , -OR 12D , -SR 12D , -NR 12A SO2R 12D , -NR 12A C(O)R 12C , -NR 12A C(O)OR 12C , -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0543] In embodiments, R 12 is hydrogen, halogen, —CCl3, —CBr3, —CF3, —CI3, —CHCl2, —CHBr2, —CHF2, —CHI2, —CH2Cl, —CH2Br, —CH2F, —CH2I, —OCCl3, —OCF3, —OCBr3, —OCI3, —OCHCl2, —OCHBr2, —OCHI2, —OCHF2, —OCH2Cl, —OCH2Br, —OCHI, —OCH2F, —CN, —SOH, —OSOH, —SONH2, —C(O)H, —C(O)OH, —CONH2, —OH, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0544] In embodiments, R 12represents hydrogen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -SO3H, -OSO3H, -SO 2NH2, -NHC(O)NH2, -NH2, -C(O)H, -C(O)OH, -CONH2, -OH, -SH, -NHSO2H, -NHC(O)H, -NHC(O)OH, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0545] In embodiments, R 12 is hydrogen, -C(O)R 12C , -SO n12 R 12D , -SO v12 NR 12A R 12B , -C(O)OR 12C , -C(O)NR 12A R 12B , unsubstituted C1-C6 alkyl, unsubstituted C3-C8 cycloalkyl, or unsubstituted 3- to 8-membered heterocycloalkyl.

[0546] In embodiments, R 12A is hydrogen, unsubstituted C1-C6 alkyl, or unsubstituted C3-C8 cycloalkyl, and R 12B is hydrogen. In embodiments, R 12A is hydrogen. In embodiments, R 12A is an unsubstituted C1-C6 alkyl. In embodiments, R 12A is unsubstituted methyl. In embodiments, R 12A is unsubstituted ethyl. In embodiments, R 12A is unsubstituted propyl. In embodiments, R 12A is unsubstituted n-propyl. In embodiments, R 12Ais unsubstituted isopropyl. In embodiments, R 12A is unsubstituted butyl. In embodiments, R 12A is unsubstituted n-butyl. In embodiments, R 12A is unsubstituted isobutyl. In embodiments, R 12A is unsubstituted tert-butyl. In embodiments, R 12A is unsubstituted pentyl. In embodiments, R 12A is unsubstituted hexyl. In embodiments, R 12A is unsubstituted C3-C8 cycloalkyl. In embodiments, R 12A is unsubstituted cyclopropyl. In embodiments, R 12A is unsubstituted cyclobutyl. In embodiments, R 12A is unsubstituted cyclopentyl. In embodiments, R 12A is unsubstituted cyclohexyl. In embodiments, R 12B is hydrogen.

[0547] In embodiments, R 12C is a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted 2-6 membered heteroalkyl, or a substituted or unsubstituted C3-C8 cycloalkyl. 12C is hydrogen. In embodiments, R 12C is an unsubstituted C1-C6 alkyl. In embodiments, R 12C is unsubstituted methyl. In embodiments, R 12C is unsubstituted ethyl. In embodiments, R 12C is unsubstituted propyl. In embodiments, R 12C is unsubstituted n-propyl. In embodiments, R 12C is unsubstituted isopropyl. In embodiments, R 12C is unsubstituted butyl. In embodiments, R 12C is unsubstituted n-butyl. In embodiments, R 12C is unsubstituted isobutyl. In embodiments, R 12C is unsubstituted tert-butyl. In embodiments, R 12C is unsubstituted pentyl. In embodiments, R12C is unsubstituted hexyl. In embodiments, R 12C is unsubstituted C3-C8 cycloalkyl. In embodiments, R 12C is unsubstituted cyclopropyl. In embodiments, R 12C is unsubstituted cyclobutyl. In embodiments, R 12C is unsubstituted cyclopentyl. In embodiments, R 12C is unsubstituted cyclohexyl.

[0548] In embodiments, R 12D is an unsubstituted C1-C6 alkyl. In embodiments, R 12D is hydrogen. In embodiments, R 12D is an unsubstituted C1-C6 alkyl. In embodiments, R 12D is unsubstituted methyl. In embodiments, R 12D is unsubstituted ethyl. In embodiments, R 12D is unsubstituted propyl. In embodiments, R 12D is unsubstituted n-propyl. In embodiments, R 12D is unsubstituted isopropyl. In embodiments, R 12D is unsubstituted butyl. In embodiments, R 12D is unsubstituted n-butyl. In embodiments, R 12D is unsubstituted isobutyl. In embodiments, R 12D is unsubstituted tert-butyl. In embodiments, R 12D is unsubstituted pentyl. In embodiments, R 12D is unsubstituted hexyl.

[0549] In embodiments, R 9 teeth,

[0550] [ka]

[0551] [ka]

[0552] [ka] is.

[0553] In embodiments, R 9 teeth,

[0554] [ka]

[0555] [ka]

[0556] [ka]

[0557] [ka] is.

[0558] In embodiments, R 9 teeth,

[0559] [ka] In an embodiment, R 9 teeth,

[0560] [ka] In an embodiment, R 9 teeth,

[0561] [ka] In an embodiment, R 9 teeth,

[0562] [ka] In an embodiment, R 9 teeth,

[0563] [ka] In an embodiment, R 9 teeth,

[0564] [ka] In an embodiment, R 9 teeth,

[0565] [ka] In an embodiment, R 9 teeth,

[0566] [ka] In an embodiment, R 9 teeth,

[0567] [ka] In an embodiment, R 9 teeth,

[0568] [ka] In an embodiment, R 9 teeth,

[0569] [ka] In an embodiment, R 9 teeth,

[0570] [ka] In an embodiment, R 9 teeth,

[0571] [ka] In an embodiment, R 9 teeth,

[0572] [ka] In an embodiment, R 9 teeth,

[0573] [ka] In an embodiment, R 9 teeth,

[0574] [ka] In an embodiment, R 9 teeth,

[0575] [ka] In an embodiment, R 9 teeth,

[0576] [ka] In an embodiment, R 9 teeth,

[0577] [ka] In an embodiment, R 9 teeth,

[0578] [ka] In an embodiment, R 9 teeth,

[0579] [ka] In an embodiment, R 9 teeth,

[0580] [ka] In an embodiment, R 9 teeth,

[0581] [ka] In an embodiment, R 9 teeth,

[0582] [ka] In an embodiment, R 9 teeth,

[0583] [ka] In an embodiment, R 9 teeth,

[0584] [ka] In an embodiment, R 9 teeth,

[0585] [ka] In an embodiment, R 9 teeth,

[0586] [ka] In an embodiment, R 9 teeth,

[0587] [ka] In an embodiment, R 9 teeth,

[0588] [ka] In an embodiment, R 9 teeth,

[0589] [ka] In an embodiment, R 9 teeth,

[0590] [ka] In an embodiment, R 9 teeth,

[0591] [ka] In an embodiment, R 9 teeth,

[0592] [ka] In an embodiment, R 9 teeth,

[0593] [ka] In an embodiment, R 9 teeth,

[0594] [ka] In an embodiment, R 9 teeth,

[0595] [ka] In an embodiment, R 9 teeth,

[0596] [ka] In an embodiment, R 9 teeth,

[0597] [ka] In an embodiment, R 9 teeth,

[0598] [ka] In an embodiment, R 9 teeth,

[0599] [ka] In an embodiment, R 9 teeth,

[0600] [ka] In an embodiment, R 9 teeth,

[0601] [ka] In an embodiment, R 9 teeth,

[0602] [ka] In an embodiment, R 9 teeth,

[0603] [ka] In an embodiment, R 9 teeth,

[0604] [ka] In an embodiment, R 9 teeth,

[0605] [ka] In an embodiment, R 9 teeth,

[0606] [ka] In an embodiment, R 9 teeth,

[0607] [ka] In an embodiment, R 9 teeth,

[0608] [ka] In an embodiment, R 9 teeth,

[0609] [ka] In an embodiment, R 9 teeth,

[0610] [ka] In an embodiment, R 9 teeth,

[0611] [ka] In an embodiment, R 9 teeth,

[0612] [ka] In an embodiment, R 9 teeth,

[0613] [ka] In an embodiment, R 9 teeth,

[0614] [ka] In an embodiment, R 9 teeth,

[0615] [ka] In an embodiment, R 9 teeth,

[0616] [ka] In an embodiment, R 9 teeth,

[0617] [ka] In an embodiment, R 9 teeth,

[0618] [ka] In an embodiment, R 9 teeth,

[0619] [ka] In an embodiment, R9 teeth,

[0620] [ka] In an embodiment, R 9 teeth,

[0621] [ka] In an embodiment, R 9 teeth,

[0622] [ka] In an embodiment, R 9 teeth,

[0623] [ka] In an embodiment, R 9 teeth,

[0624] [ka] In an embodiment, R 9 teeth,

[0625] [ka] In an embodiment, R 9 teeth,

[0626] [ka] In an embodiment, R 9 teeth,

[0627] [ka] In an embodiment, R 9 teeth,

[0628] [ka] In an embodiment, R 9 teeth,

[0629] [ka] In an embodiment, R 9 teeth,

[0630] [ka] In an embodiment, R 9 teeth,

[0631] [ka] In an embodiment, R 9 teeth,

[0632] [ka] In an embodiment, R 9 teeth,

[0633] [ka] In an embodiment, R 9 teeth,

[0634] [ka] In an embodiment, R 9 teeth,

[0635] [ka] In an embodiment, R 9 teeth,

[0636] [ka] In an embodiment, R 9 teeth,

[0637] [ka] In an embodiment, R 9 teeth,

[0638] [ka] In an embodiment, R 9 teeth,

[0639] [ka] In an embodiment, R 9 teeth,

[0640] [ka] In an embodiment, R 9 teeth,

[0641] [ka] In an embodiment, R 9 teeth,

[0642] [ka] In an embodiment, R 9 teeth,

[0643] [ka] In an embodiment, R 9 teeth,

[0644] [ka] In an embodiment, R 9 teeth,

[0645] [ka] In an embodiment, R 9 teeth,

[0646] [ka] In an embodiment, R 9 teeth,

[0647] [ka] In an embodiment, R 9 teeth,

[0648] [ka] In an embodiment, R 9 teeth,

[0649] [ka] In an embodiment, R 9 teeth,

[0650] [ka] In an embodiment, R 9 teeth,

[0651] [ka] In an embodiment, R 9 teeth,

[0652] [ka] In an embodiment, R 9 teeth,

[0653] [ka] In an embodiment, R 9 teeth,

[0654] [ka] In an embodiment, R 9 teeth,

[0655] [ka] In an embodiment, R 9 teeth,

[0656] [ka] In an embodiment, R 9 teeth,

[0657] [ka] In an embodiment, R 9 teeth,

[0658] [ka] In an embodiment, R 9 teeth,

[0659] [ka] In an embodiment, R 9 teeth,

[0660] [ka] In an embodiment, R 9 teeth,

[0661] [ka] In an embodiment, R 9 teeth,

[0662] [ka] In an embodiment, R 9 teeth,

[0663] [ka] In an embodiment, R 9 teeth,

[0664] [ka] In an embodiment, R 9 teeth,

[0665] [ka] In an embodiment, R 9 teeth,

[0666] [ka] In an embodiment, R 9 teeth,

[0667] [ka] In an embodiment, R 9 teeth,

[0668] [ka] In an embodiment, R 9 teeth,

[0669] [ka] In an embodiment, R 9 teeth,

[0670] [ka] In an embodiment, R 9 teeth,

[0671] [ka] In an embodiment, R 9 teeth,

[0672] [ka] In an embodiment, R 9 teeth,

[0673] [ka] In an embodiment, R 9 teeth,

[0674] [ka] In an embodiment, R 9 teeth,

[0675] [ka] In an embodiment, R 9 teeth,

[0676] [ka] In an embodiment, R 9 teeth,

[0677] [ka] In an embodiment, R 9 teeth,

[0678] [ka] In an embodiment, R 9 teeth,

[0679] [ka] In an embodiment, R 9 teeth,

[0680] [ka] In an embodiment, R 9 teeth,

[0681] [ka] In an embodiment, R 9 teeth,

[0682] [ka] is.

[0683] In embodiments, R 1 If is substituted, R 1 is R as explained in the definition paragraph above in the description of the "first substituent" 1.1 In an embodiment, R 1.1 If the substituent is substituted, R 1.1 The substituents are as described in the definition paragraph above in the description of the "first substituent" and R 1.2 In an embodiment, R 1.2 If the substituent is substituted, R 1.2The substituents are as described in the definition paragraph above in the description of the "first substituent" and R 1.3 In the above embodiment, R 1 , R 1.1 , R 1.2 , and R 1.3 are, respectively, R as explained in the definition paragraph above in the description of the "first substituent" WW , R WW.1 , R WW.2 , and R WW.3 has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 are R 1 , R 1.1 , R 1.2 , and R 1.3 Corresponds to.

[0684] In embodiments, R 2 If is substituted, R 2 is R as explained in the definition paragraph above in the description of the "first substituent" 2.1 In an embodiment, R 2.1 If the substituent is substituted, R 2.1 The substituents are as described in the definition paragraph above in the description of the "first substituent" and R 2.2 In an embodiment, R 2.2 If the substituent is substituted, R 2.2 The substituents are as described in the definition paragraph above in the description of the "first substituent" and R 2.3 In the above embodiment, R 2 , R 2.1 , R 2.2 , and R 2.3 are, respectively, R as explained in the definition paragraph above in the description of the "second substituent" WW , R WW.1 , R WW.2 , and R WW.3 has a value corresponding to the value of RWW , R WW.1 , R WW.2 , and R WW.3 are R 1 , R 2.1 , R 2.2 , and R 2.3 Corresponds to.

[0685] In embodiments, R 2A If is substituted, R 2A is R as explained in the definition paragraph above in the description of the "first substituent" 2A.1 In an embodiment, R 2A.1 If the substituent is substituted, R 2A.1 The substituents are as described in the definition paragraph above in the description of the "first substituent" and R 2A.2 In an embodiment, R 2A.2 If the substituent is substituted, R 2A.2 The substituents are as described in the definition paragraph above in the description of the "first substituent" and R 2A.3 In the above embodiment, R 2A , R 2A.1 , R 2A.2 , and R 2A.3 are, respectively, R as explained in the definition paragraph above in the description of the "first substituent" WW , R WW.1 , R WW.2 , and R WW.3 has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 are R 2A , R 2A.1 , R 2A.2 , and R 2A.3 Corresponds to.

[0686] In embodiments, R 2B If is substituted, R 2B is R as explained ...

Claims

1. A compound, or a pharmaceutically acceptable salt or solvate thereof, having the following formula: 【Chemical 1】 In the formula: L １ is a linking, or substituted or unsubstituted C １ -C ５ alkylene, R １ is unsubstituted C ２ -C ５ alkyl, and W ２ is N or C(R ２ ) and R ２ is hydrogen, halogen, -CX ２ ３ , -CHX ２ ２ , -CH ２ X ２ , -OCX ２ ３ , -OCH ２ X ２ , -OCHX ２ ２ , -CN, -SO ｎ２ R ２Ｄ , -SO ｖ２ NR ２Ａ R ２Ｂ , -NR ２Ｃ NR ２Ａ R ２Ｂ , -ONR ２Ａ R ２Ｂ , -NHC(O)NR ２Ｃ NR ２Ａ R ２Ｂ , -NHC(O)NR ２Ａ R ２Ｂ , -N(O) ｍ２ , -NR ２Ａ R ２Ｂ , -C(O)R ２Ｃ , -C(O)OR ２Ｃ , -C(O)NR ２Ａ R ２Ｂ , -OR ２Ｄ , -SR ２Ｄ , -NR ２Ａ SO ２ R ２Ｄ , -NR ２Ａ C(O)R ２Ｃ , -NR ２Ａ C(O)OR ２Ｃ , -NR ２Ａ OR ２Ｃ , -SF ５ , -N ３ , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, R ３ is hydrogen, halogen, -CX ３ ３ , -CHX ３ ２ , -CH ２ X ３ , -OCX ３ ３ , -OCH ２ X ３ , -OCHX ３ ２ , -CN, -SO ｎ３ R ３Ｄ , -SO ｖ３ NR ３Ａ R ３Ｂ , -NR ３Ｃ NR ３Ａ R ３Ｂ , -ONR ３Ａ R ３Ｂ , -NHC(O)NR ３Ｃ NR ３Ａ R ３Ｂ , -NHC(O)NR ３Ａ R ３Ｂ , -N(O) ｍ３ , -NR ３Ａ R ３Ｂ , -C(O)R ３Ｃ , -C(O)OR ３Ｃ , -C(O)NR ３Ａ R ３Ｂ , -OR ３Ｄ , -SR ３Ｄ , -NR ３Ａ SO ２ R ３Ｄ , -NR ３Ａ C(O)R ３Ｃ , -NR ３Ａ C(O)OR ３Ｃ , -NR ３Ａ OR ３Ｃ , -SF ５ , -N ３ , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, W ４ is N or C(R ４ ) and R ４ is hydrogen, halogen, -CX ４ ３ , -CHX ４ ２ , -CH ２ X ４ , -OCX ４ ３ , -OCH ２ X ４ , -OCHX ４ ２ , -CN, -SO ｎ４ R ４Ｄ , -SO ｖ４ NR ４Ａ R ４Ｂ , -NR ４Ｃ NR ４Ａ R ４Ｂ , -ONR ４Ａ R ４Ｂ , -NHC(O)NR ４Ｃ NR ４Ａ R ４Ｂ , -NHC(O)NR ４Ａ R ４Ｂ , -N(O) ｍ４ , -NR ４Ａ R ４Ｂ , -C(O)R ４Ｃ , -C(O)OR ４Ｃ , -C(O)NR ４Ａ R ４Ｂ , -OR ４Ｄ , -SR ４Ｄ , -NR ４Ａ SO ２ R ４Ｄ , -NR ４Ａ C(O)R ４Ｃ , -NR ４Ａ C(O)OR ４Ｃ , -NR ４Ａ OR ４Ｃ , -SF ５ , -N ３ , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, W ５ is N or C(R ５ ) and R ５ is hydrogen, halogen, -CX ５ ３ , -CHX ５ ２ , -CH ２ X ５ , -OCX ５ ３ , -OCH ２ X ５ , -OCHX ５ ２ , -CN, -SO ｎ５ R ５Ｄ , -SO ｖ５ NR ５Ａ R ５Ｂ , -NR ５Ｃ NR ５Ａ R ５Ｂ , -ONR ５Ａ R ５Ｂ , -NHC(O)NR ５Ｃ NR ５Ａ R ５Ｂ , -NHC(O)NR ５Ａ R ５Ｂ , -N(O) ｍ５ , -NR ５Ａ R ５Ｂ , -C(O)R ５Ｃ , -C(O)OR ５Ｃ , -C(O)NR ５Ａ R ５Ｂ , -OR ５Ｄ , -SR ５Ｄ , -NR ５Ａ SO ２ R ５Ｄ , -NR ５Ａ C(O)R ５Ｃ , -NR ５Ａ C(O)OR ５Ｃ , -NR ５Ａ OR ５Ｃ , -SF ５ , -N ３ is substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R ２ and R ３ The substituents may be optionally linked to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, R ３ and R ４ The substituents may be optionally linked to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R ４ and R ５ The substituents may be optionally linked to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, W ６ is N or C(R ６ ) and R ６ is hydrogen, halogen, -CX ６ ３ , -CHX ６ ２ , -CH ２ X ６ , -OCX ６ ３ , -OCH ２ X ６ , -OCHX ６ ２ , -CN, -SO ｎ６ R ６Ｄ , -SO ｖ６ NR ６Ａ R ６Ｂ , -NR ６Ｃ NR ６Ａ R ６Ｂ , -ONR ６Ａ R ６Ｂ , -NHC(O)NR ６Ｃ NR ６Ａ R ６Ｂ , -NHC(O)NR ６Ａ R ６Ｂ , -N(O) ｍ６ , -NR ６Ａ R ６Ｂ , -C(O)R ６Ｃ , -C(O)OR ６Ｃ , -C(O)NR ６Ａ R ６Ｂ , -OR ６Ｄ , -SR ６Ｄ、 -NR ６Ａ SO ２ R ６Ｄ , -NR ６Ａ C(O)R ６Ｃ , -NR ６Ａ C(O)OR ６Ｃ , -NR ６Ａ OR ６Ｃ , -SF ５ , -N ３ , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, W ７ is N, N ＋ -O － or C(R ７ ) and R ７ is hydrogen, halogen, -CX ７ ３ , -CHX ７ ２ , -CH ２ X ７ , -OCX ７ ３ , -OCH ２ X ７ , -OCHX ７ ２ , -CN, -SO ｎ７ R ７Ｄ , -SO ｖ７ NR ７Ａ R ７Ｂ , -NR ７Ｃ NR ７Ａ R ７Ｂ , -ONR ７Ａ R ７Ｂ , -NHC(O)NR ７Ｃ NR ７Ａ R ７Ｂ , -NHC(O)NR ７Ａ R ７Ｂ , -N(O) ｍ７ , -NR ７Ａ R ７Ｂ , -C(O)R ７Ｃ , -C(O)OR ７Ｃ , -C(O)NR ７Ａ R ７Ｂ , -OR ７Ｄ , -SR ７Ｄ , -NR ７Ａ SO ２ R ７Ｄ , -NR ７Ａ C(O)R ７Ｃ , -NR ７Ａ C(O)OR ７Ｃ , -NR ７Ａ OR ７Ｃ , -SF ５ , -N ３ is substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R ８ is independently halogen, -CX ８ ３ -, -CHX ８ ２ -, -CH ２ X ８ -, -OCX ８ ３ -, -OCH ２ X ８ -, -OCHX ８ ２ -, -CN, -SO ｎ８ R ８Ｄ -, -SO ｖ８ NR ８Ａ R ８Ｂ -, -NR ８Ｃ NR ８Ａ R ８Ｂ -, -ONR ８Ａ R ８Ｂ -, -NHC(O)NR ８Ｃ NR ８Ａ R ８Ｂ -, -NHC(O)NR ８Ａ R ８Ｂ -, -N(O) ｍ８ -, -NR ８Ａ R ８Ｂ -, -C(O)R ８Ｃ -, -C(O)OR ８Ｃ -, -C(O)NR ８Ａ R ８Ｂ -, -OR ８Ｄ -, -SR ８Ｄ -, -NR ８Ａ SO ２ R ８Ｄ -, -NR ８Ａ C(O)R ８Ｃ -, -NR ８Ａ C(O)OR ８Ｃ -, -NR ８Ａ OR ８Ｃ -, -SF ５ -, -N ３ is a substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and two Rs ８ The substituents may be optionally linked to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, R ９ is a substituted or unsubstituted cycloalkyl or a substituted or unsubstituted heterocycloalkyl, R ２Ａ ,R ２Ｂ ,R ２Ｃ ,R ２Ｄ ,R ３Ａ ,R ３Ｂ ,R ３Ｃ ,R ３Ｄ ,R ４Ａ ,R ４Ｂ ,R ４Ｃ ,R ４Ｄ ,R ５Ａ ,R ５Ｂ ,R ５Ｃ ,R ５Ｄ ,R ６Ａ ,R ６Ｂ ,R ６Ｃ ,R ６Ｄ ,R ７Ａ ,R ７Ｂ ,R ７Ｃ ,R ７Ｄ ,R ８Ａ ,R ８Ｂ ,R ８Ｃ RRR ８Ｄ が、电影して、水水、-CC- ３ ,-CBr ３ 、-CF ３ 、-CI ３ 、-CHCl ２ ,-CHBr ２ 、-CHF ２ 、-CHI ２ 、-CH ２ Cl、-E ２ Br、-EH ２ F、-CH ２ I、-CN、-OH、-NH ２ 、-COOH、-CONH ２ 、-OCOM ３ 、-OCF ３ ,-OCBr ３ 、-OCI ３ 、-OCHCl ２ ,-OCHBr ２ ,-OCHI ２ 、-OCHF ２ ,-OCH ２ Black, white ２ Br、-OCH ２ I, -OCH ２ F, a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom ２Ａ and R ２Ｂ The substituents may be optionally linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom ３Ａ and R ３Ｂ The substituents may be optionally linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom ４Ａ and R ４Ｂ The substituents may be optionally linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom ５Ａ and R ５Ｂ The substituents may be optionally linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom ６Ａ and R ６Ｂ The substituents may be optionally linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom ７Ａ and R ７Ｂ The substituents may be optionally linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom ８Ａ and R ８Ｂ The substituents may be optionally linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl X ２ 、 X ３ 、 X ４ 、 X ５ 、 X ６ 、 X ７ 、 and X ８ are, independently, -F, -Cl, -Br, or -I, n2, n3, n4, n5, n6, n7, and n8 are each independently an integer from 0 to 4; m2, m3, m4, m5, m6, m7, m8, v2, v3, v4, v5, v6, v7, and v8 are each independently 1 or 2; z8 is an integer from 0 to 3, a compound, or a pharmaceutically acceptable salt or solvate thereof.

2. The formula: 【Chemical 2】 The compound according to Claim 1, having the formula.

3. The formula: 【Chemical Formula 3】 The compound according to Claim 1, having the formula.

4. The formula: 【Chemical Formula 4】 The compound according to Claim 1, having the formula.

5. The formula: 【Chemical Formula 5】 The compound according to Claim 1, having the formula.

6. R １ is unsubstituted C ３ alkyl, the compound according to claim 1.

7. R １ The compound according to claim 1, wherein R is isopropyl.

8. A compound, or a pharmaceutically acceptable salt or solvate thereof, having the following formula: 【Chemical Formula 6】 In the formula: L １ is a linking, or substituted or unsubstituted C １ -C ５ alkylene, R ２ is hydrogen, halogen, -CX ２ ３ , -CHX ２ ２ , -CH ２ X ２ , -OCX ２ ３ , -OCH ２ X ２ , -OCHX ２ ２ , -CN, -SO ｎ２ R ２Ｄ , -SO ｖ２ NR ２Ａ R ２Ｂ , -NR ２Ｃ NR ２Ａ R ２Ｂ , -ONR ２Ａ R ２Ｂ , -NHC(O)NR ２Ｃ NR ２Ａ R ２Ｂ , -NHC(O)NR ２Ａ R ２Ｂ , -N(O) ｍ２ , -NR ２Ａ R ２Ｂ , -C(O)R ２Ｃ , -C(O)OR ２Ｃ , -C(O)NR ２Ａ R ２Ｂ , -OR ２Ｄ , -SR ２Ｄ , -NR ２Ａ SO ２ R ２Ｄ , -NR ２Ａ C(O)R ２Ｃ , -NR ２Ａ C(O)OR ２Ｃ , -NR ２Ａ OR ２Ｃ , -SF ５ , -N ３ is substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R ３ is hydrogen, halogen, -CX ３ ３ , -CHX ３ ２ , -CH ２ X ３ , -OCX ３ ３ , -OCH ２ X ３ , -OCHX ３ ２ , -CN, -SO ｎ３ R ３Ｄ , -SO ｖ３ NR ３Ａ R ３Ｂ , -NR ３Ｃ NR ３Ａ R ３Ｂ , -ONR ３Ａ R ３Ｂ , -NHC(O)NR ３Ｃ NR ３Ａ R ３Ｂ , -NHC(O)NR ３Ａ R ３Ｂ , -N(O) ｍ３ , -NR ３Ａ R ３Ｂ , -C(O)R ３Ｃ , -C(O)OR ３Ｃ , -C(O)NR ３Ａ R ３Ｂ , -OR ３Ｄ , -SR ３Ｄ , -NR ３Ａ SO ２ R ３Ｄ , -NR ３Ａ C(O)R ３Ｃ , -NR ３Ａ C(O)OR ３Ｃ , -NR ３Ａ OR ３Ｃ , -SF ５ , -N ３ , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, R ４ is hydrogen, halogen, -CX ４ ３ , -CHX ４ ２ , -CH ２ X ４ , -OCX ４ ３ , -OCH ２ X ４ , -OCHX ４ ２ , -CN, -SO ｎ４ R ４Ｄ , -SO ｖ４ NR ４Ａ R ４Ｂ , -NR ４Ｃ NR ４Ａ R ４Ｂ , -ONR ４Ａ R ４Ｂ , -NHC(O)NR ４Ｃ NR ４Ａ R ４Ｂ , -NHC(O)NR ４Ａ R ４Ｂ , -N(O) ｍ４ , -NR ４Ａ R ４Ｂ , -C(O)R ４Ｃ , -C(O)OR ４Ｃ , -C(O)NR ４Ａ R ４Ｂ , -OR ４Ｄ , -SR ４Ｄ , -NR ４Ａ SO ２ R ４Ｄ , -NR ４Ａ C(O)R ４Ｃ , -NR ４Ａ C(O)OR ４Ｃ , -NR ４Ａ OR ４Ｃ , -SF ５ , -N ３ , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, R ５ is hydrogen, halogen, -CX ５ ３ , -CHX ５ ２ , -CH ２ X ５ , -OCX ５ ３ , -OCH ２ X ５ , -OCHX ５ ２ , -CN, -SO ｎ５ R ５Ｄ , -SO ｖ５ NR ５Ａ R ５Ｂ , -NR ５Ｃ NR ５Ａ R ５Ｂ , -ONR ５Ａ R ５Ｂ , -NHC(O)NR ５Ｃ NR ５Ａ R ５Ｂ , -NHC(O)NR ５Ａ R ５Ｂ , -N(O) ｍ５ , -NR ５Ａ R ５Ｂ , -C(O)R ５Ｃ , -C(O)OR ５Ｃ , -C(O)NR ５Ａ R ５Ｂ , -OR ５Ｄ , -SR ５Ｄ , -NR ５Ａ SO ２ R ５Ｄ , -NR ５Ａ C(O)R ５Ｃ , -NR ５Ａ C(O)OR ５Ｃ , -NR ５Ａ OR ５Ｃ , -SF ５ , -N ３ , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, R ２ and R ３ The substituents may be optionally linked to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R ３ and R ４ The substituents may be optionally linked to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, R ４ and R ５ the substituents may be optionally linked to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, W ６ is N or C(R ６ ) and R ６ is hydrogen, halogen, -CX ６ ３ , -CHX ６ ２ , -CH ２ X ６ , -OCX ６ ３ , -OCH ２ X ６ , -OCHX ６ ２ , -CN, -SO ｎ６ R ６Ｄ , -SO ｖ６ NR ６Ａ R ６Ｂ , -NR ６Ｃ NR ６Ａ R ６Ｂ , -ONR ６Ａ R ６Ｂ , -NHC(O)NR ６Ｃ NR ６Ａ R ６Ｂ , -NHC(O)NR ６Ａ R ６Ｂ , -N(O) ｍ６ , -NR ６Ａ R ６Ｂ , -C(O)R ６Ｃ , -C(O)OR ６Ｃ , -C(O)NR ６Ａ R ６Ｂ , -OR ６Ｄ , -SR ６Ｄ , -NR ６Ａ SO ２ R ６Ｄ , -NR ６Ａ C(O)R ６Ｃ , -NR ６Ａ C(O)OR ６Ｃ , -NR ６Ａ OR ６Ｃ , -SF ５ , -N ３ and is substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, W ７ is N, N ＋ -O － or C(R ７ ) and R ７ is hydrogen, halogen, -CX ７ ３ , -CHX ７ ２ , -CH ２ X ７ , -OCX ７ ３ , -OCH ２ X ７ , -OCHX ７ ２ , -CN, -SO ｎ７ R ７Ｄ , -SO ｖ７ NR ７Ａ R ７Ｂ , -NR ７Ｃ NR ７Ａ R ７Ｂ , -ONR ７Ａ R ７Ｂ , -NHC(O)NR ７Ｃ NR ７Ａ R ７Ｂ , -NHC(O)NR ７Ａ R ７Ｂ , -N(O) ｍ７ , -NR ７Ａ R ７Ｂ , -C(O)R ７Ｃ , -C(O)OR ７Ｃ , -C(O)NR ７Ａ R ７Ｂ , -OR ７Ｄ , -SR ７Ｄ , -NR ７Ａ SO ２ R ７Ｄ , -NR ７Ａ C(O)R ７Ｃ , -NR ７Ａ C(O)OR ７Ｃ , -NR ７Ａ OR ７Ｃ , -SF ５ , -N ３ , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, R ８ is independently halogen, -CX ８ ３ , -CHX ８ ２ , -CH ２ X ８ , -OCX ８ ３ , -OCH ２ X ８ , -OCHX ８ ２ , -CN, -SO ｎ８ R ８Ｄ , -SO ｖ８ NR ８Ａ R ８Ｂ , -NR ８Ｃ NR ８Ａ R ８Ｂ , -ONR ８Ａ R ８Ｂ , -NHC(O)NR ８Ｃ NR ８Ａ R ８Ｂ , -NHC(O)NR ８Ａ R ８Ｂ , -N(O) ｍ８ , -NR ８Ａ R ８Ｂ , -C(O)R ８Ｃ , -C(O)OR ８Ｃ , -C(O)NR ８Ａ R ８Ｂ , -OR ８Ｄ , -SR ８Ｄ , -NR ８Ａ SO ２ R ８Ｄ , -NR ８Ａ C(O)R ８Ｃ , -NR ８Ａ C(O)OR ８Ｃ , -NR ８Ａ OR ８Ｃ , -SF ５ , -N ３ , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, and two Rs ８ The substituents may be optionally linked to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R ９ is a substituted or unsubstituted cycloalkyl, or a substituted or unsubstituted heterocycloalkyl, and R １０ is hydrogen, halogen, -CX １０ ３ , -CHX １０ ２ , -CH ２ X １０ , -OCX １０ ３ , -OCH ２ X １０ , -OCHX １０ ２ , -CN, -SO ｎ１０ R １０Ｄ , -SO ｖ１０ NR １０Ａ R １０Ｂ , -NR １０Ｃ NR １０Ａ R １０Ｂ , -ONR １０Ａ R １０Ｂ , -NHC(O)NR １０Ｃ NR １０Ａ R １０Ｂ , -NHC(O)NR １０Ａ R １０Ｂ , -N(O) ｍ１０ , -NR １０Ａ R １０Ｂ , -C(O)R １０Ｃ , -C(O)OR １０Ｃ , -C(O)NR １０Ａ R １０Ｂ , -OR １０Ｄ , -SR １０Ｄ , -NR １０Ａ SO ２ R １０Ｄ , -NR １０Ａ C(O)R １０Ｃ , -NR １０Ａ C(O)OR １０Ｃ , -NR １０Ａ OR １０Ｃ , -SF ５ , -N ３ , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, R １０ and R ２ the substituents may be optionally linked to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R ２Ａ ,R ２Ｂ ,R ２Ｃ ,R ２Ｄ ,R ３Ａ ,R ３Ｂ ,R ３Ｃ ,R ３Ｄ ,R ４Ａ ,R ４Ｂ ,R ４Ｃ ,R ４Ｄ ,R ５Ａ ,R ５Ｂ ,R ５Ｃ ,R ５Ｄ ,R ６Ａ ,R ６Ｂ ,R ６Ｃ ,R ６Ｄ ,R ７Ａ ,R ７Ｂ ,R ７Ｃ ,R ７Ｄ ,R ８Ａ ,R ８Ｂ ,R ８Ｃ ,R ８Ｄ ,R １０Ａ ,R １０Ｂ ,R １０Ｃ RRR １０Ｄ が、电影して、水水、-CC- ３ ,-CBr ３ 、-CF ３ 、-CI ３ 、-CHCl ２ ,-CHBr ２ 、-CHF ２ 、-CHI ２ 、-CH ２ Cl、-E ２ Br、-EH ２ F、-CH ２ I、-CN、-OH、-NH ２ 、-COOH、-CONH ２ 、-OCO, ３ 、-OCF ３ ,-OCBr ３ 、-OCI ３ 、-OCHCl ２ ,-OCHBr ２ ,-OCHI ２ 、-OCHF ２ ,-OCH ２ Black, white ２ Br、-OCH ２ I, -OCH ２ F, a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom ２Ａ and R ２Ｂ The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom ３Ａ and R ３Ｂ The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom ４Ａ and R ４Ｂ The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom ５Ａ and R ５Ｂ The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom ６Ａ and R ６Ｂ The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom ７Ａ and R ７Ｂ The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom ８Ａ and R ８Ｂ The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom １０Ａ and R １０Ｂ The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl X ２ 、 X ３ 、 X ４ 、 X ５ 、 X ６ 、 X ７ 、 X ８ 、 and X １０ is independently -F, -Cl, -Br, or -I, n2, n3, n4, n5, n6, n7, n8, and n10 are each independently an integer from 0 to 4; m2, m3, m4, m5, m6, m7, m8, m10, v2, v3, v4, v5, v6, v7, v8, and v10 are each independently 1 or 2; z8 is an integer from 0 to 3; W ６ or W ７ at least one of which is N, W ６ is C(R ６ ), or when W ７ is C(R ７ ), R １０ is not hydrogen, W ６ and W ７ If both are N, R ３ is, -S(O) ２ CH ３ rather than W ６ is CH, and when W ７ is N, -L １ -R ９ is 【Chemical Formula 7】 A compound, or a pharmaceutically acceptable salt or solvate thereof, which is not.

9. The formula: 【Chemical 8】 The compound according to Claim 8, having the formula.

10. The formula: 【Chemical Formula 9】 The compound according to Claim 8, having the formula.

11. R １０ is hydrogen or unsubstituted C １ ~C ６ alkyl, the compound according to claim 8.

12. R １０ The compound according to claim 8, wherein R is isopropyl.

13. R ６ is hydrogen, -OCHF ２ , unsubstituted C １ ~C ６ alkyl, or unsubstituted 2- to 6-membered heteroalkyl, the compound according to claim 1.

14. R ６ is hydrogen, -OCHF ２ , unsubstituted methoxy, or unsubstituted isopropoxy, the compound according to claim 1.

15. R ７ is -F, -Cl, -Br, or -OCHF ２ The compound according to claim 1, wherein

16. R ８ is independently halogen, -CCl ３ , -CBr ３ , -CF ３ , -CI ３ , -CHCl ２ , -CHBr ２ , -CHF ２ , -CHI ２ , -CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -OCl ３ , -OCF ３ , -OCBr ３ , -OCI ３ , -OCHCl ２ , -OCHBr ２ , -OCHI ２ , -OCHF ２ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ I, -OCH ２ F, -CN, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHCONHNH ２ , -NHCONH ２ , -NO ２ , -NH ２ , -COH, -COOH, -CONH ２ , -OH, -SH, -NHSO ２ H, -NHCOH, -NHCOOH, -NHOH, -SF ５ , -N ３ , a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, the compound according to claim 1.

17. R ８ is, independently, halogen, -CF ３ , -CHF ２ , -CN, -OCHF ２ , -C(O)R ８Ｃ , -C(O)OR ８Ｃ , -OR ８Ｄ , unsubstituted C １ ~C ６ alkyl, unsubstituted 2- to 8-membered heteroalkyl, unsubstituted C ３ ~C ８ cycloalkyl, or unsubstituted phenyl, the compound according to claim 1.

18. R ８Ｃ is, independently, hydrogen or unsubstituted C １ -C ６ -C alkyl, the compound according to claim 17.

19. R ８Ｄ is independently unsubstituted C １ -C ６ alkyl, the compound according to claim 17.

20. R ８ is independently, -F, -Cl, -Br, -CF ３ , -CHF ２ , -CN, -C(O)H, -C(O)OCH ３ , -OCHF ２ , -OCH ３ , -OCH ２ CH ３ , -OCH ２ CF ３ , -OCH(CH ３ ), CH ２ OCH ３ , -OCH ２ CHF ２ The compound according to claim 1, which is unsubstituted methyl, unsubstituted cyclopropyl, or unsubstituted phenyl.

21. Two Rs ８ The substituents are linked to form an unsubstituted C ５ The compound according to claim 1, wherein the substituents are linked to form an unsubstituted cycloalkyl.

22. L １ is a bonded or unsubstituted C １ -C ５ alkylene, the compound according to claim 1.

23. L １ The compound according to claim 1, wherein L is a bond.

24. L １ The compound according to claim 1, wherein L is unsubstituted methylene.

25. R ９ is R １１ substituted or unsubstituted heteroalkyl, or R １１ is substituted or unsubstituted heterocycloalkyl, R １１ is independently oxo, halogen, -CX １１ ３ , -CHX １１ ２ , -CH ２ X １１ , -OCX １１ ３ , -OCH ２ X １１ , -OCHX １１ ２ , -CN, -SO ｎ１１ R １１Ｄ , -SO ｖ１１ NR １１Ａ R １１Ｂ , -NR １１Ｃ NR １１Ａ R １１Ｂ , -ONR １１Ａ R １１Ｂ , -NHC(O)NR １１Ｃ NR １１Ａ R １１Ｂ , -NHC(O)NR １１Ａ R １１Ｂ , -N(O) ｍ１１ , -NR １１Ａ R １１Ｂ , -C(O)R １１Ｃ , -C(O)OR １１Ｃ , -C(O)NR １１Ａ R １１Ｂ , -OR １１Ｄ , -SR １１Ｄ , -NR １１Ａ SO ２ R １１Ｄ , -NR １１Ａ C(O)R １１Ｃ , -NR １１Ａ C(O)OR １１Ｃ , -NR １１Ａ OR １１Ｃ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and two Rs １１ The substituents may be optionally linked to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. R １１Ａ 、R １１Ｂ 、R １１Ｃ 、and R １１Ｄ are, independently, hydrogen, -CCl ３ 、-CBr ３ 、-CF ３ 、-CI ３ 、-CHCl ２ 、-CHBr ２ 、-CHF ２ 、-CHI ２ 、-CH ２ Cl、-CH ２ Br、-CH ２ F、-CH ２ I、-CN、-OH、-NH ２ 、-COOH、-CONH ２ 、-OCl、-OCF ３ 、-OCF ３ 、-OCBr ３ 、-OCI ３ 、-OCHCl ２ 、-OCHBr ２ 、-OCHI ２ 、-OCHF ２ 、-OCH ２ Cl、-OCH ２ Br、-OCH ２ I、-OCH ２ F, a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, and the R １１Ａ and R １１Ｂ substituents bonded to the same nitrogen atom may optionally be linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, X １１ is independently -F, -Cl, -Br, or -I, n11 is independently an integer from 0 to 4; m11 and v11 are each independently 1 or 2, the compound according to Claim 1.

26. R ９ is R １１ substituted or unsubstituted C ３ to C ８ cycloalkyl, or R １１ substituted or unsubstituted 3- to 8-membered heteroalkyl, the compound according to claim 25.

27. R ９ wherein R １１ is a substituted or unsubstituted spirocyclic cycloalkyl, or R １１ is a substituted or unsubstituted spirocyclic heterocycloalkyl, the compound according to claim 25.

28. R ９ is 【Chemical 10】 wherein R １２ is hydrogen, halogen, -CX １２ ３ , -CHX １２ ２ , -CH ２ X １２ , -OCX １２ ３ , -OCH ２ X １２ , -OCHX １２ ２ , -SO ｎ１２ R １２Ｄ , -SO ｖ１２ NR １２Ａ R １２Ｂ , -C(O)R １２Ｃ , -C(O)OR １２Ｃ , -C(O)NR １２Ａ R １２Ｂ , -OR １２Ｄ and is a substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R １２Ａ 、 R １２Ｂ 、 R １２Ｃ 、 and R １２Ｄ are, independently, hydrogen, -CCl ３ , -CBr ３ , -CF ３ , -CI ３ , -CHCl ２ , -CHBr ２ , -CHF ２ , -CHI ２ , -CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CN, -OH, -NH ２ , -COOH, -CONH ２ , -OCl, -OCF ３ , -OCF ３ , -OCBr ３ , -OCI ３ , -OCHCl ２ , -OCHBr ２ , -OCHI ２ , -OCHF ２ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ I, -OCH ２ F, a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, wherein the R １２Ａ and R １２Ｂ substituents bonded to the same nitrogen atom may optionally be linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl, X １２ is independently -F, -Cl, -Br, or -I, n12 is independently an integer from 0 to 4; v12 is independently 1 or 2; z11 is an integer from 0 to 13, the compound according to Claim 25.

29. R ９ is 【Chemical Formula 11】 The compound according to Claim 28, which is.

30. R １１ is independently oxo, halogen, -CX １１ ３ , -CHX １１ ２ , -CN, -SO ｎ１１ R １１Ｄ , -C(O)R １１Ｃ , -C(O)OR １１Ｃ , -C(O)NR １１Ａ R １１Ｂ , -C(O)R １１Ｃ , -OR １１Ｄ , -NR １１Ａ SO ２ R １１Ｄ , -NR １１Ａ C(O)R １１Ｃ , -NR １１Ａ C(O)OR １１Ｃ , substituted or unsubstituted C １ ~C ６ alkyl, substituted or unsubstituted 2- to 5-membered heteroalkyl, or substituted or unsubstituted 5- to 10-membered heteroaryl, the compound according to claim 25.

31. R １１Ａ is independently hydrogen or unsubstituted C １ ~C ６ alkyl, and R １１Ｂ is independently hydrogen, the compound according to claim 30.

32. R １１Ｃ is, independently, hydrogen or unsubstituted C １ ~C ６ alkyl, the compound according to claim 30.

33. R １１Ｄ is, independently, hydrogen or unsubstituted C １ -C ６ -alkyl, the compound according to claim 30.

34. Two Rs １１ The compound according to claim 25, wherein two substituents are linked to form a substituted or unsubstituted cycloalkyl.

35. R １２ is hydrogen, -C(O)R １２Ｃ , -SO ｎ１２ R １２Ｄ , -SO ｖ１２ NR １２Ａ R １２Ｂ , -C(O)OR １２Ｃ , -C(O)NR １２Ａ R １２Ｂ , unsubstituted C １ ~C ６ alkyl, unsubstituted C ３ ~C ８ cycloalkyl, or unsubstituted 3- to 8-membered heterocycloalkyl, the compound according to claim 28.

36. R １２Ａ is hydrogen, unsubstituted C １ ~C ６ alkyl, or unsubstituted C ３ ~C ８ cycloalkyl, and R １２Ｂ is hydrogen, the compound according to claim 35.

37. R １２Ｃ is a substituted or unsubstituted C １ to C ６ alkyl, substituted or unsubstituted 2-6 membered heteroalkyl, or substituted or unsubstituted C ３ to C ８ cycloalkyl, the compound according to claim 35.

38. R １２Ｄ is unsubstituted C １ -C ６ alkyl, the compound according to claim 35.

39. R ９ is 【Chemical 12】 【Chemical 13】 【Chemical Formula 14】 【Chemical Formula 15】 The compound according to Claim 1, which is.

40. A compound, or a pharmaceutically acceptable salt or solvate thereof, having the following formula: 【Chemical 16】 【Chemical 17】 【Chemical 18】 【Chemical 19】 【Chemical 20】 【Chemical 21】 【Chemical 22】 【Chemical 23】 【Chemical Formula 24】 【Chemical 25】 【Chemical 26】 【Chemical 27】 【Chemical Formula 28】 【Chemical Formula 29】 【Chemical Formula 30】 【Chemical 31】 【Chemical Formula 32】

41. A pharmaceutical composition comprising a compound according to any one of claims 1 to 40, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

42. A pharmaceutical composition for treating neurodegenerative disorders in a subject in need thereof, comprising a compound according to any one of claims 1 to 40, or a pharmaceutically acceptable salt or solvate thereof.

43. A pharmaceutical composition for treating inflammatory diseases in a subject in need thereof, comprising a compound according to any one of claims 1 to 40, or a pharmaceutically acceptable salt or solvate thereof.

44. The pharmaceutical composition according to claim 43, wherein the inflammatory disease is encephalitis.

45. The pharmaceutical composition according to claim 44, wherein the encephalitis is post-hemorrhagic encephalitis.

46. A pharmaceutical composition for treating demyelinating diseases in a subject in need thereof, comprising a compound according to any one of claims 1 to 40, or a pharmaceutically acceptable salt or solvate thereof.

47. The pharmaceutical composition according to claim 46, wherein the demyelinating disease is a demyelinating disease of the central nervous system.

48. The pharmaceutical composition according to claim 47, wherein the demyelinating disease is multiple sclerosis.

49. The pharmaceutical composition according to claim 46, wherein the demyelinating disease is a demyelinating disease of the peripheral nervous system.

50. A pharmaceutical composition for treating fibrotic diseases in a subject in need thereof, comprising a compound according to any one of claims 1 to 40, or a pharmaceutically acceptable salt or solvate thereof.

51. The pharmaceutical composition according to claim 50, wherein the fibrotic disease is pulmonary fibrosis, dermal fibrosis, hepatic fibrosis, or ocular fibrosis.

52. The pharmaceutical composition according to claim 50, wherein the fibrotic disease is idiopathic pulmonary fibrosis, scleroderma, non-alcoholic steatohepatitis, or ocular fibrosis.

53. A pharmaceutical composition for treating cancer in a subject in need thereof, comprising a compound according to any one of claims 1 to 40, or a pharmaceutically acceptable salt or solvate thereof.

54. The pharmaceutical composition according to claim 53, wherein the cancer is brain cancer.

55. The pharmaceutical composition according to claim 54, wherein the cancer is glioblastoma.

56. A pharmaceutical composition for regulating LPAR1 activity in a subject, comprising a compound according to any one of claims 1 to 40, or a pharmaceutically acceptable salt or solvate thereof.

Images