Beta-lactam derivatives for disease treatment

Abstract

Provided herein are compounds and methods for modulating or inhibiting glutaminyl-peptide cyclotransferase-like protein (QPCTL).In one embodiment, described herein are compounds of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba) and (IIbb), stereoisomers thereof, or salts or solvates thereof.Further provided herein is a method for treating disease or condition, comprising administering a compound of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba) or (IIbb), stereoisomers thereof, or salts or solvates thereof. TIFF2024523552000361.tif10089

Description

[Technical Field]

[0001] Cross-referencing of related passwords

[0001] This application claims the interests of PCT / CN2021 / 102061 filed on 24 June 2021, PCT / CN2021 / 107806 filed on 22 July 2021, and PCT / CN2021 / 142624 filed on 29 December 2021, each of which is incorporated herein by reference in whole.

[0002] Field of Invention

[0002] This disclosure relates to a beta-lactam derivative that functions as an inhibitor of glutaminyl-peptide cyclotransferase-like protein (QPCTL). [Background technology]

[0003]

[0003] Glutaminyl-peptide cyclotransferase, also known as glutaminylcyclase (GC), catalyzes the conversion of the N-terminal L-glutamyl residue of peptides to a pyroglutamyl group. This enzyme belongs to the family of transferases, particularly aminoacyltransferases, and is present in the pituitary gland and adrenal gland, where it is important for the formation of the N-terminal pyroglutamyl group of peptide hormones such as neurotensin and thyroid-stimulating hormone-releasing hormone. Glutaminylcyclase also catalyzes the conversion of the N-terminal L-glutamyl residue to a pyroglutamyl residue. This activity contributes to the formation of several amyloid-associated plaque-forming peptides and may contribute to the pathogenesis of Alzheimer's disease. Glutaminylcyclase is also considered a diagnostic marker for thyroid tumors. [Overview of the project]

[0004]

[0004] This disclosure addresses the above-mentioned needs and also provides further advantages.

[0005] In some embodiments, the present disclosure provides a compound represented by formula (I), or a pharmaceutically acceptable salt or solvate thereof:

[0005] [Chemical formula]

[0006] (In the formula, R 6 , 1 , 4 , , 12a , 12a , 1 , 3 , 2 , 7 , , 5 , 12b , , 12b , 2 is halogen, -OH, -OR 10a , -SR 10a , -CN, amino, -NR 22 R 23 , substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, and R 2 is H, halogen, -OH, -OR 10b , substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl, or R<​​​​​​​​​​​​​​​​​​​​​​​​​​​​​11 , halogen, -SR 11 -S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -S(=O)2NR 22 R 23 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 , substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted C1-C8 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl, R 10a and R 10b Each of these is independently a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, or a substituted or unsubstituted C1-C6 heteroalkyl. R 11This is a substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic, or R 21 , R 22 and R 23 Each of these is independently hydrogen, a C1-C6 alkyl group, a C1-C6 heteroalkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted.

[0007]

[0006] In some embodiments, the present disclosure provides compounds represented by formula (I), or pharmaceutically acceptable salts or solvates thereof:

[0008] [ka]

[0009] (In the formula, R 1 H, halogen, -OH, -OR 10a , -SR 10a -CN, amino, -NR 22 R 23 , substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, R 2 H, halogen, -OH, -OR 10b , substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl, R1 and R 2 together with the carbon atom to which they are attached form a 3- to 7-membered cyclic or heterocyclic ring, or R 1 and R 2 together form an oxo or C═CR 12a R 12b double bond, and R 12a and R 12b are each independently hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R 4 , R 5 , R 6 and R 7 each is independently selected from H and halogen, R 3 is -OR 11 , -SR 11 , -S(═O)R 21 , -S(═O)2R 21 , -NHS(═O)2R 21 , -S(═O)2NR 22 R 23 , -C(═O)R 21 , -OC(═O)R 21 , -C(═O)OR 22 , -OC(═O)OR 22 , -C(═O)NR 22 R 23 , -OC(═O)NR 22 R 23 , -NR 22 R 23 , NO2, -NHS(═O)2R 21 , -NR 22 C(═O)NR 22 R 23 , -NR 22 C(═O)R 21 , -NR 22 C(═O)OR21 、 substituted C1-C8 alkyl, substituted C2-C8 alkenyl, substituted C2-C8 alkynyl, substituted C1-C8 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl, wherein the alkyl, alkenyl, alkynyl or heteroalkyl is substituted with at least one substituent selected from substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl and substituted or unsubstituted bicyclic or polycyclic heteroaryl, R 10a and R 10b are each independently substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, or substituted or unsubstituted C1-C6 heteroalkyl, R 11 is substituted C1-C6 alkyl, substituted C2-C6 alkenyl, substituted C2-C6 alkynyl, substituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl, wherein the alkyl, alkenyl, alkynyl or heteroalkyl is substituted with at least one substituent selected from substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl and substituted or unsubstituted bicyclic or polycyclic heteroaryl, R 21 、 R 22 and R 23Each of these is independently hydrogen, a C1-C6 alkyl group, a C1-C6 heteroalkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted.

[0010]

[0007] In some embodiments, the present disclosure provides a compound represented by formula (Ia), or a pharmaceutically acceptable salt or solvate thereof:

[0011] [ka]

[0012]

[0008] In some embodiments, the present disclosure provides a compound represented by formula (Ib), or a pharmaceutically acceptable salt or solvate thereof:

[0013] [ka]

[0014]

[0009] In some embodiments, the present disclosure provides a compound represented by formula (Iaa), or a pharmaceutically acceptable salt or solvate thereof:

[0015] [ka]

[0016]

[0010] In some embodiments, the present disclosure provides a compound represented by formula (Iab), or a pharmaceutically acceptable salt or solvate thereof:

[0017] [ka]

[0018]

[0011] In some embodiments, the present disclosure provides a compound represented by formula (Iba), or a pharmaceutically acceptable salt or solvate thereof:

[0019] [ka]

[0020]

[0012] In some embodiments, the present disclosure provides a compound represented by formula (Ibb), or a pharmaceutically acceptable salt or solvate thereof:

[0021] [ka]

[0022]

[0013] In another embodiment, the present disclosure provides a compound of formula (II), or a pharmaceutically acceptable salt or solvate thereof:

[0023] [ka]

[0024] (In the formula, R 1 H, halogen, -OH, -OR 10a , -SR 10a -CN, amino, -NR 22 R 23 , substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, R 2 H, halogen, -OH, -OR 10b , substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl, R 1 and R2 These, together with the carbon atoms to which they are bonded, form a 3- to 7-membered ring or a heterocyclic ring, or R 1 and R 2 They combine to form oxo or CR 12a R 12b Forms a double bond to R 12a and R 12b Each of these is independently hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. Ring Q is a substituted or unsubstituted 5 or 6-membered heteroaryl, R 10a and R 10b Each of these is independently a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, or a substituted or unsubstituted C1-C6 heteroalkyl. R 22 and R 23 Each of these is independently hydrogen, a C1-C6 alkyl group, a C1-C6 heteroalkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted.

[0025]

[0014] In some embodiments, the compound of formula (II) has the structure of formula (IIa), its pharmaceutically acceptable salt, or solvate:

[0026] [ka]

[0027]

[0015] In some embodiments, the compound of formula (II) has the structure of formula (IIb), a pharmaceutically acceptable salt or solvate thereof:

[0028] [ka]

[0029]

[0016] In some embodiments, the compound of formula (II) has the structure of formula (IIaa), a pharmaceutically acceptable salt or solvate thereof:

[0030] [ka]

[0031]

[0017] In some embodiments, the compound of formula (II) has the structure of formula (IIab), its pharmaceutically acceptable salt, or solvate:

[0032] [ka]

[0033]

[0018] In some embodiments, the compound of formula (II) has the structure of formula (IIba), its pharmaceutically acceptable salt, or solvate:

[0034] [ka]

[0035]

[0019] In some embodiments, the compound of formula (II) has the structure of formula (IIbb), its pharmaceutically acceptable salt or solvate:

[0036] [ka]

[0037]

[0020] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 These are halogen, -OH, and -SR. 10a -CN, amino, -NR 22 R 23 , -OR 10a These are substituted or unsubstituted C1-C6 alkyl groups, substituted or unsubstituted C2-C6 alkenyl groups, substituted or unsubstituted C2-C6 alkynyl groups, substituted or unsubstituted C1-C6 heteroalkyl groups, substituted or unsubstituted C3-C8 cycloalkyl groups, or substituted or unsubstituted C2-C7 heterocycloalkyl groups. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 -OH, -OR 10a , substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C3-C6 cycloalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 is -OH. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 は-OR 10a And R 10a R is a substituted or unsubstituted C1-C6 alkyl group. In some embodiments, R 1 is -OCH3. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1R is a substituted or unsubstituted C1-C6 alkyl group. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 These are halogen, -OH, amino, cyano, oxime, oxo, mono-C 1~6 Alkylamino, di-C 1~6 Alkylamino, substituted, or unsubstituted C 1~6 alkoxy, substituted, or unsubstituted C 3~7 Cycloalkyl, substituted, or unsubstituted C 2~8 C1-C6 alkyls optionally substituted with 1-5 substituents selected from heterocycloalkyls, substituted or unsubstituted aryls, and substituted or unsubstituted heteroaryls. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 -CH3, -CHF2, -CF3,

[0038] [ka]

[0039] , -CH2OH, -CH2CH3, -CH2CH2CH3, -CH2CH2CH2CH3, or benzyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 R is a substituted or unsubstituted C2-C7 heterocycloalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 teeth,

[0040] [ka]

[0041] In some embodiments, R 1 H is H.

[0021] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 2 R is H, a halogen, -OH, or a substituted or unsubstituted C1-C6 alkyl group. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 2 is H. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 2 It is -CH3.

[0042]

[0022] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 and R 2 These, together with the carbon atoms to which they are bonded, form a 3- to 7-membered ring or a heterocyclic ring. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 and R 2These, together with the carbon atoms to which they are bonded, form cyclopropyl or cyclobutyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 and R 2 These combine to form an oxo. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 and R 2 Together, CR 12a R 12b Forms a double bond to R 12a and R 12b Each of these is independently hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 12a is hydrogen, R 12b R is hydrogen, a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted phenyl, or a substituted or unsubstituted monocyclic heteroaryl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 12a is hydrogen, R 12bis hydrogen or phenyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 12a is hydrogen, R 12b It is hydrogen.

[0043]

[0023] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 5 is H, F, Cl, or Br. In some embodiments, R 5 is F. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 7 is H, F, Cl, or Br. In some embodiments, R 7 is F. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 4 is H, F, Cl, or Br. In some embodiments, R 4 is H. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 6 is H, F, Cl, or Br. In some embodiments, R 6 H is H.

[0044]

[0024] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 R is a substituted or unsubstituted monocyclic heteroaryl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 R is a substituted or unsubstituted 5 or 6-membered monocyclic heteroaryl having 1 to 4 ring heteroatoms independently selected from N, O, and S. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 R is a substituted or unsubstituted five-membered monocyclic heteroaryl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 R is a substituted or unsubstituted bicyclic heteroaryl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 This is a condensed bicyclic heteroaryl having 8 to 10 ring atoms and 1, 2, 3, 4, or 5 ring heteroatoms independently selected from N, O, and S. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3R is a substituted or unsubstituted C2-C7 heterocycloalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 R is a monocyclic 5 or 6-membered heterocycloalkyl having 1 to 3 ring heteroatoms independently selected from N, O, and S. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 R is a substituted or unsubstituted C3-C8 cycloalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 R is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, each of which is optionally substituted. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 is phenyl or naphthyl, each of which is optionally substituted. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 is one or more R 31 It is replaced by each R 31 These are independently cyano, oxime, oxo, halogen, hydroxy, amino, and mono-C. 1~6 Alkylamino, di-C 1~6 Alkylamino, substituted, or unsubstituted C 1~6 Alkyl, substituted, or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6Alkynyl, substituted or unsubstituted C 1~6 alkoxy, substituted, or unsubstituted C 3~7 Cycloalkyl, substituted, or unsubstituted C 2~8 Heterocycloalkyl, heteroaryl, substituted or unsubstituted heterocycloalkyl-C 1~6 Alkyl, substituted, or unsubstituted C 1~6 Alkyl-heterocycloalkyl, substituted or unsubstituted C 1~6 Alkyl-aryl, substituted or unsubstituted C 1~6 Alkyl-heteroaryl, substituted or unsubstituted C 1~6 Alkoxyaryl, substituted or unsubstituted C 1~6 Alkoxy-heterocycloalkyl and substituted or unsubstituted C 1~6 Selected from alkoxy-heteroaryl compounds. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 is -OR 11 , -SR 11 -S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -S(=O)2NR 22 R 23 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21, halogen, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, or substituted or unsubstituted C1-C8 heteroalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 is -OR 11 , -SR 11 , substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, or substituted or unsubstituted C1-C8 heteroalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 は-OR 11 That is the case.

[0045]

[0025] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 These are substituted or unsubstituted C1-C6 alkyls, substituted or unsubstituted C2-C6 alkenyls, substituted or unsubstituted C2-C6 alkynyls, substituted or unsubstituted C1-C6 heteroalkyls, substituted or unsubstituted C3-C8 cycloalkyls, substituted or unsubstituted C2-C7 heterocycloalkyls, substituted or unsubstituted phenyls, substituted or unsubstituted naphthyls, substituted or unsubstituted monocyclic heteroaryls, or substituted or unsubstituted bicyclic heteroaryls. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11R is a substituted or unsubstituted C1-C6 alkyl, or a substituted or unsubstituted C3-C6 cycloalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 is a substituted C1-C4 alkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 These include cyano, oxime, oxo, halogen, -CN, -NH2, -NH(CH3), -N(CH3)2, -OH, -CO2H, -CO2(C1~C4 alkyl), -C(=O)NH2, -C(=O)NH(C1~C4 alkyl), -C(=O)N(C1~C4 alkyl)2, -S(=O)2NH2, -S(=O)2NH(C1~C4 alkyl), -S(=O)2N(C1~C4 alkyl)2, -SC1~C4 alkyl, -S(=O)C1~C4 alkyl, S(=O)2(C1~C4 alkyl), mono-C 1~6 Alkylamino, di-C 1~6 Alkylamino, substituted, or unsubstituted C 1~6 Alkyl, substituted, or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 1~6 alkoxy, substituted, or unsubstituted C 3~7 Cycloalkyl, substituted, or unsubstituted C 2~8 Heterocycloalkyl, heteroaryl, substituted or unsubstituted heterocycloalkyl-C 1~6 Alkyl, substituted, or unsubstituted C 1~6 Alkyl-heterocycloalkyl, substituted or unsubstituted C 1~6 Alkyl-aryl, substituted or unsubstituted C 1~6 Alkyl-heteroaryl, substituted or unsubstituted C 1~6 Alkoxyaryl, substituted or unsubstituted C 1~6 Alkoxy-heterocycloalkyl and substituted or unsubstituted C 1~6It is substituted with one or more substituents selected from alkoxy-heteroaryls. In some embodiments, R 11 R is substituted with one or more substituents selected from halogens, -OH, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 fluoroalkyl, C1-C4 heteroalkyl, C1-C4 alkoxy, or C1-C4 fluoroalkoxy. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 R is substituted with one or more substituents selected from halogens, -OH, and C3-C6 cycloalkyl groups. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 It is replaced by one or more Fs.

[0046]

[0026] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 is -S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -S(=O)2NR 22 R 23 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR22 R 23 , -NR 22 C(=O)R 21 or -NR 22 C(=O)OR 21 In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 21 , R 22 and R 23 Each is independently selected from hydrogen and C1-C4 alkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 is a substituted C1-C8 alkyl, a substituted C2-C8 alkenyl, a substituted C2-C8 alkynyl, or a substituted C1-C8 heteroalkyl, wherein the alkyl, alkenyl, alkynyl, or heteroalkyl is substituted with at least one substituent selected from substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, and substituted or unsubstituted bicyclic or polycyclic heteroaryl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 is -OR 11 or -SR 11 And R 11The alkyl, alkenyl, alkynyl, or heteroalkyl is substituted with at least one substituent selected from the substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl.

[0047]

[0027] In some embodiments, provided herein are stereoisomers of compounds of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb).

[0048]

[0028] In some embodiments, the compound is a compound from Table 1, or a pharmaceutically acceptable salt or solvate thereof. In some embodiments, the compound is a compound from Table 3, or a pharmaceutically acceptable salt or solvate thereof. In some embodiments, the compound is a compound of formula (Iaa). In some embodiments, the compound is a compound of formula (IIaa).

[0049]

[0029] In some embodiments, the compounds have a brain / blood AUC of at most about 0.0001, 0.001, 0.01, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 5, or 10.

[0050]

[0030] In another embodiment, the present disclosure provides a pharmaceutical composition comprising the compounds described herein and at least one pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical composition is formulated for administration to mammals by oral, intravenous, or subcutaneous administration. In some embodiments, the pharmaceutical composition is in the form of a tablet, pill, capsule, liquid, suspension, dispersion, solution, or emulsion.

[0051]

[0031] In another embodiment, the Disclosure provides a method for modulating glutaminyl-peptide cyclotransferase-like protein (QPCTL) activity in a subject, comprising the step of administering to a subject a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein. In another embodiment, the Disclosure provides a method for inhibiting glutaminyl-peptide cyclotransferase-like protein (QPCTL) activity in a subject, comprising the step of administering to a subject a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein. In another embodiment, the Disclosure provides a method for treating a disease or condition in a subject requiring treatment of the disease or condition, comprising the step of administering to a subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein. In some embodiments, the disease or condition is associated with abnormal glutaminyl-peptide cyclotransferase-like protein (QPCTL) activity. In some embodiments, the disease or condition associated with abnormal QPCTL activity is cancer. In another embodiment, the Disclosure provides a method for treating cancer in a subject requiring treatment of cancer, comprising the step of administering a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein, to the subject.

[0052]

[0032] In some embodiments, cancer is leukemia, acute myeloid leukemia (AML), chronic myeloid leukemia, acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), multiple myeloma (MM), or myelodysplastic syndrome (MDS). In some embodiments, cancer is AML. In some embodiments, cancer is a solid tumor or metastatic cancer. In some embodiments, cancer is skin cancer, eye cancer, gastrointestinal cancer, thyroid cancer, breast cancer, ovarian cancer, central nervous system cancer, laryngeal cancer, cervical cancer, lymphatic system cancer, genitourinary cancer, bone cancer, biliary tract cancer, endometrial cancer, liver cancer, lung cancer, prostate cancer, or colon cancer.

[0053]

[0033] In one embodiment, the method described herein is a method for treating a disease or condition in a subject requiring treatment of the disease or condition, comprising the step of administering a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein, to the subject, wherein the disease or condition is a disease involving the innate immune system. In some embodiments, the disease is atherosclerosis, fibrous disease, ischemia-reperfusion injury, or an infection caused by a pathogen. In some embodiments, the disease is a fibrous disease selected from hepatic fibrosis, pulmonary fibrosis, renal fibrosis, and scleroderma. In some embodiments, the disease is a chronic kidney disease, including diabetic nephropathy and focal segmental glomerulosclerosis (FSGS).

[0054]

[0034] In one embodiment, a method for treating a disease or condition in a subject requiring treatment of the disease or condition comprises the step of administering a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein, to the subject, wherein the disease or condition is Kennedy disease, duodenal cancer with or without Helicobacter pylori infection, Zolliger-Ellison syndrome, gastric cancer with or without Helicobacter pylori infection, or a pathogenic psychotic state. The method is used for conditions such as schizophrenia, infertility, neoplasms, inflammatory host responses, cancer, psoriasis, humoral and cell-mediated immune response disorders, leukocyte adhesion and migration processes in the endothelium, food intake disorders, sleep-wake disorders, impaired homeostasis of energy metabolism, autonomic dysfunction, hormonal imbalances or fluid imbalances, multiple sclerosis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuritis, mild cognitive impairment, Alzheimer's disease, familial British dementia, familial Danish dementia, neurodegeneration in Down syndrome, Huntington's disease, rheumatoid arthritis, pancreatitis, and restenosis. In some embodiments, the method includes the step of administering a second therapeutic agent. In some embodiments, the second therapeutic agent is a monoclonal antibody. In some embodiments, the monoclonal antibody is selected from edrecolomab, rituximab, gemtuzumab ozogamicin, alemtuzumab, ibritumomab tiuxetan, tocitumomab, cetuximab, bevacizumab, and trastuzumab. In some embodiments, the second therapeutic agent is an immune checkpoint inhibitor. In some embodiments, the immune checkpoint inhibitor is a CTLA-4 inhibitor, a PD-1 inhibitor, or a PD-L1 inhibitor. In some embodiments, the immune checkpoint inhibitor is ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, or semiprimab.

[0055]

[0035] Additional aspects and advantages of the present disclosure will be readily apparent to those skilled in the art from the following detailed description, which shows and describes only exemplary embodiments of the present disclosure. As will be understood, other different embodiments of the present disclosure are possible, and some of their details can be modified in various obvious ways without departing from the present disclosure. Accordingly, the drawings and description are to be considered exemplary in nature and not restrictive.

[0056] Embedding by reference

[0036] All publications, patents, and patent applications referenced herein are incorporated by reference to the same extent as each individual publication, patent, or patent application is specifically and individually indicated as being incorporated by reference. If any publication or patent or patent application incorporated by reference conflicts with any disclosure contained herein, this specification is intended to supersede and / or take precedence over any such conflicting material. [Modes for carrying out the invention]

[0057]

[0037] Various embodiments of the present invention have been shown and described herein, but it will be apparent to those skilled in the art that such embodiments are provided only as examples. Numerous variations, modifications and substitutions can be conceived by those skilled in the art without departing from the present invention. It should be understood that various alternatives to the embodiments of the present invention described herein may be available.

[0058] A.Definition

[0038] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which the present invention pertains. All patents and publications referenced herein are incorporated by reference.

[0059]

[0039] "Alkyl" consists only of carbon and hydrogen atoms, does not contain unsaturated atoms, and preferably has 1 to 15 carbon atoms (i.e., C1 to C 15Alkyl) refers to a linear or branched hydrocarbon chain radical. In certain embodiments, alkyl contains 1 to 13 carbon atoms (i.e., C1 to C13). 13 Alkyl). In certain embodiments, the alkyl group contains 1 to 8 carbon atoms (i.e., C1-C8 alkyl). In other embodiments, the alkyl group contains 1 to 5 carbon atoms (i.e., C1-C5 alkyl). In other embodiments, the alkyl group contains 1 to 4 carbon atoms (i.e., C1-C4 alkyl). In other embodiments, the alkyl group contains 1 to 3 carbon atoms (i.e., C1-C3 alkyl). In other embodiments, the alkyl group contains 1 to 2 carbon atoms (i.e., C1-C2 alkyl). In other embodiments, the alkyl group contains 1 carbon atom (i.e., C1 alkyl). In other embodiments, the alkyl group contains 5 to 15 carbon atoms (i.e., C5-C 15Alkyl). In other embodiments, the alkyl group contains 5 to 8 carbon atoms (i.e., C5 to C8 alkyl). In other embodiments, the alkyl group contains 2 to 5 carbon atoms (i.e., C2 to C5 alkyl). In other embodiments, the alkyl group contains 3 to 5 carbon atoms (i.e., C3 to C5 alkyl). In certain embodiments, the alkyl group is selected from methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (isopropyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl), 1,1-dimethylethyl (tert-butyl), and 1-pentyl (n-pentyl). The alkyl group is bonded to the rest of the molecule by a single bond. Unless otherwise specified herein, the alkyl group may be optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkyl group is optionally substituted with oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkyl group is optionally substituted with halogen, -CN, -OH, or -OMe. In some embodiments, the alkyl group is optionally substituted with halogen.

[0060]

[0040] When used with chemical parts such as alkyl, alkenyl, or alkynyl, the term "C x~y " is intended to mean that the chain contains a group with x to y carbon atoms. For example, "C 1~6 The term "alkyl" refers to substituted or unsubstituted saturated hydrocarbon groups, including straight-chain and branched-chain alkyl groups containing 1 to 6 carbon atoms. Term-C x~y Alkylene- refers to a substituted or unsubstituted alkylene chain having x to y carbon atoms in the alkylene chain. For example, -C 1~6The alkylene may be selected from methylene, ethylene, propylene, butylene, pentylene, and hexylene, with one of these being optionally substituted. The alkenylene chain may have one or more double bonds in the alkenylene chain. Term-C x~y Alkynylene- refers to a substituted or unsubstituted alkynylene chain having x to y carbon atoms in the alkynylene chain. For example, -C 2~6 The alkenylene- may be selected from ethynylene, propynylene, butynylene, pentynylene, and hexynylene, one of which may be optionally substituted. The alkynylene chain may have one triple bond or more triple bonds in the alkynylene chain.

[0061]

[0041] "Alkoxy" refers to a radical bonded via an oxygen atom of the formula -O-alkyl, where alkyl is an alkyl chain as defined above. Unless otherwise specified herein, the alkoxy group may be optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkoxy is optionally substituted with a halogen, -CN, -COOH, COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkoxy is optionally substituted with a halogen, -CN, -OH, or -OMe. In some embodiments, the alkoxy is optionally substituted with a halogen.

[0062]

[0042] An "alkenyl" consists only of carbon and hydrogen atoms, contains at least one carbon-carbon double bond, and preferably has 2 to 12 carbon atoms (i.e., C2 to C2). 12Alkenyl refers to a linear or branched hydrocarbon chain radical group. In certain embodiments, the alkenyl contains 2 to 8 carbon atoms (i.e., C2-C8 alkenyl). In certain embodiments, the alkenyl contains 2 to 6 carbon atoms (i.e., C2-C6 alkenyl). In other embodiments, the alkenyl contains 2 to 4 carbon atoms (i.e., C2-C4 alkenyl). The alkenyl is attached to the rest of the molecule by a single bond, for example, ethenyl (i.e., vinyl), propa-1-enyl (i.e., allyl), buta-1-enyl, pento-1-enyl, penta-1,4-dienyl, etc. Unless otherwise specified herein, the alkenyl group may be optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkenyl is optionally substituted with oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkenyl is optionally substituted with halogen, -CN, -OH, or -OMe. In some embodiments, the alkenyl is optionally substituted with halogen.

[0063]

[0043] "Alkynyl" consists only of carbon atoms and hydrogen atoms, contains at least one carbon-carbon triple bond, and preferably has 2 to 12 carbon atoms (i.e., C2 to C2 12Alkynyl refers to a linear or branched hydrocarbon chain radical group. In certain embodiments, the alkynyl contains 2 to 8 carbon atoms (i.e., C2-C8 alkynyl). In other embodiments, the alkynyl contains 2 to 6 carbon atoms (i.e., C2-C6 alkynyl). In other embodiments, the alkynyl contains 2 to 4 carbon atoms (i.e., C2-C4 alkynyl). The alkynyl is attached to the rest of the molecule by a single bond, such as ethynyl, propynyl, butynyl, pentynyl, hexynyl, etc. Unless otherwise specified herein, the alkynyl group may be optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkynyl is optionally substituted with oxo, halogen, -CN, -COOH, COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkynyl is optionally substituted with a halogen, -CN, -OH, or -OMe.

[0064]

[0044] "Alkylene" or "alkylene chain" refers to a straight or branched divalent hydrocarbon chain consisting only of carbon and hydrogen, unsaturated, and preferably having 1 to 12 carbon atoms, linking the rest of the molecule to a radical group, such as methylene, ethylene, propylene, n-butylene, etc. The alkylene chain is bonded to the rest of the molecule via single bonds and to the radical group via single bonds. The bonding points of the alkylene chain to the rest of the molecule and to the radical group may be via any two carbon atoms in the chain. In certain embodiments, the alkylene contains 1 to 10 carbon atoms (i.e., C1-C8 alkylene). In certain embodiments, the alkylene contains 1 to 8 carbon atoms (i.e., C1-C8 alkylene). In other embodiments, the alkylene contains 1 to 5 carbon atoms (i.e., C1-C5 alkylene). In other embodiments, the alkylene contains 1 to 4 carbon atoms (i.e., C1-C4 alkylene). In other embodiments, the alkylene contains 1 to 3 carbon atoms (i.e., C1-C3 alkylene). In other embodiments, the alkylene contains 1 to 2 carbon atoms (i.e., C1-C2 alkylene). In other embodiments, the alkylene contains 1 carbon atom (i.e., C1 alkylene). In other embodiments, the alkylene contains 5 to 8 carbon atoms (i.e., C5-C8 alkylene). In other embodiments, the alkylene contains 2 to 5 carbon atoms (i.e., C2-C5 alkylene). In other embodiments, the alkylene contains 3 to 5 carbon atoms (i.e., C3-C5 alkylene). Unless otherwise specified herein, the alkylene group may be optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkylene is optionally substituted with oxo, halogen, -CN, -COOH, COOMe, -OH, -OMe, -NH2, or -NO2.In some embodiments, the alkylene is optionally substituted with a halogen.

[0065]

[0045] "Alkenylene" or "alkenylene chain" refers to a straight or branched divalent hydrocarbon chain that consists only of carbon and hydrogen, contains at least one carbon-carbon double bond, and preferably has 2 to 12 carbon atoms, linking the rest of the molecule to a radical group. The alkenylene chain is linked to the rest of the molecule via single bonds and to the radical group via single bonds. The linkage points of the alkenylene chain to the rest of the molecule and to the radical group may be via any two carbon atoms in the chain. In certain embodiments, the alkenylene contains 2 to 10 carbon atoms (i.e., C2 to C2). 10Alkenylenes). In certain embodiments, the alkenylenes contain 2 to 8 carbon atoms (i.e., C2-C8 alkenylenes). In other embodiments, the alkenylenes contain 2 to 5 carbon atoms (i.e., C2-C5 alkenylenes). In other embodiments, the alkenylenes contain 2 to 4 carbon atoms (i.e., C2-C4 alkenylenes). In other embodiments, the alkenylenes contain 2 to 3 carbon atoms (i.e., C2-C3 alkenylenes). In other embodiments, the alkenylenes contain 2 carbon atoms (i.e., C2 alkenylenes). In other embodiments, the alkenylenes contain 5 to 8 carbon atoms (i.e., C5-C8 alkenylenes). In other embodiments, the alkenylenes contain 3 to 5 carbon atoms (i.e., C3-C5 alkenylenes). Unless otherwise specified herein, the alkenylene group may be optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkenylene is optionally substituted with oxo, halogen, -CN, -COOH, COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkenylene is optionally substituted with halogen, -CN, -OH, or -OMe. In some embodiments, the alkenylene is optionally substituted with halogen.

[0066]

[0046] "Alkynylene" or "Alkynylene chain" refers to a linear or branched divalent hydrocarbon chain that consists only of carbon and hydrogen, contains at least one carbon-carbon triple bond, and preferably has 2 to 12 carbon atoms, linking the rest of the molecule to a radical group. The alkynylene chain is bonded to the rest of the molecule via single bonds and to the radical group via single bonds. The bonding points of the alkynylene chain to the rest of the molecule and to the radical group may be via any two carbon atoms in the chain. In certain embodiments, the alkynylene contains 2 to 10 carbon atoms (i.e., C2 to C2). 10Alkynylene). In certain embodiments, the alkynylene contains 2 to 8 carbon atoms (i.e., C2-C8 alkynylene). In other embodiments, the alkynylene contains 2 to 5 carbon atoms (i.e., C2-C5 alkynylene). In other embodiments, the alkynylene contains 2 to 4 carbon atoms (i.e., C2-C4 alkynylene). In other embodiments, the alkynylene contains 2 to 3 carbon atoms (i.e., C2-C3 alkynylene). In other embodiments, the alkynylene contains 2 carbon atoms (i.e., C2 alkynylene). In other embodiments, the alkynylene contains 5 to 8 carbon atoms (i.e., C5-C8 alkynylene). In other embodiments, the alkynylene contains 3 to 5 carbon atoms (i.e., C3-C5 alkynylene). Unless otherwise specified herein, the alkylylene group may be optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, alkylylene is optionally substituted with oxo, halogen, -CN, -COOH, COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, alkylylene is optionally substituted with halogen, -CN, -OH, or -OMe. In some embodiments, alkylylene is optionally substituted with halogen.

[0067]

[0047] "Aryl" refers to a radical derived from an aromatic monocyclic or aromatic polycyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. The aromatic monocyclic or aromatic polycyclic hydrocarbon ring system may consist only of hydrogen and carbon, and 5 to 18 carbon atoms, where at least one of the rings in the ring system is aromatic, i.e., it contains a cyclic delocalized (4n+2)π-electron system according to Hückel's theory. Examples of ring systems from which the aryl group is derived include, but are not limited to, benzene, fluorene, indan, indene, tetralin, and naphthalene. The aryl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include condensation (when condensed with a cycloalkyl or heterocycloalkyl ring, the aryl is bonded via aromatic ring atoms) or cross-linking ring systems. In some embodiments, the aryl is a 6- to 10-membered aryl. In some embodiments, the aryl is a 6-membered aryl (phenyl). Examples of aryl radicals include, but are not limited to, aryl radicals derived from hydrocarbon ring systems of anthreene, naphthylene, phenanthrylene, anthracene, azulene, benzene, chrysene, fluorantene, fluorene, as-indacene, s-indacene, indan, indene, naphthalene, phenalene, phenanthrene, pleiadene, pyrene, and triphenylene. Unless otherwise specified herein, aryls may be optionally substituted with, for example, halogens, aminos, nitriles, nitros, hydroxyls, alkyls, alkenyls, alkynyls, haloalkyls, alkoxys, carboxyls, carboxylates, aryls, cycloalkyls, heterocycloalkyls, heteroaryls, etc. In some embodiments, aryls are optionally substituted with halogens, methyls, ethyls, -CN, -COOH, COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the aryl group is optionally substituted with a halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the aryl group is optionally substituted with a halogen.

[0068]

[0048] "Aralkill" is formula-R c - Refers to the aryl radical, where R c These are alkylene chains as defined above, such as methylene and ethylene.

[0049] "Aralkenyl" is a compound of formulas -R d - Refers to the aryl radical, where R d This is the alkenylene chain defined above. "Aralkynyl" is defined by formula -R e - Refers to the aryl radical, where R e This is the alkynylene chain as defined above.

[0069]

[0050] "Carbocyclic ring" refers to a saturated, unsaturated, or aromatic ring in which each atom of the ring is carbon. Carbocyclic rings may include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. Each ring in a bicyclic carbocyclic ring may be selected from saturated, unsaturated, and aromatic rings. An aromatic ring, such as phenyl, may be condensed with a saturated or unsaturated ring, such as cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated, and aromatic bicyclic rings is included in the definition of a carbocyclic ring, provided the valence is permissible. Exemplary carbocyclic rings include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. Unless otherwise specified herein, carbocyclic rings may be optionally substituted.

[0070]

[0051] "Cycloalkyl" refers to a fully saturated monocyclic or polycyclic hydrocarbon radical consisting only of carbon and hydrogen atoms, which includes condensed or cross-linked ring systems and preferably has 3 to 12 carbon atoms. In certain embodiments, the cycloalkyl contains 3 to 10 carbon atoms. In other embodiments, the cycloalkyl contains 5 to 7 carbon atoms. The cycloalkyl may be bonded to the rest of the molecule by single bonds. Examples of monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of polycyclic cycloalkyl radicals include, for example, adamantyl, norbornyl (i.e., bicyclo[2.2.1]heptanyl), norborneyl, dekalinyl, and 7,7-dimethyl-bicyclo[2.2.1]heptanyl. Cycloalkyl may also refer to a partially saturated monocyclic or polycyclic carbocyclic ring, such as a cycloalkenyl. Cycloalkyls include condensed (when condensed with an aryl or heteroaryl ring, the cycloalkyl is bonded via a non-aromatic ring atom), spiro, or bridging ring systems. Typical cycloalkyls have 3 to 15 carbon atoms (C3-C3). 15 C3-C containing cycloalkenyl 15 Cycloalkyl), 3 to 10 carbon atoms (C3 to C 10Examples of monocyclic cycloalkyls include, but are not limited to, cycloalkyls having 3 to 8 carbon atoms (C3-C8 cycloalkyl), 3 to 6 carbon atoms (C3-C6 cycloalkyl), 3 to 5 carbon atoms (C3-C5 cycloalkyl), or 3 to 4 carbon atoms (C3-C4 cycloalkyl). In some embodiments, the cycloalkyl is a 3 to 10-membered cycloalkyl, for example, a 3 to 10-membered cycloalkenyl. In some embodiments, the cycloalkyl is a 3 to 6-membered cycloalkyl, for example, a 3 to 6-membered cycloalkenyl. In some embodiments, the cycloalkyl is a 5 to 6-membered cycloalkyl, for example, a 5 to 6-membered cycloalkenyl. Examples of monocyclic cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of polycyclic cycloalkyls include adamantyl, norbornyl, dekalinyl, bicyclo[3.3.0]octane, bicyclo[4.3.0]nonane, cis-decalin, trans-decalin, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, bicyclo[3.3.2]decane, and 7,7-dimethyl-bicyclo[2.2.1]heptanyl. Examples of partially saturated cycloalkyls include cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Unless otherwise specified herein, cycloalkyls are optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl compounds. In some embodiments, the cycloalkyl group is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF3, -OH, -OMe, -NH2, or -NO2.In some embodiments, the cycloalkyl group is optionally substituted with a halogen.

[0071]

[0052] "Cycloalkenyl" refers to an unsaturated non-aromatic monocyclic or polycyclic hydrocarbon radical consisting only of carbon and hydrogen atoms, which includes fused ring systems or bridged ring systems, preferably having 3 to 12 carbon atoms and containing at least one double bond. In certain embodiments, the cycloalkenyl contains 3 to 10 carbon atoms. In other embodiments, the cycloalkenyl contains 5 to 7 carbon atoms. The cycloalkenyl may be bonded to the rest of the molecule by single bonds. Examples of monocyclic cycloalkenyls include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl.

[0072]

[0053] "Cycloalkylalkyl" is a compound of the formula -R c - refers to a cycloalkyl radical, where R c This is the alkylene chain mentioned above.

[0054] "Cycloalkylalkoxy" is a compound of the formula -OR c - Refers to a radical bonded via the oxygen atom of a cycloalkyl group, where R c This is the alkylene chain mentioned above.

[0073]

[0055] "Halo" or "halogen" refers to halogen substituents such as bromo, chloro, fluoro, and iodo substituents. In some embodiments, halogen is fluoro or chloro. In some embodiments, halogen is fluoro.

[0074]

[0056] As used herein, the terms “haloalkyl” or “haloalkane” refer to the alkyl radicals defined above, which are substituted by one or more halogen radicals, such as trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, and the like. In some embodiments, the alkyl portion of the fluoroalkyl radical is optionally further substituted. Examples of halogen-substituted alkanes ("haloalkanes") include halomethanes (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), di- and trihalomethanes (e.g., trichloromethane, tribromomethane, trifluoromethane, triiodomethane), 1-haloethane, 2-haloethane, 1,2-dihaloethane, 1-halopropane, 2-halopropane, 3-halopropane, 1,2-dihalopropane, 1,3-dihalopropane, 2,3-dihalopropane, 1,2,3-trihalopropane, and any other suitable combination of alkane (or substituted alkane) and halogen (e.g., Cl, Br, F, I, etc.). If the alkyl group is substituted with one or more halogen radicals, each halogen may be selected independently, e.g., 1-chloro,2-fluoroethane.

[0075]

[0057] "Fluoroalkyl" refers to the alkyl radical defined above which is substituted by one or more fluororadicals, such as trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, etc.

[0076]

[0058] "Hydroxyalkyl" refers to the alkyl radical as defined above, which is substituted with one or more hydroxyls. In some embodiments, the alkyl is substituted with one hydroxyl. In some embodiments, the alkyl is substituted with one, two, or three hydroxyls. Examples of hydroxyalkyls include hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, or hydroxypentyl. In some embodiments, the hydroxyalkyl is hydroxymethyl.

[0077]

[0059] "Aminoalkyl" refers to the alkyl radical as defined above, which is substituted with one or more amines. In some embodiments, the alkyl is substituted with one amine. In some embodiments, the alkyl is substituted with one, two, or three amines. Examples of aminoalkyls include aminomethyl, aminoethyl, aminopropyl, aminobutyl, or aminopentyl. In some embodiments, the aminoalkyl is aminomethyl.

[0078]

[0060] "Heteroalkyl" refers to an alkyl group in which one or more of the alkyl backbone atoms are atoms other than carbon, for example, oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, phosphorus, or a combination thereof. The heteroalkyl group is bonded to the rest of the molecule at the carbon atoms of the heteroalkyl group. In one embodiment, the heteroalkyl group is a C1-C6 heteroalkyl group, which consists of 1-6 carbon atoms and one or more atoms other than carbon, for example, oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, phosphorus, or a combination thereof, and the heteroalkyl group is bonded to the rest of the molecule at the carbon atoms of the heteroalkyl group. Examples of such heteroalkyl groups are, for example, -CH2OCH3, -CH2CH2OCH3, -CH2CH2OCH2CH2OCH3, -CH(CH3)OCH3, -CH2NHCH3, -CH2N(CH3)2, -CH2CH2NHCH3, or -CH2CH2N(CH3)2. Unless otherwise specified herein, heteroalkyls are optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, heteroalkyls are optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, heteroalkyls are optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, heteroalkyls are optionally substituted with halogens.

[0079]

[0061] "Heterocycloalkyl" refers to a 3-24 membered partial or fully saturated ring radical containing 2-23 carbon atoms and 1-8 heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus, silicon, and sulfur. In some embodiments, the heterocycloalkyl is fully saturated. In some embodiments, the heterocycloalkyl contains 1-3 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heterocycloalkyl contains 1-3 heteroatoms selected from the group consisting of nitrogen and oxygen. In some embodiments, the heterocycloalkyl contains 1-3 nitrogen atoms. In some embodiments, the heterocycloalkyl contains 1 or 2 nitrogen atoms. In some embodiments, the heterocycloalkyl contains 1 nitrogen atom. In some embodiments, the heterocycloalkyl contains 1 nitrogen atom and 1 oxygen atom. Unless otherwise specified herein, heterocycloalkyl radicals may be monocyclic, bicyclic, tricyclic, or tetracyclic ring systems, which may include condensed (when condensed with an aryl or heteroaryl ring, the heterocycloalkyl is bonded via a non-aromatic ring atom), spiro, or bridging ring systems, and the nitrogen, carbon, or sulfur atoms in the heterocycloalkyl radical may be optionally oxidized, and the nitrogen atom may be optionally quaternized. Typical heterocycloalkyls include those with 2 to 15 carbon atoms (C2-C2). 15 Heterocycloalkyl or C2-C 15 Heterocycloalkenyl), 2 to 10 carbon atoms (C2 to C 10 Heterocycloalkyl or C2-C 10Examples of heterocycloalkyls include, but are not limited to, heterocycloalkenyls, heterocycloalkyls having 2 to 8 carbon atoms (C2-C8 heterocycloalkyl or C2-C8 heterocycloalkenyl), heterocycloalkyls having 2 to 7 carbon atoms (C2-C7 heterocycloalkyl or C2-C7 heterocycloalkenyl), heterocycloalkyls having 2 to 6 carbon atoms (C2-C6 heterocycloalkyl or C2-C7 heterocycloalkenyl), heterocycloalkyls having 2 to 5 carbon atoms (C2-C5 heterocycloalkyl or C2-C5 heterocycloalkenyl), or heterocycloalkyls having 2 to 4 carbon atoms (C2-C4 heterocycloalkyl or C2-C4 heterocycloalkenyl). Examples of such heterocycloalkyl radicals include azilidinyl, azetidinyl, oxetanyl, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperadinyl, 4-piperidonyl, pyrrolidinyl Examples include, but are not limited to, yl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianil, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxo-thiomorpholinyl, 1,3-dihydroisobenzofuran-1-yl, 3-oxo-1,3-dihydroisobenzofuran-1-yl, methyl-2-oxo-1,3-dioxol-4-yl, and 2-oxo-1,3-dioxol-4-yl. The term heterocycloalkyl also includes all ring forms of carbohydrates, including but not limited to monosaccharides, disaccharides, and oligosaccharides. In some embodiments, heterocycloalkyls have 2 to 10 carbon atoms in the ring. When referring to the number of carbon atoms in a heterocycloalkyl, it should be understood that the number of carbon atoms in a heterocycloalkyl is not the same as the total number of atoms constituting the heterocycloalkyl (including heteroatoms) (i.e., the skeletal atoms of the heterocycloalkyl ring). In some embodiments, the heterocycloalkyl is a 3- to 8-membered heterocycloalkyl.In some embodiments, the heterocycloalkyl is a 3- to 7-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 3- to 6-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 4- to 6-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 5- to 6-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 3- to 8-membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 3- to 7-membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 3- to 6-membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 4- to 6-membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 5- to 6-membered heterocycloalkenyl. Unless otherwise specified herein, the heterocycloalkyl may be optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc., as described below. In some embodiments, the heterocycloalkyl group is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the heterocycloalkyl group is optionally substituted with halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heterocycloalkyl group is optionally substituted with halogen.

[0080]

[0062] A "heterocycle" refers to a saturated, unsaturated, or aromatic ring containing one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycles include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. Each ring in a bicyclic heterocycle may be selected from saturated, unsaturated, and aromatic rings. A "heterocycle" refers to a divalent heterocycle that links the rest of the molecule to a radical group.

[0081]

[0063] "Heteroaryl" or "aromatic heterocyclic" refers to a radical derived from a heteroaromatic ring radical containing 1 to 11 carbon atoms and at least one heteroatom, each heteroatom may be selected from N, O, and S. As used herein, heteroaryl rings can be selected from monocyclic or bicyclic and fused or bridging ring systems, where at least one of the rings in the ring system is aromatic, i.e., containing a cyclic delocalized (4n+2)π-electron system according to Hückel's theory. Heteroatoms in heteroaryl radicals may be oxidized by choice. If present, one or more nitrogen atoms may be quaternized by choice. Heteroaryls may be bonded to the rest of the molecule via any atom of the heteroaryl, such as the carbon or nitrogen atom of the heteroaryl, if the valence allows. Examples of heteroaryls include, but are not limited to, pyridines, pyrimidines, oxazoles, furans, thiophenes, benzthiazoles, and imudazopyridines. "X-membered heteroaryl" refers to the number of intra-ring atoms in the ring, i.e., X. For example, a five-membered heteroaryl ring or a five-membered aromatic heterocycle has five intraring atoms and includes, for example, triazoles, oxazoles, and thiophenes. In some embodiments, the heteroaryl contains one to three heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heteroaryl contains one to three nitrogen atoms. In some embodiments, the heteroaryl contains one or two nitrogen atoms. In some embodiments, the heteroaryl contains one nitrogen atom. The heteroaryl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include condensation (when condensed with a cycloalkyl or heterocycloalkyl ring, the heteroaryl is bonded via aromatic ring atoms) or cross-linking ring systems, and the nitrogen, carbon, or sulfur atoms in the heteroaryl radical may optionally be oxidized, and the nitrogen atom may optionally be quaternized. In some embodiments, the heteroaryl is a five- to ten-membered heteroaryl.In some embodiments, the heteroaryl is a 5- to 6-membered heteroaryl. In some embodiments, the heteroaryl is a 6-membered heteroaryl. In some embodiments, the heteroaryl is a 5-membered heteroaryl. Examples include azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzoindolyl, benzodioxolyl, benzofuranil, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, 1,4-benzodioxanil, benzonaphthofuranil, benzoxazolyl, benzodioxolyl, benzodioxynil, benzopyranil, benzopyranonil, benzofuranil, benzothienyl (benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, sinnolinil, dibenzofuranil, dibenzothiophenyl, furanil, furanonil, isothiazolyl, imidazolyl, indazolyl, indazolyl, isoindolyl, in Examples include, but are not limited to, dolinyl, isoindolinyl, isoquinolyl, indolidinyl, isoxazolyl, naphthilidinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxyranil, 1-oxidepyridinyl, 1-oxidepyrimidinyl, 1-oxidepyradinyl, 1-oxidepyridazinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxadinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridadinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl (i.e., thienyl). Unless otherwise specified herein, heteroaryls may be optionally substituted with, for example, halogens, aminos, nitriles, nitros, hydroxyls, alkyls, alkenyls, alkynyls, haloalkyls, alkoxys, carboxyls, carboxylates, aryls, cycloalkyls, heterocycloalkyls, heteroaryls, etc.In some embodiments, the heteroaryl is optionally substituted with a halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the heteroaryl is optionally substituted with a halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heteroaryl is optionally substituted with a halogen.

[0082]

[0064] The terms “optional” or “optionally” mean that the events or situations described thereafter may or may not occur, and that the description includes examples in which such events or situations occur and examples in which they do not occur. For example, “optionally substituted alkyl” means either “alkyl” or “substituted alkyl” as defined above. Furthermore, the optionally substituted group may be unsubstituted (e.g., -CH2CH3), fully substituted (e.g., -CF2CF3), monosubstituted (e.g., CH2CH2F), or substituted at any level between fully substituted and monosubstituted (e.g., -CH2CHF2, -CH2CF3, -CF2CH3, -CFHCHF2, etc.).

[0083]

[0065] The term “substituted” refers to a portion of a structure having substituents that replace one or more carbons or substituteable heteroatoms, such as hydrogens on NH groups. “Substituted” or “substituted with” is understood to include the implicit condition that such substitutions are subject to the acceptable valencies of the substituted atom and substituent, and that the substitution results in a stable compound, i.e., a compound that does not spontaneously undergo transformation by rearrangement, cyclization, elimination, etc. In particular embodiments, “substituted” refers to a portion having substituents that replace two hydrogen atoms on the same carbon atom, such as substituting two hydrogen atoms on one carbon with an oxo, imino, or thioxo group. As used herein, the term “substituted” is intended to include all acceptable substituents of an organic compound. In broad embodiments, acceptable substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of an organic compound. There may be one or more acceptable substituents for a given organic compound, and they may be the same or different. For the purposes of this disclosure, the heteroatom, such as nitrogen, may have any acceptable substituents of the organic compound described herein that satisfy the hydrogen substituent and / or the valence of the heteroatom.

[0084]

[0066] In some embodiments, the substituent may include any substituent described herein, for example: halogen, hydroxy, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxymo (=N-OH), hydrazino (=N-NH2), -R b -OR a ,-R b -OC(O)-R a ,-R b -OC(O)-OR a , -R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b -C(O)R a ,-R b -C(O)OR a,-R b -C(O)N(R a )2, -R b -OR c -C(O)N(R a )2, -R b -N(R a )C(O)OR a ,-R b -N(R a )C(O)R a ,-R b -N(R a )S(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2), -R b -S(O) t Ure a (where t is 1 or 2), and -R b -S(O) t N(R a )2 (where t is 1 or 2), as well as alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralquinyl, cycloalkyl, cycloalkylalkyl and heterocyclic, any of which are alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxymo (=N-OH), hydrazine (=N-NH2), -R b -OR a ,-R b -OC(O)-R a ,-R b -OC(O)-OR a , -R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b -C(O)R a ,-R b -C(O)OR a ,-R b -C(O)N(R a )2, -R b-OR c -C(O)N(R a )2, -R b -N(R a )C(O)OR a ,-R b -N(R a )C(O)R a ,-R b -N(R a )S(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2), -R b -S(O) t Ure a (where t is 1 or 2), and -R b -S(O) t N(R a )2 (where t is 1 or 2) may be arbitrarily replaced by each R a R is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl and heterocycle, and each R a If the valency is permissible, alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxymo (=N-OH), hydrazine (=N-NH2), -R b -OR a ,-R b -OC(O)-R a ,-R b -OC(O)-OR a ,-R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b -C(O)R a ,-R b -C(O)OR a ,-R b -C(O)N(R a )2, -R b -OR c -C(O)N(Ra )2, -R b -N(R a )C(O)OR a ,-R b -N(R a )C(O)R a ,-R b -N(R a )S(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2), -R b -S(O) t Ure a (where t is 1 or 2), and -R b -S(O) t N(R a )2 (where t is 1 or 2) may be arbitrarily substituted, and each R b These are independently directly bonded, or selected from linear or branched alkylene, alkenylene, or alkynylene chains, and each R c These are linear or branched alkylene, alkenylene, or alkynylene chains.

[0085]

[0067] As used herein and in the claims, the singular forms “a,” “an,” and “the” include plural references unless the context clearly indicates otherwise.

[0068] The terms “salt” or “pharmaceutically acceptable salt” refer to salts derived from various organic and inorganic counterions known in the art. Pharmaceutically acceptable acid addition salts can be formed using inorganic and organic acids. Examples of inorganic acids from which salts can be derived include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Examples of organic acids from which salts can be derived include acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, and salicylic acid. Pharmaceutically acceptable base addition salts can be formed using inorganic and organic bases. Examples of inorganic bases from which salts can be derived include sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, and aluminum. Examples of organic bases from which salts can be derived include primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins, specifically including isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. In some embodiments, pharmaceutically acceptable base addition salts are selected from ammonium, potassium, sodium, calcium, and magnesium salts.

[0086]

[0069] As used herein, the terms “parenteral administration” and “administered parenterally” mean modes of administration other than enteral and topical administration, which are usually by injection, and include, but are not limited to, intravenous, intramuscular, intra-arterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, intradermal, intra-articular, subcapsular, subarachnoid, intraspinal and intrasternal injections and infusions.

[0087]

[0070] The term "pharmaceutically acceptable" is used herein to mean a compound, material, composition and / or dosage form that is suitable for use in contact with human and animal tissues without excessive toxicity, irritation, allergic response or other problems or complications, within the bounds of sound medical judgment, and that is commensurate with a reasonable benefit / risk ratio.

[0088]

[0071] As used herein, the terms “pharmaceutically acceptable excipient” or “pharmaceutically acceptable carrier” mean a pharmaceutically acceptable material, composition or vehicle such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material. Each carrier must be “acceptable” in the sense that it is compatible with the other components of the formulation and is not harmful to the patient. Some examples of materials that may function as pharmaceutically acceptable carriers include: (1) sugars such as lactose, glucose and sucrose; (2) starches such as corn starch and potato starch; (3) cellulose and its derivatives such as sodium carboxymethylcellulose, ethylcellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients such as cocoa butter and suppository wax; (9) peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil (10) Oils such as corn oil and soybean oil; glycols such as propylene glycol; (11) polyols such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters such as ethyl oleate and ethyl laurate; (13) agar; (14) buffers such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline solution; (18) Ringer's solution; (19) ethyl alcohol; (20) phosphate buffer solution; and (21) other non-toxic suitable substances used in pharmaceutical formulations.

[0089]

[0072] In certain embodiments, the terms “prevent” or “prevent” in relation to a disease or disorder may refer to a compound that reduces the incidence of the disorder or condition in a treated sample compared to an untreated control sample, or delays the onset or reduces the severity of one or more symptoms of the disorder or condition compared to an untreated control sample.

[0090]

[0073] As used herein, the terms “to treat,” “to treat,” or “to treat” may include relieving, reducing or improving the symptoms of a disease or condition, preventing further symptoms, improving or preventing the underlying cause of symptoms, inhibiting a disease or condition, for example, preventing the onset of a disease or condition, alleviating a disease or condition, causing regression of a disease or condition, alleviating a condition caused by a disease or condition, or preventing and / or therapeutically cessating the symptoms of a disease or condition.

[0091] B. Compounds of the present disclosure

[0074] In one embodiment, the present disclosure provides a compound represented by formula (I), or a pharmaceutically acceptable salt or solvate thereof:

[0092] [ka]

[0093] (In the formula, R 1 These are halogen, -OH, and -OR 10a , -SR 10a -CN, amino, -NR 22 R 23 , substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, R 2H, halogen, -OH, -OR 10b , substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl, R 1 and R 2 These, together with the carbon atoms to which they are bonded, form a 3- to 7-membered ring or a heterocyclic ring, or R 1 and R 2 They combine to form oxo or CR 12a R 12b Forms a double bond to R 12a and R 12b Each of these is independently hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. R 4 , R 5 , R 6 and R 7 Each of these is independently selected from H and halogen, R 3 is -OR 11 , halogen, -SR 11 -S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -S(=O)2NR 22 R 23 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , NR 22C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 , substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted C1-C8 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl, R 10a and R 10b Each of these is independently a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, or a substituted or unsubstituted C1-C6 heteroalkyl. R 11 These are substituted or unsubstituted C1-C6 alkyl groups, substituted or unsubstituted C2-C6 alkenyl groups, substituted or unsubstituted C2-C6 alkynyl groups, substituted or unsubstituted C1-C6 heteroalkyl groups, substituted or unsubstituted C3-C8 cycloalkyl groups, substituted or unsubstituted C2-C7 heterocycloalkyl groups, substituted or unsubstituted phenyl groups, substituted or unsubstituted naphthyl groups, substituted or unsubstituted monocyclic heteroaryl groups, or substituted or unsubstituted bicyclic or polycyclic heteroaryl groups. R 21 , R 22 and R 23 Each of these is independently hydrogen, a C1-C6 alkyl group, a C1-C6 heteroalkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted.

[0094]

[0075] In another embodiment, the present disclosure provides a compound represented by formula (I), or a pharmaceutically acceptable salt or solvate thereof:

[0095] [ka]

[0096] (In the formula, R 1 H, halogen, -OH, -OR 10a , -SR 10a -CN, amino, -NR 22 R 23 , substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, R 2 H, halogen, -OH, -OR 10b , substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl, R 1 and R 2 These, together with the carbon atoms to which they are bonded, form a 3- to 7-membered ring or a heterocyclic ring, or R 1 and R 2 They combine to form oxo or CR 12a R 12b Forms a double bond to R 12a and R 12b Each of these is independently hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. R 4 , R 5 , R 6 and R 7 Each of these is independently selected from H and halogen, R 3 is -OR 11 , -SR 11 -S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -S(=O)2NR 22 R 23 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 , substituted C1-C8 alkyl, substituted C2-C8 alkenyl, substituted C2-C8 alkynyl, substituted C1-C8 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl, wherein the alkyl, alkenyl, alkynyl, or heteroalkyl is substituted with at least one substituent selected from substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, and substituted or unsubstituted bicyclic or polycyclic heteroaryl. R 10a and R 10b Each of these is independently a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, or a substituted or unsubstituted C1-C6 heteroalkyl. R 11 These are substituted C1-C6 alkyls, substituted C2-C6 alkenyls, substituted C2-C6 alkynyls, substituted C1-C6 heteroalkyls, substituted or unsubstituted C3-C8 cycloalkyls, substituted or unsubstituted C2-C7 heterocycloalkyls, substituted or unsubstituted phenyls, substituted or unsubstituted naphthyls, substituted or unsubstituted monocyclic heteroaryls, or substituted or unsubstituted bicyclic or polycyclic heteroaryls, wherein the alkyl, alkenyl, alkynyl, or heteroalkyl is substituted with at least one substituent selected from substituted or unsubstituted C3-C8 cycloalkyls, substituted or unsubstituted C2-C7 heterocycloalkyls, substituted or unsubstituted phenyls, substituted or unsubstituted naphthyls, substituted or unsubstituted monocyclic heteroaryls, and substituted or unsubstituted bicyclic or polycyclic heteroaryls. R 21 , R 22 and R 23 Each of these is independently hydrogen, a C1-C6 alkyl group, a C1-C6 heteroalkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted.

[0097]

[0076] In another embodiment, the present disclosure provides a compound represented by formula (I), or a pharmaceutically acceptable salt or solvate thereof:

[0098] [ka]

[0099] (In the formula, R 1 H, halogen, -OH, -OR 10a , -SR 10a -CN, amino, -NR 22 R 23, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, R 2 H, halogen, -OH, -OR 10b , substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl, R 1 and R 2 These, together with the carbon atoms to which they are bonded, form a 3- to 7-membered ring or a heterocyclic ring, or R 1 and R 2 They combine to form oxo or CR 12a R 12b Forms a double bond to R 12a and R 12b Each of these is independently hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. R 4 , R 5 , R 6 and R 7 Each of these is independently selected from H and halogen, R 3 is -OR 11 , -SR 11 -S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -S(=O)2NR 22 R 23 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 , substituted C1-C8 alkyl, substituted C2-C8 alkenyl, substituted C2-C8 alkynyl, substituted C1-C8 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl, R 10a and R 10b Each of these is independently a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, or a substituted or unsubstituted C1-C6 heteroalkyl. R 11 These are substituted or unsubstituted C1-C6 alkyl groups, substituted or unsubstituted C2-C6 alkenyl groups, substituted or unsubstituted C2-C6 alkynyl groups, substituted or unsubstituted C1-C6 heteroalkyl groups, substituted or unsubstituted C3-C8 cycloalkyl groups, substituted or unsubstituted C2-C7 heterocycloalkyl groups, substituted or unsubstituted phenyl groups, substituted or unsubstituted naphthyl groups, substituted or unsubstituted monocyclic heteroaryl groups, or substituted or unsubstituted bicyclic or polycyclic heteroaryl groups. R 21 , R 22 and R 23Each of these is independently hydrogen, a C1-C6 alkyl group, a C1-C6 heteroalkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted.

[0100]

[0077] In some embodiments of formula (I), in the formula, R 1 H, halogen, -OH, -OR 10a , -SR 10a -CN, amino, -NR 22 R 23 , substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, R 3 -SR 11 ,SF5,-S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -N=S(=O)R 22 R 23 -S(=O)2NR 22 R 23 -S(=O)(NR 21 )R 21 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR21 ,-P(=O)R 22 R 23 , substituted C1-C8 alkyl, substituted C2-C8 alkenyl, substituted C2-C8 alkynyl, substituted C1-C8 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl, wherein the alkyl, alkenyl, alkynyl, or heteroalkyl is substituted with at least one substituent selected from substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, and substituted or unsubstituted bicyclic or polycyclic heteroaryl. R 11 These are substituted or unsubstituted C1-C6 alkyl groups, substituted or unsubstituted C2-C6 alkenyl groups, substituted or unsubstituted C2-C6 alkynyl groups, substituted or unsubstituted C1-C6 heteroalkyl groups, substituted or unsubstituted C3-C8 cycloalkyl groups, substituted or unsubstituted C2-C7 heterocycloalkyl groups, substituted or unsubstituted phenyl groups, substituted or unsubstituted naphthyl groups, substituted or unsubstituted monocyclic heteroaryl groups, or substituted or unsubstituted bicyclic or polycyclic heteroaryl groups.

[0101]

[0078] In some embodiments of formula (I), in the formula, R 1 H, halogen, -OH, -OR 10a , -SR 10a -CN, amino, -NR 22 R 23 , substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, R 3 is -OR 11 , -SR11 ,SF5,-S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -N=S(=O)R 22 R 23 -S(=O)2NR 22 R 23 -S(=O)(NR 21 )R 21 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 ,-P(=O)R 22 R 23 , substituted C1-C8 alkyl, substituted C2-C8 alkenyl, substituted C2-C8 alkynyl, substituted C1-C8 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl, wherein the alkyl, alkenyl, alkynyl, or heteroalkyl is substituted with at least one substituent selected from substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, and substituted or unsubstituted bicyclic or polycyclic heteroaryl. R 3 ga-OR 11 When R 11These are substituted or unsubstituted C2-C6 alkenyls, substituted or unsubstituted C2-C6 alkynyls, substituted or unsubstituted C1-C6 heteroalkyls, substituted or unsubstituted C3-C8 cycloalkyls, substituted or unsubstituted C2-C7 heterocycloalkyls, substituted or unsubstituted phenyls, substituted or unsubstituted naphthyls, substituted or unsubstituted monocyclic heteroaryls, or substituted or unsubstituted bicyclic or polycyclic heteroaryls.

[0102]

[0079] In another embodiment, the present disclosure provides a compound represented by formula (I), its stereoisomers, or pharmaceutically acceptable salts or solvates:

[0103] [ka]

[0104] (In the formula, R 1 These are halogen, -OH, and -OR 10a , -SR 10a -CN, amino, -NR 22 R 23 , substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, R 2 H, halogen, -OH, -OR 10b , substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl, R 1 and R 2 These, together with the carbon atoms to which they are bonded, form a 3- to 7-membered ring or a heterocyclic ring, or R 1 and R 2 They combine to form oxo or CR 12a R 12b Forms a double bond to R 12a and R12b Each of these is independently hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. R 4 , R 5 , R 6 and R 7 Each of these is independently selected from H, halogens, and substituted or unsubstituted C1-C6 alkyl (alky) elements. R 3 is -OR 11 , halogen, -SR 11 ,SF5,-S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -N=S(=O)R 22 R 23 -S(=O)2NR 22 R 23 -S(=O)(NR 21 )R 21 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 ,-P(=O)R 22 R 23, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted C1-C8 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl, R 10a and R 10b Each of these is independently a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, or a substituted or unsubstituted C1-C6 heteroalkyl. R 11 These are substituted or unsubstituted C1-C6 alkyl groups, substituted or unsubstituted C2-C6 alkenyl groups, substituted or unsubstituted C2-C6 alkynyl groups, substituted or unsubstituted C1-C6 heteroalkyl groups, substituted or unsubstituted C3-C8 cycloalkyl groups, substituted or unsubstituted C2-C7 heterocycloalkyl groups, substituted or unsubstituted phenyl groups, substituted or unsubstituted naphthyl groups, substituted or unsubstituted monocyclic heteroaryl groups, or substituted or unsubstituted bicyclic or polycyclic heteroaryl groups. R 21 , R 22 and R 23 Each of these is independently hydrogen, a C1-C6 alkyl group, a C1-C6 heteroalkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted.

[0105]

[0080] In another embodiment, the present disclosure provides a compound represented by formula (I), its stereoisomers, or pharmaceutically acceptable salts or solvates:

[0106] [ka]

[0107] (In the formula, R 1 H, halogen, -OH, -OR 10a , -SR 10a -CN, amino, -NR 22 R 23 , substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, R 2 H, halogen, -OH, -OR 10b , substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl, R 1 and R 2 These, together with the carbon atoms to which they are bonded, form a 3- to 7-membered ring or a heterocyclic ring, or R 1 and R 2 They combine to form oxo or CR 12a R 12b Forms a double bond to R 12a and R 12b Each of these is independently hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. R 4 , R 5 , R 6 and R 7 Each of these is independently H, -OR 11 , -NR 22 R 23 , selected from halogens and substituted or unsubstituted C1-C6 alkyl groups, R 3 is -OR11 , -SR 11 ,SF5,-S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -N=S(=O)R 22 R 23 -S(=O)2NR 22 R 23 -S(=O)(NR 21 )R 21 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 ,-P(=O)R 22 R 23 , substituted C1-C8 alkyl, substituted C2-C8 alkenyl, substituted C2-C8 alkynyl, substituted C1-C8 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl, wherein the alkyl, alkenyl, alkynyl, or heteroalkyl is substituted with at least one substituent selected from substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, and substituted or unsubstituted bicyclic or polycyclic heteroaryl. R 10a and R 10bEach of these is independently a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, or a substituted or unsubstituted C1-C6 heteroalkyl. R 11 These are substituted C1-C6 alkyls, substituted C2-C6 alkenyls, substituted C2-C6 alkynyls, substituted C1-C6 heteroalkyls, substituted or unsubstituted C3-C8 cycloalkyls, substituted or unsubstituted C2-C7 heterocycloalkyls, substituted or unsubstituted phenyls, substituted or unsubstituted naphthyls, substituted or unsubstituted monocyclic heteroaryls, or substituted or unsubstituted bicyclic or polycyclic heteroaryls, wherein the alkyl, alkenyl, alkynyl, or heteroalkyl is substituted with at least one substituent selected from substituted or unsubstituted C3-C8 cycloalkyls, substituted or unsubstituted C2-C7 heterocycloalkyls, substituted or unsubstituted phenyls, substituted or unsubstituted naphthyls, substituted or unsubstituted monocyclic heteroaryls, and substituted or unsubstituted bicyclic or polycyclic heteroaryls. R 21 , R 22 and R 23 Each of these is independently hydrogen, a C1-C6 alkyl group, a C1-C6 heteroalkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted.

[0108]

[0081] In some embodiments, the compound of formula (I) is represented by formula (Ia), or a pharmaceutically acceptable salt or solvate thereof:

[0109] [ka]

[0110]

[0082] In some embodiments, the compound of formula (I) is represented by formula (Ib), or a pharmaceutically acceptable salt or solvate thereof:

[0111] [ka]

[0112]

[0083] In some embodiments, the compound of formula (I) is represented by formula (Iaa), or a pharmaceutically acceptable salt or solvate thereof:

[0113] [ka]

[0114]

[0084] In some embodiments, the compound of formula (I) is represented by formula (Iab), or a pharmaceutically acceptable salt or solvate thereof:

[0115] [ka]

[0116]

[0085] In some embodiments, the compound of formula (I) is represented by formula (Iba), or a pharmaceutically acceptable salt or solvate thereof:

[0117] [ka]

[0118]

[0086] In some embodiments, the compound of formula (I) is represented by formula (Ibb), or a pharmaceutically acceptable salt or solvate thereof:

[0119] [ka]

[0120]

[0087] In another embodiment, the present disclosure provides a stereoisomer compound represented by formula (Ia), or a pharmaceutically acceptable salt or solvate thereof:

[0121] [ka]

[0122] (In the formula, R 1 These are halogen, -OH, and -OR 10a , -SR 10a -CN, amino, -NR 22 R 23 , substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, R 2 H, halogen, -OH, -OR 10b , substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl, R 1 and R 2 These, together with the carbon atoms to which they are bonded, form a 3- to 7-membered ring or a heterocyclic ring, or R 1 and R 2 They combine to form oxo or CR 12a R 12b Forms a double bond to R 12a and R 12b Each of these is independently hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. R 4 , R 5 , R 6 and R 7Each of these is independently selected from H, halogens, and substituted or unsubstituted C1-C6 alkyl groups. R 3 is -OR 11 , halogen, -SR 11 ,SF5,-S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -N=S(=O)R 22 R 23 -S(=O)2NR 22 R 23 -S(=O)(NR 21 )R 21 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 ,-P(=O)R 22 R 23 , substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted C1-C8 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl, R 10a and R 10bEach of these is independently a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, or a substituted or unsubstituted C1-C6 heteroalkyl. R 11 These are substituted or unsubstituted C1-C6 alkyl groups, substituted or unsubstituted C2-C6 alkenyl groups, substituted or unsubstituted C2-C6 alkynyl groups, substituted or unsubstituted C1-C6 heteroalkyl groups, substituted or unsubstituted C3-C8 cycloalkyl groups, substituted or unsubstituted C2-C7 heterocycloalkyl groups, substituted or unsubstituted phenyl groups, substituted or unsubstituted naphthyl groups, substituted or unsubstituted monocyclic heteroaryl groups, or substituted or unsubstituted bicyclic or polycyclic heteroaryl groups. R 21 , R 22 and R 23 Each of these is independently hydrogen, a C1-C6 alkyl group, a C1-C6 heteroalkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted.

[0123]

[0088] In another embodiment, the present disclosure provides a stereoisomer compound represented by formula (Iaa), or a pharmaceutically acceptable salt or solvate thereof:

[0124] [ka]

[0125] (In the formula, R 1 These are halogen, -OH, and -OR 10a , -SR 10a -CN, amino, -NR 22 R 23, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, R 2 H, halogen, -OH, -OR 10b , substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl, R 1 and R 2 They combine to form oxo or CR 12a R 12b Forms a double bond to R 12a and R 12b Each of these is independently hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. R 4 , R 5 , R 6 and R 7 Each of these is independently H, -OR 11 , -NR 22 R 23 , selected from halogens and substituted or unsubstituted C1-C6 alkyl groups, R 3 is -OR 11 , halogen, -SR 11 ,SF5,-S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -N=S(=O)R 22 R 23 -S(=O)2NR 22 R 23 -S(=O)(NR 21 )R 21 -C(=O)R 21-OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 ,-P(=O)R 22 R 23 , substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted C1-C8 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl, R 10a and R 10b Each of these is independently a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, or a substituted or unsubstituted C1-C6 heteroalkyl. R 11 These are substituted or unsubstituted C1-C6 alkyl groups, substituted or unsubstituted C2-C6 alkenyl groups, substituted or unsubstituted C2-C6 alkynyl groups, substituted or unsubstituted C1-C6 heteroalkyl groups, substituted or unsubstituted C3-C8 cycloalkyl groups, substituted or unsubstituted C2-C7 heterocycloalkyl groups, substituted or unsubstituted phenyl groups, substituted or unsubstituted naphthyl groups, substituted or unsubstituted monocyclic heteroaryl groups, or substituted or unsubstituted bicyclic or polycyclic heteroaryl groups. R 21 , R 22 and R23 is independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C8 cycloalkyl, or C2-C7 heterocycloalkyl, and each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl is optionally substituted).

[0126]

[0089] In another aspect, the present disclosure provides a stereoisomeric compound represented by formula (Iab), or a pharmaceutically acceptable salt or solvate thereof:

[0127]

Chemical formula

[0128] (wherein, R 1 [[ID=|21]]is halogen, -OH, -OR 10a [[ID=|23]], -SR 10a [[ID=|25]], -CN, amino, -NR 22 [[ID=|27]]R 23 [[ID=|29]], substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, and [[ID=|31]]R 2 [[ID=|33]]is H, halogen, -OH, -OR 10b [[ID=|35]], substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl, or [[ID=|37]]R 1 [[ID=|39]]and R 2 [[ID=|41]]together form an oxo or a double bond to CR 12a [[ID=|43]]R 12b [[ID=|45]], and R 12a [[ID=|47]]and R 12bEach of these is independently hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. R 4 , R 5 , R 6 and R 7 Each of these is independently H, -OR 11 , -NR 22 R 23 , selected from halogens and substituted or unsubstituted C1-C6 alkyl groups, R 3 is -OR 11 , halogen, -SR 11 ,SF5,-S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -N=S(=O)R 22 R 23 -S(=O)2NR 22 R 23 -S(=O)(NR 21 )R 21 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 ,-P(=O)R 22 R 23, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted C1-C8 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl, R 10a and R 10b Each of these is independently a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, or a substituted or unsubstituted C1-C6 heteroalkyl. R 11 These are substituted or unsubstituted C1-C6 alkyl groups, substituted or unsubstituted C2-C6 alkenyl groups, substituted or unsubstituted C2-C6 alkynyl groups, substituted or unsubstituted C1-C6 heteroalkyl groups, substituted or unsubstituted C3-C8 cycloalkyl groups, substituted or unsubstituted C2-C7 heterocycloalkyl groups, substituted or unsubstituted phenyl groups, substituted or unsubstituted naphthyl groups, substituted or unsubstituted monocyclic heteroaryl groups, or substituted or unsubstituted bicyclic or polycyclic heteroaryl groups. R 21 , R 22 and R 23 Each of these is independently hydrogen, a C1-C6 alkyl group, a C1-C6 heteroalkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted.

[0129]

[0090] In some embodiments of formula (I), (Ia), (Ib), (Iaa)(Iab), (Iba), or (Ibb), in the formula, R 1 These are halogen, -OH, and -OR 10a -SH, -SR 10a -CN, amino, -NR 22 R 23、is a substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, or substituted or unsubstituted C3-C8 cycloalkyl, R 2 is H or halogen, or R 1 and R 2 together form a double bond to CR 12a R 12b where R 12a is hydrogen and R 12b is hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R 4 、R 5 、R 6 and R 7 each are independently selected from H, halogen, substituted or unsubstituted C1-C6 alkyl, / R 3 is -OR 11 、halogen, -SR 11 、SF5, -S(=O)R 21 、-S(=O)2R 21 、-NHS(=O)2R 21 、-N=S(=O)R 22 R 23 、-S(=O)2NR 22 R 23 、-S(=O)(NR 21 )R 21 、-C(=O)R 21 、-OC(=O)R 21 、-C(=O)OR 22 / / 这里的“ / 0003612”可能是重复或错误标注,按照原文翻译为“ ”,但不影响整体理解 、-OC(=O)OR 22 、-C(=O)NR 22 R 23 、-OC(=O)NR 22 R 23 、-NR 22 R 23 、-NO2, -NHS(=O)2R 21 / 21 、-NR 22 C(=O)NR22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 ,-P(=O)R 22 R 23 , substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl, R 10a and R 10b Each of these is independently a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, or a substituted or unsubstituted C2-C6 alkynyl. R 11 These are substituted or unsubstituted C1-C6 alkyl groups, substituted or unsubstituted C2-C6 alkenyl groups, substituted or unsubstituted C2-C6 alkynyl groups, substituted or unsubstituted C3-C8 cycloalkyl groups, substituted or unsubstituted C2-C7 heterocycloalkyl groups, substituted or unsubstituted phenyl groups, substituted or unsubstituted naphthyl groups, substituted or unsubstituted monocyclic heteroaryl groups, or substituted or unsubstituted bicyclic or polycyclic heteroaryl groups. R 21 , R 22 and R 23 Each of these is independently hydrogen, a C1-C6 alkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted.

[0130]

[0091] In some embodiments of formula (I), (Ia), (Ib), (Iaa)(Iab), (Iba), or (Ibb), R 4 , R 5 , R 6 and R 7Each of these is independently H, halogen, -OH, oxo, -NO2, CN, SH, -OR 11 , -SR 11 -S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -S(=O)2NR 22 R 23 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 Selected from substituted or unsubstituted C1-C6 alkyls, substituted or unsubstituted C2-C6 alkenyls, substituted or unsubstituted C2-C6 alkynyls, substituted or unsubstituted C1-C8 heteroalkyls, substituted or unsubstituted C3-C8 cycloalkyls, substituted or unsubstituted C2-C7 heterocycloalkyls, substituted or unsubstituted aryls, and substituted or unsubstituted heteroaryls. In some embodiments of formula (I), (Ia), (Ib), (Iaa)(Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 4 , R 5 , R 6 and R 7 Each of these is independently H, -OR 11 , -NR 22 R 23 , selected from halogens and substituted or unsubstituted C1-C6 alkyl groups.

[0131]

[0092] In another embodiment, the present disclosure provides a compound of formula (II), or a pharmaceutically acceptable salt or solvate thereof:

[0132] [ka]

[0133] (In the formula, R 1 H, halogen, -OH, -OR 10a , -SR 10a -CN, amino, -NR 22 R 23 , substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, R 2 H, halogen, -OH, -OR 10b , substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl, R 1 and R 2 These, together with the carbon atoms to which they are bonded, form a 3- to 7-membered ring or a heterocyclic ring, or R 1 and R 2 They combine to form oxo or CR 12a R 12b Forms a double bond to R 12a and R 12b Each of these is independently hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. Ring Q is a substituted or unsubstituted 5 or 6-membered heteroaryl, R 10a and R 10b Each of these is independently a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, or a substituted or unsubstituted C1-C6 heteroalkyl. R 22 and R 23 Each of these is independently hydrogen, a C1-C6 alkyl group, a C1-C6 heteroalkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted.

[0134]

[0093] In another embodiment, the present disclosure provides a stereoisomer compound represented by formula (II), or a pharmaceutically acceptable salt or solvate thereof:

[0135] [ka]

[0136] (In the formula, ring Q is a substituted or unsubstituted aryl (such as phenyl), The remaining bases have the same definitions as described above.

[0094] In some embodiments, the compound of formula (II) has the structure of formula (IIa), its pharmaceutically acceptable salt, or solvate:

[0137] [ka]

[0138]

[0095] In some embodiments, the compound of formula (II) has the structure of formula (IIb), a pharmaceutically acceptable salt or solvate thereof:

[0139] [ka]

[0140]

[0096] In some embodiments, the compound of formula (II) has the structure of formula (IIaa), a pharmaceutically acceptable salt or solvate thereof:

[0141] [ka]

[0142]

[0097] In some embodiments, the compound of formula (II) has the structure of formula (IIab), its pharmaceutically acceptable salt, or solvate:

[0143] [ka]

[0144]

[0098] In some embodiments, the compound of formula (II) has the structure of formula (IIba), its pharmaceutically acceptable salt, or solvate:

[0145] [ka]

[0146]

[0099] In some embodiments, the compound of formula (II) has the structure of formula (IIbb), a pharmaceutically acceptable salt or solvate thereof:

[0147] [ka]

[0148]

[0100] In another embodiment, the present disclosure provides a stereoisomer compound represented by formula (IIa), or a pharmaceutically acceptable salt or solvate thereof:

[0149] [ka]

[0150] (In the formula, R 1 H, halogen, -OH, -OR 10a , -SR 10a -CN, amino, -NR 22 R 23 , substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, R 2 H, halogen, -OH, -OR 10b , substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl, R 1 and R 2 These, together with the carbon atoms to which they are bonded, form a 3- to 7-membered ring or a heterocyclic ring, or R 1 and R 2 They combine to form oxo or CR 12a R 12b Forms a double bond to R 12a and R 12b Each of these is independently hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. Ring Q is a substituted or unsubstituted 5 or 6-membered heteroaryl, R 10a and R 10bEach of these is independently a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, or a substituted or unsubstituted C1-C6 heteroalkyl. R 22 and R 23 Each of these is independently hydrogen, a C1-C6 alkyl group, a C1-C6 heteroalkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted.

[0151]

[0101] In another embodiment, the present disclosure provides a stereoisomer compound represented by formula (IIaa), or a pharmaceutically acceptable salt or solvate thereof:

[0152] [ka]

[0153] (In the formula, R 1 H, halogen, -OH, -OR 10a , -SR 10a -CN, amino, -NR 22 R 23 , substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, R 2 H, halogen, -OH, -OR 10b , substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl, R 1 and R 2 They combine to form oxo or CR 12a R 12b Forms a double bond to R 12a and R 12bEach of these is independently hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. Ring Q is a substituted or unsubstituted 5 or 6-membered heteroaryl, R 10a and R 10b Each of these is independently a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, or a substituted or unsubstituted C1-C6 heteroalkyl. R 22 and R 23 Each of these is independently hydrogen, a C1-C6 alkyl group, a C1-C6 heteroalkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted.

[0154]

[0102] In another embodiment, the present disclosure provides a stereoisomer compound represented by formula (IIaa), or a pharmaceutically acceptable salt or solvate thereof:

[0155] [ka]

[0156] (In the formula, ring Q is a substituted or unsubstituted aryl (such as phenyl), The remaining bases have the same definitions as described above.

[0103] In another embodiment, the present disclosure provides a stereoisomer compound represented by formula (IIab), or a pharmaceutically acceptable salt or solvate thereof:

[0157] [ka]

[0158] (In the formula, R 1 H, halogen, -OH, -OR 10a , -SR 10a -CN, amino, -NR 22 R 23 , substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, R 2 H, halogen, -OH, -OR 10b , substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl, R 1 and R 2 They combine to form oxo or CR 12a R 12b Forms a double bond to R 12a and R 12b Each of these is independently hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. Ring Q is a substituted or unsubstituted 5 or 6-membered heteroaryl, R 10a and R 10b Each of these is independently a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, a substituted or unsubstituted C2-C6 alkynyl, or a substituted or unsubstituted C1-C6 heteroalkyl. R 22 and R 23Each of these is independently hydrogen, a C1-C6 alkyl group, a C1-C6 heteroalkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted.

[0159]

[0104] In another embodiment, the present disclosure provides a stereoisomer compound represented by formula (IIab), or a pharmaceutically acceptable salt or solvate thereof:

[0160] [ka]

[0161] (In the formula, ring Q is a substituted or unsubstituted aryl (such as phenyl), The remaining bases have the same definitions as described above.

[0105] In some embodiments of compounds of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), in the formula, R 1 H, halogen, -OH, -OR 10a -SH, -SR 10a -CN, amino, -NR 22 R 23 , substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, R 2 is either H or a halogen, or R 1 and R 2 Together, CR 12a R 12b Forms a double bond to R 12a is hydrogen, R 12bThese are hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. Ring Q is a substituted or unsubstituted 5- or 6-membered heteroaryl, or a substituted or unsubstituted phenyl. R 10a and R 10b Each of these is independently a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, or a substituted or unsubstituted C2-C6 alkynyl. R 22 and R 23 Each of these is independently hydrogen, a C1-C6 alkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted.

[0162]

[0106] In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q is a substituted or unsubstituted 5-membered heteroaryl having 1 to 4 ring heteroatoms independently selected from N, O, and S. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q is pyrrolyl, furyl, thiophenyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, thiadiazolyl, or oxadiazolyl, each of which is optionally substituted. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q is a substituted or unsubstituted pyrrolyl. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q is a substituted or unsubstituted furyl. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q is a substituted or unsubstituted thiophenyl. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q is a substituted or unsubstituted pyrazolyl. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q is a substituted or unsubstituted imidazolyl. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q is a substituted or unsubstituted thiazolyl. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q is a substituted or unsubstituted isothiazolyl. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q is a substituted or unsubstituted triazolyl.In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q is a substituted or unsubstituted tetrazolyl. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q is a substituted or unsubstituted thiadiazolyl. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q is a substituted or unsubstituted oxadiazolyl. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q is a substituted or unsubstituted phenyl. In some embodiments of formulas (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q is a substituted or unsubstituted aryl.

[0163]

[0107] In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q is a substituted or unsubstituted 6-membered heteroaryl having 1 to 4 ring heteroatoms independently selected from N, O, and S. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q is a substituted or unsubstituted 6-membered heteroaryl having 1 to 3 ring nitrogen atoms.

[0164]

[0108] In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q has 0 to 3 halogen groups and 0 to 4 R 3 Substituted with R 3 These are independently -OH, -SH, oxo, and -OR. 11 , halogen, -SR 11 ,SF5,-S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -N=S(=O)R 22 R23 -S(=O)2NR 22 R 23 -S(=O)(NR 21 )R 21 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 ,-P(=O)R 22 R 23 These are substituted or unsubstituted C1-C8 alkyl groups, substituted or unsubstituted C2-C8 alkenyl groups, substituted or unsubstituted C2-C8 alkynyl groups, substituted or unsubstituted C1-C8 heteroalkyl groups, substituted or unsubstituted C3-C8 cycloalkyl groups, substituted or unsubstituted C2-C7 heterocycloalkyl groups, substituted or unsubstituted phenyl groups, substituted or unsubstituted naphthyl groups, substituted or unsubstituted monocyclic heteroaryl groups, or substituted or unsubstituted bicyclic or polycyclic heteroaryl groups.

[0165]

[0109] In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), ring Q has 0 to 3 halogen groups and 0 to 1 R 3 Substituted with R 3 is -OR 11 , halogen, -SR 11 -S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -S(=O)2NR 22 R 23 -C(=O)R21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 These are substituted or unsubstituted C1-C8 alkyl groups, substituted or unsubstituted C2-C8 alkenyl groups, substituted or unsubstituted C2-C8 alkynyl groups, substituted or unsubstituted C1-C8 heteroalkyl groups, substituted or unsubstituted C3-C8 cycloalkyl groups, substituted or unsubstituted C2-C7 heterocycloalkyl groups, substituted or unsubstituted phenyl groups, substituted or unsubstituted naphthyl groups, substituted or unsubstituted monocyclic heteroaryl groups, or substituted or unsubstituted bicyclic or polycyclic heteroaryl groups.

[0166]

[0110] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11The alkyl, alkenyl, alkynyl, or heteroalkyl is substituted with at least one substituent selected from the substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 R is a C1-C6 alkyl group that is optionally substituted. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 These are substituted or unsubstituted C3-C8 cycloalkyl groups.

[0167]

[0111] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 21 , R 22 and R 23 Each of these is independently hydrogen, a C1-C6 alkyl group, a C1-C6 heteroalkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted.

[0168]

[0112] In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the ring Q is

[0169] [ka]

[0170] (In the formula, A 5 is N or CR 5 And, A 4 is N or CR 4 And, A 6 is N or CR 6 And, A 7 is N or CR 7 And, R 4 , R 5 , R 6 and R 7 Each of these is independently selected from H and halogen, R 3 is -OR 11 , halogen, -SR 11 -S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -S(=O)2NR 22 R 23 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR22 C(=O)OR 21 , substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted C1-C8 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl, R 11 These are substituted C1-C6 alkyls, substituted C2-C6 alkenyls, substituted C2-C6 alkynyls, substituted C1-C6 heteroalkyls, substituted or unsubstituted C3-C8 cycloalkyls, substituted or unsubstituted C2-C7 heterocycloalkyls, substituted or unsubstituted phenyls, substituted or unsubstituted naphthyls, substituted or unsubstituted monocyclic heteroaryls, or substituted or unsubstituted bicyclic or polycyclic heteroaryls, wherein the alkyl, alkenyl, alkynyl, or heteroalkyl is substituted with at least one substituent selected from substituted or unsubstituted C3-C8 cycloalkyls, substituted or unsubstituted C2-C7 heterocycloalkyls, substituted or unsubstituted phenyls, substituted or unsubstituted naphthyls, substituted or unsubstituted monocyclic heteroaryls, and substituted or unsubstituted bicyclic or polycyclic heteroaryls. R 21 , R 22 and R 23 Each of these is independently hydrogen, a C1-C6 alkyl group, a C1-C6 heteroalkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted. That is the case.

[0171]

[0113] In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the ring Q is

[0172] [ka]

[0173] (In the formula, A 5 is N or CR 5 And, A 4 is N or CR 4 And, A 6 is N or CR 6 And, A 7 is N or CR 7 And, R 4 , R 5 , R 6 and R 7 Each of these is independently H, halogen, -OH, oxo, -NO2, CN, SH, -OR 11 , -SR 11 -S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -S(=O)2NR 22 R 23 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21Selected from substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C8 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. R 3 is -OR 11 , halogen, -SR 11 -S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -S(=O)2NR 22 R 23 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 , substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted C1-C8 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl, R 11These are substituted C1-C6 alkyls, substituted C2-C6 alkenyls, substituted C2-C6 alkynyls, substituted C1-C6 heteroalkyls, substituted or unsubstituted C3-C8 cycloalkyls, substituted or unsubstituted C2-C7 heterocycloalkyls, substituted or unsubstituted phenyls, substituted or unsubstituted naphthyls, substituted or unsubstituted monocyclic heteroaryls, or substituted or unsubstituted bicyclic or polycyclic heteroaryls, wherein the alkyl, alkenyl, alkynyl, or heteroalkyl is substituted with at least one substituent selected from substituted or unsubstituted C3-C8 cycloalkyls, substituted or unsubstituted C2-C7 heterocycloalkyls, substituted or unsubstituted phenyls, substituted or unsubstituted naphthyls, substituted or unsubstituted monocyclic heteroaryls, and substituted or unsubstituted bicyclic or polycyclic heteroaryls. R 21 , R 22 and R 23 Each of these is independently hydrogen, a C1-C6 alkyl group, a C1-C6 heteroalkyl group, a C3-C8 cycloalkyl group, or a C2-C7 heterocycloalkyl group, and each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl groups is optionally substituted. That is the case.

[0174]

[0114] In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb),

[0175] [ka]

[0176] teeth,

[0177] [ka]

[0178] In some embodiments,

[0179] [ka]

[0180] teeth,

[0181] [ka]

[0182] In some embodiments,

[0183] [ka]

[0184] teeth,

[0185] [ka]

[0186] In some embodiments,

[0187] [ka]

[0188] teeth,

[0189] [ka]

[0190] In some embodiments,

[0191] [ka]

[0192] teeth,

[0193] [ka]

[0194] In some embodiments,

[0195] [ka]

[0196] teeth,

[0197] [ka]

[0198] In some embodiments,

[0199] [ka]

[0200] teeth,

[0201] [ka]

[0202] In some embodiments,

[0203] [ka]

[0204] teeth,

[0205] [ka]

[0206] In some embodiments,

[0207] [ka]

[0208] teeth,

[0209] [ka]

[0210] In some embodiments,

[0211] [ka]

[0212] teeth,

[0213] [ka]

[0214] In some embodiments,

[0215] [ka]

[0216] teeth,

[0217] [ka]

[0218] In some embodiments,

[0219] [ka]

[0220] teeth,

[0221] [ka]

[0222] That is the case.

[0115] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), or (Ibb),

[0223] [ka]

[0224] teeth,

[0225] [ka]

[0226] In some embodiments,

[0227] [ka]

[0228] teeth,

[0229] [ka]

[0230] In some embodiments,

[0231] [ka]

[0232] teeth,

[0233] [ka]

[0234] In some embodiments,

[0235] [ka]

[0236] teeth,

[0237] [ka]

[0238] In some embodiments,

[0239] [ka]

[0240] teeth,

[0241] [ka]

[0242] In some embodiments,

[0243] [ka]

[0244] teeth,

[0245] [ka]

[0246] In some embodiments,

[0247] [ka]

[0248] teeth,

[0249] [ka]

[0250] That is the case.

[0116] In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), A 5 is N. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), A 5 CR 5 In some embodiments of formulas (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), A 4 is N. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), A 4 CR 4 In some embodiments of formulas (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), A 6 is N. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), A 6 CR 6 In some embodiments of formulas (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), A 7 is N. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), A 7 CR 7 In some embodiments of formulas (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), A 5 CR 5 A4 is N, and A 6 CR 6 A 7 CR 7 In some embodiments of formulas (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), A 5 CR 5 A 4 CR 4 A 6 is N, and A 7 CR 7 In some embodiments of formulas (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), A 4 , A 5 , A 6 , A 7 At least one of them is N. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), A 4 , A 5 , A 6 , A 7 One of them is N. In some embodiments of formula (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), A 4 , A 5 , A 6 , A 7 Two of these are N. In some embodiments of formulas (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), A 4 , A 5 , A 6 , A 7 Three of them are N.

[0251]

[0117] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 These are halogen, -OH, and -SR. 10a-CN, amino, -NR 22 R 23 , -OR 10a , substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl. In some embodiments, R 1 is -OH. In some embodiments, R 1 is -SH. In some embodiments, R 1 Ha-SR 10a In some embodiments, R 1 is -CN. In some embodiments, R 1 is an amino acid. In some embodiments, R 1 -NR 22 R 23 In some embodiments, R 1 は-OR 10a In some embodiments, R 1 R is a substituted or unsubstituted C1-C6 alkyl group. In some embodiments, R 1 is a substituted or unsubstituted C2-C6 alkenyl. In some embodiments, R 1 is a substituted or unsubstituted C2-C6 alkynyl. In some embodiments, R 1 R is a substituted or unsubstituted C1-C6 heteroalkyl. In some embodiments, R 1 R is a substituted or unsubstituted C3-C8 cycloalkyl. In some embodiments, R 1 These are substituted or unsubstituted C2-C7 heterocycloalkyl groups.

[0252]

[0118] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1is a halogen, a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C1-C6 heteroalkyl, or a substituted or unsubstituted C3-C8 cycloalkyl. In some embodiments, R 1 These are halogens, substituted or unsubstituted C1-C6 alkyl groups, substituted or unsubstituted C1-C6 heteroalkyl groups, and substituted or unsubstituted C3-C8 cycloalkyl groups.

[0253]

[0119] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 -OH, -OR 10a , substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C3-C6 cycloalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 is -OH. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 は-OR 10a And R 10a R is a substituted or unsubstituted C3-C6 cycloalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 is -OH. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 は-OR 10a And R 10aR is a substituted or unsubstituted C1-C6 alkyl group. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 It is -OCH3.

[0254]

[0120] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 R is a substituted or unsubstituted C1-C6 alkyl group. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 These are halogen, -OH, amino, cyano, oxime, oxo, mono-C 1~6 Alkylamino, di-C 1~6 Alkylamino, substituted, or unsubstituted C 1~6 alkoxy, substituted, or unsubstituted C 3~7 Cycloalkyl, substituted, or unsubstituted C 2~8 These are C1-C6 alkyl groups that are optionally substituted with 1-5 substituents selected from heterocycloalkyl groups, substituted or unsubstituted aryl groups, and substituted or unsubstituted heteroaryl groups.

[0255]

[0121] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 These are halogen, -OH, and -OR 10a , -SR 10a -CN, amino, -NR 22 R 23, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, or substituted or unsubstituted C2-C7 heterocycloalkyl, wherein alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl or heteroalkyl can be optionally and independently halogen, -OH, oxo, -NO2, CN, SH, -OR 11 , -SR 11 -S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -S(=O)2NR 22 R 23 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 They are substituted with 1 to 5 substituents selected from C1-C6 alkyl, C1-C6 aminoalkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C8 heteroalkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C2-C7 heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl.

[0256]

[0122] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 These are optional and can be independently selected from halogen, -OH, oxo, -NO2, CN, SH, and -OR. 11 , -SR 11 -S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -S(=O)2NR 22 R 23 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 , substituted with 1 to 5 substituents selected from C1-C6 alkyl, C1-C6 aminoalkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C8 heteroalkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C2-C7 heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 These are optional and can be independently selected from halogen, -OH, oxo, -NO2, CN, SH, and -OR. 11, -SR 11 , substituted with 1 to 5 substituents selected from C1-C6 alkyl, C1-C6 aminoalkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C2-C7 heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 is optionally and independently substituted with 1 to 3 substituents selected from halogens, -OH, oxo, NH2, -NO2, CN, SH, -O(C1~C6 alkyl), -S(C1~C6 alkyl), -C1~C6 alkyl, C1~C6 aminoalkyl, C1~C6 haloalkyl, C1~C6 hydroxyalkyl, C1~C6 heteroalkyl, C3~C8 cycloalkyl, C2~C7 heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 R is optionally and independently substituted with 1 to 3 substituents selected from halogens, OH, oxo, -NO2, CN, SH, NH2, -O(C1~C6 alkyl), -S(C1~C6 alkyl), -C1~C6 alkyl, C1~C6 aminoalkyl, C1~C6 haloalkyl, C1~C6 hydroxyalkyl, C3~C8 cycloalkyl, C2~C7 heterocycloalkyl, aryl, and heteroaryl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1R is optionally and independently substituted with 1 to 3 substituents selected from halogens, -OH, oxo, -NO2, CN, NH2, -O(C1-C6 alkyl), and -S(C1-C6 alkyl). In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 R is optionally and independently substituted with 1 to 3 substituents. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 It is optionally and independently substituted with one or two substituents.

[0257]

[0123] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 These are halos (such as F or Cl), -CH3, -CHF2, -CF3, -CH2OH,

[0258] [ka]

[0259] , -CH2CH3, -CH2CH2CH3, -CH2CH2CH2CH3, or benzyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 is -CH3. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 teeth,

[0260] [ka]

[0261] In some embodiments, R 1 is ethyl. In some embodiments, R 1 R is propyl. In some embodiments, R 1 is butyl. In some embodiments, R 1 is -CH2-phenyl. In some embodiments, R 1 is -CH2CF3. In some embodiments, R 1 is -CHF2. In some embodiments, R 1 It is -CH2OH.

[0262]

[0124] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 R is a substituted or unsubstituted C3-C6 cycloalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 R is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 is cyclopropyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 teeth,

[0263] [ka]

[0264] That is the case.

[0125] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 R is a substituted or unsubstituted C2-C7 heterocycloalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 R is a substituted or unsubstituted C3-C5 heterocycloalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 teeth,

[0265] [ka]

[0266] That is the case.

[0126] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 H is H.

[0267]

[0127] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 2 H, halogen, -OH, -OR 10b, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 2 R is H, a halogen, -OH, or a substituted or unsubstituted C1-C6 alkyl group. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 2 is H or a halogen. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 2 is a halogen. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 2 is H. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 2 It is -CH3.

[0268]

[0128] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 and R 2These, together with the carbon atoms to which they are bonded, form a 3- to 7-membered ring or a heterocyclic ring. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 and R 2 These, together with the carbon atoms to which they are bonded, form cyclopropyl or cyclobutyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 and R 2 These, together with the carbon atoms to which they are bonded, form a cyclopropyl group. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 and R 2 These, together with the carbon atoms to which they are bonded, form cyclobutyl.

[0269]

[0129] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 and R 2 They combine to form an oxo.

[0270]

[0130] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 1 and R 2 Together, CR 12a R 12b Forms a double bond to R 12a and R 12bEach of these is independently hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0271]

[0131] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 12a and R 12b Each of these is independently hydrogen, halogen, -OH, amino, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C2-C7 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0272]

[0132] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 12a is hydrogen, R 12b These are hydrogen, substituted or unsubstituted C1-C6 alkyl groups, substituted or unsubstituted phenyl groups, or substituted or unsubstituted monocyclic heteroaryl groups.

[0273]

[0133] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 12a is hydrogen, R 12bis hydrogen or phenyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 12a is hydrogen, R 12b is hydrogen. In some embodiments, R 1 and R 2 Together

[0274] [ka]

[0275] Forms R 1 and R 2 Together

[0276] [ka]

[0277] It forms.

[0134] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 4 , R 5 , R 6 and R 7 Each of these is independently selected H, -OR 11 , -NR 22 R 23 These are halogens and substituted or unsubstituted C1-C6 alkyl groups.

[0278]

[0135] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 4 , R 5 , R 6and R 7 Each of these is independently selected from H, halogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C8 cycloalkyl and substituted or unsubstituted C2-C7 heterocycloalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 4 , R 5 , R 6 and R 7 Each of these is independently selected from H and halogens. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 4 , R 5 , R 6 and R 7 Each of these is independently selected from H, halogens, and substituted or unsubstituted C1-C6 alkyl groups. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 4 , R 5 , R 6 and R 7 Each of these is independently selected from H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, or C1-C6 aminoalkyl.

[0279]

[0136] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 4 H, -OR 11 , -NR 22 R 23, selected from halogens and substituted or unsubstituted C1-C6 alkyl groups. In some embodiments, R 4 is -OR 11 (For example, C1-C6 alkoxys). In some embodiments, R 4 -NR 22 R 23 (e.g., amino, NH(C1-C6 alkyl) and N(C1-C6 alkyl)2). In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 4 is H and halogen. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 4 is H, F, Cl, or Br. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 4 is F. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 4 is Cl. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 4 is Br. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 4 is H. In some embodiments, R 4is H, halogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl. In some embodiments, R 4 These are H, halogen, -C1~C6 alkyl, C1~C6 aminoalkyl, C1~C6 haloalkyl, C1~C6 hydroxyalkyl, and C1~C6 heteroalkyl. In some embodiments, R 4 is H, halogen, -C1-C6 alkyl, C1-C6 aminoalkyl, C1-C6 haloalkyl, or C1-C6 hydroxyalkyl. In some embodiments, R 4 CF3 is . In some embodiments, R 4 It is methyl.

[0280]

[0137] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 5 H, -OR 11 , -NR 22 R 23 , selected from halogens and substituted or unsubstituted C1-C6 alkyl groups. In some embodiments, R 5 is -OR 11 (For example, C1-C6 alkoxys). In some embodiments, R 5 -NR 22 R 23 (e.g., amino, NH(C1-C6 alkyl) and N(C1-C6 alkyl)2). In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 5 are H and halogens. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 5is H, F, Cl, or Br. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 5 is F. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 5 is Cl. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 5 is Br. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 5 is H. In some embodiments, R 5 is H, halogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl. In some embodiments, R 5 These are H, halogen, -C1~C6 alkyl, C1~C6 aminoalkyl, C1~C6 haloalkyl, C1~C6 hydroxyalkyl, and C1~C6 heteroalkyl. In some embodiments, R 5 is H, halogen, -C1-C6 alkyl, C1-C6 aminoalkyl, C1-C6 haloalkyl, or C1-C6 hydroxyalkyl. In some embodiments, R 5 CF3 is . In some embodiments, R 5 It is methyl.

[0281]

[0138] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R6 H, -OR 11 , -NR 22 R 23 , selected from halogens and substituted or unsubstituted C1-C6 alkyl groups. In some embodiments, R 6 is -OR 11 (For example, C1-C6 alkoxys). In some embodiments, R 6 -NR 22 R 23 (e.g., amino, NH(C1-C6 alkyl) and N(C1-C6 alkyl)2). In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 6 are H and halogens. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 6 is H, F, Cl, or Br. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 6 is F. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 6 is Cl. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 6 is Br. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 6is H. In some embodiments, R 6 is H, halogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl. In some embodiments, R 6 These are H, halogen, -C1~C6 alkyl, C1~C6 aminoalkyl, C1~C6 haloalkyl, C1~C6 hydroxyalkyl, and C1~C6 heteroalkyl. In some embodiments, R 6 is H, halogen, -C1-C6 alkyl, C1-C6 aminoalkyl, C1-C6 haloalkyl, or C1-C6 hydroxyalkyl. In some embodiments, R 6 CF3 is . In some embodiments, R 6 It is methyl.

[0282]

[0139] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 7 H, -OR 11 , -NR 22 R 23 , selected from halogens and substituted or unsubstituted C1-C6 alkyl groups. In some embodiments, R 7 is -OR 11 (For example, C1-C6 alkoxys). In some embodiments, R 7 -NR 22 R 23 (e.g., amino, NH(C1-C6 alkyl) and N(C1-C6 alkyl)2). In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 7 are H and halogens. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R7 is H, F, Cl, or Br. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 7 is F. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 7 is Cl. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 7 is Br. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 7 is H. In some embodiments, R 7 is H, halogen, substituted or unsubstituted C1-C6 alkyl, or substituted or unsubstituted C1-C6 heteroalkyl. In some embodiments, R 7 R is H, halogen, C1-C6 alkyl, C1-C6 aminoalkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, or C1-C6 heteroalkyl. In some embodiments, R 7 is H, halogen, -C1-C6 alkyl, C1-C6 aminoalkyl, C1-C6 haloalkyl, or C1-C6 hydroxyalkyl. In some embodiments, R 7 CF3 is . In some embodiments, R 7 It is methyl.

[0283]

[0140] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 is -OR 11 , halogen, -SR 11 -S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -S(=O)2NR 22 R 23 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 These are substituted or unsubstituted C1-C8 alkyl groups, substituted or unsubstituted C2-C8 alkenyl groups, substituted or unsubstituted C2-C8 alkynyl groups, substituted or unsubstituted C1-C8 heteroalkyl groups, substituted or unsubstituted C3-C8 cycloalkyl groups, substituted or unsubstituted C2-C7 heterocycloalkyl groups, substituted or unsubstituted phenyl groups, substituted or unsubstituted naphthyl groups, substituted or unsubstituted monocyclic heteroaryl groups, or substituted or unsubstituted bicyclic or polycyclic heteroaryl groups.

[0284]

[0141] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3R is a substituted or unsubstituted monocyclic heteroaryl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 R is a substituted or unsubstituted 5 or 6-membered monocyclic heteroaryl having 1 to 4 ring heteroatoms independently selected from N, O, and S. In some embodiments, R 3 R is a substituted or unsubstituted five-membered monocyclic heteroaryl. In some embodiments, R 3 R is a substituted or unsubstituted 6-membered monocyclic heteroaryl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 R is a substituted or unsubstituted five-membered monocyclic heteroaryl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 It is a substituted or unsubstituted 6-membered monocyclic heteroaryl.

[0285]

[0142] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0286] [ka]

[0287] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3teeth,

[0288] [ka]

[0289] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0290] [ka]

[0291] In some embodiments, R 3 teeth,

[0292] [ka]

[0293] In some embodiments, each R 31 C is hydrogen, cyano, halogen, hydroxy, substituted or unsubstituted. 1~6 Alkyl, -OCH3, -OCD3, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 1~6 alkoxy, substituted, or unsubstituted C 3~7 Cycloalkyl, substituted, or unsubstituted C 2~8 Heterocycloalkyl, heteroaryl, substituted or unsubstituted heterocycloalkyl-C 1~6 Alkyl, substituted, or unsubstituted C 1~6 Alkyl-aryl, substituted or unsubstituted C 1~6 Alkyl-heterocycloalkyl, substituted or unsubstituted C 1~6 Alkyl-heteroaryl, substituted or unsubstituted C 1~6 Alkoxyaryl, substituted or unsubstituted C 1~6Alkoxy-heterocycloalkyl, substituted or unsubstituted C 1~6 Alkoxy-heteroaryl and hydroxy-substituted C 1~6 Alkoxy, C 1~6 Alkoxy, amino, mono-C 1~6 Alkylamino and di-C 1~6 m is independently selected from alkylaminos, and m is 0, 1, 2, or 3. In some embodiments, each R 31 These are independently hydrogen, cyano, halogen, hydroxy, substituted or unsubstituted C 1~6 Alkyl, -OCH3, -OCD3, CN, NO2, -OR 11 , -SR 11 -S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -S(=O)2NR 22 R 23 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 , substitution or non-substitution C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 1~6 alkoxy, substituted, or unsubstituted C 3~7 Cycloalkyl, substituted, or unsubstituted C 2~8 Heterocycloalkyl, heteroaryl, substituted or unsubstituted heterocycloalkyl-C 1~6 Alkyl, substituted, or unsubstituted C 1~6Alkyl-aryl, substituted or unsubstituted C 1~6 Alkyl-heterocycloalkyl, substituted or unsubstituted C 1~6 Alkyl-heteroaryl, substituted or unsubstituted C 1~6 Alkoxyaryl, substituted or unsubstituted C 1~6 Alkoxy-heterocycloalkyl, substituted or unsubstituted C 1~6 Alkoxy-heteroaryl and hydroxy-substituted C 1~6 Alkoxy, C 1~6 Alkoxy, amino, mono-C 1~6 Alkylamino and di-C 1~6 Selected from alkylaminos, where m is 0, 1, 2, or 3.

[0294]

[0143] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 This is 1, 2, 3, or 4 R 31 It is a 6-membered heteroaryl substituted with each R 31 These are independently cyano, halogen, hydroxy, substituted or unsubstituted C 1~6 Alkyl, -OCH3, -OCD3, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 1~6 alkoxy, substituted, or unsubstituted C 3~7 Cycloalkyl, substituted, or unsubstituted C 2~8 Heterocycloalkyl, heteroaryl, substituted or unsubstituted heterocycloalkyl-C 1~6 Alkyl, substituted, or unsubstituted C 1~6 Alkyl-aryl, substituted or unsubstituted C 1~6 Alkyl-heterocycloalkyl, substituted or unsubstituted C 1~6 Alkyl-heteroaryl, substituted or unsubstituted C 1~6 Alkoxyaryl, substituted or unsubstituted C 1~6 Alkoxy-heterocycloalkyl, substituted or unsubstituted C 1~6Alkoxy-heteroaryl and hydroxy-substituted C 1~6 Alkoxy, C 1~6 Alkoxy, amino, mono-C 1~6 Alkylamino and di-C 1~6 Selected from alkylaminos, where m is 0, 1, 2, or 3.

[0295]

[0144] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0296] [ka]

[0297] In some embodiments, R 3 teeth,

[0298] [ka]

[0299] That is the case.

[0145] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0300] [ka]

[0301] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0302] [ka]

[0303] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0304] [ka]

[0305] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0306] [ka]

[0307] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0308] [ka]

[0309] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R3 teeth,

[0310] [ka]

[0311] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0312] [ka]

[0313] That is the case.

[0146] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 R is a substituted or unsubstituted bicyclic heteroaryl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 It is a condensed bicyclic heteroaryl having 8 to 10 ring atoms and 1, 2, 3, 4, or 5 ring heteroatoms independently selected from N, O, and S.

[0314]

[0147] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3R is a substituted or unsubstituted C2-C7 heterocycloalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 It is a monocyclic 5- or 6-membered heterocycloalkyl having 1 to 3 ring heteroatoms independently selected from N, O, and S.

[0315]

[0148] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0316] [ka]

[0317] And each R 31 These are independently cyano, halogen, hydroxy, substituted or unsubstituted C 1~6 Alkyl, -OCH3, -OCD3, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 1~6 alkoxy, substituted, or unsubstituted C 3~7 Cycloalkyl, substituted, or unsubstituted C 2~8 Heterocycloalkyl, heteroaryl, substituted or unsubstituted heterocycloalkyl-C 1~6 Alkyl, substituted, or unsubstituted C 1~6 Alkyl-aryl, substituted or unsubstituted C 1~6 Alkyl-heterocycloalkyl, substituted or unsubstituted C 1~6 Alkyl-heteroaryl, substituted or unsubstituted C 1~6 Alkoxyaryl, substituted or unsubstituted C 1~6 Alkoxy-heterocycloalkyl, substituted or unsubstituted C 1~6 Alkoxy-heteroaryl and hydroxy-substituted C1~6 Alkoxy, C 1~6 Alkoxy, amino, mono-C 1~6 Alkylamino and di-C 1~6 Selected from alkylaminos, where m is 0, 1, 2, 3, 4, or 5.

[0318]

[0149] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0319] [ka]

[0320] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0321] [ka]

[0322] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0323] [ka]

[0324] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0325] [ka]

[0326] That is the case.

[0150] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 R is a substituted or unsubstituted C3-C8 cycloalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 R is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, each of which is optionally substituted. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 is cyclopropyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 is cyclobutyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3is cyclopentyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 is cyclohexyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0327] [ka]

[0328] That is the case.

[0151] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 is phenyl or naphthyl, each of which is optionally substituted. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 R is phenyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 It is naphthyl.

[0329]

[0152] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 is one or more R 31 Replaced by each R31 These are independently cyano, oxime, oxo, halogen, hydroxy, NO2, amino, and -OR 11 , -SR 11 -S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -S(=O)2NR 22 R 23 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21 Mono-C 1~6 Alkylamino, di-C 1~6 Alkylamino, substituted, or unsubstituted C 1~6 Alkyl, substituted, or unsubstituted C 2~6 Alkenyl, substituted, or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 1~6 alkoxy, substituted, or unsubstituted C 3~7 Cycloalkyl, substituted, or unsubstituted C 2~8 Heterocycloalkyl, heteroaryl, substituted or unsubstituted heterocycloalkyl-C 1~6 Alkyl, substituted, or unsubstituted C 1~6 Alkyl-heterocycloalkyl, substituted or unsubstituted C 1~6 Alkyl-aryl, substituted or unsubstituted C 1~6 Alkyl-heteroaryl, substituted or unsubstituted C 1~6 Alkoxyaryl, substituted or unsubstituted C 1~6 Alkoxy-heterocycloalkyl groups, and substituted or unsubstituted C 1~6Selected from alkoxy-heteroaryl compounds. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 is one or more R 31 Replaced by each R 31 These are independently cyano, oxo, halogen, hydroxy, -SH, NO2, amino, and C. 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl and C 1~6 Selected from heteroalkyl groups.

[0330]

[0153] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 is -OR 11 , -SR 11 -S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -S(=O)2NR 22 R 23 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21, halogen, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, or substituted or unsubstituted C1-C8 heteroalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 is -OR 11 , -SR 11 , substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, or substituted or unsubstituted C1-C8 heteroalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 is -OR 11 , -SR 11 -S(=O)R 21 -S(=O)2R 21 , -NHS(=O)2R 21 -S(=O)2NR 22 R 23 -C(=O)R 21 -OC(=O)R 21 , -C(=O)OR 22 , -OC(=O)OR 22 -C(=O)NR 22 R 23 -OC(=O)NR 22 R 23 , -NR 22 R 23 -NO2, -NHS(=O)2R 21 , -NR 22 C(=O)NR 22 R 23 , -NR 22 C(=O)R 21 , -NR 22 C(=O)OR 21In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 は-OR 11 In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 Ha-SR 11 That is the case.

[0331]

[0154] In some embodiments, R 3 is -OR 11 , -SR 11 , -NR 22 R 23 , substituted or unsubstituted C1-C8 alkyl, or substituted or unsubstituted monocyclic heteroaryl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0332] [ka]

[0333] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0334] [ka]

[0335] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0336] [ka]

[0337] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0338] [ka]

[0339] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0340] [ka]

[0341] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0342] [ka]

[0343] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 3 teeth,

[0344] [ka]

[0345] That is the case.

[0155] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 These are substituted or unsubstituted C1-C6 alkyl groups, substituted or unsubstituted C2-C6 alkenyl groups, substituted or unsubstituted C2-C6 alkynyl groups, substituted or unsubstituted C1-C6 heteroalkyl groups, substituted or unsubstituted C3-C8 cycloalkyl groups, substituted or unsubstituted C2-C7 heterocycloalkyl groups, substituted or unsubstituted phenyl groups, substituted or unsubstituted naphthyl groups, substituted or unsubstituted monocyclic heteroaryl groups, or substituted or unsubstituted bicyclic heteroaryl groups.

[0346]

[0156] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 R is a substituted or unsubstituted C1-C6 alkyl, or a substituted or unsubstituted C3-C6 cycloalkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11R is a substituted or unsubstituted C1-C6 alkyl group. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 These are substituted or unsubstituted C3-C6 cycloalkyl groups.

[0347]

[0157] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 These are substituted C1-C4 alkyl groups.

[0348]

[0158] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 These include cyano, oxime, oxo, halogen, -CN, -NH2, -NH(CH3), -N(CH3)2, -OH, -CO2H, -CO2(C1~C4 alkyl), -C(=O)NH2, -C(=O)NH(C1~C4 alkyl), -C(=O)N(C1~C4 alkyl)2, -S(=O)2NH2, -S(=O)2NH(C1~C4 alkyl), -S(=O)2N(C1~C4 alkyl)2, -SC1~C4 alkyl, -S(=O)C1~C4 alkyl, -S(=O)2(C1~C4 alkyl), mono-C 1~6 Alkylamino, di-C 1~6 Alkylamino, substituted, or unsubstituted C 1~6 Alkyl, substituted, or unsubstituted C 2~6 Alkenyl, substituted, or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 1~6 alkoxy, substituted, or unsubstituted C 3~7 Cycloalkyl, substituted, or unsubstituted C 2~8 Heterocycloalkyl, heteroaryl, substituted or unsubstituted heterocycloalkyl-C 1~6 Alkyl, substituted, or unsubstituted C1~6 Alkyl-heterocycloalkyl, substituted or unsubstituted C 1~6 Alkyl-aryl, substituted or unsubstituted C 1~6 Alkyl-heteroaryl, substituted or unsubstituted C 1~6 Alkoxyaryl, substituted or unsubstituted C 1~6 Alkoxy-heterocycloalkyl and substituted or unsubstituted C 1~6 It is substituted with one or more substituents selected from alkoxy-heteroaryls. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 R is substituted with one or more substituents selected from halogens, -OH, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 fluoroalkyl, C1-C4 heteroalkyl, C1-C4 alkoxy, or C1-C4 fluoroalkoxy. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 It is substituted with one or more substituents selected from halogens, -OH groups, and C3-C6 cycloalkyl groups.

[0349]

[0159] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 It is replaced by one or more F's.

[0350]

[0160] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 teeth,

[0351] [ka]

[0352] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 teeth,

[0353] [ka]

[0354] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 teeth,

[0355] [ka]

[0356] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 teeth,

[0357] [ka]

[0358] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 teeth,

[0359] [ka]

[0360] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 teeth,

[0361] [ka]

[0362] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 11 teeth,

[0363] [ka]

[0364] That is the case.

[0161] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 21 , R 22 and R 23 Each is independently selected from hydrogen and C1-C4 alkyl. In some embodiments, R 21 , R 22 and R 23Each is independently selected from C1-C4 alkyl groups. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 21 R is selected from hydrogen and C1-C4 alkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 21 is hydrogen. In some embodiments of In formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 22 R is selected from hydrogen and C1-C4 alkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 22 is hydrogen. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 23 R is selected from hydrogen and C1-C4 alkyl. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), R 23 It is hydrogen.

[0365]

[0162] In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds prepared in the following examples are prepared from racemic starting materials (and / or intermediates) and separated into individual enantiomers by chiral chromatography as final products or intermediates. Unless otherwise stated, it should be understood that the absolute configurations of the separated intermediates and final compounds depicted are arbitrarily assigned and not determined.

[0366]

[0163] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0367] [ka]

[0368] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0369] [ka]

[0370] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0371] [ka]

[0372] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0373] [ka]

[0374] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0375] [ka]

[0376] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0377] [ka]

[0378] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0379] [ka]

[0380] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0381] [ka]

[0382] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0383] [ka]

[0384] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0385] [ka]

[0386] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0387] [ka]

[0388] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0389] [ka]

[0390] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0391] [ka]

[0392] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0393] [ka]

[0394] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0395] [ka]

[0396] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0397] [ka]

[0398] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0399] [ka]

[0400] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0401] [ka]

[0402] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0403] [ka]

[0404] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0405] [ka]

[0406] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0407] [ka]

[0408] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0409] [ka]

[0410] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0411] [ka]

[0412] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0413] [ka]

[0414] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0415] [ka]

[0416] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0417] [ka]

[0418] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0419] [ka]

[0420] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0421] [ka]

[0422] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0423] [ka]

[0424] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0425] [ka]

[0426] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0427] [ka]

[0428] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0429] [ka]

[0430] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0431] [ka]

[0432] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0433] [ka]

[0434] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0435] [ka]

[0436] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0437] [ka]

[0438] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0439] [ka]

[0440] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0441] [ka]

[0442] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0443] [ka]

[0444] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0445] [ka]

[0446] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0447] [ka]

[0448] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0449] [ka]

[0450] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0451] [ka]

[0452] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0453] [ka]

[0454] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0455] [ka]

[0456] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0457] [ka]

[0458] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0459] [ka]

[0460] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0461] [ka]

[0462] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0463] [ka]

[0464] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0465] [ka]

[0466] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0467] [ka]

[0468] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0469] [ka]

[0470] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0471] [ka]

[0472] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0473] [ka]

[0474] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0475] [ka]

[0476] or a pharmaceutically acceptable salt or solvate thereof.

[0164] In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0477] [ka]

[0478] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0479] [ka]

[0480] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0481] [ka]

[0482] , its stereoisomer, or a pharmaceutically acceptable salt or solvate. In some embodiments of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0483] [ka]

[0484] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0485] [ka]

[0486] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0487] [ka]

[0488] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0489] [ka]

[0490] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0491] [ka]

[0492] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0493] [ka]

[0494] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0495] [ka]

[0496] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0497] [ka]

[0498] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0499] [ka]

[0500] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0501] [ka]

[0502] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0503] [ka]

[0504] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0505] [ka]

[0506] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0507] [ka]

[0508] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0509] [ka]

[0510] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0511] [ka]

[0512] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0513] [ka]

[0514] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0515] [ka]

[0516] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0517] [ka]

[0518] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0519] [ka]

[0520] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0521] [ka]

[0522] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0523] [ka]

[0524] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0525] [ka]

[0526] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0527] [ka]

[0528] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0529] [ka]

[0530] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0531] [ka]

[0532] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0533] [ka]

[0534] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0535] [ka]

[0536] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0537] [ka]

[0538] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0539] [ka]

[0540] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0541] [ka]

[0542] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0543] [ka]

[0544] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0545] [ka]

[0546] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0547] [ka]

[0548] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0549] [ka]

[0550] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0551] [ka]

[0552] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0553] [ka]

[0554] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0555] [ka]

[0556] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0557] [ka]

[0558] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0559] [ka]

[0560] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0561] [ka]

[0562] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0563] [ka]

[0564] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0565] [ka]

[0566] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0567] [ka]

[0568] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0569] [ka]

[0570] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0571] [ka]

[0572] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0573] [ka]

[0574] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0575] [ka]

[0576] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0577] [ka]

[0578] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0579] [ka]

[0580] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0581] [ka]

[0582] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0583] [ka]

[0584] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0585] [ka]

[0586] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0587] [ka]

[0588] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0589] [ka]

[0590] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0591] [ka]

[0592] or a pharmaceutically acceptable salt or solvate thereof. In some embodiments of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), the compounds described herein are

[0593] [ka]

[0594] or a pharmaceutically acceptable salt or solvate thereof.

[0165] Non-limiting examples of the compounds described herein are the compounds shown in Table 1 and their pharmaceutically acceptable salts or solvates.

[0595] [Table 1-1]

[0596] Table 1-2

[0597] Table 1-3

[0598] Table 1-4

[0599] Table 1-5

[0600] Table 1-6

[0601] Table 1-7

[0602] Table 1-8

[0603] Table 1-9

[0604] Table 1-10

[0605] Table 1-11

[0606] [Table 1-12]

[0607] [Table 1-13]

[0608] [Table 1-14]

[0609] [Table 1-15]

[0610] [Table 1-16]

[0611] [Table 1-17]

[0612] [Table 1-18]

[0613] [Table 1-19]

[0614] [Table 1-20]

[0615]

[0166] In some embodiments, the compounds described herein are in racemic form. For example,

[0616] [ka]

[0617] These are racemic compounds,

[0618] [ka]

[0619] It may encompass four stereoisomers, including . In some embodiments, the compounds provided herein are in cis and racemic forms. For example, compound 7 in cis and racemic forms is

[0620] [ka]

[0621] It includes two stereoisomers, including . In some embodiments, the compounds provided herein are in trans and racemic forms. For example, compound 7 in trans and racemic forms is

[0622] [ka]

[0623] It includes two stereoisomers,

[0624] [ka]

[0625] These are racemic compounds,

[0626] [ka]

[0627] It may include two stereoisomers, including [the specified element].

[0167] In some embodiments, the compounds described herein have a structure selected from Table 1 and exist in racemic form. In some embodiments, the compounds described herein have a structure selected from Table 1 and exist in cis and racemic form. In some embodiments, the compounds described herein have a structure selected from Table 1 and exist in trans and racemic form. In some embodiments, the compounds described herein have a structure selected from Table 1 and are stereochemically pure. Those skilled in the art will understand that all stereoisomers and racemic forms of the compounds disclosed in Table 1 are encompassed by this disclosure.

[0628]

[0168] In some embodiments, the compounds of formula (I), (Ia), (Ib), (II), (IIa), or (IIb) are not racemates. In some embodiments, the compounds of the Disclosure are substantially free of other isomers. In some embodiments, the compounds are a single isomer substantially free of other isomers. In some embodiments, the compounds contain 25% or less of other isomers. In some embodiments, the compounds contain 20% or less of other isomers. In some embodiments, the compounds contain 15% or less of other isomers. In some embodiments, the compounds contain 10% or less of other isomers. In some embodiments, the compounds contain 5% or less of other isomers. In some embodiments, the compounds contain 1% or less of other isomers. In some embodiments, the compounds have a stereochemical purity of at least 75%. In some embodiments, the compounds have a stereochemical purity of at least 80%. In some embodiments, the compounds have a stereochemical purity of at least 85%. In some embodiments, the compounds have a stereochemical purity of at least 90%. In some embodiments, the compounds have a stereochemical purity of at least 95%. In some embodiments, the compound has a stereochemical purity of at least 96%. In some embodiments, the compound has a stereochemical purity of at least 97%. In some embodiments, the compound has a stereochemical purity of at least 98%. In some embodiments, the compound has a stereochemical purity of at least 99%. In some embodiments, the compound is stereochemically pure.

[0629]

[0169] Included in this disclosure are salts of the compounds described herein, in particular pharmaceutically acceptable salts. Compounds of the present invention having functional groups that are sufficiently acidic, sufficiently basic, or both, can react with a number of inorganic bases as well as any of inorganic and organic acids to form salts. Alternatively, compounds that are inherently charged, such as those having quaternary nitrogen, can form salts with suitable counterions, such as bromides, chlorides, or fluorides, and halides, particularly bromides.

[0630]

[0170] Chemical entities having a carbon-carbon double bond or a carbon-nitrogen double bond may exist in Z or E form (or cis or trans form). Furthermore, some chemical entities may exist in various tautomer forms. Unless otherwise specified, the compounds described herein are intended to include all Z, E, and tautomer forms.

[0631]

[0171] A "tautomer" refers to a molecule in which a proton shift can occur from one atom of the molecule to another atom of the same molecule. The compounds presented herein exist as tautomers in certain embodiments. Under conditions where tautomerization is possible, a chemical equilibrium of tautomers exists. The exact ratio of tautomers depends on several factors, including physical conditions, temperature, solvent, and pH. Some examples of tautomer equilibrium include:

[0632] [ka]

[0633]

[0172] Compounds disclosed herein, in some embodiments, for example, 2 H, 3 H, 11 C, 13 C and / or 14 It is used in different concentrated isotopic forms in which the C content is concentrated. In one specific embodiment, the compound is deuterated at at least one position. Such deuterated forms can be prepared by the procedures described in U.S. Patents 5,846,514 and 6,334,997. As described in U.S. Patents 5,846,514 and 6,334,997, deuteration can improve metabolic stability and / or potency, and thus prolong the duration of action of the drug.

[0634]

[0173] Unless otherwise specified, the compounds described herein are intended to include compounds that differ only in the presence of one or more isotopically enriched atoms, for example, hydrogen substitution with deuterium or tritium, or 13 C or 14 Compounds having the structure of the present invention, excluding carbon substitution by carbon-enriched carbon, are within the scope of this disclosure.

[0635]

[0174] The compounds of the present disclosure optionally contain one or more atomic isotopes in unnatural proportions in one or more atoms constituting such compounds. For example, the compounds may contain, for example, deuterium ( 2 H), tritium ( 3 H), Iodine-125 ( 125 I) or carbon-14 ( 14 It can be labeled with isotopes such as C). 2 H, 11 C, 13 C, 14 C, 15 C, 12 N, 13 N, 15 N, 16 N, 16 O, 17 O, 14 F, 15 F, 16 F, 17 F, 18 F, 33 S, 34 S, 35 S, 36 S, 35 Cl, 37 Cl, 79 Br, 81 Br and 125 All isotopic substitutions with I are intended. All isotopic variations of the compounds of the present invention, whether radioactive or not, are included within the scope of the present invention.

[0636]

[0175] In some embodiments of the compounds disclosed herein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6, R 7 , R 10a , R 10b , R 12a , R 12b , R 21 , R 22 , R 23 and R 31 One or more of the groups contain deuterium at a higher percentage than its natural abundance.

[0637]

[0176] In some embodiments of the compounds disclosed herein, the following group R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 10a , R 10b , R 12a , R 12b , R 21 , R 22 , R 23 and R 31 In one or more of these, one or more hydrogen atoms are replaced by one or more deuterium atoms.

[0638]

[0177] In some embodiments of the compounds disclosed herein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 10a , R 10b , R 12a , R 12b , R 21 , R 22 , R 23 and R 31 The abundance of deuterium in each of these is independently at least 1%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% of the total amount of hydrogen and deuterium.

[0639]

[0178] In some embodiments of the compounds disclosed herein, one or more hydrogen atoms of ring Q are replaced by one or more deuterium atoms.

[0179] In certain embodiments, the compounds disclosed herein are 1 Some or all of the H atoms 2 It is replaced by a hydrogen atom. The synthesis methods for deuterium-containing compounds are known in the art, and the following synthesis method is merely an example of a non-limiting method.

[0640]

[0180] Deuterium-substituted compounds are synthesized using various methods, as described below: Dean, Dennis C.; Editor. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [Curr., Pharm. Des., 2000; 6(10) in] 2000, 110 pp; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21, and Evans, E. Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

[0641]

[0181] Deuterated starting materials are readily available and are subjected to the synthesis methods described herein to result in the synthesis of deuterium-containing compounds. Numerous deuterium-containing reagents and component blocks are commercially available from chemical suppliers such as Aldrich Chemical Co.

[0642]

[0182] The compounds of the present invention include, for example, polymorphs, pseudopolymorphs, solvates, hydrates, non-solvated polymorphs (including anhydrous), conformational polymorphs and amorphous forms of the compounds, as well as mixtures thereof, crystalline and amorphous forms of these compounds, pharmaceutically acceptable salts, and active metabolites of these compounds having the same kind of activity.

[0643]

[0183] The compounds described herein may, in some cases, exist as diastereomers, enantiomers, or other stereoisomeric forms. Where absolute stereochemistry is not specified, the compounds presented herein include all diastereomeric, enantiomeric, and epimeric forms, as well as suitable mixtures thereof. Separation of stereoisomers may be performed by chromatography, or by forming diastereomers and separating them by recrystallization, chromatography, or any combination thereof. (Jean Jacques, Andre Collet, Samuel H. Wilen, “Enantiomers, Racemates and Resolutions”, John Wiley And Sons, Inc., 1981, incorporated herein by reference). Stereoiomers may also be obtained by stereoselective synthesis.

[0644]

[0184] The methods and compositions described herein include the use of amorphous forms as well as crystalline forms (which are also known as polymorphs). The compounds described herein may also be in the form of pharmaceutically acceptable salts. Similarly, in some embodiments, active metabolites of these compounds having the same kind of activity are included in the scope of this disclosure. Furthermore, the compounds described herein may exist not only in non-solvated forms but also in solvated forms with pharmaceutically acceptable solvents such as water and ethanol. The solvated forms of the compounds presented herein are also considered to be disclosed herein.

[0645]

[0185] In certain embodiments, the compound or salt of the compound may be a prodrug in which, for example, the hydroxyl in the parent compound is presented as an ester or carbonate, or the carboxylic acid present in the parent compound is presented as an ester. The term “prodrug” is intended to encompass compounds that are converted into the pharmaceutical agents of the present disclosure under physiological conditions. One method for making a prodrug is to include one or more selected moieties that are hydrolyzed under physiological conditions to reveal a desired molecule. In other embodiments, the prodrug is converted by the enzymatic activity of a host animal, such as specific target cells in the host animal. For example, esters or carbonates (e.g., esters of alcohols or carboxylic acids or carbonates and phosphonic acids) are preferred prodrugs of the present disclosure.

[0646]

[0186] Prodrug forms of the compounds described herein, in which the prodrug is metabolized in vivo to produce the compounds described herein, are included in the claims. In some cases, a portion of the compounds described herein may be a prodrug of another derivative or active compound.

[0647]

[0187] Prodrugs are often useful because, in some situations, they may be easier to administer than the parent drug. For example, a prodrug may be bioavailable by oral administration, while the parent drug is not. Prodrugs may help enhance the cellular permeability of a compound compared to the parent drug. Prodrugs may also have improved solubility in pharmaceutical compositions than the parent drug. Prodrugs may be designed as reversible drug derivatives to be used as modifiers to enhance drug delivery to site-specific tissues or to increase drug retention inside cells.

[0648]

[0188] In some embodiments, the design of the prodrug increases the lipophilicity of the pharmaceutical agent. In some embodiments, the design of the prodrug increases the effective water solubility. For example, all such disclosures are incorporated herein by reference: Fedorak et al., Am. J. Physiol., 269:G210-218 (1995); McLoed et al., Gastroenterol, 106:405-413 (1994); Hochhaus et al., Biomed. Chrom., 6:283-286 (1992); J. Larsen and H. Bundgaard, Int. J. Pharmaceutics, 37, 87 (1987); J. Larsen et al., Int. J. Pharmaceutics, 47, 103 (1988); Sinkula et al., J. Pharm. Sci., 64:181-210 (1975); T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14 of the ACS Symposium Series; and Drug Design, American Pharmaceutical Association. See Edward B. Roche, Bioreversible Carriers, in Pergamon Press, 1987. According to another embodiment, the present disclosure provides a method for producing the compounds defined above. The compounds can be synthesized using prior art. Advantageously, these compounds can be easily synthesized from readily available starting materials.

[0649]

[0189] Useful synthetic chemical transformations and methodologies for synthesizing the compounds described herein are known in the art and include, for example, those described in R. Larock, Comprehensive Organic Transformations (1989); TW Greene and PGM Wuts, Protective Groups in Organic Synthesis, 2d. Ed. (1991); L. Fieser and M. Fieser, Fieser and Fieser's Reagents for Organic Synthesis (1994); and L. Paquette (ed.), Encyclopedia of Reagents for Organic Synthesis (1995).

[0650] C. Pharmaceutical Compositions

[0190] In certain embodiments, compositions comprising a therapeutically effective amount of any one compound or salt of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa), (IIab), (IIba), and (IIbb) (also referred to herein as “pharmaceutical agent”) are provided herein.

[0651]

[0191] Pharmaceutical compositions can be formulated using one or more physiologically acceptable carriers, including excipients and adjuvants that facilitate the processing of the pharmaceutical agent into preparations for pharmaceutical use. Appropriate formulation depends on the selected route of administration. Outlines of pharmaceutical compositions can be found, for example, in Remington: The Science and Practice of Pharmacy, Nineteenth Ed (Easton, Pa., Mack Publishing Company, 1995); Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, HA and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, NY, 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, 7th edition (Lippincott Williams & Wilkins, 1999).

[0652]

[0192] The compositions and methods of the present disclosure may be used to treat individuals in need of treatment. In certain embodiments, the individuals are mammals such as humans or non-human mammals. When administered to animals such as humans, the compositions or pharmaceutical agents are preferably administered as a pharmaceutical composition comprising, for example, a pharmaceutical agent and a pharmaceutically acceptable carrier or excipient. Pharmaceutically acceptable carriers are well known in the art and include, for example, aqueous solutions such as water or physiologically buffered saline, or oils such as glycols, glycerols, olive oil, or other solvents or vehicles such as injectable organic esters. In preferred embodiments, if such a pharmaceutical composition is for human administration, particularly for invasive routes of administration such as injection or implantation to avoid transport or diffusion across the epithelial barrier, the aqueous solution is pyrogen-free or substantially pyrogen-free. Excipients may be selected, for example, to provide delayed release of the drug or to selectively target one or more cells, tissues or organs. The pharmaceutical composition may be in unit dosage forms such as tablets, capsules, granules, lyophilized reconstituted products, powders, solutions, syrups, suppositories, or injections. The composition may also be present in transdermal delivery systems, such as skin patches. The composition may also be present in solutions suitable for topical administration, such as eye drops.

[0653]

[0193] Pharmaceutically acceptable excipients may include, for example, physiologically acceptable agents that act to stabilize compounds such as pharmaceuticals, increase their solubility, or increase their absorption. Examples of such physiologically acceptable agents include carbohydrates such as glucose, sucrose, or dextran; antioxidants such as ascorbic acid or glutathione; chelating agents; low molecular weight proteins or other stabilizers or excipients. The selection of pharmaceutically acceptable excipients, including physiologically acceptable agents, depends, for example, on the route of administration of the composition. The preparation or pharmaceutical composition may also be a self-emulsifying drug delivery system or a self-microemulsifying drug delivery system. The pharmaceutical composition (preparation) may also be a liposome or other polymer matrix, which can, for example, incorporate the compounds of the present invention therein. For example, liposomes containing phospholipids or other lipids are non-toxic, physiologically acceptable, and metabolizable carriers that are relatively easy to prepare and administer.

[0654]

[0194] Pharmaceutical compositions (preparations) can be administered to a target by any of a number of routes of administration, including, for example, oral, liquid drugs such as aqueous or non-aqueous solutions or suspensions, tablets, capsules including sprinkle capsules and gelatin capsules, boluses, powders, granules, pastes for application to the tongue; absorption through the oral mucosa, e.g. sublingually; anally, rectally or vaginally, e.g. as pessaries, creams or foams; parenterally, including intramuscular, intravenous, subcutaneous or intrathecal, e.g. as sterile solutions or suspensions; nasally; intraperitoneally; subcutaneously; transdermally, e.g. as patches applied to the skin; and topically, e.g. as creams, ointments or sprays applied to the skin, or as eye drops. Compounds may also be formulated for inhalation. In certain embodiments, compounds can be simply dissolved or suspended in sterile water.

[0655]

[0195] The pharmaceutical composition may be a sterile aqueous or non-aqueous solution, suspension, or emulsion, such as a microemulsion. The excipients described herein are illustrative and not limiting. An effective dose or therapeutically effective dose refers to the amount of one or more pharmaceutical agents administered to a subject as a single dose or as part of a series of doses that is effective in producing the desired therapeutic effect.

[0656]

[0196] Subjects may generally be monitored for therapeutic efficacy using assays and methods appropriate to the condition being treated, such assays which are familiar to those skilled in the art and are described herein. The pharmacokinetics of a medicinal agent or one or more of its metabolites administered to a subject can be monitored by determining the levels of the medicinal agent or metabolite in biological fluids, e.g., blood, blood fractions, e.g., serum and / or urine, and / or other biological samples or biological tissues from the subject. Any method practiced in the art to detect a drug and described herein may be used to measure the levels of the medicinal agent or metabolite during the course of treatment.

[0657]

[0197] The dosage of the medicinal agents described herein for treating a disease or disorder may depend on the condition of the subject, i.e., the stage of the disease, the severity of the symptoms caused by the disease, the general health status, as well as age, sex and weight, and other factors that are apparent to a person skilled in the art of the medical field. The medicinal composition may be administered in a manner appropriate to the disease being treated, as determined by a person skilled in the art of the medical field. In addition to the factors described herein and above relating to the use of medicinal agents for treating a disease or disorder, the appropriate duration and frequency of administration of the medicinal agent may also be determined or adjusted by factors such as the patient's condition, the type and severity of the patient's disease, the specific form of the active ingredient, and the method of administration. The optimal dose of the agent may generally be determined using experimental models and / or clinical trials. The optimal dose may depend on the subject's body mass, weight, or blood volume. It is usually preferable to use the minimum dose sufficient to produce an effective treatment. The design and conduct of preclinical and clinical trials of the medicinal agents described herein, including when administered for prophylactic benefit, are well within the skill of a person skilled in the art of the relevant field. When administering two or more medicinal agents to treat a disease or disorder, the optimal dose of each medicinal agent may differ, such as being less than when either agent is administered alone as monotherapy. In certain specific embodiments, the combined use of two medicinal agents may result in synergistic or additive effects, allowing for the use of lower doses than when either agent is administered alone. The amount of medicinal agent that can be administered per day may be, for example, about 0.01 mg / kg to 100 mg / kg, e.g., about 0.1 to 1 mg / kg, about 1 to 10 mg / kg, about 10 to 50 mg / kg, or about 50 to 100 mg / kg body weight. In other embodiments, the amount of medicinal agent that can be administered per day may be about 0.01 mg / kg to 1000 mg / kg, about 100 to 500 mg / kg, or about 500 to 1000 mg / kg body weight. The optimal dose per day or per treatment course may vary depending on the disease or disorder being treated, as well as the route of administration and the treatment regimen.

[0658]

[0198] Pharmaceutical compositions containing pharmaceutical agents can be formulated in a manner suitable for a delivery method by using techniques routinely practiced in the art. The composition may be in the form of a solid, e.g., a tablet or capsule; a semi-solid, e.g., a gel; a liquid; or a gas, e.g., an aerosol. In other embodiments, the pharmaceutical composition is administered as a bolus injection.

[0659]

[0199] Pharmaceutically acceptable excipients are well known in the pharmaceutical technology and are described, for example, in Rowe et al., Handbook of Pharmaceutical Excipients: A Comprehensive Guide to Uses, Properties, and Safety, 5th edition, 2006, and Remington: The Science and Practice of Pharmacy (Gennaro, 21st edition, Mack Pub. Co., Easton, PA (2005)). Exemplary pharmaceutically acceptable excipients include sterile saline and phosphate-buffered saline at physiological pH. Preservatives, stabilizers, dyes, buffers, etc., may be provided in the pharmaceutical composition. Antioxidants and suspending agents may also be used. Generally, the type of excipient is selected based on the mode of administration, as well as the chemical composition of the active ingredient. Alternatively, the compositions described herein may be formulated as lyophilized products. The compositions described herein may be formulated by lyophilization or other methods using one or more suitable excipient solutions to solubilize and / or dilute the pharmaceutical agent of the composition at administration. In other embodiments, the pharmaceutical agent may be encapsulated in liposomes using techniques known and practiced in the art. In certain specific embodiments, the pharmaceutical agent is not formulated in liposomes for application to stents used to treat arteries that are not completely but highly occluded. The pharmaceutical composition may be formulated for any suitable method of administration described herein and in the art.

[0660]

[0200] For example, pharmaceutical compositions for oral administration, or for injection, infusion, subcutaneous delivery, intramuscular delivery, intraperitoneal delivery, or other methods may be in liquid form. Liquid pharmaceutical compositions may include, for example, one or more of the following: sterile diluents, such as water, saline, preferably physiological saline, Ringer's solution, isotonic sodium chloride, fixing oils that can function as a solvent or suspension medium, polyethylene glycol, glycerin, propylene glycol, or other solvents; antimicrobial agents; antioxidants; chelating agents; buffers and tension modifiers such as sodium chloride or dextrose. Parenteral compositions can be sealed in glass or plastic ampoules, disposable syringes, or multi-dose vials. Physiological saline is preferred, and pharmaceutical compositions for injection are preferably sterile. In another embodiment, liquid pharmaceutical compositions may be applied to the eye in the form of eye drops for the treatment of ophthalmic conditions or diseases. Liquid pharmaceutical compositions may be delivered orally.

[0661]

[0201] In the case of oral formulations, at least one of the pharmaceutical agents described herein may be used alone or in combination with appropriate additives for making tablets, powders, granules or capsules, and optionally with diluents, buffers, wetting agents, preservatives, colorants and flavoring agents. The pharmaceutical agents may be formulated with buffers and / or enteric coatings to protect the compounds from the low pH of the gastric environment. Pharmaceutical agents contained in pharmaceutical compositions may be formulated for oral delivery together with flavoring agents, for example, in liquid, solid or semi-solid formulations and / or using enteric coatings.

[0662]

[0202] A pharmaceutical composition comprising any one of the pharmaceutical agents described herein may be formulated for sustained release or controlled release, also known as timed release or controlled release. Such compositions may be prepared using generally known techniques and may be administered, for example, by oral, rectal, intradermal or subcutaneous implantation, or implantation into a desired target site. Sustained-release formulations may contain the compound dispersed in a carrier matrix and / or contained in a reservoir surrounded by a rate-controlled membrane. Excipients for use in such formulations may be biocompatible and further biodegradable; preferably, the formulation results in a relatively constant level of active ingredient release. The amount of pharmaceutical agent contained in a sustained-release formulation depends on the implantation site, release rate and expected duration, as well as the nature of the condition, disease or disorder to be treated or prevented.

[0663]

[0203] In certain embodiments, the pharmaceutical composition comprising the pharmaceutical agent is formulated for transdermal, intradermal, or topical administration. The composition may be administered as a powder / talc or other solid, liquid, spray, aerosol, ointment, foam, cream, gel, paste, using a syringe, bandage, transdermal patch, insert, or syringe-like applicator. It may be in the form of a controlled-release or sustained-release formulation that is preferably administered topically, or directly into the skin adjacent to or within the area to be treated, for example, by intradermal or subcutaneous injection. The active composition may also be delivered by iontophoresis. Preservatives may be used to prevent the growth of fungi and other microorganisms. Suitable preservatives include, but are not limited to, benzoic acid, butylparaben, ethylparaben, methylparaben, propylparaben, sodium benzoate, sodium propionate, benzalkonium chloride, benzethonium chloride, benzyl alcohol, cetylpyridinium chloride, chlorobutanol, phenol, phenylethyl alcohol, thimerosal, and combinations thereof.

[0664]

[0204] A pharmaceutical composition containing a pharmaceutical agent can be formulated as an emulsion for topical application. The emulsion comprises one liquid dispersed in a large portion of a second liquid. The emulsion may be an oil-in-water emulsion or a water-in-oil emulsion. Either or both of the oil phase and the aqueous phase may contain one or more surfactants, emulsifiers, emulsion stabilizers, buffers, and other excipients. The oil phase may also contain other oily, pharmaceutically approved excipients. Suitable surfactants include, but are not limited to, anionic surfactants, nonionic surfactants, cationic surfactants, and amphoteric surfactants. The composition for topical application may also contain at least one suitable suspending agent, antioxidant, chelating agent, emollient, or humectant.

[0665]

[0205] Ointments and creams can be formulated using, for example, an aqueous or oily base with appropriate thickeners and / or gelling agents added. Lotions can be formulated using an aqueous or oily base and generally also contain one or more emulsifiers, stabilizers, dispersants, suspending agents, thickeners, or colorants. Liquid sprays may be delivered from a pressurized pack, for example, via a specially shaped closure. Oil-in-water emulsions can also be used in compositions, patches, bandages, and articles. These systems are semi-solid emulsions, microemulsions, or foam emulsion systems.

[0666]

[0206] In some embodiments, the pharmaceutical agents described herein can be formulated as inhalants. Inhalation methods can deliver the drug directly to the airways. Pharmaceutical agents can be formulated as aerosols, microspheres, liposomes, or nanoparticles. Pharmaceutical agents can be formulated with solvents, gases, nitrates, or any combination thereof. The compositions described herein are optionally formulated for delivery as liquid aerosols or inhalable dry powders. Liquid aerosol formulations are optionally nebulized to a particle size that can be preferentially delivered to terminal and respiratory bronchioles. Liquid aerosol and inhalable dry powder formulations are preferably delivered from the entire bronchial tree to the terminal bronchioles and ultimately to the parenchymal tissue.

[0667]

[0207] The aerosolized formulations described herein are optionally delivered using an aerosol-forming device such as a jet, a vibrating perforated plate, or an ultrasonic nebulizer, which is preferably selected to enable the formation of aerosol particles having a mass median mean diameter of 1 to 5 μm. Furthermore, the formulations preferably have equilibrium osmotic ionic strength and chloride concentration and have the minimum aerosolizable volume capable of delivering an effective dose of the pharmaceutical agent. In addition, the aerosolized formulations preferably do not adversely affect airway function and do not cause undesirable side effects.

[0668]

[0208] Aerosolizing devices suitable for administering aerosol formulations described herein include, for example, jets, vibrating perforated plates, ultrasonic nebulizers and electrically charged dry powder inhalers that can preferentially nebulize formulations into aerosol particle sizes in the 1-5 μm size range. Preferred in this application means that at least 70%, but preferably more than 90%, of the total aerosol particles produced are in the 1-5 μm range. Jet nebulizers operate by decomposing a liquid solution into aerosol droplets using air pressure. Vibrating perforated plate nebulizers operate by using an ultrasonic vacuum created by a rapidly vibrating perforated plate to push solvent droplets through the perforated plate. Ultrasonic nebulizers operate by a piezoelectric crystal that shears the liquid into small aerosol droplets. For example, various suitable devices are available, including AeroNeb® and AeroDose® vibrating perforated plate nebulizers (AeroGen, Inc., Sunnyvale, California), Sidestream® nebulizers (Medic-Aid Ltd., West Sussex, UK), Pari LC® and Pari LC Star® jet nebulizers (Pari Respiratory Equipment, Inc., Richmond, Virginia), as well as Aerosonic® (DeVilbiss Medizinische Produkte GmbH, Heiden, Germany) and UltraAire® (Omron Healthcare, Inc., Vernon Hills, Illinois) ultrasonic nebulizers.

[0669]

[0209] In some embodiments, the pharmaceutical agent may be formulated with an oily base or ointment to form a semi-solid composition having a desired shape. In addition to the pharmaceutical agent, these semi-solid compositions may include a solubilizing and / or suspending bactericide, a preservative and / or a buffering system. The petrolatum component that may be included may be isobutylene, colloidal silica, or any paraffin in the viscosity range from mineral oil to paraffin wax incorporating stearate. The absorbent base can be used with the oily system. Examples of additives include cholesterol, lanolin (lanolin derivatives), beeswax, fatty alcohols, wool wax alcohol, low HLB (hydrophilic-lipophilic balance) emulsifiers, and various ionic and nonionic surfactants, either alone or in combination.

[0670]

[0210] Controlled or sustained-release transdermal or topical formulations can be achieved by adding time-release additives such as polymer structures, matrices, etc., available in the art. For example, the composition may be administered using a hot-melt extruded product such as a bioadhesive hot-melt extruded film. The formulation may include a crosslinked polycarboxylic acid polymer formulation. The crosslinking agent may be present in an amount that provides sufficient adhesion to allow the system to remain bound to the surface of target epithelial or endothelial cells for a sufficient time to allow the desired release of the compound.

[0671]

[0211] Insertions, transdermal patches, bandages, or articles may include a mixture or coating of polymers that result in the release of a pharmaceutical agent at a constant rate over a long period of time. In some embodiments, articles, transdermal patches, or inserts include a water-soluble pore-forming agent, such as polyethylene glycol (PEG), which can be mixed with a water-insoluble polymer to increase the durability of the insert and extend the release of the active ingredient.

[0672]

[0212] Transdermal devices (insertions, patches, bandages) may also contain water-insoluble polymers. Rate-controlled polymers may be useful for administration to sites where release can be controlled using pH changes. These rate-controlled polymers can be applied using a continuous coating film during a spraying and drying process with the active compound. In one embodiment, the coating formulation is used to coat a pellet containing an active ingredient that is compressed to form a solid biodegradable insert.

[0673]

[0213] Polymer formulations can also be used to provide controlled or sustained release. Bioadhesive polymers described in the Art can be used. For example, sustained-release gels and compounds can be incorporated into polymer matrices such as hydrophobic polymer matrices. Examples of polymer matrices include microparticles. The microparticles may be microspheres, and the core may be made of a different material from the polymer shell. Alternatively, the polymer can be cast as a thin slab or film, a powder produced by grinding or other standard techniques, or a gel such as a hydrogel. The polymer may also be in the form of a coating or part of a bandage, stent, catheter, artificial blood vessel, or other device to facilitate the delivery of pharmaceutical agents. The matrix can be formed by solvent evaporation, spray drying, solvent extraction and other methods known to those skilled in the art.

[0674]

[0214] Kits are provided that typically contain one or more unit doses of the drugs described herein, usually in orally or injectable doses. Such kits may include a container containing the unit doses, an informational leaflet describing the use of the drug in the treatment of a disease and the associated benefits, and optionally an instrument or device for delivering the composition. D. Treatment Method

[0215] The compounds described herein can be used in the preparation of drugs for the prevention or treatment of diseases or conditions. Furthermore, a method for treating any of the diseases or conditions described herein in a subject requiring treatment of any of the diseases or conditions described herein includes administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising at least one of the compounds described herein, or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable prodrug, or a pharmaceutically acceptable solvate thereof.

[0675]

[0216] Compositions comprising the compounds described herein may be administered for prophylactic and / or therapeutic purposes. For therapeutic use, the composition is administered to a patient already suffering from a disease or condition in an amount sufficient to cure or at least partially cessate the symptoms of the disease or condition. The effective amount for this use depends on the severity and course of the disease or condition, previous treatments, the patient's health status, weight and response to the drug, and the judgment of the treating physician.

[0676]

[0217] For prophylactic use, compositions containing the compounds described herein are administered to patients who are susceptible to or otherwise at risk of a particular disease, disorder, or condition. Such amounts are defined as “effective prophylactic doses or doses.” In this use, the exact amount also depends on the patient’s health condition, weight, etc. When used in patients, the effective amount for this use depends on the severity and course of the disease, disorder, or condition, previous treatments, the patient’s health condition and response to the drug, and the judgment of the treating physician.

[0677]

[0218] If the patient's condition does not improve, the physician may, at his discretion, administer the compound chronically, i.e., over a long period including the patient's entire life, to improve or otherwise control or limit the symptoms of the patient's disease or condition.

[0678]

[0219] Once the patient's condition improves, a maintenance dose should be administered as needed. Subsequently, the dose, frequency, or both can be reduced according to the symptoms to a level at which the improved disease, disability, or condition is maintained. However, the patient may require long-term, intermittent treatment if any symptoms recur.

[0679]

[0220] The amount of a given drug corresponding to such a quantity will vary depending on factors such as the specific compound, the disease or condition and its severity, and the individual characteristics of the subject or host requiring treatment (e.g., body weight). Nevertheless, it can be determined in a manner recognized in the art, depending on the specific circumstances surrounding the case, including, for example, the specific drug administered, the route of administration, the condition being treated, and the subject or host being treated. However, generally, doses used for the treatment of adult humans are typically in the range of about 0.02 to about 5000 mg per day, and in some embodiments, about 1 to about 1500 mg per day. The desired dose may be presented as a single dose, or as divided doses administered simultaneously (or over a short period), or as subdoses at appropriate intervals, for example, two, three, or four or more per day.

[0680]

[0221] The pharmaceutical compositions described herein may be in unit dosage forms suitable for single-dose administration of precise doses. In unit dosage forms, the formulation is divided into unit doses containing appropriate amounts of one or more compounds. Unit doses may be in the form of packaging containing discrete amounts of the formulation. Non-limiting examples include packaged tablets or capsules, and powders in vials or ampoules. Aqueous suspension compositions may be packaged in single-dose, non-resealable containers. Alternatively, multi-dose resealable containers may be used, in which case it is common to include preservatives in the composition. For example, parenteral injection formulations may be presented in unit dosage forms, including but not limited to ampoules, or in multi-dose containers with added preservatives.

[0681]

[0222] The toxicity and therapeutic efficacy of such treatment regimens can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, which include LD 50 (A lethal dose in 50% of the population) and ED 50 This includes, but is not limited to, determining the dose that is therapeutically effective in 50% of the population. The dose ratio between the toxic effect and the therapeutic effect is the therapeutic index, LD 50 and ED 50 It can be expressed as a ratio between [values]. Compounds exhibiting a high therapeutic index are preferred. Data obtained from cell culture assays and animal experiments can be used when formulating the dosage range for use in humans. The dosage of such compounds is preferably ED with minimal toxicity. 50 It is within the range of circulating concentrations, including [the substance]. The dosage may vary within this range depending on the dosage form and route of administration used.

[0682]

[0223] In one embodiment, the compounds described herein or their pharmaceutically acceptable salts or solvates have a brain / blood AUC of at most about 0.0001, 0.001, 0.01, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 5, or 10. The brain permeability values ​​and characteristics of the compounds described herein can be determined by any suitable method known in the art, such as in vivo or in vitro assays, e.g., Caco-2 permeability assays and MDR1-MDCK assays.

[0683]

[0224] Glutaminyl-peptide cyclotransferase-like protein (QPCTL) is located in a cellular organelle called the Golgi apparatus and has been identified as a key regulator of the CD47 / SIRPα axis. CD47 expression is frequently observed in cancer cells in NHL, acute myeloid leukemia, myelodysplastic syndromes, and in both hematological malignancies and solid tumors, including glioblastoma, gastric cancer, breast cancer, colon cancer, hepatocellular carcinoma, and prostate cancer. Cancer cells use SIRPα-mediated CD47 to evade detection by the immune system and subsequent destruction by macrophages. The N-terminus of the CD47 protein contains a pyroglutamic acid residue essential for creating a high-affinity SIRPα binding site, and this modification immediately after protein synthesis has been shown to be dependent on the QPCTL protein. Inhibition of QPCTL by pharmacological tools or biotechnological knockout methods has been shown to result in decreased or lost binding between CD47 and SIRPα, as well as increased antibody-dependent cellular phagocytosis and neutrophil-induced cytotoxicity.

[0684]

[0225] In addition to the involvement of the CD47 / SIRPα axis, QPCTLs also pyroglutamine-oxidize CC motif chemokine ligand proteins, CCL2, CCL7, CCL8, and CCL13, which are ligands for the chemokine receptor CCR2, responsible for directing the migration of myeloid cell lineages, including monocytes / macrophages and dendritic cells. Modification of CCL chemokine family members by QPCTLs enhances the stability of these chemokines against degradation and enhances CCR2 activation and signaling. The CCL2 / CCR2 axis is involved in cancer cell survival, migration, and metastasis through the recruitment of immune cells into the tumor microenvironment. Therefore, downregulation of CCL2 / CCR2 signaling by inhibiting QPCTLs can be used to attenuate the biological function of CCL2 / CCR2 signaling in cancer development.

[0685]

[0226] In one embodiment, the present disclosure provides a method for modulating glutaminyl-peptide cyclotransferase-like protein (QPCTL) activity in a subject, comprising the step of administering the compound described herein or a pharmaceutically acceptable salt or solvate thereof to the subject.

[0686]

[0227] In one embodiment, the present disclosure provides a method for inhibiting glutaminyl-peptide cyclotransferase-like protein (QPCTL) activity in a subject, comprising the step of administering the compound described herein or a pharmaceutically acceptable salt or solvate thereof to the subject.

[0687]

[0228] In one embodiment, the present disclosure provides a method for treating cancer in a subject requiring treatment of cancer, comprising the step of administering a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein.

[0688]

[0229] In one embodiment, the present disclosure provides a method for treating a disease or condition in a subject requiring treatment of the disease or condition, comprising the step of administering a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein, to the subject. In some embodiments, the disease or condition is associated with abnormal glutaminyl-peptide cyclotransferase-like protein (QPCTL) activity. In some embodiments, the disease or condition associated with abnormal QPCTL activity is cancer.

[0689]

[0230] In some embodiments, cancer is leukemia, acute myeloid leukemia (AML), chronic myeloid leukemia, acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), multiple myeloma (MM), or myelodysplastic syndrome (MDS).

[0690]

[0231] In some embodiments, the cancer is leukemia. In some embodiments, the cancer is acute myeloid leukemia (AML). In some embodiments, the cancer is chronic myeloid leukemia. In some embodiments, the cancer is acute lymphoblastic leukemia (ALL). In some embodiments, the cancer is non-Hodgkin lymphoma (NHL). In some embodiments, the cancer is Hodgkin lymphoma (HL). In some embodiments, the cancer is multiple myeloma (MM). In some embodiments, the cancer is myelodysplastic syndrome (MDS).

[0691]

[0232] In some embodiments, the cancer is a solid tumor or a metastatic cancer. In some embodiments, the cancer is a solid tumor. In some embodiments, the cancer is a metastatic cancer.

[0692]

[0233] Some general cancers include skin cancer, eye cancer, gastrointestinal cancer, thyroid cancer, breast cancer, ovarian cancer, central nervous system cancer, laryngeal cancer, cervical cancer, lymphatic system cancer, genitourinary cancer, bone cancer, biliary tract cancer, endometrial cancer, liver cancer, lung cancer, prostate cancer, or colon cancer.

[0693]

[0234] In a particular embodiment, the present invention provides a method for treating or preventing a disease, condition or condition in a patient requiring treatment or prevention of a disease, condition or condition, comprising the step of administering to the patient an effective amount of any one compound of any embodiment of the present invention or a pharmaceutically acceptable salt thereof. The disease, condition or condition may be selected from the group consisting of colorectal cancer, gastric cancer, breast cancer, lung cancer, pancreatic cancer, prostate cancer, multiple myeloma, chronic myeloid leukemia, cancer metastasis, fibrosis, and psychiatric disorders.

[0694]

[0235] In one embodiment, a method for treating a disease or condition in a subject requiring treatment of the disease or condition comprises the step of administering a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein, to the subject, wherein the disease or condition is a disease involving the innate immune system. In some embodiments, the disease is atherosclerosis, fibrous disease, ischemia-reperfusion injury, or an infection caused by a pathogen. In some embodiments, the disease is a fibrous disease selected from hepatic fibrosis, pulmonary fibrosis, renal fibrosis, and scleroderma.

[0695]

[0236] In one embodiment, a method for treating a disease or condition in a subject requiring treatment of the disease or condition comprises the step of administering a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein, to the subject, wherein the disease or condition is chronic kidney disease (CKD). In some embodiments, chronic kidney disease is diabetic nephropathy. Diabetic nephropathy, a complication of diabetes and a major cause of CKD, is typically characterized by damage to the capillaries supplying the renal glomeruli, which results in decreased filtration efficiency in the kidneys and progressive loss of renal function that can lead to end-stage renal disease requiring dialysis or a kidney transplant. In some embodiments, diabetic nephropathy is caused by diabetic or type 2 diabetes. In some embodiments, chronic kidney disease is focal segmental glomerulosclerosis (FSGS). FSGS is a chronic, progressive form of kidney disease characterized by scarring (sclerosis) of the glomeruli. Scarring can be caused by infections, medications such as anabolic steroids, or systemic diseases such as diabetes, HIV infection, sickle cell disease, or lupus.

[0696]

[0237] In one embodiment, the following is described herein as a method for treating a disease or condition in a subject requiring treatment of the disease or condition, comprising the step of administering a compound of formula (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa)(IIab), (IIba), or (IIbb), a stereoisomer thereof, or a salt or solvate thereof. In one embodiment, the method described herein relates to a method for treating a disease or condition in a subject requiring treatment of the disease or condition, comprising the step of administering a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition described herein, to the subject, wherein the disease or condition is Kennedy disease, duodenal cancer with or without Helicobacter pylori infection, colorectal cancer, Zolliger-Ellison syndrome, gastric cancer with or without Helicobacter pylori infection, pathogenic psychotic state, schizophrenia, infertility. The method is for neoplasms, inflammatory host responses, cancer, malignant metastasis, melanoma, psoriasis, humoral and cell-mediated immune response disorders, leukocyte adhesion and migration processes in the endothelium, food intake disorders, sleep-wake disorders, impaired homeostasis of energy metabolism, autonomic dysfunction, hormonal imbalances or fluid imbalances, multiple sclerosis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuritis, mild cognitive impairment, Alzheimer's disease, familial British dementia, familial Danish dementia, neurodegeneration in Down syndrome, Huntington's disease, rheumatoid arthritis, atherosclerosis, pancreatitis and restenosis. In some embodiments, the disease or condition is chronic kidney disease (CKD). In some embodiments, the disease or condition is an immunoneoplastic disease. In some embodiments, the disease or condition is a tumor. In some embodiments, the disease or condition is kidney disease. In some embodiments, the disease or condition is FSGS. In some embodiments, FSGS is primary FSGS. In some embodiments, FSGS is secondary FSGS. In some embodiments, FSGS is hereditary. In some embodiments, the underlying cause of FSGS cannot be determined.In some embodiments, the disease or condition is diabetic nephropathy. In some embodiments, the disease or condition is stage 1 diabetic nephropathy. In some embodiments, the disease or condition is stage 2 diabetic nephropathy. In some embodiments, the disease or condition is stage 4 diabetic nephropathy. In some embodiments, the disease or condition is stage 4 diabetic nephropathy. In some embodiments, the subject has diabetes. In some embodiments, the subject has type 1 diabetes. In some embodiments, the subject has type 2 diabetes.

[0697]

[0238] In some embodiments, the method includes the step of administering a second therapeutic agent. In some embodiments, the second therapeutic agent is a monoclonal antibody. In some embodiments, the monoclonal antibody is an anti-CD20 antibody. In some embodiments, the monoclonal antibody is selected from edrecolomab, rituximab, gemtuzumab ozogamicin, alemtuzumab, ibritumomab tiuxetan, tocitumomab, cetuximab, bevacizumab, and trastuzumab. In some embodiments, the second therapeutic agent is an epidermal growth factor receptor (EGFR) inhibitor. In some embodiments, the second therapeutic agent is edrecolomab. In some embodiments, the second therapeutic agent is rituximab. In some embodiments, the second therapeutic agent is gemtuzumab ozogamicin. In some embodiments, the second therapeutic agent is alemtuzumab. In some embodiments, the second therapeutic agent is ibritumomab tiuxetan. In some embodiments, the second therapeutic agent is tocitumomab. In some embodiments, the second therapeutic agent is cetuximab. In some embodiments, the second therapeutic agent is bevacizumab. In some embodiments, the second therapeutic agent is trastuzumab.

[0698]

[0239] In some embodiments, the second therapeutic agent is an immune checkpoint inhibitor. In some embodiments, the immune checkpoint inhibitor is a CTLA-4 inhibitor, a PD-1 inhibitor, or a PD-L1 inhibitor. In some embodiments, the immune checkpoint inhibitor is ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, or semiprimab. [Examples]

[0699]

[0240] The following embodiments are provided to illustrate the claimed invention, but are not intended to limit it. The following embodiments further illustrate the present invention, but of course, they should not be construed as limiting its scope in any way.

[0700]

[0241] The following synthesis schemes are provided for illustrative purposes only and are not limiting. The following examples illustrate various methods for preparing the compounds described herein. Those skilled in the art will understand that these compounds may be prepared by similar methods or by combining other methods known to those skilled in the art. They will also understand that they may be prepared in a manner similar to those described below by using appropriate starting materials and, if necessary, modifying the synthesis route. Generally, starting materials and reagents can be obtained from commercial suppliers, synthesized according to sources known to those skilled in the art, or prepared as described herein.

[0701]

[0242] Compounds and salts of formulas (I), (Ia), (Ib), (Iaa), (Iab), (Iba), (Ibb), (II), (IIa), (IIb), (IIaa), (IIab), (IIba), and (IIbb) can be synthesized according to one or more exemplary schemes herein and / or techniques known in the art. The materials used herein are commercially available or prepared by synthetic methods generally known in the art. These schemes are not limited to the compounds listed in the examples or to any particular substituents used for illustrative purposes. Various steps are described and depicted in the following synthesis schemes, but in some cases the steps may be carried out in an order different from that shown below. The numbering or R groups in each scheme do not necessarily correspond to those in the claims or other schemes or tables herein.

[0702]

[0243] When used herein in the examples and specification, the same structure may be given different numbering in different examples and / or sections herein. Example 1

[0244] Synthesis of Compounds 7A and 7B

[0245]

[0703] [ka]

[0704]

[0246] Step 1: General procedure for the preparation of 2,6-difluoro-4-(3-hydroxypropoxy)benzonitrile

[0247] 2,6-difluoro-4-hydroxybenzonitrile (5.00 g, 32.2 mmol, 1 equivalent) and K2CO3 (6.68 g, 48.3 mmol, 1.5 equivalents) were dissolved in DMF (10 mL), to which 3-bromopropan-1-ol (6.72 g, 48.4 mmol, 4.36 mL, 1.5 equivalents) was added. The mixture was stirred at 35°C for 12 hours. The reaction mixture was filtered. The filtrate was diluted with siRNA (200 mL), washed with saturated NaCl (50 mL x 4), dehydrated with Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (ISCO®; SepaFlash® silica flash column 120 g, eluent with a 0-37% ethyl acetate / petroleum ether concentration gradient at 85 mL / min). The target compound (5.5 g, 23.20 mmol, yield 71.98%) was obtained as a colorless oil.

[0705]

[0248] LCMS: Retention time: 0.834 min, (M+H) + =214.1, 10~80AB_2min_Agilent.

[0249] 1 HNMR: (400 MHz, DMSO-d6) δ = 7.11 - 7.05 (m, 2H), 4.61 (t, J = 5.2 Hz, 1H), 4.17 (t, J = 6.4 Hz, 2H), 3.57 - 3.49 (m, 2H), 1.90 - 1.82 (m, 2H).

[0706]

[0250] Step 2: General procedure for the preparation of 2,6-difluoro-4-(3-oxopropoxy)benzonitrile

[0251] 2,6-difluoro-4-(3-hydroxypropoxy)benzonitrile (1.00 g, 4.69 mmol, 1 equivalent) was dissolved in DCM (30 mL) and DMP (2.98 g, 7.04 mmol, 2.18 mL, 1.5 equivalents) was added. The mixture was stirred at 0°C for 1 hour. The reaction mixture was quenched by adding saturated Na2S2O3 aqueous solution (30 mL). The organic layer was washed with NaHCO3 aqueous solution (30 mL), dehydrated with Na2SO4, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by flash silica gel chromatography (ISCO®; SepaFlash® silica flash column 20 g, 20 mL / min with an eluent gradient of 0-30% ethyl acetate / petroleum ether). The target compound (500 mg, 2.11 mmol, yield 44.92%) was obtained as a yellow solid.

[0707]

[0252] LCMS: Retention time: 0.791 min, (M+H)=212.1, 10~80AB_2 min_Agilent.

[0253] Step 3: General procedure for the preparation of 4-(3,3-difluoropropoxy)-2,6-difluorobenzonitrile

[0254] 2,6-difluoro-4-(3-oxopropoxy)benzonitrile (310 mg, 1.47 mmol, 1 equivalent) was dissolved in DCM (10 mL) and DAST (473 mg, 2.94 mmol, 388 μL, 2 equivalents) was added at 0°C under N2. The mixture was stirred at 25°C for 1 hour. The reaction mixture was quenched by adding water (10 mL), diluted with water (50 mL), and extracted with siRNA (50 mL x 3). The combined organic layers were washed with brine (30 mL), dehydrated with Na2SO4, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by flash silica gel chromatography (ISCO®; SepaFlash® silica flash column 4 g, eluent with a 0-20% ethyl acetate / petroleum ether concentration gradient at 20 mL / min). The target compound (120 mg, 515 μmol, yield 35.06%) was obtained as a colorless oil.

[0708]

[0255] LCMS: Retention time: 1.005 min, (M+H) = 234.1, 10~80AB_2 min_220 and 254.

[0256] 1 HNMR: (400 MHz, DMSO-d6) δ = 7.16 - 7.14 (m, 1H), 7.13 - 7.11 (m, 1H), 6.40 - 6.07 (m, 1H), 4.27 (t, J = 6.0 Hz, 2H), 2.43 - 2.28 (m, 2H).

[0709]

[0257] Step 4: General procedure for the preparation of 4-(3,3-difluoropropoxy)-2,6-difluorobenzaldehyde

[0258] A solution of 4-(3,3-difluoropropoxy)-2,6-difluorobenzonitrile (9.50 g, 40.7 mmol, 1 equivalent) in DCM (100 mL) was mixed with DIBAL-H (1 M, 57.0 mL, 1.4 equivalents) under N2 at -78°C. The mixture was stirred at 25°C for 12 hours. The reaction mixture was quenched by adding 200 mL of saturated potassium sodium 2,3-dihydroxysuccinate aqueous solution and extracted with DCM (150 mL x 3). The combined organic layers were washed with brine (100 mL), dehydrated with Na2SO4, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by flash silica gel chromatography (ISCO®; SepaFlash® silica flash column 110 g, 85 mL / min with a 0-15% ethyl acetate / petroleum ether concentration gradient). The target compound (5.1 g, 20.82 mmol, yield 51.11%) was obtained as a white solid.

[0710]

[0259] LCMS: Retention time: 1.080 min, (M+H) = 237.2, 10~80AB_2 min_220 and 254.

[0260] 1HNMR: (400 MHz, DMSO-d6) δ = 10.07 (s, 1H), 6.96 - 6.88 (m, 2H), 6.43 - 6.06 (m, 1H), 4.27 (t, J = 6.0 Hz, 2H), 2.41 - 2.29 (m, 2H).

[0711]

[0261] Step 5: General procedure for the preparation of 1-(4-(3,3-difluoropropoxy)-2,6-difluorophenyl)-N-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-yl)methanimine

[0262] 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-amine (1.30 g, 4.94 mmol, 1 equivalent) was added to a solution of 4-(3,3-difluoropropoxy)-2,6-difluorobenzaldehyde (1.17 g, 4.94 mmol, 1 equivalent) in toluene (50 mL). The mixture was stirred at 120 °C for 12 hours. The mixture was concentrated under reduced pressure to obtain the residue. The residue was purified by flash silica gel chromatography (ISCO®; SepaFlash® silica flash column, 20 g, 25 mL / min, eluent with a 0-100% ethyl acetate / petroleum ether concentration gradient). The target compound (1.80 g, 3.74 mmol, yield 75.74%) was obtained as an orange oil.

[0712]

[0263] 1HNMR: (400 MHz, DMSO-d6) δ = 8.63 (d, J = 2.0 Hz, 1H), 8.37 (d, J = 9.6 Hz, 1H), 7.67 (dd, J = 6.4, 8.4 Hz, 1H), 7.56 - 7.51 (m, 1H), 7.24 - 7.18 (m, 1H), 6.97 - 6.89 (m, 2H), 6.46 - 6.05 (m, 1H), 5.65 (d, J = 7.2 Hz, 2H), 4.25 (t, J = 6.4 Hz, 2H), 3.57 - 3.46 (m, 2H), 2.43 - 2.31 (m, 2H), 0.84 (t, J = 8.0 Hz, 2H), -0.09 (d, J = 3.6 Hz, 9H).

[0713]

[0264] Step 6: General procedure for the preparation of 4-(4-(3,3-difluoropropoxy)-2,6-difluorophenyl)-3-methyl-1-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-yl)azetidine-2-one

[0265] To a solution of Zn (54.3 mg, 831 μmol, 2 equivalents) in toluene (20 mL), Ar-based TMS-Cl (31.6 mg, 291 μmol, 36.9 μL, 0.7 equivalents) was added. The mixture was stirred under reflux (120 °C) for 0.25 hours. After cooling to 25 °C, compound 7.5 was added. * Compound 7.6 (128 mg, 706 μmol, 92.0 μL, 1.7 equivalents) and compound 7.5 (200 mg, 415 μmol, 1 equivalent) were added. The resulting mixture was refluxed (120°C) for 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the residue. The residue was purified by flash silica gel chromatography (ISCO®; SepaFlash® silica flash column 4 g, 20 mL / min with an eluent gradient of 0-75% ethyl acetate / petroleum ether). A mixture of compound 7.6 and compound 7.6A (180 mg, 334.81 μmol, yield 80.61%) was obtained as a yellow solid.

[0714]

[0266] LCMS: Retention time: 1.191 min, (M+H) = 538.3, 10~80AB_2 min_220 and 254.

[0267] Step 7: General procedure for the preparation of 1-(1H-benzo[d]imidazole-5-yl)-4-(4-(3,3-difluoropropoxy)-2,6-difluorophenyl)-3-methylazetidine-2-one

[0268] To a solution of compound 7.6 (180 mg, 335 μmol, 1 equivalent), TBAF (1 M, 4.50 mL, 13.4 equivalents) was added. The mixture was stirred at 25°C for 12 hours. The reaction mixture was poured into water (10 mL) and extracted with RINKAN (10 mL x 3). The combined organic layer was dehydrated with Na2SO4, filtered, and concentrated under reduced pressure to obtain the residue. Solutions of TFA (2.77 g, 24.3 mmol, 1.8 mL, 72.6 equivalents) and DCM (0.2 mL) were added to the residue. The mixture was stirred at 25°C for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain the residue. The residue was purified by preparative HPLC (column: Phenomenex Gemini-NX 80 × 40 mm × 3 μm; mobile phase: [water (0.05% NH3H2O)-ACN]; B%: 33%~63%, 8 min). Compound 7 (30.72 mg, 71.55 μmol, yield 21.37%) was obtained as a white solid.

[0715]

[0269] LCMS: Retention time: 0.943 min, (M+H) = 408.2, 10~80AB_2 min_220 and 254.

[0270] 1 HNMR: (400 MHz, DMSO-d6) δ = 12.61 - 12.24 (m, 1H), 8.23 ​​- 8.06 (m, 1H), 7.62 - 7.01 (m, 3H), 6.92 - 6.70 (m, 2H), 6.37 - 6.02 (m, 1H), 5.64 - 5.01 (m, 1H), 4.24 - 4.05 (m, 2H), 3.92 - 3.46 (m, 1H), 2.35 - 2.19 (m, 2H), 1.43 - 0.96 (m, 3H).

[0716]

[0271] Step 8: General procedure for the preparation of (3S,4R)-1-(1H-benzo[d]imidazole-5-yl)-4-(4-(3,3-difluoropropoxy)-2,6-difluorophenyl)-3-methylazetidine-2-one (compound 7A) and (3R,4R)-1-(1H-benzo[d]imidazole-5-yl)-4-(4-(3,3-difluoropropoxy)-2,6-difluorophenyl)-3-methylazetidine-2-one (compound 7B)

[0272] Compound 7 was separated by SFC (column: Phenomenex-Cellulose-2 (250 mm × 30 mm, 10 μm); mobile phase: [0.1% NH3H2O ​​EtOH]; B%: 30%~30%, min). Compound 7A (17.80 mg, 41.24 μmol, yield 7.00%) was obtained as a white solid, and compound 7B (10.63 mg, 24.15 μmol, yield 4.10%) was obtained as a white solid.

[0717]

[0273] Compound 7A: SFC: Retention time: 5.117 minutes. LCMS: Retention time: 0.805 min, (M+H)=408.1, 5~95AB_220 and 254_Agilent. 1 HNMR: (400 MHz, DMSO-d6) δ = 12.55 - 12.29 (m, 1H), 8.20 - 8.10 (m, 1H), 7.59 - 7.45 (m, 1H), 7.40 - 7.27 (m, 1H), 7.26 - 7.00 (m, 1H), 6.87 - 6.76 (m, 2H), 6.37 - 6.03 (m, 1H), 5.09 - 5.04 (m, 1H), 4.13 (t, J = 6.0 Hz, 2H), 3.57 - 3.44 (m, 1H), 2.33 - 2.20 (m, 2H), 1.40 (d, J = 7.2 Hz, 3H).

[0718]

[0274] Compound 7B: SFC: Retention time: 6.271 minutes. LCMS: Retention time: 0.802 min, (M+H)=408.1, 5~95AB_220 and 254_Agilent. 1HNMR: (400 MHz, DMSO-d6) δ = 12.54 - 12.15 (m, 1H), 8.18 - 8.11 (m, 1H), 7.61 - 7.43 (m, 1H), 7.42 - 7.31 (m, 1H), 7.30 - 7.03 (m, 1H), 6.96 - 6.59 (m, 2H), 6.39 - 6.03 (m, 1H), 5.59 (d, J = 6.0 Hz, 1H), 4.14 (t, J = 6.0 Hz, 2H), 3.92 - 3.83 (m, 1H), 2.35 - 2.24 (m, 2H), 1.00 (d, J = 7.2 Hz, 3H.

[0719] Example 2

[0275] Synthesis of Compound 9

[0276]

[0720] [ka]

[0721]

[0277] Step 1: General procedure for the preparation of 1-(4-bromo-2,6-difluorophenyl)-N-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-yl)methanymine

[0278] A mixture of 4-bromo-2,6-difluorobenzaldehyde (2.68 g, 12.15 mmol, 1 equivalent) and 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-amine (3.2 g, 12.15 mmol, 1 equivalent) in toluene (40 mL) was degassed three times and purged with N2, and then the mixture was stirred at 120°C for 12 hours under an N2 atmosphere. The mixture was concentrated under reduced pressure and purified by flash silica gel chromatography (ISCO®; SepaFlash® silica flash column 40 g, 60 mL / min with an eluent gradient of 0-60% ethyl acetate / petroleum ether) to obtain the target compound (4.7 g, 10.08 mmol, yield 82.95%) as a brownish oily substance.

[0722]

[0279] 1 HNMR: (400 MHz, DMSO-d6) 8.70 (s, 1H), 8.40 (d, J = 6.4 Hz, 1H), 7.79 - 7.53 (m, 4H), 7.39 - 7.19 (m, 1H), 5.66 (d, J = 7.2 Hz, 2H), 3.58 - 3.41 (m, 2H), 0.84 (t, J = 8.0 Hz, 2H), 0.11 - -0.30 (m, 9H).

[0723]

[0280] Step 2: General procedure for the preparation of 4-(4-bromo-2,6-difluorophenyl)-1-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-yl)azetidine-2-one

[0281] To a mixture of Zn (28.04 mg, 428.82 μmol, 2 equivalents) in toluene (5 mL), TMS-Cl (16.31 mg, 150.09 μmol, 19.05 μL, 0.7 equivalents) was added all at once under Ar at 25°C. The mixture was stirred at 120°C for 15 minutes and then cooled to 25°C. Ethyl 2-bromoacetate (60.87 mg, 364.50 μmol, 40.31 μL, 1.7 equivalents) and 1-(4-bromo-2,6-difluorophenyl)-N-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-yl)methanymine (100 mg, 214.41 μmol, 1 equivalent) were added. The mixture was stirred at 120°C for 12 hours. The mixture was concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (ISCO®; SepaFlash® silica flash column, 4 g, 18 mL / min, with an eluent gradient of 0-60% ethyl acetate / petroleum ether) to obtain the target compound (62 mg, 121.94 μmol, yield 56.87%) as a brownish oily substance.

[0724]

[0282] LCMS: Holding time: 0.940 min, (M+H)=509.9, 5~95AB_1.5 min_220 and 254_Shimadzu.

[0283] Step 3: General procedure for the preparation of 4-(2,6-difluoro-4-(1-methyl-1H-pyrazole-4-yl)phenyl)-1-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-yl)azetidine-2-one

[0284] 4-(4-bromo-2,6-difluorophenyl)-1-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-yl)azetidine-2-one (30 mg, 59.01 μmol, 1 equivalent), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (14.73 mg, 70.81 μmol, 1.2 equivalents), and K2CO3 (24.47 mg, 177.02 μmol, 3 equivalents), and Pd(dppf)Cl2 (4.32 mg, 5.90 μmol, 0.1 equivalents) were dissolved in dioxane (2 mL) and H2O (0.4 mL) under N2 in a microwave tube. The sealed tube was heated under microwaves at 100°C for 30 minutes. The mixture was filtered. The filtrate was concentrated under reduced pressure to obtain the target compound (40 mg, crude) as a brownish solid, which was used in the next step without further purification.

[0725]

[0285] LCMS: Retention time: 3.257 mins, (M+H) = 510.3, 10~80AB_7 mins_220 and 254.

[0286] Step 4: General procedure for the preparation of 1-(1H-benzo[d]imidazole-5-yl)-4-(2,6-difluoro-4-(1-methyl-1H-pyrazole-4-yl)phenyl)azetidine-2-one

[0287] 4-(2,6-difluoro-4-(1-methyl-1H-pyrazole-4-yl)phenyl)-1-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-yl)azetidine-2-one compound 9.4 (40.00 mg, 78.49 μmol, 1 equivalent) was dissolved in DCM (2 mL) and TFA (1 mL) was added. The mixture was stirred at 25°C for 0.5 hours. The mixture was filtered. The filtrate was concentrated under reduced pressure and purified by preparative HPLC (column: Phenomenex Gemini-NX C18 75 × 30 mm × 3 μm; mobile phase: [water (0.225% FA)-ACN]; B%: 10%~30%, 7 min) to obtain compound 9 (1 mg, 2.64 μmol, yield 3.36%) as a white solid.

[0726]

[0288] LCMS: Holding time: 0.734 mins, (M+H) = 380.0, 5~95AB_1.5 mins_220 and 254_Shimadzu. Example 3

[0289] Synthesis of Compound 4

[0290]

[0727] [ka]

[0728]

[0291] Step 1: General procedure for the preparation of 4-(2,6-difluoro-4-(4-methylpiperazin-1-yl)phenyl)-1-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-yl)azetidine-2-one

[0292] 4-(4-bromo-2,6-difluorophenyl)-1-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-yl)azetidine-2-one compound 9.2 (250 mg, 491.71 μmol, 1 equivalent), 1-methylpiperazine (59.10 mg, 590.05 μmol, 65.45 μL, 1.2 equivalents), Cs2CO3 (320.42 mg, 983.42 μmol, 2 equivalents), and 1,4-dioxane (2 mL) were added to a 10 mL round-bottom flask, sparged with N2 for 5 minutes, and then treated with Xphos-Pd-G3 (41.62 mg, 49.17 μmol, 0.1 equivalent). The mixture was sparged with N2 for a further 5 minutes, then stirred at 100°C for 3 hours. The mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was separated into TLC (SiO2, THF:MeOH = 4:1, R f The target compound (60 mg, crude product) was purified using a method involving a concentration of 0.3.

[0729]

[0293] LCMS: Retention time: 2.083 minutes, (M+H) + = 528.2, 10~80CD_3 min_220 and 254.

[0294] Step 2: General procedure for the preparation of 1-(1H-benzo[d]imidazole-5-yl)-4-(2,6-difluoro-4-(4-methylpiperazine-1-yl)phenyl)azetidine-2-one

[0295] A solution of compound 4.1 (40 mg, 75.80 μmol, 1 equivalent) of 4-(2,6-difluoro-4-(4-methylpiperazin-1-yl)phenyl)-1-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-yl)azetidine-2-one was added to a solution of compound 4.1 (40 mg, 75.80 μmol, 1 equivalent) in DCM (1 mL), to which TFA (1.54 g, 13.51 mmol, 1.00 mL, 178.17 equivalents) was added. The mixture was stirred at 40°C for 1.5 hours. The reaction mixture was combined with the reaction mixture from the other batch (0.5 equivalents), concentrated under reduced pressure, and the crude product was obtained. The crude product was basicized to pH=9-10 with NH3·H2O and purified by preparative HPLC (column: Phenomenex Gemini-NX 80×40mm×3um; mobile phase: [water (0.05%NH3·H2O)-ACN]; B%: 34%-64%, 8 min). Compound 4 (1.07 mg, 2.06 μmol, yield 1.81%) was obtained as a white solid.

[0730]

[0296] LCMS: Retention time: 1.464 minutes, (M+H) + =398.1, 10~80CD_3 min_220 and 254.

[0297] 1 H NMR: (400 MHz, DMSO-d6) δ = 12.48 - 12.31 (m, 1H), 8.18 - 8.12 (m, 1H), 7.59 - 7.42 (m, 1H), 7.39 - 7.26 (m, 1H), 7.25 - 7.03 (m, 1H), 6.65 (d, J = 12.8 Hz, 2H), 5.42 - 5.32 (m, 1H), 3.61 - 3.52 (m, 1H), 3.20 - 3.15 (m, 4H), 3.11 - 3.03 (m, 1H), 2.41 - 2.33 (m, 4H), 2.18 (s, 3H).

[0731] Example 4

[0298] Synthesis of Compound 2

[0299]

[0732] [ka]

[0733]

[0300] General procedure for the preparation of 1-(1H-benzo[d]imidazole-5-yl)-4-(4-(3,3-difluoropropoxy)-2,6-difluorophenyl)-3,3-dimethylazetidine-2-one

[0301] To a mixture of Zn (37.23 mg, 569.32 μmol, 2 equivalents) in toluene (5 mL), TMS-Cl (21.65 mg, 199.26 μmol, 25.29 μL, 0.7 equivalents) was added all at once under Ar at 25°C. The mixture was stirred at 120°C for 15 minutes and then cooled to 25°C. (Z)-N-(1H-benzo[d]imidazole-5-yl)-1-(4-(3,3-difluoropropoxy)-2,6-difluorophenyl)methaneimine (100 mg, 284.66 μmol, 1 equivalent) and ethyl 2-bromo-2-methylpropanoate (94.39 mg, 483.92 μmol, 70.97 μL, 1.7 equivalents) were added, and the mixture was stirred at 120°C for 12 hours. The mixture was concentrated under reduced pressure and purified by preparative HPLC (column: Phenomenex Gemini-NX C18 75×30mm×3um; mobile phase: [water (0.225% FA)-ACN]; B%: 23%~43%, 7 min). Compound 2 (25.26 mg, 59.94 μmol, yield 21.06%) was obtained as a white solid.

[0734]

[0302] LCMS: Retention time: 2.750 minutes, (M+H) + =422.2, 10~80AB_7 min_220 and 254.

[0303] 1 H NMR: (400 MHz, DMSO-d6) δ = 12.81 - 11.97 (m, 1H), 8.34 - 8.12 (m, 1H), 7.52 (s, 1H), 7.45 - 7.05 (m, 2H), 7.00 - 6.57 (m, 2H), 6.39 - 6.02 (m, 1H), 5.23 (s, 1H), 4.13 (t, J = 6.4 Hz, 2H), 2.37 - 2.21 (m, 2H), 1.46 (s, 3H), 0.99 (s, 3H).

[0735] Example 5

[0304] Synthesis of Compound 3

[0305]

[0736] [ka]

[0737]

[0306] General procedure for the preparation of 2-(1H-benzo[d]imidazole-5-yl)-3-(4-(3,3-difluoropropoxy)-2,6-difluorophenyl)-2-azaspiro[3.3]heptan-1-one

[0307] To a mixture of Zn (37.23 mg, 569.32 μmol, 2 equivalents) in toluene (5 mL), TMS-Cl (21.65 mg, 199.26 μmol, 25.29 μL, 0.7 equivalents) was added all at once under Ar at 25°C. The mixture was stirred at 120°C for 15 minutes and then cooled to 25°C. (Z)-N-(1H-benzo[d]imidazole-5-yl)-1-(4-(3,3-difluoropropoxy)-2,6-difluorophenyl)methaneimine compound 2.1 (100 mg, 284.66 μmol, 1 equivalent) and ethyl 1-bromocyclobutane-1-carboxylate (100.20 mg, 483.92 μmol, 78.28 μL, 1.7 equivalents) were added, and the mixture was stirred at 120°C for 12 hours. The mixture was concentrated under reduced pressure and purified by preparative HPLC (column: Phenomenex Gemini-NX C18 75×30mm×3um; mobile phase: [water (0.225% FA)-ACN]; B%: 20%~50%, 7 min). Compound 3 (24.35 mg, 56.18 μmol, yield 19.74%) was obtained as a white solid.

[0738]

[0308] LCMS: Retention time: 2.886 minutes, (M+H) + =434.2, 10~80AB_7 min_220 and 254.

[0309] 1H NMR: (400 MHz, DMSO-d6) δ = 12.62 - 12.14 (m, 1H), 8.15 (s, 1H), 7.63 - 7.43 (m, 1H), 7.41 - 7.03 (m, 2H), 7.02 - 6.57 (m, 2H), 6.40 - 6.02 (m, 1H), 5.36 (s, 1H), 4.24 - 4.05 (m, 2H), 2.49 - 2.44 (m, 2H), 2.37 - 2.20 (m, 3H), 2.02 - 1.70 (m, 3H).

[0739] Example 6

[0310] Synthesis of Compound 11CR

[0311]

[0740] [ka]

[0741]

[0312] Step 1: General procedure for the preparation of (cis and racemic)-4-(4-bromo-2,6-difluorophenyl)-3-methyl-1-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-yl)azetidine-2-one

[0313] To a solution of N-isopropylpropan-2-amine (282.05 mg, 2.79 mmol, 393.92 μL, 1.3 equivalents) in THF (4 mL), n-BuLi (2.5 M, 1.03 mL, 1.2 equivalents) was added under N2 at -70°C. The mixture was stirred at -70°C for 1 hour. A mixture of (Z)-1-(4-bromo-2,6-difluorophenyl)-N-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-yl)methanymine (218.98 mg, 2.14 mmol, 246.05 μL, 1 equivalent) in THF (1 mL) was added under N2 at -70°C, and the mixture was stirred at -70°C for 1 hour. A mixture of ethyl propionate (1 g, 2.14 mmol, 1 equivalent) in THF (1 mL) was added under N2 at -70°C, and the mixture was stirred at 20°C for 12 hours. HCl aqueous solution (10 mL, 1 M) was added, and the mixture was extracted with ethyl acetate (20 mL x 3). The combined organic extract was washed with brine (30 mL), dehydrated with anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (ISCO®; SepaFlash® silica flash column, 20 g, 40 mL / min, with an eluent gradient of 0-100% ethyl acetate / petroleum ether) to obtain the target compound (900 mg, crude product) as a brownish oily substance.

[0742]

[0314] LCMS: Holding time: 0.952 mins, (M+H)=523.7, 5~95AB_1.5 mins_220 and 254_Shimadzu.

[0315] Step 2: General procedure for the preparation of (cis and racemic)-4-(2,6-difluoro-4-(2-methylthiazole-5-yl)phenyl)-3-methyl-1-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-yl)azetidine-2-one

[0316] (3R,4R)-4-(4-bromo-2,6-difluorophenyl)-3-methyl-1-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-yl)azetidine-2-one (100 mg, 191.40 μmol, 1 equivalent), 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazole (64.63 mg, 287.11 μmol, 1.5 equivalents), Na2CO3 (60.86 mg, 574.21 μmol, 3 equivalents), and Pd(PPh3)4 (22.12 mg, 19.14 μmol, 0.1 equivalents) were dissolved in dioxane (3 mL) and H2O (0.6 mL) under N2 in a microwave tube. The sealed tube was heated under microwave at 80°C for 30 minutes. The mixture was filtered. The filtrate was concentrated under reduced pressure and purified by flash silica gel chromatography (ISCO®; SepaFlash® silica flash column, 4g, 18mL / min, with an eluent gradient of 0-60% ethyl acetate / petroleum ether) to obtain the target compound (90 mg, crude product) as a yellow oily substance.

[0743]

[0317] LCMS: Retention time: 1.119 min, (M+H) = 541.3, 10~80AB_2 min_220 and 254.

[0318] Step 3: General procedure for the preparation of (cis and racemic)-1-(1H-benzo[d]imidazole-5-yl)-4-(2,6-difluoro-4-(2-methylthiazole-5-yl)phenyl)-3-methylazetidine-2-one

[0319] To a solution of (cis and racemic)-4-(2,6-difluoro-4-(2-methylthiazole-5-yl)phenyl)-3-methyl-1-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-yl)azetidine-2-one (90 mg, 166.45 μmol, 1 equivalent) in DCM (2 mL), TFA (1 mL) was added. The mixture was stirred at 25°C for 0.5 hours. The mixture was concentrated under reduced pressure and adjusted to pH 7 with saturated NaHCO3. The mixture was extracted with ethyl acetate (20 mL x 3). The combined organic extract was washed with brine (30 mL), dehydrated with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by preparative HPLC (column: Phenomenex Gemini-NX 80×40mm×3um; mobile phase: [water (0.05%NH3H2O)-ACN]; B%: 27%~57%, 8 min) to obtain compound 11CR (10 mg, 24.36 μmol, yield 14.64%) as a white solid (in cis and racemic forms).

[0744]

[0320] LCMS: Retention time: 0.656 min, (M+H) = 411.2, 5~95AB_220 and 254_Agilent.

[0321] 1 H NMR: (400MHz, DMSO-d6) δ = 8.22 - 8.18 (m, 1H), 8.14 (s, 1H), 7.59 - 7.33 (m, 4H), 7.23 - 7.13 (m, 1H), 5.68 (d, J = 6.0 Hz, 1H), 4.02 - 3.88 (m, 1H), 2.67 (s, 3H), 1.03 (d, J = 7.6 Hz, 3H).

[0745] Example 7

[0322] Synthesis of Compound 10CR

[0323]

[0746] [ka]

[0747]

[0324] Step 1: General procedure for the preparation of 2-methyl-4-(tributylstannyl)thiazole

[0325] 4-bromo-2-methylthiazole (2.00 g, 11.2 mmol, 1 equivalent) in THF (40 mL) was mixed with n-BuLi (1 M, 13.5 mL, 1.2 equivalents) under N2 at -78°C. The mixture was stirred at -78°C for 1 hour. A mixture of tributylchlorostannan (6.25 g, 19.2 mmol, 5.17 mL, 1.71 equivalents) in THF (20 mL) was added dropwise at -78°C. The resulting mixture was stirred at -78°C for 1 hour. The reaction mixture was quenched by adding aqueous NH4Cl solution (20 mL), diluted with H2O (100 mL), and extracted with siRNA (100 mL x 3). The combined organic layers were washed with brine (50 mL), dehydrated with Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (ISCO®; SepaFlash® silica flash column, 20 g, 30 mL / min, with an eluent gradient of 0-10% ethyl acetate / petroleum ether). The target compound (1.00 g, 2.29 mmol, yield 20.41%) was obtained as a yellow oily substance.

[0748]

[0326] LCMS: Holding time: 1.140 min, (M+H)=389.4, 5~95AB_1.5 min_220 and 254_Shimadzu.

[0327] 1 HNMR: (400 MHz, DMSO-d6) δ = 7.59 - 7.54 (m, 1H), 2.69 (s, 3H), 1.61 - 1.43 (m, 6H), 1.33 - 1.25 (m, 6H), 1.17 - 1.01 (m, 6H), 0.86 (t, J = 7.2 Hz, 9H).

[0749]

[0328] Step 2: General procedure for the preparation of (cis and racemic)-4-(2,6-difluoro-4-(2-methylthiazole-4-yl)phenyl)-3-methyl-1-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-yl)azetidine-2-one

[0329] A mixture of 2-methyl-4-(tributylstannyl)thiazole (156 mg, 402 μmol, 1.5 equivalents), (3R,4R)-4-(4-bromo-2,6-difluorophenyl)-3-methyl-1-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole-5-yl)azetidine-2-one compound 11.1 (140 mg, 268 μmol, 1 equivalent), Pd(PPh3)4 (31.0 mg, 26.8 μmol, 0.1 equivalents), CuI (51.0 mg, 268 μmol, 1 equivalent), and LiCl (17.0 mg, 402 μmol, 8.23 ​​μL, 1.5 equivalents) in toluene (3 mL) was degassed three times and purged with N2. The mixture was stirred at 120°C for 12 hours under an N2 atmosphere. The reaction mixture was concentrated under reduced pressure and purified by flash silica gel chromatography (ISCO®; SepaFlash® silica flash column, 4 g, 12 m...

Claims

1. Compound of formula (I), its stereoisomer, or pharmaceutically acceptable salt or solvate 【Chemistry 1】 (In the formula, R ２ , ７ , ８ is halogen, -OH, -OR １０ａ , -SR １０ａ , -CN, amino, -NR ２２ R ２３ , substituted or unsubstituted C １ ~C ６ alkyl, substituted or unsubstituted C ２ ~C ６ alkenyl, substituted or unsubstituted C ２ ~C ６ alkynyl, substituted or unsubstituted C １ ~C ６ heteroalkyl, substituted or unsubstituted C ３ ~C ８ cycloalkyl, or substituted or unsubstituted C ２ ~C ７ heterocycloalkyl, and R ２ H, halogen, -OH, -OR １０ｂ , substitution or non-substitution C １ ~C ６ Alkyl, or substituted or unsubstituted C １ ~C ６ It is heteroalkyl, or R １ and R ２ These, together with the carbon atoms to which they are bonded, form a 3- to 7-membered ring or a heterocyclic ring, or R １ and R ２ together, oxo or CR １２ａ R １２ｂ Forms a double bond to R １２ａ and R １２ｂ These are, independently, hydrogen, halogen, -OH, amino, and substituted or unsubstituted C. １ ~C ６ Alkyl, substituted, or unsubstituted C ２ ~C ６ Alkenyl, substituted or unsubstituted C ２ ~C ６ Alkynyl, substituted or unsubstituted C １ ~C ６ Heteroalkyl, substituted, or unsubstituted C ３ ~C ８ Cycloalkyl, substituted, or unsubstituted C ２ ~C ７ A heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, R ４ , R ５ , R ６ and R ７ Each of these is independently selected from H and halogen, R ３ is -OR １１ , halogen, -SR １１ , -S(=O)R ２１ , -S(=O) ２ R ２１ , -NHS(=O) ２ R ２１ , -S(=O) ２ NR ２２ R ２３ , -C(=O)R ２１ , -OC(=O)R ２１ , -C(=O)OR ２２ , -OC(=O)OR ２２ , -C(=O)NR ２２ R ２３ , -OC(=O)NR ２２ R ２３ , -NR ２２ R ２３ , -NO ２ , -NHS(=O) ２ R ２１ , -NR ２２ C(=O)NR ２２ R ２３ , -NR ２２ C(=O)R ２１ , -NR ２２ C(=O)OR A ２１ , substituted or unsubstituted C １ ~C ８ alkyl, substituted or unsubstituted C ２ ~C ８ alkenyl, substituted or unsubstituted C ２ ~C<00OOOO84>alkynyl, substituted or unsubstituted C １ ~C ８ heteroalkyl, substituted or unsubstituted C ３ ~C ８ cycloalkyl, substituted or unsubstituted C ２ ~C ７ heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl, and R １０ａ and R １０ｂ are each independently a substituted or unsubstituted C １ -C ６ alkyl, a substituted or unsubstituted C ２ -C ６ alkenyl, a substituted or unsubstituted C ２ -C ６ alkynyl, or a substituted or unsubstituted C １ -C ６ heteroalkyl, R １１ is a substitution or non-substitution C １ ~C ６ Alkyl, substituted, or unsubstituted C ２ ~C ６ Alkenyl, substituted or unsubstituted C ２ ~C ６ Alkynyl, substituted or unsubstituted C １ ~C ６ Heteroalkyl, substituted, or unsubstituted C ３ ~C ８ Cycloalkyl, substituted, or unsubstituted C ２ ~C ７ Heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic or polycyclic heteroaryl, R ２１ , R ２２ and R ２３ These are hydrogen and C, respectively, independently. １ ~C ６ Alkyl, C １ ~C ６ Heteroalkyl, C ３ ~C ８ Cycloalkyl, or C ２ ~C ７ It is a heterocycloalkyl group, where each of the alkyl, heteroalkyl, cycloalkyl, or heterocycloalkyl groups may be substituted.

2. The compound according to claim 1, its stereoisomer, or a pharmaceutically acceptable salt or solvate, wherein the compound has the structure of formula (Iaa) or (Ibb). 【Chemistry 2】

3. R １ -OH, -OR １０ａ , substitution or non-substitution C １ ~C ６ Alkyl, or substituted or unsubstituted C ３ ~C ６ A compound according to claim 1, which is a cycloalkyl compound, a stereoisomer thereof, or a pharmaceutically acceptable salt or solvate thereof.

4. R １ However, halogen, -OH, amino, cyano, oxime, oxo, mono-C １～６ Alkylamino, D-C １～６ Alkylamino, substituted, or unsubstituted C １～６ Alkoxy, substituted, or unsubstituted C ３～７ Cycloalkyl, substituted, or unsubstituted C ２～８ C may be substituted with 1 to 5 substituents selected from heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. １ ~C ６ A compound according to claim 3, which is alkyl, a stereoisomer thereof, or a pharmaceutically acceptable salt or solvate thereof.

5. R １ ga-CH ３ The compound according to claim 3, a stereoisomer thereof, or a pharmaceutically acceptable salt or solvate, which is cyclopropyl.

6. R ２ The compound according to claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt or solvate, wherein is H.

7. R ５ F is R ７ The compound according to claim 1, its stereoisomer, or a pharmaceutically acceptable salt or solvate, wherein F is present.

8. R ４ H is R ６ The compound according to claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt or solvate, wherein is H.

9. R ３ The compound according to claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is a substituted or unsubstituted 5 or 6-membered monocyclic heteroaryl having 1 to 4 ring heteroatoms independently selected from N, O, and S.

10. R ３ but, 【Transformation 3】 And each R ３１ is hydrogen, cyano, halogen, hydroxy, substituted or unsubstituted C １～６ Alkyl, -OCH ３ , -OCD ３ , substitution or non-substitution C ２～６ Alkenyl, substituted, or unsubstituted C ２～６ Alkynyl, substituted or unsubstituted C １～６ Alkoxy, substituted, or unsubstituted C ３～７ Cycloalkyl, substituted, or unsubstituted C ２～８ Heterocycloalkyl, heteroaryl, substituted or unsubstituted heterocycloalkyl-C １～６ Alkyl, substituted, or unsubstituted C １～６ Alkyl-aryl, substituted, or unsubstituted C １～６ Alkyl-heterocycloalkyl, substituted or unsubstituted C １～６ Alkyl-heteroaryl, substituted or unsubstituted C １～６ Alkoxyaryl, substituted, or unsubstituted C １～６ Alkoxy-heterocycloalkyl, substituted or unsubstituted C １～６ Alkoxy-heteroaryl, hydroxy-substituted C １～６ Alkoxy, C １～６ Alkoxy, amino, mono-C １～６ Alkylamino and di-C １～６ A compound according to claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt or solvate, independently selected from alkylaminos, wherein m is 0, 1, 2, or 3.

11. R ３ but, 【Chemistry 4】 And each R ３１ However, independently, cyano, halogen, hydroxy, substituted or unsubstituted C １～ ６ Alkyl, -OCH ３ , -OCD ３ , substitution or non-substitution C ２～６ Alkenyl, substituted, or unsubstituted C ２～６ Alkynyl, substituted or unsubstituted C １～６ Alkoxy, substituted, or unsubstituted C ３～７ Cycloalkyl, substituted, or unsubstituted C ２～８ Heterocycloalkyl, heteroaryl, substituted or unsubstituted heterocycloalkyl-C １～６ Alkyl, substituted, or unsubstituted C １～６ Alkyl-aryl, substituted, or unsubstituted C １～６ Alkyl-heterocycloalkyl, substituted or unsubstituted C １～６ Alkyl-heteroaryl, substituted or unsubstituted C １～６ Alkoxyaryl, substituted, or unsubstituted C １～６ Alkoxy-heterocycloalkyl, substituted or unsubstituted C １～６ Alkoxy-heteroaryl, hydroxy-substituted C １～６ Alkoxy, C １～６ Alkoxy, amino, mono-C １～６ Alkylamino and di-C １～６ A compound according to claim 2, a stereoisomer thereof, or a pharmaceutically acceptable salt or solvate, selected from alkylaminos, wherein m is 0, 1, 2, 3, 4, or 5.

12. R ３ However, -OR １１ , -SR １１ , substitution or non-substitution C １ ~C ８ Alkyl, substituted, or unsubstituted C ２ ~C ８ Alkenyl, substituted or unsubstituted C ２ ~C ８ Alkynyl, or substituted or unsubstituted C １ ~C ８ It is heteroalkyl, R １１ is a substitution or non-substitution C １ ~C ６ Alkyl, or substituted or unsubstituted C ３ ~C ６ It is a cycloalkyl, and R １１ If substituted, halogen, -OH, C １ ~C ４ Alkyl, C ３ ~C ６ Cycloalkyl, C １ ~C ４ Fluoroalkyl, C １ ~C ４ Heteroalkyl, C １ ~C ４ Alkoxy, or C １ ~C ４ The compound according to claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt or solvate thereof, substituted with one or more substituents selected from fluoroalkoxys.

13. The compound is: 【Chemistry 5-1】 【Chemistry 5-2】 【Chemistry 5-3】 【Chemistry 5-4】 【Transformation 5-5】 [Transformation 5-6] [Transformation 5-7] [Transformation 5-8] 【Chemistry 5-9】 【Chemistry 5-10】 【Chemistry 5-11】 【Chemistry 5-12】 【Chemistry 5-13】 【Chemistry 5-14】 【Chemistry 5-15】 【Chemistry 5-16】 【Chemistry 5-17】 【Chemistry 5-18】 【Chemistry 5-19】 A compound according to claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt or solvate, selected from the group consisting of the above.

14. The compound, 【Transformation 6】 The compound according to claim 13, its stereoisomer, or a pharmaceutically acceptable salt or solvate.

15. A pharmaceutical composition comprising a compound according to any one of claims 1 to 14, a stereoisomer thereof, or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.

16. Use of a compound according to any one of claims 1 to 14, a stereoisomer thereof, or a pharmaceutically acceptable salt or solvate in the manufacture of a pharmaceutical for treating cancer in a subject requiring cancer treatment.

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