Cystic fibrosis membrane conductance regulator modulator

Abstract

The present disclosure provides cystic fibrosis transmembrane conductance regulator (CFTR) modulators, pharmaceutical compositions comprising at least one such modulator, methods of treating cystic fibrosis using such modulators and pharmaceutical compositions, and processes for making such modulators. TIFF2022545359001150.tif3961

Description

[Technical field]

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 886,611, filed August 14, 2019, and U.S. Provisional Patent Application No. 62 / 886,739, filed August 14, 2019, the disclosures of which are incorporated by reference in their entireties.

[0002] The present invention relates to cystic fibrosis transmembrane conductance regulator (CFTR) modulators, pharmaceutical compositions comprising the modulators, methods of treating cystic fibrosis using such modulators and pharmaceutical compositions, and processes for making such modulators. [Background technology]

[0003] Cystic fibrosis (CF) is a recessive genetic disease that affects approximately 70,000 children and adults worldwide. Despite advances in CF treatment, there is no cure for it.

[0004] In patients with CF, mutations in endogenously expressed CFTR in respiratory epithelia reduce apical anion secretion, causing an imbalance in ion and fluid transport. The resulting reduction in anion transport contributes to increased mucus accumulation in the lungs, accompanied by microbial infections that ultimately cause death in CF patients. In addition to respiratory disease, CF patients typically suffer from gastrointestinal disorders and pancreatic insufficiency that, if left untreated, can lead to death. Additionally, the majority of men with cystic fibrosis are infertile, and fertility is reduced in women with cystic fibrosis.

[0005] Sequence analysis of the CFTR gene has revealed a variety of disease-causing mutations (Cutting, GR et al. (1990) Nature 346:366-369, Dean, M. et al. (1990) Cell 61:863:870, and Kerem, BS. et al. (1989) Science 245:1073-1080, Kerem, BS et al. (1990) Proc. Natl. Acad. Sci. USA 87:8447-8451). To date, over 2,000 mutations have been identified in the CF gene, and the CFTR2 database currently contains information on only 432 of these identified mutations, with 352 mutations being sufficient evidence to define them as disease-causing. The most common disease-causing mutation is a deletion of phenylalanine at position 508 of the CFTR amino acid sequence, commonly referred to as the F508del mutation. This mutation occurs in many cases of cystic fibrosis and is associated with severe disease.

[0006] The deletion of residue 508 in CFTR prevents the nascent protein from folding correctly. This prevents the mutant protein from leaving the endoplasmic reticulum (ER) and from entering or exiting the plasma membrane. As a result, the number of CFTR channels for anion transport present in the membrane is much lower than that observed in cells expressing wild-type CFTR, i.e., CFTR without the mutation. In addition to the trafficking defect, the mutation also results in a channel gating defect. The reduced number of channels in the membrane combined with the gating defect leads to reduced anion and fluid transport across the epithelium. (Quinton, PM (1990), FASEB J. 4: 2709-2727). The channels defective due to the F508del mutation are less functional than the wild-type CFTR channels, but are still functional. (Dalemans et al. (1991), Nature Lond. 354:526-528; Pasyk and Foskett (1995), J. Cell. Biochem. 270:12347-50). In addition to F508del, other disease-causing mutations in CFTR that result in transport, synthesis, and / or channel gating defects alter anion secretion and can be up- or down-regulated to modify disease progression and / or severity.

[0007] CFTR is a cAMP / ATP-mediated anion channel expressed in various cell types, including absorptive and secretory epithelial cells, where it controls anion flux across the membrane and also regulates the activity of other ion channels and proteins. In epithelial cells, normal function of CFTR is essential for maintaining electrolyte transport throughout the body, including respiratory and digestive tissues. CFTR is composed of 1480 amino acids that encode a protein composed of tandem repeats of transmembrane domains, each of which contains six transmembrane helices and a nucleotide-binding domain. The two transmembrane domains are linked via large polar regulatory (R) domains to multiple phosphorylation sites that control channel activity and cellular trafficking. Chloride transport is mediated by the coordinated activity of ENaC and CFTR on the apical membrane and Na + -K + This occurs through the coordinated activity of the -ATPase pump and the Cl- channels. Secondary active transport of chloride from the luminal side leads to the accumulation of intracellular chloride, which is then transported through the Cl - It can passively leave the cell through channels, resulting in vectorial transport. + / 2Cl - / K + Symporter, Na on the basolateral surface + -K + -ATPase pump and basolateral membrane K + The positioning of the channel, and of luminal CFTR, regulates luminal CFTR-mediated chloride secretion: presumably because water itself is not actively transported, its flow across the epithelium depends on a small transepithelial osmotic gradient generated by the bulk flow of sodium and chloride. [Prior art documents] [Non-patent literature]

[0008] [Non-Patent Document 1] Cutting, GRet al. (1990) Nature 346:366-369 [Non-Patent Document 2] Dean, M. et al. (1990) Cell 61:863:870 [Non-Patent Document 3] Kerem, BS. et al. (1989) Science 245:1073-1080 [Non-Patent Document 4] Kerem, BS et al. (1990) Proc. Natl. Acad. Sci. USA 87:8447-8451 [Non-Patent Document 5] Quinton, PM (1990), FASEB J.4:2709-2727 [Non-Patent Document 6] Dalemans et al. (1991), Nature Lond.354:526-528 [Non-Patent Document 7] Pasyk and Foskett (1995), J.Cell.Biochem.270:12347-50 Summary of the Invention [Means for solving the problem]

[0009] Recently, several CFTR modulating compounds have been identified. However, there remains a need for compounds that can treat or reduce the severity of cystic fibrosis and other CFTR mediated diseases, especially the more severe forms of these diseases. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] One aspect of the present invention is a compound of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1 to 298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), , (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing.

[0011] Formula (I) encompasses compounds that fall within the structure: [ka] including tautomers of those compounds, deuterated derivatives of any of those compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing; wherein ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; Ring B is a phenyl, pyridinyl, or pyrimidinyl ring; -X is O, NH, or N(C 1 -C 6 alkyl), -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 0 But R 11 or [ka] and Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, or a 3- to 8-membered cycloalkenyl; -R 4 each independently represents a halogen, an oxo group, a hydroxyl group, a cyano group, and -(Y) k -R 7 or optionally two R 4 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl or heterocyclyl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; wherein k is 0, 1, 2, 3, 4, 5, or 6; -Y is independently C(R 5 )(R 6 ) groups, -O-, and -NR a - group, where -(Y) k -R 7 The heteroatom in the -(Y) k -R 7 is not bonded to another heteroatom in -In the formula, R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a hydroxyl group, or C 1 -C 6 Alkyl groups, and C 3 - 5 Cycloalkyl groups or R on the same carbon 5 and R 6 Together, C 3 - 5 forming a cycloalkyl group or oxo; -R 5 and R 6 Each of the following may be independently selected: C 1 -C6 Alkyl group, C 1 -C 6 Haloalkyl groups, halogens, hydroxyl groups, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -R a each independently represents hydrogen and C 1 -C 6 alkyl groups, -R 7 But, C 1 -C 6 Alkyl group, C 1 -C 6 hydrogen, halogen, cyano, and C, optionally substituted with one or more groups selected from haloalkyl groups and halogens; 3 -C 10 cycloalkyl groups, - q is 1, 2, 3, or 4, -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2-C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atom to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl).

[0012] Formula (I) is a compound of formula (II): [ka] including tautomers of those compounds, deuterated derivatives of any of those compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing; wherein ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; Ring B is a phenyl, pyridinyl, or pyrimidinyl ring; -X is O, NH, or N(C 1 -C 6 alkyl), -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl).

[0013] Formula (I) is a compound of formula (III): [ka] Also included are tautomers of those compounds, deuterated derivatives of any of those compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, wherein ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; Ring B is a phenyl, pyridinyl, or pyrimidinyl ring; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, or a 3- to 8-membered cycloalkenyl; -X is O, NH, or N(C 1 -C 6 alkyl), -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or optionally two R 2 together with the atoms to which they are attached form a phenyl or 6-membered heteroaryl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -R 4 each independently represents a halogen, an oxo group, a hydroxyl group, a cyano group, and -(Y) k -R 7 or optionally two R 4 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl or heterocyclyl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; wherein k is 0, 1, 2, 3, 4, 5, or 6; -Y is independently C(R 5 )(R 6 ) groups, -O-, and -NR a - group, where -(Y) k -R 7 The heteroatom in the -(Y) k -R 7 is not bonded to another heteroatom in -In the formula, R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a hydroxyl group, or C 1 -C 6 Alkyl groups, and C 3 - 5 Cycloalkyl groups or R on the same carbon 5 and R 6 Together, C 3 - 5 forming a cycloalkyl group or oxo; -R 5 and R 6 Each of the following may be independently selected: C 1 -C 6 Alkyl group, C 1 -C 6 Haloalkyl groups, halogens, hydroxyl groups, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -R a each independently represents hydrogen and C 1 -C 6 alkyl groups, -R 7 But, C 1 -C 6 Alkyl group, C 1 -C 6hydrogen, halogen, cyano, and C, optionally substituted with one or more groups selected from haloalkyl groups and halogens; 3 -C 10 cycloalkyl groups, - q is 1, 2, 3, or 4, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon8 and R 9 together to form oxo, -R b are each independently hydrogen, phenyl, and C 1 -C 6 alkyl group, wherein the C 1 -C 6 The alkyl group may optionally be independently selected from C 1 -C 6 hydroxyl, -C(O)N(R x )(R y ), cyano, 4- to 6-membered heterocyclyl, and 5-membered heteroaryl; -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl), However, R 8 and R 9 At least one of them is independently C 3 -C 6 Haloalkyl group, C 3 -C 6 Alkyl group, C 2 -C6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Alkoxy group, C 3 -C 6 haloalkoxyl group, phenyl, 5- to 6-membered heteroaryl group, and 5- to 6-membered heterocyclyl group, or at least one R 3 is substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 2 -C 6 C substituted by alkyl, or 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups 1 Alkyl or two R 3 Combined, C 3 -C 6 Provided that a cycloalkyl ring is formed.

[0014] Another aspect of the present invention provides a pharmaceutical composition comprising at least one compound selected from the novel compounds disclosed herein, their pharma- ceutically acceptable salts, and deuterated derivatives of any of the foregoing, and at least one pharma- ceutically acceptable carrier, which may further comprise at least one additional active pharmaceutical ingredient.Accordingly, another aspect of the present invention provides a method of treating CFTR-mediated disease cystic fibrosis, comprising administering to a subject in need thereof at least one compound selected from the novel compounds disclosed herein, their pharma- ceutically acceptable salts, and deuterated derivatives of any of the foregoing, and at least one pharma- ceutically acceptable carrier, optionally as part of a pharmaceutical composition comprising at least one additional ingredient.

[0015] In certain embodiments, the pharmaceutical compositions of the present invention include compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Avi ... and at least one compound selected from compounds of formula (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing.In some embodiments, the compounds of formula (I), formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and Compounds of (II-Cvi), Compounds 1 to 298, Formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (I II-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (I Compositions comprising at least one compound selected from compounds of formula II-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing may optionally further comprise at least one compound selected from (a) tezacaftor, and pharma- ceutically acceptable salts and deuterated derivatives thereof, (b) at least one compound selected from ivacaftor, and pharma- ceutically acceptable salts and deuterated derivatives thereof, e.g., D-ivacaftor, and / or (c) at least one compound selected from lumacaftor, and pharma- ceutically acceptable salts and deuterated derivatives thereof.

[0016] Another aspect of the present invention is a method of treating the CFTR-mediated disease cystic fibrosis by administering to a patient in need thereof at least one compound selected from the novel compounds disclosed herein, their pharma- ceutically acceptable salts, and deuterated derivatives of any of the foregoing, and (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide (tezacaftor), N-[2,4-bis(1,1-dimethylethyl)-5-hydroxy-2,4-difluorobenzo[d][1,3]dioxol-5-yl] ... and optionally further administering one or more additional CFTR modulators selected from N-(2-(tert-butyl)-5-hydroxy-4-(2-(methyl-d3)propan-2-yl-1,1,1,3,3,3-d6)phenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (Ivacaftor) or N-(2-(tert-butyl)-5-hydroxy-4-(2-(methyl-d3)propan-2-yl-1,1,1,3,3,3-d6)phenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (D-Ivacaftor), and 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid (Lumacaftor).

[0017] definition As used herein, "tezacaftor" refers to (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide, and can be represented by the following structure: [ka] Tezacaftor may be in the form of a pharma- ceutically acceptable salt. Tezacaftor and methods of making and using tezacaftor are disclosed in WO2010 / 053471, WO2011 / 119984, WO2011 / 133751, WO2011 / 133951, WO2015 / 160787, and US2009 / 0131492, each of which is incorporated herein by reference.

[0018] As used throughout this disclosure, "ivacaftor" refers to N-(5-hydroxy-2,4-di-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide and is represented by the following structure: [ka] Ivacaftor may also be in the form of a pharma- ceutically acceptable salt. Ivacaftor and methods of making and using ivacaftor are disclosed in WO2006 / 002421, WO2007 / 079139, WO2010 / 108162, and WO2010 / 019239, each of which is incorporated herein by reference.

[0019] In some embodiments, the deuterated derivative of ivacaftor (D-ivacaftor) is used in the compositions and methods disclosed herein. The chemical name of D-ivacaftor is N-(2-(tert-butyl)-5-hydroxy-4-(2-(methyl-d3)propan-2-yl-1,1,1,3,3,3-d6)phenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide and is represented by the following structure: [ka] D-ivacaftor may be in the form of a pharma- ceutically acceptable salt.D-ivacaftor and methods of making and using D-ivacaftor are disclosed in WO2012 / 158885, WO2014 / 078842, and U.S. Patent No. 8,865,902, which are incorporated herein by reference.

[0020] As used herein, "lumacaftor" refers to 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid and is represented by the following chemical structure: [ka] Lumacaftor may be in the form of a pharma- ceutically acceptable salt. Lumacaftor and methods of making and using lumacaftor are disclosed in WO2007 / 056341, WO2009 / 073757, and WO2009 / 076142, which are incorporated herein by reference.

[0021] As used herein, the term "alkyl" refers to a saturated branched or unbranched aliphatic hydrocarbon having carbon atoms (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms, etc.). An alkyl group can be substituted or unsubstituted.

[0022] As used herein, the term "haloalkyl" refers to an alkyl or alkyl group substituted with one or more halogen atoms.

[0023] The term "alkoxy" as used herein refers to an alkyl or cycloalkyl covalently linked to an oxygen atom. An alkoxy group can be substituted or unsubstituted.

[0024] As used herein, the term "haloalkoxyl group" refers to an alkoxy group substituted with one or more halogen atoms.

[0025] As used herein, "cycloalkyl" refers to a cyclic, bicyclic, tricyclic, or polycyclic non-aromatic hydrocarbon group having 3 to 12 carbons (e.g., 3 to 10 carbons). "Cycloalkyl" groups encompass monocyclic, bicyclic, tricyclic, bridged, fused, and spirocyclic rings, including monospiro and dispiro rings. Non-limiting examples of cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, adamantyl, norbornyl, and dispiro[2.0.2.1]heptane. Cycloalkyl groups can be substituted or unsubstituted.

[0026] The term "heteroaryl ring," as used herein, refers to an aromatic ring that contains at least one ring atom that is a heteroatom, such as O, N, or S.

[0027] As used herein, the term "heterocyclyl ring" refers to a non-aromatic hydrocarbon having 3 to 12 atoms (e.g., 3 to 10 atoms) in the ring, including at least one ring atom that is a heteroatom such as O, N, or S. "Heterocyclyl" rings encompass monocyclic, bicyclic, tricyclic, polycyclic, bridged, fused, and spiro rings, including monospiro and dispiro rings.

[0028] "Substituted," whether preceded by the term "optionally," indicates that at least one hydrogen of the "substituted" group is replaced by a substituent. Unless otherwise indicated, an "optionally substituted" group may have a suitable substituent at each of the substitutable positions of the group, and when more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituent may be the same or different at each position.

[0029] Examples of nitrogen protecting groups include, for example, t-butyl carbamate (Boc), benzyl (Bn), para-methoxybenzyl (PMB), tetrahydropyranyl (THP), 9-fluorenylmethyl carbamate (Fmoc), benzyl carbamate (Cbz), methyl carbamate, ethyl carbamate, 2,2,2-trichloroethyl carbamate (Troc), 2-trimethylsilylethyl carbamate (Teoc), allyl carbamate (Aloc or Alloc), formamide, acetamide, benzamide, allylamine, trifluoroacetamide, triphenylmethylamine, benzylideneamine, and p-toluenesulfonamide. A comprehensive list of nitrogen protecting groups can be found in Wuts, PGM "Greene's Protective Groups in Organic Synthesis: Fifth Edition," 2014, John Wiley and Sons.

[0030] As used herein, a "deuterated derivative" refers to a compound having the same chemical structure as a reference compound, in which one or more hydrogen atoms have been replaced by deuterium atoms.

[0031] As used herein, "CFTR" means cystic fibrosis transmembrane conductance regulator.

[0032] As used herein, the term "CFTR modulator" refers to a compound that increases the activity of CFTR. The increased activity provided by a CFTR modulator includes, but is not limited to, compounds that correct, enhance, stabilize, and / or amplify CFTR.

[0033] As used herein, the term "CFTR corrector" refers to a compound that enhances the processing and transport of CFTR, increasing the amount of CFTR at the cell surface. The novel compounds disclosed herein are CFTR correctors.

[0034] As used herein, the term "CFTR potentiator" refers to a compound that increases the channel activity of the CFTR protein located on the cell surface, resulting in enhanced ion transport. Ivacaftor and D-ivacaftor disclosed herein are CFTR potentiators. Compounds of formula (I), compounds of formula (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1 to 298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (II

[0043] Where a description is provided herein of a combination of compounds selected from compounds of formula I-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of those compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, with other specified CFTR modulating agents, it is understood that a reference to "ivacaftor and D-ivacaftor" in the context of that combination means that either ivacaftor or D-ivacaftor is included in that combination, but not both.

[0035] As used herein, the term "active pharmaceutical ingredient" or "therapeutic agent" ("API") refers to a biologically active compound.

[0036] The terms "patient" and "subject" are used interchangeably and refer to animals, including humans.

[0037] The terms "effective dose" and "effective amount" are used interchangeably herein and refer to the amount of a compound that, when administered, results in a desired effect (e.g., amelioration of CF or symptoms of CF, or reduction in the severity of CF or symptoms of CF). The exact amount of an effective dose will vary depending on the purpose of the treatment, and may be ascertained by one of skill in the art using known techniques (see, e.g., Lloyd (1999) The Art, Science and Technology of Pharmaceutical Compounding).

[0038] As used herein, the terms "treatment", "treating" and the like generally refer to the improvement of one or more symptoms of CF in a subject, or the reduction of the severity of CF or one or more symptoms of CF. As used herein, "treatment" includes, but is not limited to, the increase in growth of a subject, the increase in weight gain, the reduction of mucus in the lungs, the improvement of pancreatic and / or liver function, the reduction of lung infection, and / or the reduction of cough or shortness of breath. The improvement of any of these symptoms or the reduction of their severity can be easily evaluated according to standard methods and techniques known in the art.

[0039] As used herein, the term "in combination with" when referring to two or more compounds, agents, or additional active pharmaceutical ingredients, means that the two or more compounds, agents, or active pharmaceutical ingredients are administered to a patient before or after each other, or simultaneously with each other.

[0040] The terms "about" and "approximately", when used in connection with a dose, amount, or weight percent of a component of a composition or dosage form, include the specified dose, amount, or weight percent value, or a range of doses, amounts, or weight percents that would be recognized by a person skilled in the art to provide an equivalent pharmacological effect to that obtained from the specified dose, amount, or weight percent. The terms "about" and "approximately" may refer to an acceptable range of error for a particular value as determined by a person skilled in the art, which depends in part on how the value is measured or determined. In some embodiments, the terms "about" and "approximately" mean within 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1%, or 0.5% of a given value or range.

[0041] As used herein, the term "solvent" refers to any liquid in which the product is at least partially soluble (solubility of product >1 g / l).

[0042] As used herein, the term "room temperature" or "ambient temperature" means 15°C to 30°C.

[0043] It is understood that certain compounds of the present invention may exist as separate stereoisomers or enantiomers and / or as mixtures of such stereoisomers or enantiomers.

[0044] Certain compounds disclosed herein may exist as tautomers, and both tautomeric forms are intended, even though only a single tautomeric structure is shown. For example, a description of compound A is understood to include its tautomeric compound B, and vice versa, as well as mixtures thereof. [ka]

[0045] As used herein, "minimal function (MF) mutations" refer to CFTR gene mutations associated with minimal CFTR function (a CFTR protein that has little or no function), including, for example, mutations associated with severe defects in the ability of the CFTR channel to open and close, known as channel gating defects or "gating mutations," mutations associated with severe defects in the cellular processing of CFTR and its delivery to the cell surface, mutations associated with no or minimal CFTR synthesis, and mutations associated with severe defects in channel conductance.

[0046] As used herein, the term "pharmaceutically acceptable salt" refers to the salt form of the disclosed compound, where the salt is non-toxic.The pharmaceutically acceptable salt of the disclosed compound includes those derived from suitable inorganic and organic acids and bases.The "free base" form of the compound does not include, for example, ionically bonded salts.

[0047] The phrase "and pharma- ceutically acceptable salts and deuterated derivatives thereof" is used interchangeably with "and pharma- ceutically acceptable salts thereof and deuterated derivatives of any of the foregoing" in reference to one or more compounds or formulas of the invention. These phrases are intended to encompass pharma- ceutically acceptable salts of any one of the referenced compounds, deuterated derivatives of any one of the referenced compounds, and pharma- ceutically acceptable salts of the deuterated derivatives thereof.

[0048] One of ordinary skill in the art will recognize that when an amount of "a compound or a pharma- ceutically acceptable salt thereof" is disclosed, the amount of the pharma- ceutically acceptable salt form of the compound is the amount equivalent to the concentration of the free base of the compound. Note that the disclosed amounts of the compounds or their pharma- ceutically acceptable salts are based on their free base forms.

[0049] Suitable pharma- ceutically acceptable salts are, for example, those disclosed in SM Berge, et al. J. Pharmaceutical Sciences, 1977, 66, 1-19. For example, Table 1 of that article provides the following pharma- ceutically acceptable salts: [Table 1]

[0050] Non-limiting examples of pharma- ceutically acceptable acid addition salts include salts formed with inorganic acids such as hydrochloric, hydrobromic, phosphoric, sulfuric, or perchloric acids, salts formed with organic acids such as acetic, oxalic, maleic, tartaric, citric, succinic, or malonic acids, and salts formed using other methods used in the art, such as ion exchange. Non-limiting examples of pharma-ceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethoxybenzoate ... Pharmaceutically acceptable salts derived from appropriate bases include alkali metal salts, alkaline earth metal salts, ammonium salts, and N-butyl salts. Pharmaceutically acceptable salts derived from appropriate bases include alkali metal salts, alkaline earth metal salts, ammonium salts, and N-butyl salts. Pharmaceutically acceptable salts derived from appropriate bases include alkali metal salts, alkaline earth metal salts, ammonium salts, and N-butyl salts. + (C 1-4 Alkyl) 4The present disclosure also contemplates the quaternization of any basic nitrogen-containing group of the compounds disclosed herein. Suitable non-limiting examples of alkali metal salts and alkaline earth metal salts include sodium, lithium, potassium, calcium, and magnesium. Further non-limiting examples of pharmaceutically acceptable salts include ammonium, quaternary ammonium, and amine cations formed using counterions such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, lower alkylsulfonates, and arylsulfonates. Other suitable non-limiting examples of pharmaceutically acceptable salts include besylate and glucosamine salts.

[0051] Detailed Description of the Preferred Embodiments In addition to the compounds of formula (II), their tautomers, deuterated derivatives of those compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, the present disclosure provides compounds of formulas (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, their tautomers, deuterated derivatives of those compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing.

[0052] For example, in some embodiments, the compound of formula (II) is a compound of formula (II-Ai): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; -wherein ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; -X is O, NH, or N(C 1 -C 6 alkyl), -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2-C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl).

[0053] In some embodiments, the compound of formula (II) is a compound of formula (II-Aii), (II-Aiii), or (II-Aiv): [ka] [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl).

[0054] In some embodiments, the compound of formula (II) is a compound of formula (II-Av): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein the carbon marked * has S or R stereochemistry; Ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1-C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl).

[0055] In some embodiments, the compound of formula (II) is a compound of formula (II-Avi): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl).

[0056] In some embodiments, the compound of formula (II) is a compound of formula (II-Bi), (II-Bii), (II-Biii), or (II-Biv): [ka] [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; -In the formula, R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1-C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl).

[0057] In some embodiments, the compound of formula (II) is a compound of formula (II-Bv): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein the carbon marked * has S or R stereochemistry; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl).

[0058] In some embodiments, the compound of formula (II) is a compound of formula (II-Bvi): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; -In the formula, R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl).

[0059] In some embodiments, the compound of formula (II) is a compound of formula (II-Ci), (II-Cii), (II-Ciii), or (II-Civ): [ka] [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; -In the formula, R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, wherein r is 1, 2, 3, 4, 5, or 6; -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(Rx )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl).

[0060] In some embodiments, the compound of formula (II) is a compound of formula (II-Cv): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein the carbon marked * has S or R stereochemistry; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, wherein r is 1, 2, 3, 4, 5, or 6; -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano,1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl).

[0061] In some embodiments, the compound of formula (II) is a compound of formula (II-Cvi): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; -In the formula, R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, wherein r is 1, 2, 3, 4, 5, or 6; -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(Rx )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl).

[0062] In some embodiments, the compound of formula (II) is a compound other than compounds 1, 43, 216, 223, 242, 251, 257, 258, 266, 270, and 271.

[0063] Also disclosed herein are compounds having the structural formulas shown in Table 3A, their tautomers, deuterated derivatives of those compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing.

[0064] In addition to the compounds of formula (III), their tautomers, deuterated derivatives of those compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, the present disclosure provides compounds of formula (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, their tautomers, deuterated derivatives of those compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing.

[0065] For example, in some embodiments, the compound of formula (III) is a compound of formula (III-Ai), (III-Aii), or (III-Aiii): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, or a 3- to 8-membered cycloalkenyl; -X is O, NH, or N(C 1 -C 6 alkyl), -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or optionally two R 2together with the atoms to which they are attached form a phenyl or 6-membered heteroaryl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -R 4 each independently represents a halogen, an oxo group, a hydroxyl group, a cyano group, and -(Y) k -R 7 or optionally two R 4 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl or heterocyclyl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; wherein k is 0, 1, 2, 3, 4, 5, or 6; -Y is independently C(R 5 )(R 6 ) groups, -O-, and -NR a - group, where -(Y) k -R 7 The heteroatom in the -(Y) k -R 7 is not bonded to another heteroatom in -In the formula, R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a hydroxyl group, or C 1 -C 6 Alkyl groups, and C 3 - 5 Cycloalkyl groups or R on the same carbon 5 and R 6 Together, C 3 - 5 forming a cycloalkyl group or oxo; -R 5 and R 6 Each of the following may be independently selected: C 1 -C 6 Alkyl group, C 1 -C 6 Haloalkyl groups, halogens, hydroxyl groups, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -R a each independently represents hydrogen and C 1 -C 6 alkyl groups, -R 7 But, C 1 -C 6 Alkyl group, C 1 -C 6 hydrogen, halogen, cyano, and C, optionally substituted with one or more groups selected from haloalkyl groups and halogens; 3 -C 10 cycloalkyl groups, - q is 1, 2, 3, or 4, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NRb - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(Rx )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, phenyl, and C 1 -C 6 alkyl group, wherein the C 1 -C 6 The alkyl group may optionally be independently selected from C 1 -C 6 hydroxyl, -C(O)N(R x )(R y ), cyano, 4- to 6-membered heterocyclyl, and 5-membered heteroaryl; -R x and R yare each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl), However, R 8 and R 9 At least one of them is independently C 3 -C 6 Haloalkyl group, C 3 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Alkoxy group, C 3 -C 6 haloalkoxyl group, phenyl, 5- to 6-membered heteroaryl group, and 5- to 6-membered heterocyclyl group, or at least one R 3 is substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 2 -C 6 C substituted by alkyl, or 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups 1Alkyl or two R 3 Combined, C 3 -C 6 Provided that a cycloalkyl ring is formed.

[0066] In some embodiments, the compound of formula (III) is a compound of formula (III-Aiv), (III-Av), or (III-Avi): [ka] [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein the carbon marked * has S or R stereochemistry; Ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, or a 3- to 8-membered cycloalkenyl; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1-C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or optionally two R 2 together with the atoms to which they are attached form a phenyl or 6-membered heteroaryl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -R 4 each independently represents a halogen, an oxo group, a hydroxyl group, a cyano group, and -(Y) k -R 7 or optionally two R 4 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl or heterocyclyl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; wherein k is 0, 1, 2, 3, 4, 5, or 6; -Y is independently C(R 5 )(R6 ) groups, -O-, and -NR a - group, where -(Y) k -R 7 The heteroatom in the -(Y) k -R 7 is not bonded to another heteroatom in -In the formula, R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a hydroxyl group, or C 1 -C 6 Alkyl groups, and C 3 - 5 Cycloalkyl groups or R on the same carbon 5 and R 6 Together, C 3 - 5 forming a cycloalkyl group or oxo; -R 5 and R 6 Each of the following may be independently selected: C 1 -C 6 Alkyl group, C 1 -C 6 Haloalkyl groups, halogens, hydroxyl groups, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -R a each independently represents hydrogen and C 1 -C 6 alkyl groups, -R 7 But, C 1 -C 6 Alkyl group, C 1 -C 6 hydrogen, halogen, cyano, and C, optionally substituted with one or more groups selected from haloalkyl groups and halogens; 3 -C 10 cycloalkyl groups, - q is 1, 2, 3, or 4, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, phenyl, and C 1 -C 6 alkyl group, wherein the C 1 -C 6 The alkyl group may optionally be independently selected from C1 -C 6 hydroxyl, -C(O)N(R x )(R y ), cyano, 4- to 6-membered heterocyclyl, and 5-membered heteroaryl; -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl), However, R 8 and R 9 At least one of them is independently C 3 -C 6 Haloalkyl group, C 3 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Alkoxy group, C 3 -C 6 haloalkoxyl group, phenyl, 5- to 6-membered heteroaryl group, and 5- to 6-membered heterocyclyl group, or at least one R3 is substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 2 -C 6 C substituted by alkyl, or 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups 1 Alkyl or two R 3 Combined, C 3 -C 6 Provided that a cycloalkyl ring is formed.

[0067] In some embodiments, the compound of formula (III) is a compound of formula (III-Avii) or (III-Aviii): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein the carbon marked * has S or R stereochemistry; Ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or optionally two R 2 together with the atoms to which they are attached form a phenyl or 6-membered heteroaryl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -R 4 each independently represents a halogen, an oxo group, a hydroxyl group, a cyano group, and -(Y) k -R 7 or optionally two R 4 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl or heterocyclyl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; wherein k is 0, 1, 2, 3, 4, 5, or 6; -Y is independently C(R5 )(R 6 ) groups, -O-, and -NR a - group, where -(Y) k -R 7 The heteroatom in the -(Y) k -R 7 is not bonded to another heteroatom in -In the formula, R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a hydroxyl group, or C 1 -C 6 Alkyl groups, and C 3 - 5 Cycloalkyl groups or R on the same carbon 5 and R 6 Together, C 3 - 5 forming a cycloalkyl group or oxo; -R 5 and R 6 Each of the following may be independently selected: C 1 -C 6 Alkyl group, C 1 -C 6 Haloalkyl groups, halogens, hydroxyl groups, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -R a each independently represents hydrogen and C 1 -C 6 alkyl groups, -R 7 But, C 1 -C 6 Alkyl group, C 1 -C 6 hydrogen, halogen, cyano, and C, optionally substituted with one or more groups selected from haloalkyl groups and halogens; 3 -C 10 cycloalkyl groups, - q is 1, 2, 3, or 4, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, phenyl, and C 1 -C 6 alkyl group, wherein the C 1 -C 6The alkyl group may optionally be independently selected from C 1 -C 6 hydroxyl, -C(O)N(R x )(R y ), cyano, 4- to 6-membered heterocyclyl, and 5-membered heteroaryl; -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl), However, R 8 and R 9 At least one of them is independently C 3 -C 6 Haloalkyl group, C 3 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Alkoxy group, C 3 -C 6haloalkoxyl group, phenyl, 5- to 6-membered heteroaryl group, and 5- to 6-membered heterocyclyl group, or at least one R 3 is substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 2 -C 6 C substituted by alkyl, or 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups 1 Alkyl or two R 3 Combined, C 3 -C 6 Provided that a cycloalkyl ring is formed.

[0068] In some embodiments, the compound of formula (III) is a compound of formula (III-Bi), (III-Bii), (III-Biii), or (III-Biv): [ka] [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein the carbon marked * has S or R stereochemistry; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, or a 3- to 8-membered cycloalkenyl; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or optionally two R 2 together with the atoms to which they are attached form a phenyl or 6-membered heteroaryl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -R 4 each independently represents a halogen, an oxo group, a hydroxyl group, a cyano group, and -(Y) k -R 7 or optionally two R 4 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl or heterocyclyl ring, which optionally and independently contains halogen, C 1 -C 6Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; wherein k is 0, 1, 2, 3, 4, 5, or 6; -Y is independently C(R 5 )(R 6 ) groups, -O-, and -NR a - group, where -(Y) k -R 7 The heteroatom in the -(Y) k -R 7 is not bonded to another heteroatom in -In the formula, R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a hydroxyl group, or C 1 -C 6 Alkyl groups, and C 3 - 5 Cycloalkyl groups or R on the same carbon 5 and R 6 Together, C 3 - 5 forming a cycloalkyl group or oxo; -R 5 and R 6 Each of the following may be independently selected: C 1 -C 6 Alkyl group, C 1 -C 6 Haloalkyl groups, halogens, hydroxyl groups, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -R a each independently represents hydrogen and C 1 -C 6 alkyl groups, -R 7 But, C 1 -C 6 Alkyl group, C 1 -C6 hydrogen, halogen, cyano, and C, optionally substituted with one or more groups selected from haloalkyl groups and halogens; 3 -C 10 cycloalkyl groups, - q is 1, 2, 3, or 4, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, phenyl, and C 1 -C 6 alkyl group, wherein the C 1 -C 6 The alkyl group may optionally be independently selected from C 1 -C 6 hydroxyl, -C(O)N(R x )(R y ), cyano, 4- to 6-membered heterocyclyl, and 5-membered heteroaryl; -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl), However, R 8 and R 9 At least one of them is independently C 3 -C 6 Haloalkyl group, C 3 -C 6 Alkyl group, C2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Alkoxy group, C 3 -C 6 haloalkoxyl group, phenyl, 5- to 6-membered heteroaryl group, and 5- to 6-membered heterocyclyl group, or at least one R 3 is substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 2 -C 6 C substituted by alkyl, or 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups 1 Alkyl or two R 3 Combined, C 3 -C 6 Provided that a cycloalkyl ring is formed.

[0069] In some embodiments, the compound of formula (III) is a compound of formula (III-Bv) or (III-Bvi): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein the carbon marked * has S or R stereochemistry; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or optionally two R 2 together with the atoms to which they are attached form a phenyl or 6-membered heteroaryl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -R 4 each independently represents a halogen, an oxo group, a hydroxyl group, a cyano group, and -(Y) k -R 7 or optionally two R 4 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl or heterocyclyl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; wherein k is 0, 1, 2, 3, 4, 5, or 6; -Y is independently C(R 5 )(R 6 ) groups, -O-, and -NR a - group, where -(Y) k -R 7 The heteroatom in the -(Y) k -R 7 is not bonded to another heteroatom in -In the formula, R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a hydroxyl group, or C 1 -C 6 Alkyl groups, and C 3 - 5 Cycloalkyl groups or R on the same carbon 5 and R 6 Together, C 3 - 5 forming a cycloalkyl group or oxo; -R 5 and R 6 Each of the following may be independently selected: C 1 -C 6 Alkyl group, C 1 -C 6 Haloalkyl groups, halogens, hydroxyl groups, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -R a each independently represents hydrogen and C 1 -C 6 alkyl groups, -R 7 But, C 1 -C 6 Alkyl group, C 1 -C 6hydrogen, halogen, cyano, and C, optionally substituted with one or more groups selected from haloalkyl groups and halogens; 3 -C 10 cycloalkyl groups, - q is 1, 2, 3, or 4, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon8 and R 9 together to form oxo, -R b are each independently hydrogen, phenyl, and C 1 -C 6 alkyl group, wherein the C 1 -C 6 The alkyl group may optionally be independently selected from C 1 -C 6 hydroxyl, -C(O)N(R x )(R y ), cyano, 4- to 6-membered heterocyclyl, and 5-membered heteroaryl; -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl), However, R 8 and R 9 At least one of them is independently C 3 -C 6 Haloalkyl group, C 3 -C 6 Alkyl group, C 2 -C6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Alkoxy group, C 3 -C 6 haloalkoxyl group, phenyl, 5- to 6-membered heteroaryl group, and 5- to 6-membered heterocyclyl group, or at least one R 3 is substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 2 -C 6 C substituted by alkyl, or 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups 1 Alkyl or two R 3 Combined, C 3 -C 6 Provided that a cycloalkyl ring is formed.

[0070] In some embodiments, the compound of formula (III) is a compound of formula (III-Ci), (III-Cii), (III-Ciii), or (III-Civ): [ka] [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, or a 3- to 8-membered cycloalkenyl; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or optionally two R 2 together with the atoms to which they are attached form a phenyl or 6-membered heteroaryl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -R 4 each independently represents a halogen, an oxo group, a hydroxyl group, a cyano group, and -(Y) k -R 7 or optionally two R 4together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl or heterocyclyl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; wherein k is 0, 1, 2, 3, 4, 5, or 6; -Y is independently C(R 5 )(R 6 ) groups, -O-, and -NR a - group, where -(Y) k -R 7 The heteroatom in the -(Y) k -R 7 is not bonded to another heteroatom in -In the formula, R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a hydroxyl group, or C 1 -C 6 Alkyl groups, and C 3 - 5 Cycloalkyl groups or R on the same carbon 5 and R 6 Together, C 3 - 5 forming a cycloalkyl group or oxo; -R 5 and R 6 Each of the following may be independently selected: C 1 -C 6 Alkyl group, C 1 -C 6 Haloalkyl groups, halogens, hydroxyl groups, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -R a each independently represents hydrogen and C 1 -C 6alkyl groups, -R 7 But, C 1 -C 6 Alkyl group, C 1 -C 6 hydrogen, halogen, cyano, and C, optionally substituted with one or more groups selected from haloalkyl groups and halogens; 3 -C 10 cycloalkyl groups, - q is 1, 2, 3, or 4, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, phenyl, and C 1 -C 6 alkyl group, wherein the C 1 -C 6 The alkyl group may optionally be independently selected from C 1 -C 6 hydroxyl, -C(O)N(R x )(R y ), cyano, 4- to 6-membered heterocyclyl, and 5-membered heteroaryl; -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl), However, R 8 and R 9 At least one of them is independently C 3 -C 6 Haloalkyl group, C 3 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Alkoxy group, C 3 -C 6 haloalkoxyl group, phenyl, 5- to 6-membered heteroaryl group, and 5- to 6-membered heterocyclyl group, or at least one R 3 is substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 2 -C 6C substituted by alkyl, or 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups 1 Alkyl or two R 3 Combined, C 3 -C 6 Provided that a cycloalkyl ring is formed.

[0071] In some embodiments, the compound of formula (III) is a compound of formula (III-Cv) or (III-Cvi): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; -In the formula, R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or optionally two R 2together with the atoms to which they are attached form a phenyl or 6-membered heteroaryl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -R 4 each independently represents a halogen, an oxo group, a hydroxyl group, a cyano group, and -(Y) k -R 7 or optionally two R 4 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl or heterocyclyl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; wherein k is 0, 1, 2, 3, 4, 5, or 6; -Y is independently C(R 5 )(R 6 ) groups, -O-, and -NR a - group, where -(Y) k -R 7 The heteroatom in the -(Y) k -R 7 is not bonded to another heteroatom in -In the formula, R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a hydroxyl group, or C 1 -C 6 Alkyl groups, and C 3 - 5 Cycloalkyl groups or R on the same carbon 5 and R 6 Together, C 3 - 5 forming a cycloalkyl group or oxo; -R 5 and R 6 Each of the following may be independently selected: C 1 -C 6 Alkyl group, C 1 -C 6 Haloalkyl groups, halogens, hydroxyl groups, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -R a each independently represents hydrogen and C 1 -C 6 alkyl groups, -R 7 But, C 1 -C 6 Alkyl group, C 1 -C 6 hydrogen, halogen, cyano, and C, optionally substituted with one or more groups selected from haloalkyl groups and halogens; 3 -C 10 cycloalkyl groups, - q is 1, 2, 3, or 4, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, phenyl, and C 1 -C 6 alkyl group, wherein the C 1 -C 6 The alkyl group may optionally be independently selected from C 1 -C 6 hydroxyl, -C(O)N(R x )(R y ), cyano, 4- to 6-membered heterocyclyl, and 5-membered heteroaryl; -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl), However, R 8 and R 9 At least one of them is independently C 3 -C 6 Haloalkyl group, C 3 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Alkoxy group, C 3 -C 6 haloalkoxyl group, phenyl, 5- to 6-membered heteroaryl group, and 5- to 6-membered heterocyclyl group, or at least one R 3 is substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 2 -C 6 C substituted by alkyl, or 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups 1 Alkyl or two R 3 Combined, C 3 -C 6 Provided that a cycloalkyl ring is formed.

[0072] Also disclosed herein are compounds having the structural formulas shown in Table 3B, their tautomers, deuterated derivatives of those compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing.

[0073] Treatment method For example, the compounds of formula (I), the compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1 to 298, the compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Av) Any of the novel compounds disclosed herein, such as compounds of formula (III-III), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, can act as CFTR modulators, i.e., modulate CFTR activity in the body. Individuals suffering from mutations in the gene encoding CFTR may benefit from receiving CFTR modulators. CFTR mutations may affect CFTR amount, i.e., the number of CFTR channels at the cell surface, or may affect CFTR function, i.e., the functional ability of each channel to open and transport ions. Mutations that affect CFTR abundance include those that cause synthesis defects (class I defects), processing and trafficking defects (class II defects), reduced synthesis of CFTR (class V defects), and reduced surface stability of CFTR (class VI defects). Mutations that affect CFTR function include those that cause gating defects (class III defects) and conductance defects (class IV defects). Some CFTR mutations exhibit characteristics of more than one class. Certain mutations in the CFTR gene cause cystic fibrosis.

[0074] Accordingly, in some embodiments, the present invention provides a method of treating, reducing the severity of, or symptomatically treating cystic fibrosis in a patient, comprising administering to the patient, for example, a compound of formula (I), a compound of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III- The present invention provides methods of administering an effective amount of any of the novel compounds disclosed herein, such as compounds of formula (Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, alone or in combination with another active ingredient, such as one or more CFTR modulating agents. In some embodiments, the one or more CFTR modulating agents are selected from ivacaftor, D-ivacaftor, lumacaftor, and tezacaftor. In some embodiments, the patient has a F508del / minimal function (MF) genotype, a F508del / F508del genotype (homozygous for the F508del mutation), a F508del / gating genotype, or a F508del / residual function (RF) genotype. In some embodiments, the patient is heterozygous and has one F508del mutation. In some embodiments, the patient is homozygous for the N1303K mutation.

[0075] In some embodiments, between 5 mg and 500 mg of a compound disclosed herein, a tautomer thereof, a deuterated derivative of the compound or tautomer, or a pharma- ceutically acceptable salt of any of the foregoing is administered daily.

[0076] In some embodiments, the patient is heterozygous and carries an F508del mutation in one allele and a mutation selected from Table 2 in the other allele. [Table 2-1] [Table 2-2]

[0077] In some embodiments, the present disclosure is also directed to methods of treatment using isotopically labeled compounds of the aforementioned compounds or pharma- ceutically acceptable salts thereof, wherein the formulas and variables of such compounds and salts are each independently as described above or as described in any other embodiment above, except that one or more atoms therein are replaced (isotopically labeled) by an atom having an atomic mass or mass number different from the atomic mass or mass number of the atom that is normally found in nature. Examples of isotopes that are commercially available and suitable for the present disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine, e.g., 2 H, 3 H, 13 C. 14 C. 15 N, 18 O. 17 O. 31 P, 32 P, 35 S, 18 F, and 36 Examples include Cl.

[0078] Isotopically labeled compounds and salts can be used in a number of beneficial ways. They may be suitable for various types of assays, such as drug and / or substrate tissue distribution assays. For example, tritium (3 H) labeling and / or carbon-14 ( 14 C) labeled compounds are particularly useful for various types of assays, such as substrate tissue distribution assays, due to their relatively simple preparation and excellent detectability. 2 H) The labeled compound is therapeutically useful and non- 2 3H-labeled compounds have potential therapeutic advantages over H-labeled compounds. 2 H) Labeled compounds and salts can have higher metabolic stability compared to those that are not isotopically labeled due to the kinetic isotope effect described below. Higher metabolic stability directly translates into increased in vivo half-life or lower dosage, which may be desirable. Isotopically labeled compounds and salts can be prepared by generally carrying out the procedures disclosed in the synthesis scheme and related description, examples section, and preparation section of this specification, and replacing non-isotopically labeled reactants with readily available isotopically labeled reactants.

[0079] In some embodiments, isotopically labeled compounds and salts contain deuterium ( 2 H) labeled compounds and salts. In some specific embodiments, the isotopically labeled compounds and salts are deuterium ( 2 H) Labeled compounds and salts in which one or more hydrogen atoms have been replaced by deuterium. In the chemical structures, deuterium is represented by "D".

[0080] In discovering and developing therapeutic agents, those skilled in the art attempt to optimize pharmacokinetic parameters while retaining desirable in vitro properties, and it may be reasonable to assume that many compounds with poor pharmacokinetic profiles are susceptible to oxidative metabolism.

[0081] deuterium( 2H) labeled compounds and salts can manipulate the oxidative metabolism of compounds through the primary kinetic isotope effect. The primary kinetic isotope effect is the change in the rate of a chemical reaction resulting from the exchange of an isotope nucleus, which is then caused by the change in the ground state energy required for covalent bond formation after this isotope exchange. The exchange of a heavier isotope usually results in a lowering of the ground state energy of the chemical bond and therefore a decrease in the rate-limiting bond breaking. If the bond breaking occurs in or near a saddle point region along the configuration of a multi-product reaction, the product distribution ratio can change significantly. For illustrative purposes, when deuterium is attached to a carbon atom in a non-exchangeable position, k M / k D Rate differences of =2-7 are typical. For further discussion, see S.L. Harbeson and R.D. Tung, Deuterium In Drug Discovery and Development, Ann. Rep. Med. Chem. 2011, 46, 403-417, which is incorporated herein by reference.

[0082] The concentration of an isotope (e.g., deuterium) incorporated into the isotopically labeled compounds and salts of the present disclosure can be defined by the isotopic enrichment factor. As used herein, the term "isotopic enrichment factor" refers to the ratio between the isotopic abundance and the natural abundance of a specified isotope. In some embodiments, when a substituent of a compound of the disclosure is represented by deuterium, such compounds have an isotopic enrichment factor for each of the designated deuterium atoms of at least 3500 (52.5% deuterium incorporation at each designated deuterium atom), at least 4000 (60% deuterium incorporation), at least 4500 (67.5% deuterium incorporation), at least 5000 (75% deuterium incorporation), at least 5500 (82.5% deuterium incorporation), at least 6000 (90% deuterium incorporation), at least 6333.3 (95% deuterium incorporation), at least 6466.7 (97% deuterium incorporation), at least 6600 (99% deuterium incorporation), or at least 6633.3 (99.5% deuterium incorporation).

[0083] Combination therapy One embodiment disclosed herein includes, for example, compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1 to 298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), and (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, in combination with at least one additional active pharmaceutical ingredient, to treat cystic fibrosis and other CFTR-mediated diseases.

[0084] In some embodiments, the at least one additional active pharmaceutical ingredient is selected from a mucolytic agent, a bronchodilator, an antibiotic, an anti-infective, and an anti-inflammatory agent.

[0085] In some embodiments, the additional therapeutic agent is an antibiotic. Exemplary antibiotics useful herein include tobramycin, including tobramycin inhalation powder (TIP), azithromycin, aztreonam, including aerosolized forms of aztreonam, amikacin, including liposomal formulations of amikacin, ciprofloxacin, including formulations of ciprofloxacin suitable for administration by inhalation, levofloxacin, including aerosolized formulations of levofloxacin, and combinations of two antibiotics, such as fosfomycin and tobramycin.

[0086] In some embodiments, the additional agent is a mucolytic agent. Exemplary mucolytic agents useful herein include Pulmozyme®.

[0087] In some embodiments, the additional agent is a bronchodilator. Exemplary bronchodilators include albuterol, metaproterenol sulfate, pirbuterol acetate, salmeterol, or tetrabuline sulfate.

[0088] In some embodiments, the additional agent is an anti-inflammatory agent, i.e., an agent that can reduce inflammation in the lungs. Examples of such agents useful herein include ibuprofen, docosahexaenoic acid (DHA), sildenafil, inhaled glutathione, pioglitazone, hydroxychloroquine, or simavastatin.

[0089] In some embodiments, the additional agent is a nutritional agent. Exemplary nutritional agents include pancrelipase (pancreatic enzyme replacement), including Pancrease®, Pancreacarb®, Ultrase®, or Creon®, Liprotomase® (formerly Trizytek®), Aquadeks®, or glutathione inhalation. In one embodiment, the additional nutritional agent is pancrelipase.

[0090] In some embodiments, the at least one additional active pharmaceutical ingredient is selected from a CFTR modulator. In some embodiments, the at least one additional active pharmaceutical ingredient is selected from (a) tezacaftor, and pharmaceutically acceptable salts thereof, and (b) ivacaftor or D-ivacaftor, and pharmaceutically acceptable salts of ivacaftor or D-ivacaftor. Thus, in some embodiments, the combination therapy provided herein includes a compound of formula (I), a compound of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III- (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds selected from compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of such compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, (b) at least one compound selected from tezacaftor, and pharma-ceutically acceptable salts thereof, and (c) at least one compound selected from ivacaftor or D-ivacaftor, and pharma-ceutically acceptable salts thereof.In some embodiments, the combination therapy provided herein includes a compound of formula (I), a compound of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (II (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), at least one compound selected from compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of such compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing; (b) at least one compound selected from tezacaftor, and pharma-ceutically acceptable salts thereof; and (c) at least one compound selected from ivacaftor or D-ivacaftor, and pharma-ceutically acceptable salts thereof.

[0091] In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii ... At least one compound selected from compounds of formula (III-Aviii), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutical acceptable salts of any of the foregoing, are administered in combination with at least one compound selected from tezacaftor, and pharma- ceutical acceptable salts thereof.In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii ... At least one compound selected from compounds of formula (III-vii), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, are administered in combination with at least one compound selected from ivacaftor, and pharma- ceutically acceptable salts thereof.In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Av At least one compound selected from compounds of formula (III-iii), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, are administered in combination with at least one compound selected from D-ivacaftor, and pharma- ceutically acceptable salts thereof.In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi At least one compound selected from compounds of formula (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, are administered in combination with at least one compound selected from tezacaftor or a pharma- ceutically acceptable salt thereof and ivacaftor, and a pharma- ceutically acceptable salt thereof.In some embodiments, compounds of formula (I), compounds of formula (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), At least one compound selected from compounds of formula (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of such compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, are administered in combination with at least one compound selected from tezacaftor and a pharma- ceutically acceptable salt thereof, and at least one compound selected from D-ivacaftor and a pharma- ceutically acceptable salt thereof.

[0092] Compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1 to 298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III Compounds of formula (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, each independently, can be administered once daily, twice daily, or three times daily.In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III- At least one compound selected from compounds of formula (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, are administered once daily.In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III- At least one compound selected from compounds of formula (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, are administered twice daily.In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III- At least one compound selected from compounds of formula (I-Aviii), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, and at least one compound selected from tezacaftor, and pharma- ceutically acceptable salts thereof, are administered once daily.In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (II At least one compound selected from compounds of formula I-Aviii), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, and at least one compound selected from tezacaftor and pharma- ceutically acceptable salts thereof, are administered twice daily.In some embodiments, compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), , (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), at least one compound selected from compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, and at least one compound selected from ivacaftor or D-ivacaftor, and pharma-ceutically acceptable salts thereof, are administered once daily.In some embodiments, compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), , (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), at least one compound selected from compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, and at least one compound selected from ivacaftor or D-ivacaftor, and pharma-ceutically acceptable salts thereof, are administered twice daily.

[0093] In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Avii), (III-Avi ... At least one compound selected from compounds of formula III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, at least one compound selected from tezacaftor and pharma- ceutically acceptable salts thereof, and at least one compound selected from ivacaftor or D-ivacaftor and pharma- ceutically acceptable salts thereof are administered once daily.In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Avii), (III-Avi ... At least one compound selected from compounds of formula III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, and at least one compound selected from ivacaftor or D-ivacaftor, and pharma-ceutically acceptable salts thereof, and at least one compound selected from lumacaftor, and pharma-ceutically acceptable salts thereof, are administered once daily.In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Avii), (III-Avi ... At least one compound selected from compounds of formula III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, at least one compound selected from tezacaftor and pharma- ceutically acceptable salts thereof, and at least one compound selected from ivacaftor or D-ivacaftor and pharma- ceutically acceptable salts thereof are administered twice daily.In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Avii), (III-Avi ... At least one compound selected from compounds of formula III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, and at least one compound selected from ivacaftor or D-ivacaftor, and pharma- ceutically acceptable salts thereof, and at least one compound selected from lumacaftor, and pharma- ceutically acceptable salts thereof, are administered twice daily.

[0094] In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), At least one compound selected from compounds (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299 to 397, compounds 398 to 436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, and at least one compound selected from tezacaftor and a pharma-ceutically acceptable salt thereof are administered once daily, and at least one compound selected from D-ivacaftor and a pharma-ceutically acceptable salt thereof are administered twice daily.In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), At least one compound selected from compounds (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, and at least one compound selected from lumacaftor and its pharma- ceutically acceptable salts are administered once daily, and at least one compound selected from D-ivacaftor and its pharma- ceutically acceptable salts are administered twice daily.

[0095] Compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1 to 298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (II Compounds I-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, tezacaftor, (ivacaftor or D-ivacaftor), and pharma- ceutically acceptable salts thereof and deuterated derivatives thereof, may be administered in a single pharmaceutical composition or in separate pharmaceutical compositions. Such pharmaceutical compositions may be administered once a day or multiple times a day, for example twice a day. As used herein, the phrase that a given amount of an API (e.g., tezacaftor, (ivacaftor or D-ivacaftor), or a pharma- ceutically acceptable salt thereof) is administered once or twice daily or daily means that the given amount is administered once or twice daily per dose.

[0096] In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Biii), (III-Bi), At least one compound selected from compounds of formula (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing are administered in a first pharmaceutical composition; at least one compound selected from tezacaftor and a pharma- ceutically acceptable salt thereof is administered in a second pharmaceutical composition; and at least one compound selected from ivacaftor and a pharma- ceutically acceptable salt thereof is administered in a third pharmaceutical composition.

[0097] In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Biii), (I At least one compound selected from compounds of formula II-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing are administered in a first pharmaceutical composition; at least one compound selected from tezacaftor and a pharma- ceutically acceptable salt thereof is administered in a second pharmaceutical composition; and at least one compound selected from D-ivacaftor and a pharma- ceutically acceptable salt thereof is administered in a third pharmaceutical composition.

[0098] In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Biii), (III-Bi), v), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), at least one compound selected from compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing are administered in a first pharmaceutical composition, at least one compound selected from ivacaftor or D-ivacaftor and a pharma- ceutically acceptable salt thereof is administered in a second pharmaceutical composition, and at least one compound selected from lumacaftor and a pharma- ceutically acceptable salt thereof is administered in a third pharmaceutical composition.

[0099] In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Biii), At least one compound selected from compounds (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing are administered in a first pharmaceutical composition, and at least one compound selected from tezacaftor and pharma- ceutically acceptable salts thereof, and at least one compound selected from ivacaftor or D-ivacaftor and pharma- ceutically acceptable salts thereof are administered in a second pharmaceutical composition. In some embodiments, the second pharmaceutical composition comprises half of the daily dose of the at least one compound selected from ivacaftor or D-ivacaftor and pharma- ceutically acceptable salts thereof, and the other half of the at least one compound selected from ivacaftor or D-ivacaftor and pharma- ceutically acceptable salts thereof is administered in a third pharmaceutical composition.

[0100] In some embodiments, the compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III At least one compound selected from the compounds of formula (I-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, at least one compound selected from tezacaftor and pharma- ceutically acceptable salts thereof, and at least one compound selected from ivacaftor or D-ivacaftor and pharma- ceutically acceptable salts thereof are administered in a first pharmaceutical composition. In some embodiments, the first pharmaceutical composition is administered to the patient twice daily. In some embodiments, the first pharmaceutical composition is administered once daily. In some embodiments, a first pharmaceutical composition is administered once daily and a second composition comprising only ivacaftor is administered once daily.

[0101] Compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1 to 298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii ... Any suitable pharmaceutical composition of compounds of formula (III-vii), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tezacaftor, ivacaftor, D-ivacaftor, lumacaftor, and tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing may be used. Some exemplary pharmaceutical compositions of tezacaftor and pharma- ceutically acceptable salts thereof may be found in WO2011 / 119984 and WO2014 / 014841, which are incorporated herein by reference. Some exemplary pharmaceutical compositions of ivacaftor and pharma- ceutically acceptable salts thereof can be found in WO2007 / 134279, WO2010 / 019239, WO2011 / 019413, WO2012 / 027731, and WO2013 / 130669, and some exemplary pharmaceutical compositions of D-ivacaftor and pharma- ceutically acceptable salts thereof can be found in US8,865,902, US9,181,192, US9,512,079, WO2017 / 053455, and WO2018 / 080591, all of which are incorporated herein by reference.Some exemplary pharmaceutical compositions of lumacaftor and pharma- ceutically acceptable salts thereof can be found in WO2010 / 037066, WO2011 / 127421, and WO2014 / 071122, which are incorporated herein by reference.

[0102] Pharmaceutical Compositions Another aspect of the present invention is a compound of formula (I), a compound of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, a compound of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), and at least one compound selected from compounds of formula (III-Aviii), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, and at least one pharma- ceutically acceptable carrier.

[0103] In some embodiments, the present disclosure provides compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Av ii), (III-Aviii), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutical acceptable salts of any of the foregoing, in combination with at least one additional active pharmaceutical ingredient. In some embodiments, the at least one additional active pharmaceutical ingredient is a CFTR modulator. In some embodiments, the at least one additional active pharmaceutical ingredient is a CFTR corrector. In some embodiments, the at least one additional active pharmaceutical ingredient is a CFTR enhancer.In some embodiments, the pharmaceutical composition comprises a compound of formula (I), a compound of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii ... ii), (III-Bi), (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), at least one compound selected from compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing, and at least two additional active pharmaceutical ingredients, one of which is a CFTR corrector and one of which is a CFTR enhancer.

[0104] In some embodiments, the disclosure provides: (a) a compound of formula (I), a compound of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi); compounds 1-298; compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III- and (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing; (b) at least one compound selected from tezacaftor, and a pharma- ceutically acceptable salt thereof; and (c) at least one pharma- ceutical composition comprising at least one pharma- ceutical

[0105] In some embodiments, the disclosure provides compounds of formula (I), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Avii ... The present invention provides a pharmaceutical composition comprising at least one compound selected from compounds of formula (III-Bii), (III-Biii), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299 to 397, compounds 398 to 436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing; (b) at least one compound selected from ivacaftor, D-ivacaftor, and pharma- ceutically acceptable salts thereof; and (c) at least one pharma- ceutically acceptable carrier.

[0106] In some embodiments, the disclosure provides compounds of formula (I), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Bii), i), (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing; (b) at least one compound selected from tezacaftor and a pharma- ceutically acceptable salt thereof; (c) at least one compound selected from ivacaftor and a pharma- ceutically acceptable salt thereof; and (d) at least one pharma- ceutical composition comprising at least one compound selected from

[0107] In some embodiments, the disclosure provides compounds of formula (I), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Biii), (II-Ci), (II-Ci), (II-Ci), (II-Ci), (II-Ci), (II-Ci), (II-Ci), (II-Ci), (II-Ci), (II-Ci), (II-Ci), (II-Ci), (II-Ci), (II-Ci), (II-Ci), (II-Ci), (II-Ci), (II-Ci), (II-Ci), (II-Ci), (II-Ci), (III ... (III-Biv), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), at least one compound selected from compounds 299-397, compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing; (b) at least one compound selected from tezacaftor and a pharma- ceutically acceptable salt thereof; (c) at least one compound selected from D-ivacaftor and a pharma- ceutically acceptable salt thereof; and (d) at least one pharma- ceutical composition comprising at least one pharma- ceutical

[0108] In some embodiments, the disclosure provides compounds of formula (I), compounds of formula (II), (II-Ai), (II-Aii), (II-Aiii), (II-Aiv), (II-Av), (II-Avi), (II-Bi), (II-Bii), (II-Biii), (II-Biv), (II-Bv), (II-Bvi), (II-Ci), (II-Cii), (II-Ciii), (II-Civ), (II-Cv), and (II-Cvi), compounds 1-298, compounds of formula (III), (III-Ai), (III-Aii), (III-Aiii), (III-Aiv), (III-Av), (III-Avi), (III-Avii), (III-Aviii), (III-Bi), (III-Bii), (III-Biii), (II-Ci ...III-Ci), (III-Ci), (III-Ci), (III-Ci), (III-Ci), (III-Ci), (III-Ci), (III-Ci), (III-Ci), (III-Ci), (III-Ci), (III-Ci), (III- and (III-Civ), (III-Bv), (III-Bvi), (III-Ci), (III-Cii), (III-Ciii), (III-Civ), (III-Cv), and (III-Cvi), at least one compound selected from compounds 299-397, and compounds 398-436, tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing; (b) at least one compound selected from ivacaftor or D-ivacaftor, and a pharma- ceutically acceptable salt thereof; (c) at least one compound selected from lumacaftor, and a pharma- ceutically acceptable salt thereof; and (d) at least one pharma- ceutically acceptable carrier.

[0109] Any pharmaceutical composition disclosed herein may comprise at least one pharmaceutically acceptable carrier.In some embodiments, at least one pharmaceutically acceptable carrier is selected from pharmaceutically acceptable vehicle and pharmaceutically acceptable adjuvant.In some embodiments, at least one pharmaceutically acceptable is selected from pharmaceutically acceptable filler, disintegrant, surfactant, binder, lubricant.

[0110] The pharmaceutical compositions described herein are useful for the treatment of cystic fibrosis and other CFTR-mediated diseases.

[0111] As mentioned above, the pharmaceutical composition disclosed herein may further comprise at least one pharma- ceutically acceptable carrier, if desired. At least one pharma- ceutically acceptable carrier may be selected from adjuvants and vehicles. As used herein, at least one pharma- ceutically acceptable carrier includes any and all solvents, diluents, other liquid vehicles, dispersing aids, suspending aids, surfactants, isotonicity agents, thickening agents, emulsifiers, preservatives, solid binders, and lubricants that are suitable for the specific dosage form desired. Remington: The Science and Practice of Pharmacy, 21st edition, 2005, ed. DB Troy, Lippincott Williams & Wilkins, Philadelphia, and Encyclopedia of Pharmaceutical Technology, eds. J. Swarbrick and JC Boylan, 1988-1999, Marcel Dekker, New York disclose various carriers used in the formulation of pharmaceutical compositions and known techniques for their preparation. Except insofar as any conventional carrier is incompatible with the compounds of the present disclosure, for example, by imparting any undesirable biological effects or otherwise interacting in a deleterious manner with any other components of the pharmaceutical composition, its use is contemplated within the scope of the present disclosure.Non-limiting examples of suitable pharma- ceutically acceptable carriers include ion exchangers, alumina, aluminum stearate, lecithin, serum proteins (e.g., human serum albumin), buffer substances (e.g., phosphates, glycine, sorbic acid, and potassium sorbate, etc.), partial glyceride mixtures of saturated vegetable fatty acids, water, salts, and electrolytes (e.g., protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, and zinc salts), colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, wool fat, sugars (e.g., lactose, glucose, and sucrose), starches (e.g., corn starch and potato starch), cellulose and its derivatives (e.g., carboxymethylcellulose, sodium, ethylcellulose, and cellulose acetate), powdered tragacanth, malt, gelatin, talc, excipients (e.g., cocoa butter and suppository wax), oils (e.g., peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil), glycols (e.g., propylene glycol and polyethylene glycol), esters (e.g., ethyl oleate and ethyl laurate), agar, buffers (e.g., magnesium hydroxide and aluminum hydroxide), alginic acid, pyrogen-free water, isotonic saline, Ringer's solution, ethyl alcohol, phosphate buffer solutions, non-toxic compatible lubricants (e.g., sodium lauryl sulfate and magnesium stearate), colorants, releasing agents, coating agents, sweetening agents, flavoring agents, fragrances, preservatives, and antioxidants.

[0112] Additional embodiments include the following: 1. A compound of formula (I), [ka] During the ceremony, Ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; Ring B is a phenyl, pyridinyl, or pyrimidinyl ring; -X is O, NH, or N(C 1 -C 6 alkyl), -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 0 But R 11 or [ka] and Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, or a 3- to 8-membered cycloalkenyl; -R 4 each independently represents a halogen, an oxo group, a hydroxyl group, a cyano group, and -(Y) k -R 7 or optionally two R 4together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl or heterocyclyl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; wherein k is 0, 1, 2, 3, 4, 5, or 6; -Y is independently C(R 5 )(R 6 ) groups, -O-, and -NR a - group, where -(Y) k -R 7 The heteroatom in the -(Y) k -R 7 is not bonded to another heteroatom in -In the formula, R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a hydroxyl group, or C 1 -C 6 Alkyl groups, and C 3 - 5 Cycloalkyl groups or R on the same carbon 5 and R 6 Together, C 3 - 5 forming a cycloalkyl group or oxo; -R 5 and R 6 Each of the following may be independently selected: C 1 -C 6 Alkyl group, C 1 -C 6 Haloalkyl groups, halogens, hydroxyl groups, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -R a each independently represents hydrogen and C 1 -C 6alkyl groups, -R 7 But, C 1 -C 6 Alkyl group, C 1 -C 6 hydrogen, halogen, cyano, and C, optionally substituted with one or more groups selected from haloalkyl groups and halogens; 3 -C 10 cycloalkyl groups, - q is 1, 2, 3, or 4, -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6Forming a cycloalkyl ring, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C6 The compound, optionally substituted with aryl, arylalkyl), or a tautomer thereof, a deuterated derivative of said compound or tautomer, or a pharma- ceutically acceptable salt of any of the foregoing. 2. The compound of formula (I) is a compound of formula (II): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; Ring B is a phenyl, pyridinyl, or pyrimidinyl ring; -X is O, NH, or N(C 1 -C 6 alkyl), -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Form a cycloalkyl ring or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1-C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 The compound of embodiment 1, optionally substituted with (alkyl). 3. The compound of formula (II) is a compound of formula (II-Ai): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; -X is O, NH, or N(C 1 -C 6 alkyl), -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 The compound of embodiment 2, optionally substituted with alkyl). 4. The compound of formula (II) is a compound of formula (II-Aii), (II-Aiii), or (II-Aiv), [ka] [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 The compound of embodiment 2, optionally substituted with alkyl). 5. The compound of formula (II) is a compound of formula (II-Av): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein the carbon marked * has S or R stereochemistry; Ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 The compound of embodiment 2, optionally substituted with alkyl). 6. The compound of formula (II) is a compound of formula (II-Avi), [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and Ry are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 The compound of embodiment 2, optionally substituted with alkyl). 7. The compound of formula (II) is a compound of formula (II-Bi), (II-Bii), (II-Biii), or (II-Biv), [ka] [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; -In the formula, R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 The compound of embodiment 2, optionally substituted with alkyl). 8. The compound of formula (II) is a compound of formula (II-Bv): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein the carbon marked * has S or R stereochemistry; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(Ry ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 The compound of embodiment 2, optionally substituted with alkyl). 9. The compound of formula (II) is a compound of formula (II-Bvi): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; -In the formula, R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 The compound of embodiment 1, optionally substituted with (alkyl). 10. The compound of formula (II) is a compound of formula (II-Ci, (II-Cii), (II-Ciii), or (II-Civ), [ka] [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; -In the formula, R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3Combined, C 3 -C 6 Forming a cycloalkyl ring, wherein r is 1, 2, 3, 4, 5, or 6; -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 The compound of embodiment 2, optionally substituted with alkyl). 11. The compound of formula (II) is a compound of formula (II-Cv): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein the carbon marked * has S or R stereochemistry; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, wherein r is 1, 2, 3, 4, 5, or 6; -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C6 The compound of embodiment 2, optionally substituted with alkyl). 12. The compound of formula (II) is a compound of formula (II-Cvi): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; -In the formula, R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 selected from haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups; -R 11 However, hydrogen, halogens, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 Haloalkoxyl group, C 2 -C 6 Alkenyl group, C2 -C 6 Alkynyl groups, benzyl, -O-(C 3 -C 6 cycloalkyl), and cyano groups, each of which is selected from 0, 1, 2, or 3 R 12 group or optionally one R 2 and R 11 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 12 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, wherein r is 1, 2, 3, 4, 5, or 6; -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, -CO 2 H, -C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 group or optionally one R 1 and one R b together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which may contain 0, 1, 2, 3, or 4 R 10 is substituted with a group, -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 The compound of embodiment 2, optionally substituted with alkyl). 13. The compound, salt, or deuterated derivative according to embodiment 2 or 3, wherein X is O. 14. The compound, tautomer, deuterated derivative, or pharma- ceutically acceptable salt of any one of embodiments 2-6, wherein Ring A is selected from phenyl, pyridine, pyrizine, and pyrazole. 15. Ring A is phenyl; -One R 1 and one R b are taken together with the atom to which they are attached to form a pyrrole or pyridine, a tautomer, deuterated derivative, or a pharma- ceutically acceptable salt of any one of embodiments 2-7. 16. The compound, tautomer, deuterated derivative, or pharma- ceutically acceptable salt according to embodiment 2 or 4, wherein ring B is a pyridinyl ring. 17.R 1 The compound, tautomer, deuterated derivative, or pharma- ceutically acceptable salt of any one of embodiments 2-12, wherein is selected from hydrogen and hydroxyl. 18.R 3 The compound, tautomer, deuterated derivative, or pharma- ceutically acceptable salt of any one of embodiments 2-12, wherein is C1-C6 alkyl substituted with phenyl. 19.R 3 The compound, tautomer, deuterated derivative, or pharma- ceutically acceptable salt of any one of embodiments 2-12, wherein is benzyl. 20.R b But, H, CH 3 13. The compound, tautomer, deuterated derivative, or pharma- ceutically acceptable salt of any one of embodiments 2-12, wherein R is selected from R, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, R28, R29, R30, R31, R32, R33, R34, R35, R36, R37, R38, R39, 21.C(R 8 )(R 9 ) groups each independently represent -CH 2 -, -CO-, [ka] [ka] [ka] [ka] [ka] [ka] 13. The compound, tautomer, deuterated derivative, or pharma- ceutically acceptable salt of any one of embodiments 2-12, selected from: twenty two. [ka] but [ka] 10. The compound, tautomer, deuterated derivative, or pharma- ceutically acceptable salt of any one of embodiments 2-9, wherein: 23.R 11 But hydrogen, halogen, cyano, [ka] 13. The compound, tautomer, deuterated derivative, or pharma- ceutically acceptable salt of any one of embodiments 2-12, selected from: 24.R 11 The compound, tautomer, deuterated derivative, or pharma- ceutically acceptable salt of any one of embodiments 2-12, wherein is t-Bu. twenty five. -One R 2 and R 11 together with the atoms to which they are attached form a phenyl, tetrahydropyran, or cyclohexyl ring, which is selected from the group consisting of a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, a 3- to 8-membered cycloalkenyl, or 0, 1, 2, 3, or 4 R 2 is substituted with a group, -R 2 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 The compound, tautomer, deuterated derivative, or pharma- ceutically acceptable salt of any one of embodiments 2-12, wherein the aryl group is selected from a haloalkoxyl group, a halogen, a cyano group, and a hydroxyl group. 26. A compound selected from compounds 1-298 (Table 3A), tautomers thereof, deuterated derivatives of the compounds and tautomers, and pharma- ceutically acceptable salts of any of the foregoing. 27. A pharmaceutical composition comprising a compound, tautomer, deuterated derivative, or pharma- ceutically acceptable salt according to any one of embodiments 1-26, and a pharma- ceutically acceptable carrier. 28. The pharmaceutical composition of embodiment 27, further comprising one or more additional therapeutic agents. 29. The pharmaceutical composition of embodiment 28, wherein the one or more additional therapeutic agents are selected from tezacaftor, ivacaftor, D-ivacaftor, lumacaftor, and pharma- ceutically acceptable salts thereof. 30. The pharmaceutical composition of embodiment 29, wherein the composition comprises tezacaftor and ivacaftor. 31. The pharmaceutical composition of embodiment 29, wherein the composition comprises tezacaftor and D-ivacaftor. 32. A pharmaceutical composition comprising: (a) at least one compound, tautomer, deuterated derivative, or pharma- ceutically acceptable salt according to any one of embodiments 1 to 26; (b) at least one pharma- ceutically acceptable carrier; and Optionally, (c) (i) a compound selected from tezacaftor, [ka] and pharma- ceutically acceptable salts and deuterated derivatives thereof, and (ii) Ivacaftor [ka] D-Ivacaftor [ka] and one or more of the pharma- ceutically acceptable salts and deuterated derivatives thereof. 33. A method for treating cystic fibrosis, comprising administering to a patient in need thereof a compound, tautomer, deuterated derivative, or pharma- ceutically acceptable salt according to any one of embodiments 1-26, or a pharmaceutical composition according to any one of embodiments 27-32. 34. The method of embodiment 33, further comprising administering to the patient one or more additional therapeutic agents prior to, concurrently with, or after the compound or pharmaceutical composition. 35. The method of embodiment 33, wherein the one or more additional therapeutic agents comprises a compound selected from tezacaftor, ivacaftor, D-ivacaftor, lumacaftor, and pharma- ceutically acceptable salts thereof. 36. The method of embodiment 35, wherein the one or more additional therapeutic agents comprise tezacaftor and ivacaftor. 37. The method of embodiment 35, wherein the one or more additional therapeutic agents comprise tezacaftor and D-ivacaftor. 38. A compound, salt, or deuterated derivative according to any one of embodiments 1-26, or a pharmaceutical composition according to any one of embodiments 27-32, for use in the treatment of cystic fibrosis. 39. A compound, tautomer, deuterated derivative, or pharma- ceutically acceptable salt according to any one of embodiments 1-26, or a pharmaceutical composition according to any one of embodiments 27-32, for use in the manufacture of a medicament for the treatment of cystic fibrosis. 40. The compound of formula (I) is a compound of formula (III): [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; During the ceremony, Ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; Ring B is a phenyl, pyridinyl, or pyrimidinyl ring; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, or a 3- to 8-membered cycloalkenyl; -X is O, NH, or N(C 1 -C 6 alkyl), -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or optionally two R 2 together with the atoms to which they are attached form a phenyl or 6-membered heteroaryl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 forming a cycloalkyl ring, -R 4 each independently represents a halogen, an oxo group, a hydroxyl group, a cyano group, and -(Y) k -R 7 or optionally two R 4 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl or heterocyclyl ring, which optionally and independently contains halogen, C 1 -C 6Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; wherein k is 0, 1, 2, 3, 4, 5, or 6; -Y is independently C(R 5 )(R 6 ) groups, -O-, and -NR a - group, where -(Y) k -R 7 The heteroatom in the -(Y) k -R 7 is not bonded to another heteroatom in -In the formula, R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a hydroxyl group, or C 1 -C 6 Alkyl groups, and C 3 - 5 Cycloalkyl groups or R on the same carbon 5 and R 6 Together, C 3 - 5 forming a cycloalkyl group or oxo; -R 5 and R 6 Each of the following may be independently selected: C 1 -C 6 Alkyl group, C 1 -C 6 Haloalkyl groups, halogens, hydroxyl groups, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -R a each independently represents hydrogen and C 1 -C 6 alkyl groups, -R 7 But, C 1 -C 6 Alkyl group, C 1 -C6 hydrogen, halogen, cyano, and C, optionally substituted with one or more groups selected from haloalkyl groups and halogens; 3 -C 10 cycloalkyl groups, - q is 1, 2, 3, or 4, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, phenyl, and C 1 -C 6 alkyl group, wherein the C 1 -C 6 The alkyl group may optionally be independently selected from C 1 -C 6 hydroxyl, -C(O)N(R x )(R y ), cyano, 4- to 6-membered heterocyclyl, and 5-membered heteroaryl; -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl), However, R 8 and R 9 At least one of them is independently C 3 -C 6 Haloalkyl group, C 3 -C 6 Alkyl group, C2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Alkoxy group, C 3 -C 6 haloalkoxyl group, phenyl, 5- to 6-membered heteroaryl group, and 5- to 6-membered heterocyclyl group, or at least one R 3 is substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 2 -C 6 C substituted by alkyl, or 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups 1 Alkyl or two R 3 Combined, C 3 -C 6 The compound of embodiment 1, provided that it forms a cycloalkyl ring. 41. The compound of formula (III) is a compound of formula (III-Ai), (III-Aii) or (III-Aiii), [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, or a 3- to 8-membered cycloalkenyl; -X is O, NH, or N(C 1 -C 6 alkyl), -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or optionally two R 2 together with the atoms to which they are attached form a phenyl or 6-membered heteroaryl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -R 4 each independently represents a halogen, an oxo group, a hydroxyl group, a cyano group, and -(Y) k -R 7or optionally two R 4 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl or heterocyclyl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; wherein k is 0, 1, 2, 3, 4, 5, or 6; -Y is independently C(R 5 )(R 6 ) groups, -O-, and -NR a - group, where -(Y) k -R 7 The heteroatom in the -(Y) k -R 7 is not bonded to another heteroatom in -In the formula, R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a hydroxyl group, or C 1 -C 6 Alkyl groups, and C 3 - 5 Cycloalkyl groups or R on the same carbon 5 and R 6 Together, C 3 - 5 forming a cycloalkyl group or oxo; -R 5 and R 6 Each of the following may be independently selected: C 1 -C 6 Alkyl group, C 1 -C 6 Haloalkyl groups, halogens, hydroxyl groups, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -R a each independently represents hydrogen and C1 -C 6 alkyl groups, -R 7 But, C 1 -C 6 Alkyl group, C 1 -C 6 hydrogen, halogen, cyano, and C, optionally substituted with one or more groups selected from haloalkyl groups and halogens; 3 -C 10 cycloalkyl groups, - q is 1, 2, 3, or 4, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(Rx )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, phenyl, and C 1 -C 6 alkyl group, wherein the C 1 -C 6 The alkyl group may optionally be independently selected from C 1 -C 6 hydroxyl, -C(O)N(R x )(R y ), cyano, 4- to 6-membered heterocyclyl, and 5-membered heteroaryl; -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl), However, R8 and R 9 At least one of them is independently C 3 -C 6 Haloalkyl group, C 3 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Alkoxy group, C 3 -C 6 haloalkoxyl group, phenyl, 5- to 6-membered heteroaryl group, and 5- to 6-membered heterocyclyl group, or at least one R 3 is substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 2 -C 6 C substituted by alkyl, or 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups 1 Alkyl or two R 3 Combined, C 3 -C 6 The compound of embodiment 40, provided that it forms a cycloalkyl ring. 42. The compound of formula (III) is a compound of formula (III-Aiv), (III-Av) or (III-Avi), [ka] [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein the carbon marked * has S or R stereochemistry; Ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, or a 3- to 8-membered cycloalkenyl; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or optionally two R 2 together with the atoms to which they are attached form a phenyl or 6-membered heteroaryl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups;1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -R 4 each independently represents a halogen, an oxo group, a hydroxyl group, a cyano group, and -(Y) k -R 7 or optionally two R 4 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl or heterocyclyl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; wherein k is 0, 1, 2, 3, 4, 5, or 6; -Y is independently C(R 5 )(R 6 ) groups, -O-, and -NR a - group, where -(Y) k -R 7 The heteroatom in the -(Y) k -R 7 is not bonded to another heteroatom in -In the formula, R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a hydroxyl group, or C 1 -C 6 Alkyl groups, and C 3 - 5 Cycloalkyl groups or R on the same carbon 5 and R 6 Together, C 3 - 5 forming a cycloalkyl group or oxo; -R 5 and R 6 Each of the following may be independently selected: C 1 -C 6Alkyl group, C 1 -C 6 Haloalkyl groups, halogens, hydroxyl groups, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -R a each independently represents hydrogen and C 1 -C 6 alkyl groups, -R 7 But, C 1 -C 6 Alkyl group, C 1 -C 6 hydrogen, halogen, cyano, and C, optionally substituted with one or more groups selected from haloalkyl groups and halogens; 3 -C 10 cycloalkyl groups, - q is 1, 2, 3, or 4, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, phenyl, and C 1 -C 6 alkyl group, wherein the C 1 -C 6 The alkyl group may optionally be independently selected from C 1 -C 6 hydroxyl, -C(O)N(R x )(R y ), cyano, 4- to 6-membered heterocyclyl, and 5-membered heteroaryl; -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl), However, R 8 and R 9 At least one of them is independently C 3 -C 6 Haloalkyl group, C 3 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Alkoxy group, C 3 -C 6 haloalkoxyl group, phenyl, 5- to 6-membered heteroaryl group, and 5- to 6-membered heterocyclyl group, or at least one R 3 is substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 2 -C 6 C substituted by alkyl, or 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups 1 Alkyl or two R 3 Combined, C 3 -C 6 The compound of embodiment 40, provided that it forms a cycloalkyl ring. 43. The compound of formula (III) is a compound of formula (III-Avii) or (III-Aviii), [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein the carbon marked * has S or R stereochemistry; Ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or optionally two R 2 together with the atoms to which they are attached form a phenyl or 6-membered heteroaryl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups;1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -R 4 each independently represents a halogen, an oxo group, a hydroxyl group, a cyano group, and -(Y) k -R 7 or optionally two R 4 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl or heterocyclyl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; wherein k is 0, 1, 2, 3, 4, 5, or 6; -Y is independently C(R 5 )(R 6 ) groups, -O-, and -NR a - group, where -(Y) k -R 7 The heteroatom in the -(Y) k -R 7 is not bonded to another heteroatom in -In the formula, R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a hydroxyl group, or C 1 -C 6 Alkyl groups, and C 3 - 5 Cycloalkyl groups or R on the same carbon 5 and R 6 Together, C 3 - 5 forming a cycloalkyl group or oxo; -R 5 and R 6 Each of the following may be independently selected: C 1 -C 6Alkyl group, C 1 -C 6 Haloalkyl groups, halogens, hydroxyl groups, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -R a each independently represents hydrogen and C 1 -C 6 alkyl groups, -R 7 But, C 1 -C 6 Alkyl group, C 1 -C 6 hydrogen, halogen, cyano, and C, optionally substituted with one or more groups selected from haloalkyl groups and halogens; 3 -C 10 cycloalkyl groups, - q is 1, 2, 3, or 4, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO 2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, phenyl, and C 1 -C 6 alkyl group, wherein the C 1 -C 6 The alkyl group may optionally be independently selected from C 1 -C 6 hydroxyl, -C(O)N(R x )(R y ), cyano, 4- to 6-membered heterocyclyl, and 5-membered heteroaryl; -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6 alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl), However, R 8 and R 9 At least one of them is independently C 3 -C 6 Haloalkyl group, C 3 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Alkoxy group, C 3 -C 6 haloalkoxyl group, phenyl, 5- to 6-membered heteroaryl group, and 5- to 6-membered heterocyclyl group, or at least one R 3 is substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 2 -C 6 C substituted by alkyl, or 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups 1 Alkyl or two R 3 Combined, C 3 -C 6 The compound of embodiment 40, provided that it forms a cycloalkyl ring. 44. The compound of formula (III) is a compound of formula (III-Bi), (III-Bii), (III-Biii), or (III-Biv), [ka] [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein the carbon marked * has S or R stereochemistry; Ring D is a phenyl ring, a 5-membered heterocyclyl ring, a 6-membered heterocyclyl ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, or a 3- to 8-membered cycloalkenyl; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or optionally two R 2 together with the atoms to which they are attached form a phenyl or 6-membered heteroaryl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -n is 0, 1, or 2, -R 3 are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -R 4 each independently represents a halogen, an oxo group, a hydroxyl group, a cyano group, and -(Y) k -R 7 or optionally two R 4 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl or heterocyclyl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; wherein k is 0, 1, 2, 3, 4, 5, or 6; -Y is independently C(R 5 )(R 6 ) groups, -O-, and -NR a - group, where -(Y) k -R 7 The heteroatom in the -(Y) k -R 7 is not bonded to another heteroatom in -In the formula, R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a hydroxyl group, or C 1 -C 6 Alkyl groups, and C 3 - 5 Cycloalkyl groups or R on the same carbon 5 and R 6 Together, C 3 -5 forming a cycloalkyl group or oxo; -R 5 and R 6 Each of the following may be independently selected: C 1 -C 6 Alkyl group, C 1 -C 6 Haloalkyl groups, halogens, hydroxyl groups, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -R a each independently represents hydrogen and C 1 -C 6 alkyl groups, -R 7 But, C 1 -C 6 Alkyl group, C 1 -C 6 hydrogen, halogen, cyano, and C, optionally substituted with one or more groups selected from haloalkyl groups and halogens; 3 -C 10 cycloalkyl groups, - q is 1, 2, 3, or 4, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another heteroatom in Z; [ka] is a 5- or 6-membered heterocyclyl or a 5- or 6-membered heteroaryl, each of which is selected from 0, 1, 2, 3, or 4 R 10 is substituted with a group, -In the formula, R 8 and R 9 are each independently hydrogen, halogen, or C 1 -C 6 Haloalkyl group, C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, Hydroxyl, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl group, CO 2 H, C(O)N(R x )(R y ), phenyl, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, and a 5- to 6-membered heterocyclyl group, each of which is selected from 0, 1, 2, 3, 4, or 5 R 10 is substituted with a group, -R 10 each independently represents a halogen, a hydroxyl, a cyano, 1 -C 6 Alkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, -(C 1 -C 6 Alkyl)-O(C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-CO 2 (C 1 -C 6 alkyl), -(C 1 -C 6 Alkyl)-N(R x )(R y ), -(C 1 -C 6 Alkyl)-CO 2 H, C 1 -C 6 Alkoxyl, -N(R x )(R y ), -CO-N(R x )(R y ), CO2 H, -CO 2 (C 1 -C 6 Alkyl), -CO 2 Bn, -CO(C 1 -C 6 alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C 3 -C 10 cycloalkyl, each of which is optionally independently selected from halogen, cyano, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkoxyl groups, and -CO 2 (C 1 -C 6 alkyl), or R on the same carbon 8 and R 9 together to form oxo, -R b are each independently hydrogen, phenyl, and C 1 -C 6 alkyl group, wherein the C 1 -C 6 The alkyl group may optionally be independently selected from C 1 -C 6 hydroxyl, -C(O)N(R x )(R y ), cyano, 4- to 6-membered heterocyclyl, and 5-membered heteroaryl; -R x and R y are each independently hydrogen, C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 4 -C 9 Heterocyclyl, 3- to 6-membered cycloalkyl group, 5- to 6-membered heteroaryl group, benzyl, -CO 2 (C 1 -C 6alkyl), -CO(C 1 -C 6 alkyl), wherein the C 1 -C 6 Alkyl is -NMe 2 Optionally, the C 4 -C 9 Heterocyclyl is -(C 1 -C 6 Alkyl)-O(C 1 -C 6 Alkyl) or -CO 2 (C 1 -C 6 alkyl), However, R 8 and R 9 At least one of them is independently C 3 -C 6 Haloalkyl group, C 3 -C 6 Alkyl group, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, C 3 -C 6 Alkoxy group, C 3 -C 6 haloalkoxyl group, phenyl, 5- to 6-membered heteroaryl group, and 5- to 6-membered heterocyclyl group, or at least one R 3 is substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 2 -C 6 C substituted by alkyl, or 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups 1 Alkyl or two R 3 Combined, C 3 -C 6 The compound of embodiment 40, provided that it forms a cycloalkyl ring. 45. The compound of formula (III) is a compound of formula (III-Bv) or (III-Bvi), [ka] a tautomer thereof, a deuterated derivative of said compound or said tautomer, or a pharma- ceutically acceptable salt of any of the foregoing; wherein the carbon marked * has S or R stereochemistry; -R 1 are each independently, C 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or two R 1 groups, together with the atoms to which they are attached, form a 5- to 6-membered heteroaryl or 6-membered aryl ring; -m is 0, 1, 2, 3, or 4, -R 2 are each independently optionally substituted by phenyl or 5- or 6-membered heteroaryl; 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 1 -C 6 Haloalkyl group, C 1 -C 6 haloalkoxyl groups, halogens, cyano groups, and hydroxyl groups, or optionally two R 2 together with the atoms to which they are attached form a phenyl or 6-membered heteroaryl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -n is 0, 1, or 2, -R 3are each substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups; 1 -C 6 Alkyl or two R 3 Combined, C 3 -C 6 Forming a cycloalkyl ring, -R 4 each independently represents a halogen, an oxo group, a hydroxyl group, a cyano group, and -(Y) k -R 7 or optionally two R 4 together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl or heterocyclyl ring, which optionally and independently contains halogen, C 1 -C 6 Alkyl group, haloalkyl group, hydroxyl group, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; wherein k is 0, 1, 2, 3, 4, 5, or 6; -Y is independently C(R 5 )(R 6 ) groups, -O-, and -NR a - group, where -(Y) k -R 7 The heteroatom in the -(Y) k -R 7 is not bonded to another heteroatom in -In the formula, R 5 and R 6 are each independently a hydrogen atom, a halogen atom, a hydroxyl group, or C 1 -C 6 Alkyl groups, and C 3 - 5 Cycloalkyl groups or R on the same carbon 5 and R 6 Together, C 3 - 5 forming a cycloalkyl group or oxo; -R5 and R 6 Each of the following may be independently selected: C 1 -C 6 Alkyl group, C 1 -C 6 Haloalkyl groups, halogens, hydroxyl groups, C 1 -C 6 Alkoxyl groups, and C 1 -C 6 substituted with one or more groups selected from haloalkoxyl groups; -R a each independently represents hydrogen and C 1 -C 6 alkyl groups, -R 7 But, C 1 -C 6 Alkyl group, C 1 -C 6 hydrogen, halogen, cyano, and C, optionally substituted with one or more groups selected from haloalkyl groups and halogens; 3 -C 10 cycloalkyl groups, - q is 1, 2, 3, or 4, -Z is a group represented by the formula (L) r is a bivalent linker of the formula wherein r is 1, 2, 3, 4, 5, or 6; -L is independently C(R 8 )(R 9 ) group, -O-, [ka] and -NR b - group, where no heteroatom in Z is bonded to another hetero...

Claims

1. A compound of formula (II), wherein 【Chemical Formula 935】 in the formula,[[]] - Ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring; - Ring B is phenyl, pyridinyl, or pyrimidinyl; -X is O, NH, or N(C １ -C ６ alkyl), -R １ each independently is C １ -C ６ an alkyl group, C １ -C ６ an alkoxyl group, C １ -C ６ a haloalkyl group, C １ -C ６ a haloalkoxyl group, halogen, a cyano group, or a hydroxyl group, or two R １ groups together with the atoms to which they are attached form a 5- to 6-membered heteroaryl or 6-membered aryl ring, - m is 0, 1, 2, 3, or 4; -R ２ is each independently C optionally substituted by phenyl or a 5- or 6-membered heteroaryl １ -C ６ alkyl group, C １ -C ６ alkoxyl group, C １ -C ６ haloalkyl group, C １ -C ６ haloalkoxyl group, halogen, cyano group, and hydroxyl group, and is selected from -R １１ wherein R is hydrogen, halogen, C １ -C ６ alkyl group, C １ -C ６ alkoxyl group, C １ -C ６ haloalkyl group, C １ -C ６ haloalkoxyl group, C ２ -C ６ alkenyl group, C ２ -C ６ alkynyl group, benzyl, -O-(C ３ -C ６ cycloalkyl), and cyano group, and each of them is substituted with 0, 1, 2, or 3 R １２ groups, or optionally one R ２ and R １１ together with the atoms to which they are attached form a 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl, or 6-membered aryl ring, and it is a phenyl ring, 5-membered heterocyclyl ring, 6-membered heterocyclyl ring, 5-membered heteroaryl ring, 6-membered heteroaryl ring, 3- to 8-membered cycloalkyl ring, 3- to 8-membered cycloalkenyl, or is substituted with 0, 1, 2, 3, or 4 R ２ groups, -R １２ is each independently halogen, hydroxyl, cyano, C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, -(C １ -C ６ alkyl)-O(C １ -C ６ alkyl), -(C １ -C ６ alkyl)-CO ２ (C １ -C ６ alkyl), -(C １ -C ６ alkyl)-N(R ｘ )(R ｙ ), -(C １ -C ６ alkyl)-CO ２ H, C １ -C ６ alkoxyl, -N(R ｘ )(R ｙ ), -CO-N(R ｘ )(R ｙ ), CO ２ H, -CO ２ (C １ -C ６ alkyl), -CO ２ Bn, -CO(C １ -C ６ alkyl), phenyl, 5-6 membered heteroaryl, 4-6 membered heterocyclyl, and C ３ -C １０ cycloalkyl, each of which is optionally independently substituted with one or more groups selected from halogen, cyano, C １ -C ６ alkyl group, haloalkyl group, hydroxyl group, C １ -C ６ alkoxyl group, C １ -C ６ haloalkoxyl group, and -CO ２ (C １ -C ６ alkyl), - n is 0, 1, or 2; -R ３ is each, C substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups １ -C ６ is alkyl, or two Rs ３ are bonded to form C ３ -C ６ cycloalkyl forming a ring; -Z is a divalent linker of formula (L) ｒ and - in the formula, r is 1, 2, 3, 4, 5, or 6; -L is each independently a C(R ８ )(R ９ ) group, -O-, 【Chemical 936】 and -NR ｂ selected from a - group, wherein a heteroatom in Z is not bonded to another heteroatom in Z, 【Chemical Formula 937】 is a 5- or 6-membered heterocyclyl or 5- or 6-membered heteroaryl, each of which is substituted with 0, 1, 2, 3, or 4 R １０ groups - wherein, R ８ and R ９ are each independently hydrogen, halogen, C １ -C ６ haloalkyl group, C １ -C ６ alkyl group, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, hydroxyl group, C １ -C ６ alkoxyl group, C １ -C ６ haloalkoxyl group, CO ２ H, C(O)N(R ｘ )(R ｙ ), phenyl, 3- to 8-membered cycloalkyl group, 5- to 6-membered heteroaryl group, and 5- to 6-membered heterocyclyl group, and each of them is substituted with 0, 1, 2, 3, 4, or 5 R １０ groups, -R １０ is each independently halogen, hydroxyl, cyano, C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, -(C １ -C ６ alkyl)-O(C １ -C ６ alkyl), -(C １ -C ６ alkyl)-CO ２ (C １ -C ６ alkyl), -(C １ -C ６ alkyl)-N(R ｘ )(R ｙ ), -(C １ -C ６ alkyl)-CO ２ H, C １ -C ６ alkoxyl, -N(R ｘ )(R ｙ ), -CO-N(R ｘ )(R ｙ ), CO ２ H, -CO ２ (C １ -C ６ alkyl), -CO ２ Bn, -CO(C １ -C ６ alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C ３ -C １０ cycloalkyl, each of which is optionally and independently substituted with one or more groups selected from halogen, cyano, C １ -C ６ alkyl group, haloalkyl group, hydroxyl group, C １ -C ６ alkoxyl group, C １ -C ６ haloalkoxyl group, and -CO ２ (C １ -C ６ alkyl), or R on the same carbon ８ and R ９ together form an oxo, -R ｂ is each independently hydrogen, halogen, C １ -C ６ haloalkyl group, C １ -C ６ alkyl group, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, hydroxyl group, C １ -C ６ alkoxyl group, C １ -C ６ haloalkoxyl group, -CO ２ H, -C(O)N(R ｘ )(R ｙ ) and is selected from phenyl, 3- to 8-membered cycloalkyl group, 5- to 6-membered heteroaryl group, and 5- to 6-membered heterocyclyl group, each of which is substituted with 0, 1, 2, 3, 4, or 5 R １０ groups, or optionally one R １ and one R ｂ together with the atoms to which they are attached form a 5- to 6-membered heterocycloalkyl or 5- to 6-membered heteroaryl ring, each of which is substituted with 0, 1, 2, 3, or 4 R １０ groups, -R ｘ and R ｙ are each independently hydrogen, C １ -C ６ alkyl, C １ -C ６ haloalkyl, C ４ -C ９ heterocyclyl, a 3- to 6-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, benzyl, -CO ２ (C １ -C ６ alkyl), -CO(C １ -C ６ alkyl), and are selected from the group consisting of, where the C １ -C ６ alkyl is optionally substituted with -NMe ２ , the C ４ -C ９ heterocyclyl is optionally substituted with -(C １ -C ６ alkyl)-O(C １ -C ６ alkyl) or -CO ２ (C １ -C ６ alkyl). the compound, its tautomer, a deuterated derivative of the compound or tautomer, or a pharmaceutically acceptable salt of any of the foregoing.

2. Formula (II-Ai): 【Chemical 938】 Selected from, and all variables are as defined in Claim 1, the compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to Claim 1.

3. Formula (II-Aii): 【Chemical 939】 Selected from, and all variables are as defined in Claim 1, the compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to Claim 1.

4. Formula (II-Aiii): 【Chemical Formula 940】 Selected from, and all variables are as defined in Claim 1, the compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to Claim 1.

5. Formula (II-Aiv): 【Chemical Formula 941】 Selected from, and all variables are as defined in Claim 1, the compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to Claim 1.

6. Formula (II-Av): 【Chemical Formula 942】 Selected from, and all variables are as defined in Claim 1, the compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to Claim 1.

7. Formula (II-Avi): 【Chemical Formula 943】 Selected from, and all variables are as defined in Claim 1, the compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to Claim 1.

8. Formula (II-Bi): 【Chemical Formula 944】 Selected from, and all variables are as defined in Claim 1, the compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to Claim 1.

9. Formula (II-Bii): 【Chemical Formula 945】 Selected from, and all variables are as defined in Claim 1, the compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to Claim 1.

10. Formula (II-Biii): 【Chemical 946】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, selected from, and all variables being as defined in claim 1.

11. Formula (II-Biv): 【Chemical 947】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, selected from, and all variables being as defined in claim 1.

12. Formula (II-Bv): 【Chemical Formula 948】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, selected from, and all variables being as defined in claim 1.

13. Formula (II-Bvi): 【Chemical 949】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, selected from, and all variables being as defined in claim 1.

14. Formula (II-Ci): 【Chemical Formula 950】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, selected from, and all variables being as defined in claim 1.

15. Formula (II-Cii): 【Chemical 951】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, selected from, and all variables being as defined in claim 1.

16. Formula (II-Ciii): 【Chemical Formula 952】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, selected from, and all variables being as defined in claim 1.

17. Formula (II-Civ): 【Chemical Formula 953】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, selected from, and all variables being as defined in claim 1.

18. Formula (II-Cv): 【Chemical 954】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, selected from, and all variables being as defined in claim 1.

19. Formula (II-Cvi): 【Chemical 955】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 1, selected from, and all variables being as defined in claim 1.

20. A compound of formula (III), wherein 【Chemical 956】 In the formula, - Ring A is phenyl, indole, a 5-membered heteroaryl ring, or a 6-membered heteroaryl ring, - Ring B is phenyl, pyridinyl, or pyrimidinyl ring, - Ring D is a phenyl ring, a 5-membered heterocyclic ring, a 6-membered heterocyclic ring, a 5-membered heteroaryl ring, a 6-membered heteroaryl ring, a 3- to 8-membered cycloalkyl ring, or a 3- to 8-membered cycloalkenyl, - X is O, NH, or N(C １ - C ６ alkyl), and -R １ each is independently C １ -C ６ an alkyl group, C １ -C ６ an alkoxyl group, C １ -C ６ a haloalkyl group, C １ -C ６ a haloalkoxyl group, halogen, a cyano group, or a hydroxyl group, or two R １ groups together with the atoms to which they are attached form a 5- to 6-membered heteroaryl or 6-membered aryl ring, - m is 0, 1, 2, 3, or 4, -R ２ each independently is C optionally substituted by phenyl or a 5- or 6-membered heteroaryl １ -C ６ alkyl group, C １ -C ６ alkoxyl group, C １ -C ６ haloalkyl group, C １ -C ６ haloalkoxyl group, halogen, cyano group, and hydroxyl group, or optionally two Rs ２ together with the atom to which they are attached form a phenyl or 6-membered heteroaryl ring, which is optionally independently substituted by one or more groups selected from halogen, C １ -C ６ alkyl group, haloalkyl group, hydroxyl group, C １ -C ６ alkoxyl group, and C １ -C ６ haloalkoxyl group - n is 0, 1, or 2, -R ３ is each independently a C substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups １ -C ６ is alkyl, or two Rs ３ are joined to form a C ３ -C ６ cycloalkyl ring -R ４ each independently is halogen, an oxo group, a hydroxyl group, a cyano group, and -(Y) ｋ -R ７ group, or optionally two Rs ４ together with the atom to which they are attached form a 5- or 6-membered cycloalkyl or heterocyclyl ring, which is optionally independently substituted with one or more groups selected from halogen, C １ -C ６ alkyl group, haloalkyl group, hydroxyl group, C １ -C ６ alkoxyl group, and C １ -C ６ haloalkoxyl group - In the formula, k is 0, 1, 2, 3, 4, 5, or 6, -Y is each independently selected from a C(R ５ )(R ６ ) group, an -O-, and an -NR ａ - group, where the heteroatom in -(Y) ｋ -R ７ is not bonded to another heteroatom in -(Y) ｋ -R ７ and - wherein, R ５ and R ６ are each independently hydrogen, halogen, hydroxyl group, C １ -C ６ alkyl group, and C ３ - ５ cycloalkyl group, or R ５ and R ６ on the same carbon are taken together to form a C ３ - ５ cycloalkyl group or oxo, -R ５ and R ６ are each independently optionally, C １ -C ６ alkyl group, C １ -C ６ haloalkyl group, halogen, hydroxyl group, C １ -C ６ alkoxyl group, and C １ -C ６ substituted with one or more groups selected from haloalkoxyl groups, -R ａ each independently represents hydrogen and C １ -C ６ selected from an alkyl group -R ７ is C １ -C ６ an alkyl group, C １ -C ６ a haloalkyl group, and one or more groups selected from halogen, optionally substituted with hydrogen, halogen, a cyano group, and C ３ -C １０ selected from cycloalkyl groups, - q is 1, 2, 3, or 4, -Z is a divalent linker of formula (L) ｒ and - In the formula, r is 1, 2, 3, 4, 5, or 6, - L is each independently a C(R ８ )(R ９ ) group, -O-, 【Chemical Formula 957】 and -NR ｂ selected from a - group, wherein a heteroatom in Z is not bonded to another heteroatom in Z, 【Chemical 958】 is a 5- or 6-membered heterocyclyl or 5- or 6-membered heteroaryl, each of which is substituted with 0, 1, 2, 3, or 4 R １０ groups - wherein, R ８ and R ９ are each independently hydrogen, halogen, C １ - C ６ haloalkyl group, C １ - C ６ alkyl group, C ２ - C ６ alkenyl, C ２ - C ６ alkynyl, hydroxyl group, C １ - C ６ alkoxyl group, C １ - C ６ haloalkoxyl group, CO ２ H, C(O)N(R ｘ )(R ｙ ) are selected from phenyl, 3- to 8-membered cycloalkyl group, 5- to 6-membered heteroaryl group, and 5- to 6-membered heterocyclyl group, and each of them is substituted with 0, 1, 2, 3, 4, or 5 R １０ groups, -R １０ each independently represents halogen, hydroxyl, cyano, C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, -(C １ -C ６ alkyl)-O(C １ -C ６ alkyl), -(C １ -C ６ alkyl)-CO ２ (C １ -C ６ alkyl), -(C １ -C ６ alkyl)-N(R ｘ )(R ｙ ), -(C １ -C ６ alkyl)-CO ２ H, C １ -C ６ alkoxyl, -N(R ｘ )(R ｙ ), -CO-N(R ｘ )(R ｙ ), CO ２ H, -CO ２ (C １ -C ６ alkyl), -CO ２ Bn, -CO(C １ -C ６ alkyl), phenyl, 5- to 6-membered heteroaryl, 4- to 6-membered heterocyclyl, and C ３ -C １０ cycloalkyl, each of which is optionally and independently substituted with one or more groups selected from halogen, cyano, C １ -C ６ alkyl group, haloalkyl group, hydroxyl group, C １ -C ６ alkoxyl group, C １ -C ６ haloalkoxyl group, and -CO ２ (C １ -C ６ alkyl), or R on the same carbon ８ and R ９ combine to form an oxo, -R ｂ is each independently hydrogen, phenyl, and C １ -C ６ alkyl group, and said C １ -C ６ alkyl group is optionally independently substituted with one or more groups selected from C １ -C ６ alkyl, hydroxyl, -C(O)N(R ｘ )(R ｙ ), cyano, 4- to 6-membered heterocyclyl, 5-membered heteroaryl, -R ｘ and R ｙ are each independently hydrogen, C １ -C ６ alkyl, C １ -C ６ haloalkyl, C ４ -C ９ heterocyclyl, a 3- to 6-membered cycloalkyl group, a 5- to 6-membered heteroaryl group, benzyl, -CO ２ (C １ -C ６ alkyl), -CO(C １ -C ６ alkyl), and are selected from the group consisting of, wherein the C １ -C ６ alkyl is optionally substituted with -NMe ２ , and the C ４ -C ９ heterocyclyl is optionally substituted with -(C １ -C ６ alkyl)-O(C １ -C ６ alkyl) or -CO ２ (C １ -C ６ alkyl), provided that However, R ８ and R ９ at least one of which is independently selected from C ３ -C ６ haloalkyl group, C ３ -C ６ alkyl group, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C ３ -C ６ alkoxyl group, C ３ -C ６ haloalkoxyl group, phenyl, 5- to 6-membered heteroaryl group, and 5- to 6-membered heterocyclyl group, or at least one R ３ is C ２ -C ６ alkyl substituted by 0, 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups, or C １ alkyl substituted by 1, 2, 3, 4, 5, or 6 3- to 8-membered cycloalkyl rings or 5- or 6-membered aryl groups, or two Rs ３ are bonded to form a C ３ -C ６ cycloalkyl ring, a compound, a tautomer thereof, a deuterated derivative of the compound or tautomer, or a pharmaceutically acceptable salt of any of the foregoing.

21. Formula (III-Ai): 【Chemical 959】 A compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

22. Formula (III-Aii): 【Chemical Formula 960】 A compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

23. Formula (III-Aiii): 【Chemical Formula 961】 A compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

24. Formula (III-Aiv): 【Chemical Formula 962】 A compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

25. Formula (III-Av): 【Chemical Formula 963】 A compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

26. Formula (III-Avi): 【Chemical 964】 A compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

27. Formula (III-Avii): 【Chemical 965】 A compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

28. Formula (III-Aviii): 【Chemical Formula 966】 A compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

29. Formula (III-Bi): 【Chemical Formula 967】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

30. Formula (III-Bii): 【Chemical Formula 968】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

31. Formula (III-Biii): 【Chemical 969】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

32. Formula (III-Biv): 【Chemical 970】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

33. Formula (III-Bv): 【Chemical 971】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

34. Formula (III-Bvi): 【Chemical Formula 972】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

35. Formula (III-Ci): 【Chemical Formula 973】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

36. Formula (III-Cii): 【Chemical 974】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

37. Formula (III-Ciii): 【Chemical 975】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

38. Formula (III-Civ): 【Chemical 976】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

39. Formula (III-Cv): 【Chemical 977】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

40. Formula (III-Cvi): 【Chemical Formula 978】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to claim 20, selected from, and all variables being as defined in claim 20.

41. 【Fig. 979】 【Chemical 980】 【Chemical Formula 981】 【Chemical 982】 【Chemical Formula 983】 【Chemical Formula 984】 【Chemical Formula 985】 【Chemical 986】 【Chemical 987】 【Chemical 988】 【Chemical Formula 989】 【Chemical Formula 990】 【Chemical Formula 991】 【Chemical Formula 992】 【Chemical Formula 993】 【Chemical Formula 994】 【Chemical 995】 【Chemical Formula 996】 【Chemical Formula 997】 【Chemical Formula 998】 【Chemical Formula 999】 【Chemical 1000】 【Chemical 1001】 【Chemical 1002】 【Chemical 1003】 【Chemical Formula 1004】 【Chemical 1005】 【Chemical 1006】 【Chemical 1007】 【Chemical 1008】 【Chemical 1009】 【Chemical 1010】 【Chemical 1011】 【Chemical 1012】 【Chemical 1013】 【Chemical 1014】 【Chemical 1015】 【Chemical 1016】 【Chemical 1017】 【Chemical 1018】 【Chemical 1019】 【Chemical 1020】 【Chemical 1021】 【Chemical 1022】 【Chemical 1023】 【Chemical 1024】 【Chemical 1025】 【Chemical 1026】 【Chemical 1027】 【Chemical 1028】 【Chemical 1029】 【Chemical 1030】 【Chemical Formula 1031】 【Chemical 1032】 【Chemical 1033】 【Chemical 1034】 【Chemical 1035】 【Chemical 1036】 【Chemical 1037】 【Chemical 1038】 【Chemical 1039】 【Chemical 1040】 【Chemical Formula 1041】 【Chemical 1042】 【Chemical 1043】 【Chemical 1044】 【Chemical 1045】 【Chemical 1046】 【Chemical 1047】 【Chemical 1048】 【Chemical 1049】 【Chemical 1050】 【Chemical 1051】 【Chemical 1052】 【Chemical 1053】 【Chemical 1054】 【Chemical 1055】 【Chemical 1056】 【Chemical 1057】 【Chemical 1058】 The compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1 to 40, selected from, its pharmaceutically acceptable salt, and deuterated derivatives of any of the foregoing.

42. A pharmaceutical composition comprising the compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1 to 41 and a pharmaceutically acceptable carrier.

43. The pharmaceutical composition according to claim 42, further comprising one or more additional therapeutic agents.

44. The pharmaceutical composition according to claim 43, wherein the one or more additional therapeutic agents are selected from tezacaftor, ivacaftor, D-ivacaftor, lumacaftor, and pharmaceutically acceptable salts thereof.

45. The pharmaceutical composition according to claim 44, wherein the composition comprises tezacaftor and ivacaftor.

46. The pharmaceutical composition according to claim 44, wherein the composition comprises tezacaftor and D-ivacaftor.

47. In a patient in need of treatment for cystic fibrosis, a composition comprising the compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1 to 41 for treating cystic fibrosis, or the pharmaceutical composition according to any one of claims 42 to 46.

48. The composition according to claim 47, characterized in that one or more additional therapeutic agents are administered before, simultaneously with, or after the composition.

49. The composition according to claim 48, wherein the one or more additional therapeutic agents are compounds selected from tezacaftor, ivacaftor, D-ivacaftor, lumacaftor, and pharmaceutically acceptable salts thereof.

50. The composition according to claim 49, wherein the one or more additional therapeutic agents are tezacaftor and ivacaftor.

51. The composition according to claim 49, wherein the one or more additional therapeutic agents are tezacaftor and D-ivacaftor.

52. A composition comprising a compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt according to any one of claims 1 to 41 for use in the manufacture of a medicament for the treatment of cystic fibrosis, or a pharmaceutical composition according to any one of claims 42 to 46.

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