Substituted indole compounds and methods of use thereof

Abstract

Provided herein are substituted indole compounds. In certain embodiments, these compounds are inhibitors of the complement system bypass pathway, and in particular complement factor B (CFB) inhibitors. Compositions comprising these compounds and methods of use thereof are also provided. The provided compounds are useful for treating, preventing or ameliorating diseases, conditions or disorders by inhibiting the complement bypass pathway.

Description

[0001] This application is a divisional application of a Chinese patent application with an application date of June 3, 2022, an application number of 202280043461.X, and an invention title of "Substituted Indole Compounds and Methods of Use Thereof". Technical Field

[0002] Provided herein are substituted indole compounds. In certain embodiments, these compounds are inhibitors of the alternative pathway of the complement system and, in particular, inhibitors of complement factor B (CFB). Also provided are compositions containing these compounds and methods of use thereof. The provided compounds can be used to treat, prevent, or improve a disease, disorder, or condition by inhibiting the alternative complement pathway. Background Art

[0003] The complement system is a key component of the innate immune system and has two major functions: host defense against microbial pathogens and clearance of apoptotic cells. Since its first discovery by Jules Bordet and Paul Ehrlich in the 1890s, more than a century of complement research has revealed its diverse roles in immune responses, surveillance, homeostasis, and metabolism (Hajishengallis, Nat Immunol [Nature Immunology] 2017 18:1288-1298; Sim, Immunobiology [Immunobiology] 2016 221(10):1037-1045; Ricklin, Nat Immunol [Nature Immunology] 2010 11(9):785-797). The complement system contains a large number of soluble proteins that exist as inactive zymogens (activated upon cleavage by serine proteases) in the circulation and tissues. The activation of complement is tightly regulated by plasma and membrane-bound regulators. It has been found that dysregulation of complement activity caused by gene mutations, autoantibodies, or chronic inflammation leads to tissue damage in various pathological conditions (including autoimmune conditions, inflammatory conditions, neurodegenerative conditions) and a wide range of kidney diseases (Zipfel, Nat Rev Immunol [Nature Reviews Immunology] 2009 9:729-749; Holers, Annu Rev Immunol [Annual Review of Immunology] 2014 32:433-459).

[0004] There are three activation pathways: the classical pathway (CP), the lectin pathway (LP), and the alternative pathway (AP) (Merle, Front Immunol [Frontiers in Immunology] 2015 6:262). CP is activated by immunoglobulins (IgG and IgM) and immune complexes through the binding of C1q to the Fc domain (Botto, Annu Rev Immunol [Annual Review of Immunology] 2002 205:395-406). LP is activated by a group of proteins that bind to sugars on the surface of bacteria, such as mannose-binding lectin (MBL) (Garred, Immunol Rev [Immunological Reviews] 2016 274(1):74-97). Compared with the other two pathways that require specific stimuli for activation, AP maintains a low level of activation in plasma through a spontaneous hydrolysis process called "tickover" and can also be secondarily activated by the other two complement pathways (Lachmann, Adv Immunol [Advances in Immunology] 2009 104:115–149). AP forms a rapid self-amplifying loop unless inactivated by factor H and factor I. The three activation pathways generate protease complexes called "C3 convertases" (C3bBb and C4b2a) to cleave C3 and form C3bBbC3b as the C5 convertase. The terminal complement pathway assembles C5b with other complement proteins to form the C5b-9 membrane attack complex (MAC), which mediates the lysis of pathogens or apoptotic cells (Bhakdi, Immunol Today [Immunology Today] 1991 12:318-320). Two soluble fragments of the C3 and C5 cleavage products, C3a and C5a, also known as "anaphylatoxins", are potent chemoattractants that trigger pro-inflammatory responses through their receptors (Klos, Mol Immunol [Molecular Immunology] 2009 46(14):2753-2766).

[0005] Complement overactivation and renal deposition have been observed in various chronic kidney diseases (CKD), including atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G), IgA nephropathy (IgAN), membranous nephropathy (MN), ANCA-associated vasculitis (AAV), focal segmental glomerulosclerosis (FSGS), and lupus nephritis (LN) (Harris, Semin Immunopathol [Seminars in Immunopathology] 2018 40(1):125–140; Willows, Clin Med [Clinical Medicine] 2020 20(2):156-160). Preclinical and clinical evidence supports the role of complement, especially AP, in disease initiation and progression. Gene defects in complement genes such as CFH, CFI, CFHR, CFB, C3, and MCP / CD46 are directly associated with aHUS and C3G (Bu, J Am Soc Nephrol [Journal of the American Society of Nephrology] 2014 25(1):55-64; Marinozzi, J Am Soc Nephrol [Journal of the American Society of Nephrology] 2015 25:2053–2065; Xiao, Semin Thromb Hemost [Seminars in Thrombosis and Hemostasis] 2014 40(4):465-471). Activation of complement by autoantibodies and immune complexes in the kidney leads to renal injury and contributes to disease progression in various glomerular diseases (Corvillo, Front Immunol [Frontiers in Immunology] 2019 10:886; Marinozzi, J Am Soc Nephrol [Journal of the American Society of Nephrology] 2017 28(5):1603-1613; Seikrit, N Engl J Med [The New England Journal of Medicine] 2018 379(25):2479-2481). Recent studies have provided evidence of local production and activation of complement proteins in the kidney in CKD such as IgAN and diabetic kidney disease (Mühlig, Front Immunol [Frontiers in Immunology] 2020 11:1833; Zhou, Clin J Am Soc Nephrol [Journal of the American Society of Nephrology] 2021 16(2):213-224; Kelly Am J Nephrol [American Journal of Nephrology] 2015 41:48–56). It is believed that local production of complement and the unique microenvironment of the kidney make this organ more vulnerable to complement overactivation (Thurman, Clin J Am Soc Nephrol [Journal of the American Society of Nephrology] 2020 11:1856).

[0006] Considerable efforts have been made to develop complement-targeted therapies. Eculizumab, a C5 monoclonal antibody, has been approved for the treatment of aHUS. However, when tested in C3G, only a subset of patients with high levels of C5b-9 (MAC) showed improvement in the disease. This may be due to the contribution of activated fragments of C3 levels upstream of the terminal pathway (Vivarelli, Semin Thromb Hemost [Seminars in Thrombosis and Hemostasis] 2014 40(4):472-477). Multiple therapeutic agents targeting different complement pathways are currently being developed, each with advantages and limitations (Zipfel, Front Immunol [Frontiers in Immunology] 2019 10:2166; Thurman, Kidney Int [Kidney International] 2016 90(4):746-752). However, there remains a need for effective therapeutic compounds that block C3 and C5 levels of the complement system.

[0007] As a key enzyme of AP, CFB provides a highly desirable target to block the central amplification loop and the terminal complement pathway. CFB knockout has been shown to be protective in the following rodent models: C3G (Pickering, Nat Genet 2002 31(4):424-428), MN (Luo, Front Immunol 2018 9:1433), ANCA-associated vasculitis (Xiao, Am J Pathol 2007 170(1):52-64), LN (Watanabe, J Immunol 2000 164(2):786-794), and multiple kidney injury models (Thurman, Am J Physiol Renal Physiol 2012 302:F1529–F1536; Casiraghi, Am J Transplant 2017 17:2312-2325; Morigi, Sci Rep 2016 6:8445). Gene deficiency of CFB in these models led to reduced proteinuria, protection against kidney injury and extended survival. Like many complement proteins, CFB circulates at a high plasma concentration of 300-400 μg / mL in its native form. Recently, a selective CFB inhibitor, iptacopan (LNP023), has been shown to bind to active CFB (Schubart Proc Natl Acad Sci U S A. 2019 116(16):7926-7931). In a phase II clinical trial of C3G, iptacopan showed encouraging efficacy in reducing proteinuria after 12 weeks of treatment (Wong, J Am Soc Nephrol 2020 31:55A). However, variability in complement activity and patient response was also observed, indicating that highly potent compounds with stronger and more persistent in vivo complement inhibition could provide greater therapeutic benefits for patients with C3G and a wide range of CKD. Summary of the Invention

[0008] In certain embodiments, provided herein are compounds of formula (I) or pharmaceutically acceptable salts thereof. In certain embodiments, the compound is an inhibitor of the alternative complement pathway. In certain embodiments, the compound is an inhibitor of complement factor B (CFB). In certain embodiments, the compounds provided herein will confer therapeutic benefits associated with the inhibition of the alternative complement pathway or CFB, including treating or preventing certain autoimmune diseases or disorders, inflammatory diseases or disorders, metabolic diseases or disorders, neurological diseases or disorders, pulmonary diseases, respiratory diseases or disorders, ophthalmic diseases, cardiovascular diseases, and kidney diseases. Complement-mediated kidney diseases include chronic kidney disease (CKD), diabetic nephropathy, glomerular kidney diseases, complement C3 glomerulopathy (C3G), IgA nephropathy (IgAN), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome (aHUS), dense deposit disease (DDD), minimal change disease (MCD), paroxysmal nocturnal hemoglobinuria (PNH), ANCA-associated vasculitis, lupus nephritis, and polycystic kidney disease (PKD).

[0009] In certain embodiments, provided herein are compounds of formula (I):

[0010]

[0011] or pharmaceutically acceptable salts thereof, wherein:

[0012] R 1 is hydrogen, fluorine, chlorine, or methyl;

[0013] X is N or CH;

[0014] Z is NR 2 or CR 2a R 2b ;

[0015] R 2 is alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 、-C(O)NR 13 R 14 or -S(O) t R 12 wherein the alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is optionally substituted with one, two, or three independently selected R 11 substituents;

[0016] R 2a is a haloalkyl group, -R u -cycloalkyl group, -R u -heterocyclic group, cycloalkyl group, heterocyclic group, aryl group, heteroaryl group, -OR 7 、-SR 7 or -NR 8 R 9 wherein the -R u -cycloalkyl group, -R u -heterocyclic group, cycloalkyl group, heterocyclic group, aryl group or heteroaryl group is optionally substituted by one, two or three independently selected R 11 substituents;

[0017] and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl group, deuterated C 1-3 alkyl group, or halo C 1-3 alkyl group;

[0018] or R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl group or a heterocyclic group, wherein the cycloalkyl group or the heterocyclic group is optionally substituted by one, two or three independently selected R 11 substituents;

[0019] R 3 is halogenated, cyano, C 1-3 alkyl group, or halo C 1-3 alkyl group;

[0020] R 4 is hydrogen, halogenated, cyano, C 1-3 alkyl group or halo C 1-3 alkyl group;

[0021] R 5 is halogenated, C 1-3 alkyl group, C 3-5 cycloalkyl group, halo C 1-3 alkyl group, halo C 1-3 alkoxy group or C 1-3 alkoxy group;

[0022] R 6 is halogenated, cyano, C 1-3 alkyl group, C 3-5 cycloalkyl group, halo C 1-3 alkyl group, C 1-3 alkoxy group or halo C 1-3 alkoxy group;

[0023] R 7 is a haloalkyl group, deuterated alkyl group, -R u -cycloalkyl group, -R u-heterocyclic group, cycloalkyl group, heterocyclic group, or heteroaryl group, wherein the haloalkyl group, deuterated alkyl group, -R u -cycloalkyl group, -R u -heterocyclic group, cycloalkyl group, heterocyclic group or heteroaryl group is each optionally substituted by one, two or three independently selected R 11 substituents;

[0024] R 8 is hydrogen, deuterium, alkyl group, deuterated alkyl group or haloalkyl group;

[0025] R 9 is haloalkyl group, -R u -cycloalkyl group, -R u -heterocyclic group, cycloalkyl group, heterocyclic group, heteroaryl group, -C(O)R 12 -C(O)NR 13 R 14 -S(O) t R 12 - or -S(O) t NR 13 R 14 wherein the -R u -cycloalkyl group, -R u -heterocyclic group, cycloalkyl group, heterocyclic group or heteroaryl group is optionally substituted by one, two or three independently selected R 11 substituents; or

[0026] R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclic group or heteroaryl group, wherein the heterocyclic group or heteroaryl group is optionally substituted by one, two or three independently selected R 11 substituents;

[0027] Each R 11 is independently halo, cyano, oxo, C 1-3 alkyl group, deuterated C 1-3 alkyl group, halo C 1-3 alkyl group, cyano C 1-3 alkyl group, hydroxy C 1-3 alkyl group, C 1-3 alkoxy C 1-3 alkyl group, halo C 1-3 alkoxy C 1-3 alkyl group, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl, or halo C 1-3 alkylsulfinyl; or

[0028] Two Rs 11 The groups, together with the carbon atom to which they are attached, form a C 3-5 cycloalkyl, 3- to 6-membered heterocyclic group or oxo, wherein the C 3-5 cycloalkyl or 3- to 6-membered heterocyclic group is optionally substituted with one or two independently selected halo;

[0029] R 12 is alkyl, deuterated alkyl or haloalkyl;

[0030] R 13 and R 14 are each independently hydrogen, alkyl, deuterated alkyl or haloalkyl, or R 13 and R 14 together with the nitrogen atom to which they are attached form a heterocyclic group optionally substituted with one, two or three independently selected Rs 11 substituents;

[0031] R u is a methylene, ethylene or propylene linker optionally substituted with one to six independently selected halo;

[0032] k is 0, 1, 2 or 3;

[0033] t is 1 or 2;

[0034] m is 0, 1 or 2; and

[0035] n is 0, 1, or 2, provided that:

[0036] when Z is NR 2 then m is 1 and n is 1 or 2; and

[0037] when Z is CR 2a R 2b and m is 1, and R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl, then the cycloalkyl is substituted with at least one R 11 substituent.

[0038] There are also provided pharmaceutical compositions formulated for administration by a suitable route and in a suitable manner, which pharmaceutical compositions contain a therapeutically effective concentration of one or more of the compounds provided herein, or a pharmaceutically acceptable salt thereof, and optionally contain at least one pharmaceutical carrier.

[0039] On the other hand, provided herein are methods for treating diseases or disorders mediated by the complement alternative pathway and in particular by complement factor B, which methods include administering to a subject suffering from such a disease or disorder a therapeutically effective amount of one or more of the compounds disclosed herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition disclosed herein. In certain embodiments, the disease or disorder is chronic kidney disease (CKD), diabetic nephropathy, glomerular kidney disease, complement C3 glomerulopathy (C3G), IgA nephropathy (IgAN), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome (aHUS), dense deposit disease (DDD), minimal change disease (MCD), paroxysmal nocturnal hemoglobinuria (PNH), ANCA-associated vasculitis, lupus nephritis, polycystic kidney disease (PKD), autosomal dominant polycystic kidney disease (ADPKD), autosomal recessive polycystic kidney disease (ARPKD), end-stage renal disease (ESRD), acute kidney injury, or polycystic liver disease.

[0040] Also provided herein are combination therapies using one or more of the compounds or compositions provided herein in combination with other agents for treating the diseases and disorders described herein. These and other aspects of the subject matter described herein will become apparent with reference to the following detailed description and the drawings.

[0041] Also provided herein are the following items:

[0042] 1. A compound of formula (I):

[0043]

[0044] or a pharmaceutically acceptable salt thereof, wherein:

[0045] R 1 is hydrogen, fluorine, chlorine or methyl;

[0046] X is N or CH;

[0047] Z is NR 2 or CR 2a R 2b ;

[0048] R 2 is alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 、-C(O)NR 13 R 14 or -S(O) t R 12, wherein the alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group or heteroaryl is optionally substituted by one, two or three independently selected R 11 substituents;

[0049] R 2a is haloalkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 , wherein the -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, aryl or heteroaryl is optionally substituted by one, two or three independently selected R 11 substituents;

[0050] And R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl, or halo C 1-3 alkyl;

[0051] Or R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl or heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally substituted by one, two or three independently selected R 11 substituents;

[0052] R 3 is halogenated, cyano, C 1-3 alkyl, or halo C 1-3 alkyl;

[0053] R 4 is hydrogen, halogenated, cyano, C 1-3 alkyl or halo C 1-3 alkyl;

[0054] R 5 is halogenated, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy or C 1-3 alkoxy;

[0055] R 6 is halogenated, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo C1-3 Alkyl, C 1-3 Alkoxy or halogenated C 1-3 Alkoxy;

[0056] R 7 is a haloalkyl group, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl, wherein the haloalkyl, deuterated alkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 replace;

[0057] R 8 is hydrogen, deuterium, alkyl, deuterated alkyl or haloalkyl;

[0058] R 9 is a haloalkyl group, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 、-C(O)NR 13 R 14 、-S(O) t R 12 , or -S(O) t NR 13 R 14 , wherein the -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 replace; or

[0059] R 8 and R 9 Together with the nitrogen atom to which they are attached, they form a heterocyclic or heteroaryl group, wherein the heterocyclic or heteroaryl group is optionally substituted by one, two or three independently selected R 11 replace;

[0060] Each R 11 are independently halo, cyano, oxo, C 1-3 Alkyl, deuterated C 1-3 Alkyl, halogenated C 1-3 Alkyl, cyano C 1-3 Alkyl, hydroxyl C 1-3 Alkyl, C 1-3 Alkoxy C 1-3 Alkyl, halogenated C 1-3 Alkoxy C 1-3 Alkyl, hydroxyl, C 1-3 Alkoxy, halogenated C1-3 alkoxy, C 1-3 alkylthio, halo-C 1-3 alkylthio, C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl, or halo-C 1-3 alkylsulfinyl; or

[0061] two R 11 groups together with the carbon atom to which they are attached form a C 3-5 cycloalkyl, 3- to 6-membered heterocyclic group or oxo, wherein the C 3-5 cycloalkyl or 3- to 6-membered heterocyclic group is optionally substituted by one or two independently selected halogens;

[0062] R 12 is alkyl, deuterated alkyl or haloalkyl;

[0063] R 13 and R 14 are each independently hydrogen, alkyl, deuterated alkyl or haloalkyl, or R 13 and R 14 together with the nitrogen atom to which they are attached form a heterocyclic group optionally substituted by one, two or three independently selected R 11 substituents;

[0064] R u is a methylene, ethylene or propylene linker optionally substituted by one to six independently selected halogens;

[0065] k is 0, 1, 2 or 3;

[0066] t is 1 or 2;

[0067] m is 0, 1 or 2; and

[0068] n is 0, 1, or 2, provided that:

[0069] when Z is NR 2 then m is 1 and n is 1 or 2; and

[0070] when Z is CR 2a R 2b and R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl and m is 1, then the cycloalkyl is substituted by at least one R 11 substituent.

[0071] 2. The compound according to item 1, wherein m is 0 or 1; n is 0, 1 or 2, provided that when Z is NR 2 then m is 1 and n is 1 or 2.

[0072] 3. The compound according to item 1, wherein m is 0 or 1; and n is 0 or 1, provided that when Z is NR 2 , m is 1 and n is 1.

[0073] 4. The compound according to any one of items 1 to 3, said compound having the formula (II):

[0074]

[0075] or a pharmaceutically acceptable salt thereof, wherein m is 0 or 1; n is 0 or 1; and X, R 1 , R 2a , R 2b , R 3 , R 4 , R 5 , R 6 and k are as described in item 1.

[0076] 5. The compound according to any one of items 1 to 4, said compound having the formula (III):

[0077]

[0078] or a pharmaceutically acceptable salt thereof, wherein X, R 1 , R 2a , R 2b , R 3 , R 4 , R 5 , R 6 and k are as described in item 1.

[0079] 6. The compound according to any one of items 1 to 4, said compound having the formula (IV):

[0080]

[0081] or a pharmaceutically acceptable salt thereof, wherein m is 0 or 1; n is 0 or 1; and X, R 1 , R 2a , R 2b , R 3 , R 4 , R 5 , R 6 , k, m and n are as described in item 1.

[0082] 7. The compound according to any one of items 1 to 4, said compound having the formula (IVa):

[0083]

[0084] or a pharmaceutically acceptable salt thereof.

[0085] 8. A compound according to any one of items 1 to 5, said compound having formula (V):

[0086]

[0087] or a pharmaceutically acceptable salt thereof, wherein X, R 1 , R 2a , R 2b , R 3 , R 4 , R 5 , R 6 and k are as described in item 1.

[0088] 9. A compound according to any one of items 1 to 8, wherein R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl group substituted with one, two or three independently selected R 11 groups, or form a heterocyclic group optionally substituted with one, two or three independently selected R 11 groups.

[0089] 10. A compound according to any one of items 1 to 8, wherein R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl group substituted with one, two or three independently selected R 11 groups.

[0090] 11. A compound according to any one of items 1 to 8, wherein R 2b is hydrogen or methyl.

[0091] 12. A compound according to any one of items 1 to 4, said compound having formula (VI):

[0092]

[0093] or a pharmaceutically acceptable salt thereof, wherein X, R 1 , R 3 , R 4 , R 5 , R 6 , R 8 , R 9 and k are as described in items 1 to 4 respectively.

[0094] 13. A compound according to any one of items 1 to 4 or 12, said compound having formula (VIa):

[0095]

[0096] or a pharmaceutically acceptable salt thereof, wherein j is 1 or 2 and X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 , k, m and n are as described in items 1 to 4 respectively.

[0097] 14. A compound according to any one of items 1 to 4, said compound having formula (VII):

[0098]

[0099] or a pharmaceutically acceptable salt thereof, wherein q is 0, 1, 2 or 3 and X, R 1 , R 3 , R 4 , R 5 , R 6 and k are as described in items 1 to 4 respectively.

[0100] 15. A compound according to any one of items 1 to 4, said compound having formula (VIII):

[0101]

[0102] or a pharmaceutically acceptable salt thereof, wherein ring A is cycloalkyl, heterocyclic, aryl or heteroaryl; q is 0, 1, 2 or 3 and X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 and k are as described in items 1 to 4 respectively.

[0103] 16. A compound according to item 15, wherein ring A is heterocyclic or heteroaryl.

[0104] 17. A compound according to item 15 or 16, wherein ring A is heteroaryl.

[0105] 18. A compound according to any one of items 15 to 17, wherein ring A is pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazolyl, imidazolyl, thiazolyl, or pyrazolyl.

[0106] 19. A compound according to any one of items 15 to 18, wherein ring A is pyridyl or pyrazolyl; and q is 0, 1, 2 or 3.

[0107] 20. A compound according to any one of items 1 to 19, wherein each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy; or two R 11 groups together with the carbon atom to which they are attached form C 3-5 cycloalkyl or oxo.

[0108] 21. The compound according to any one of items 1 to 20, wherein each R 11 is independently fluorine, cyano, oxo, hydroxy, methyl, -CHF 2 , -CF 3 or -OCHF 2 , or two R 11 groups together with the carbon atom to which they are attached form cyclobutyl or oxo.

[0109] 22. The compound according to any one of items 1 to 19, wherein each R 11 is independently halo, cyano, halo C 1-3 alkyl, halo C 1-3 alkoxy or C 1-3 alkylsulfonyl; or two R 11 groups together with the carbon atom to which they are attached form C 3-5 cycloalkyl.

[0110] 23. The compound according to any one of items 1 to 19 or 22, wherein each R 11 is independently fluorine, cyano, -CF 3 , -CHF 2 , -OCF 3 or -S(O) 2 CH 3 , or two R 11 groups together with the carbon atom to which they are attached form cyclopropyl.

[0111] 24. The compound according to any one of items 1 to 20, wherein each R 11 is independently halo, cyano, halo C 1-3 alkyl, or hydroxy.

[0112] 25. The compound according to any one of items 1 to 20 or 22, wherein each R 11 is independently halo, cyano or halo C 1-3 alkyl.

[0113] 26. The compound according to any one of items 1 to 20, 22, or 25, wherein each R 11Independently is F, Cl, Br, cyano, -CHF 2 or -CF 3 .

[0114] 27. The compound according to item 1, wherein the compound is selected from the group consisting of: the compounds in Table A or a pharmaceutically acceptable salt of any of the foregoing compounds.

[0115] 28. A pharmaceutical composition comprising the compound according to any one of items 1 to 27, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0116] 29. A method of treating a disease or disorder associated with complement factor B (CFB), the method comprising administering to a subject suffering from such a disease or disorder a therapeutically effective amount of the compound according to any one of items 1 to 27, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to item 28.

[0117] 30. A method of treating or preventing a disease or disorder selected from the following: autoimmune diseases or disorders, inflammatory diseases or disorders, metabolic diseases or disorders, neurological diseases or disorders, pulmonary diseases, respiratory diseases or disorders, ophthalmic diseases, cardiovascular diseases, and kidney diseases, the method comprising administering to a subject suffering from such a disease or disorder a therapeutically effective amount of the compound according to any one of items 1 to 27, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to item 28.

[0118] 31. A method of treating or preventing a disease or disorder selected from the following: multiple sclerosis, Guillain-Barré syndrome, traumatic brain injury, Parkinson's disease, age-related macular degeneration, geographic atrophy, diabetic retinopathy, uveitis, retinitis pigmentosa, macular edema, Behçet's uveitis, multifocal choroiditis, Vogt-Koyanagi-Harada syndrome, intermediate uveitis, birdshot retinochoroidopathy, sympathetic ophthalmia, ocular cicatricial pemphigoid, pemphigus ophthalmicus, non-arteritic ischemic optic neuropathy, postoperative inflammation, retinal vein occlusion, hemodialysis complications, hyperacute allograft rejection, xenograft rejection, interleukin-2-induced toxicity during IL-2 therapy, inflammatory disorders, inflammation in autoimmune diseases, Crohn's disease, adult respiratory distress syndrome, myocarditis, conditions after ischemic reperfusion, myocardial infarction, stroke, balloon angioplasty, post-pump syndrome in cardiopulmonary bypass or renal bypass, atherosclerosis, hemodialysis, renal ischemia, mesenteric artery reperfusion after aortic reconstruction, infectious diseases or sepsis, immune complex disorders and autoimmune diseases, rheumatoid arthritis, systemic lupus erythematosus (SLE), SLE nephritis, proliferative nephritis, liver fibrosis, hemolytic anemia, myasthenia gravis, tissue regeneration, nerve regeneration, dyspnea, hemoptysis, ARDS, asthma, chronic obstructive pulmonary disease (COPD), emphysema, pulmonary embolism and infarction, pneumonia, fibrotic dust disease, pulmonary fibrosis, asthma, allergy, bronchoconstriction, hypersensitivity pneumonitis, parasitic diseases, Goodpasture's syndrome, pulmonary vasculitis, pauci-immune vasculitis, immune complex-related inflammation, antiphospholipid syndrome, glomerulonephritis, obesity and metabolic syndrome, the method comprising administering to a subject suffering from such a disease or disorder a therapeutically effective amount of a compound as described in any one of items 1 to 27, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in item 28.

[0119] 32. A method of treating or preventing a disease or disorder selected from the following: kidney diseases, chronic kidney diseases, diabetic nephropathy, glomerular kidney diseases, complement C3 glomerulopathy (C3G), IgA nephropathy (IgAN), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome (aHUS), dense deposit disease (DDD), minimal change disease (MCD), paroxysmal nocturnal hemoglobinuria (PNH), ANCA-associated vasculitis, lupus nephritis and polycystic kidney disease (PKD), the method comprising administering to a subject suffering from such a disease or disorder a therapeutically effective amount of a compound as described in any one of items 1 to 27, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in item 28. BRIEF DESCRIPTION OF THE DRAWINGS

[0120] Figure 1Depicts the effect of therapeutic administration of compound A of formula I (oral dose of 30 mg / kg / day, QD) against the urinary protein to creatinine ratio (UPCR) in a rat model of membranous nephropathy challenged with Fx1a (passive Heymann nephritis model or PHN).

[0121] Figure 2A Depicts at Figure 1 renal C3d deposition measured on day 14 of the same PHN rat study shown.

[0122] Figure 2B Depicts at Figure 1 the urinary complement factor Ba fragment measured on day 14 of the same PHN rat study shown.

[0123] Figure 3A Depicts at Figure 1 the urinary full-length complement factor B measured on day 14 of the PHN rat study of

[0124] Figure 3B Depicts at Figure 1 the urinary neutrophil gelatinase-associated lipocalin (NGAL-1) on day 14 of the same PHN rat study shown.

[0125] Figure 4 Depicts at Figure 1 the urinary kidney injury molecule 1 (KIM-1) on day 14 of the PHN rat study of DETAILED DESCRIPTION

[0126] A. Definitions

[0127] Unless otherwise defined, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art. If a term in this document has more than one definition, the definition in this section shall prevail unless otherwise stated.

[0128] As used herein, when used to modify a numerical value, the term "about" encompasses a numerical uncertainty range of 0% to 10% of the numerical value.

[0129] As used herein and unless otherwise indicated, the term "alkyl" refers to a saturated hydrocarbon chain that can be straight-chain or branched-chain, contains the specified number of carbon atoms or otherwise has one to ten, one to eight, one to six, one to four, or one to three carbon atoms, and is attached to the remainder of the molecule by a single bond. In certain embodiments, the hydrocarbon chain is optionally deuterated. For example, C 1 -C 3 alkyl indicates that the group can have 1 to 3 (inclusive) carbon atoms; C 1 -C 6Alkyl means that the group may have 1 to 6 (inclusive) carbon atoms. In some embodiments, alkyl is a C representing a straight-chain or branched-chain saturated monovalent hydrocarbon group having 1 to 3 carbon atoms 1 -C 3 alkyl. In some embodiments, alkyl is a C representing a straight-chain or branched-chain saturated monovalent hydrocarbon group having 1 to 6 carbon atoms 1 -C 6 alkyl. Examples of alkyl include but are not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and tert-butyl.

[0130] As used herein and unless otherwise indicated, the term "alkoxy" refers to a group of the formula -OR, where R is an alkyl as defined herein. An alkoxy can be, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, n-pentyloxy, 2-pentyloxy, 3-pentyloxy, or hexyloxy. Similarly, the term "alkylthio" refers to a group of the formula -S-(alkyl). The terms "haloalkoxy" and "haloalkylthio" refer to -O-(haloalkyl) and -S-(haloalkyl), respectively.

[0131] As used herein and unless otherwise indicated, the term "alkylsulfinyl" refers to a group of the formula -S(O)R, where R is an alkyl as defined herein.

[0132] As used herein and unless otherwise indicated, the term "alkylsulfonyl" refers to a group of the formula -S(O) 2 R, where R is an alkyl as defined herein.

[0133] As used herein and unless otherwise indicated, the term "aryl" is intended to mean any stable monocyclic or bicyclic carbocyclic ring having up to 6 members in each ring, where at least one ring is aromatic. Examples of aryl include phenyl, naphthyl, tetrahydronaphthyl, indanyl, or biphenyl.

[0134] As used herein and unless otherwise indicated, the term "azolyl" refers to a 5-membered heteroaryl ring system containing at least one nitrogen atom. Examples of azolyl include pyrrole, imidazole, pyrazole, thiazole, isothiazole, oxazole, isoxazole, thiadiazole, and oxadiazole.

[0135] As used herein and unless otherwise indicated, the term "cycloalkyl" refers to a monocyclic, bicyclic, tricyclic, or other polycyclic hydrocarbon group having a specified number of ring carbon atoms or otherwise having from three to ten carbon atoms and being fully saturated or partially unsaturated (i.e., non-aromatic). The polycyclic cycloalkyl can be a fused, bridged, and / or spiro ring system. Cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, norbornyl, bicyclo[1.1.1]pentane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, spiro[3.3]heptane, and partially unsaturated hydrocarbon rings such as cyclobutene, cyclopentene, and cyclohexene. In some embodiments, the cycloalkyl is a monocyclic C 3 -C 8 cycloalkyl.

[0136] As used herein and unless otherwise indicated, the term "deuterium" refers to the heavy isotope of hydrogen represented by the symbol D or 2 H. As used herein, when a particular position in a compound is designated as "deuterated", e.g., having deuterium or having the prefix "deutero-", it is understood that the compound is an isotope-enriched compound and that the deuterium present at that position in the compound is significantly greater than its natural abundance of 0.0156%, e.g., at least 90% deuterium is present at the designated position.

[0137] As used herein and unless otherwise indicated, the term "deuterated alkyl" refers to an alkyl group in which one or more hydrogen atoms of the alkyl are replaced by deuterium, the abundance of which is significantly greater than its natural abundance, e.g., at least 90% deuterium is present at the designated position.

[0138] As used herein, the term "enantiomerically pure" or "pure enantiomer" means that a compound contains greater than 75% by weight, greater than 80% by weight, greater than 85% by weight, greater than 90% by weight, greater than 91% by weight, greater than 92% by weight, greater than 93% by weight, greater than 94% by weight, greater than 95% by weight, greater than 96% by weight, greater than 97% by weight, greater than 98% by weight, greater than 98.5% by weight, greater than 99% by weight, greater than 99.2% by weight, greater than 99.5% by weight, greater than 99.6% by weight, greater than 99.7% by weight, greater than 99.8% by weight, or greater than 99.9% by weight of a single enantiomer, excluding its corresponding non-overlapping mirror image. Some embodiments described herein provide compounds that exist as pure enantiomers. Some embodiments also provide pharmaceutical compositions comprising the enantiomerically pure compounds described herein.

[0139] As used herein and unless otherwise indicated, the term "halo", "halogen", or "halide" refers to a monovalent fluorine, chlorine, bromine, or iodine group.

[0140] As used herein and unless otherwise indicated, the term "haloalkyl" refers to a monovalent alkyl group in which at least one hydrogen atom is replaced by a halogen. In some embodiments, more than one hydrogen atom (e.g., 2, 3, 4, 5, or 6) is replaced by independently selected halogens. In these embodiments, the hydrogen atoms may each be replaced by the same halogen (e.g., fluorine), or the hydrogen atoms may be replaced by a combination of different halogens (e.g., fluorine and chlorine). "Haloalkyl" also includes an alkyl moiety in which all hydrogens have been replaced by halogens (sometimes referred to herein as perhaloalkyl, e.g., perfluoroalkyl, such as trifluoromethyl).

[0141] As used herein and unless otherwise indicated, the term "cyano" refers to the –CN group.

[0142] As used herein and unless otherwise indicated, the term "cyanoalkyl" refers to an alkyl group in which one hydrogen atom of the alkyl is replaced by a cyano group, as defined herein.

[0143] As used herein and unless otherwise indicated, the terms "heterocycle", "heterocyclic group", or "heterocyclic" denote a stable 3-, 4-, 5-, 6-, or 7-membered monocyclic heterocyclic system, a stable 4-, 5-, 6-, or 7-membered monocyclic heterocyclic system, or a stable 6-, 7-, 8-, 9-, 10-, 11-, or 12-membered bicyclic heterocyclic system, which contains at least one non-aromatic (i.e., saturated or partially unsaturated) ring composed of carbon atoms and one to four, preferably at most three, heteroatoms selected from the group consisting of N, O, and S, wherein the nitrogen and sulfur atoms may optionally be oxidized to N-oxides, sulfoxides, or sulfones, and wherein the nitrogen atoms may optionally be quaternized. The heterocycle may be bonded through a ring carbon atom, or, if available, through a ring nitrogen atom. The bicyclic heterocyclic system may be a fused, bridged, and / or spiro bicyclic system. In some embodiments, the heterocyclic group is a monocyclic ring having 4 to 7, preferably 4 to 6, ring atoms, wherein 1 or 2 are heteroatoms independently selected from the group consisting of N, O, and S. In some embodiments, the heterocyclic group is a monocyclic ring having 4 to 7, preferably 4 to 6, ring atoms, wherein at least 1 heteroatom is N and the second heteroatom is N, O, or S. In certain embodiments, the heterocyclic group is azetidine, pyrrolidine, piperidine, piperazine, morpholine, or thiomorpholine. In some embodiments, the heterocyclic group is bicyclic, and in such cases, the first ring (the point of attachment to the remainder of the molecule) is a saturated or partially saturated monocyclic heterocyclic group as described herein, and the second ring may be an aromatic or non-aromatic ring composed of carbon atoms and one to four, preferably at most three, heteroatoms independently selected from the group consisting of N, O, and S, or the second ring may be a benzene ring, or a "cycloalkyl", or a "cycloalkenyl", as defined herein. Examples of such heterocyclic groups include, but are not limited to, azetidine, chroman, dihydrofuran, dihydropyran, dioxane, dioxolane, hexahydroaza Imidazolidine, imidazoline, indoline, isochroman, isoindoline, isothiazoline, isothiazolidine, isoxazoline, isoxazolidine, morpholine, oxazoline, oxazolidine, oxetane, piperazine, piperidine, dihydropyridine, tetrahydropyridine, dihydropyridazine, pyran, pyrazolidine, pyrazoline, pyrrolidine, pyrroline, tetrahydrofuran, tetrahydropyran, thiomorpholine, tetrahydrothiophene, thiazoline, thiazolidine, thiomorpholine, thietane, thiolane, sulfolane, 1,3-dioxolane, 1,3-oxazolidine, 1,3-thiazolidine, tetrahydrothiopyran, tetrahydrotriazine, 1,3-dioxane, 1,4-dioxane, hexahydrotriazine, tetrahydro-oxazine, tetrahydropyrimidine, perhydroazepine Perhydro-1,4-diazepine Perhydro-1,4-oxazepine 7-azabicyclo[2.2.1]heptane, 3-azabicyclo[3.2.0]heptane, 7-azabicyclo[4.1.0]heptane, 2,5-diazabicyclo[2.2.1]heptane, 2-oxa-5-azabicyclo[2.2.1]heptane, tropane, 2-oxa-6-azaspiro[3.3]heptane, dihydrobenzofuran, dihydrobenzimidazolyl, dihydrobenzoxazole, and dihydrobenzothiazolyl, and their N-oxides or sulfones or sulfoxides.

[0144] As used herein and unless otherwise indicated, the term "heteroaryl" refers to a stable 5-, 6- or 7-membered monocyclic system, or a stable 9- or 10-membered fused bicyclic system, which contains at least one aromatic ring composed of carbon atoms and one to four, preferably at most three, heteroatoms selected from the group consisting of N, O and S, wherein the nitrogen and sulfur heteroatoms or carbon atoms of the heteroaryl may optionally be oxidized, and the nitrogen heteroatoms may optionally be quaternized. In the case where "heteroaryl" is a bicyclic group, the first ring (the point of attachment to the rest of the molecule) is a monocyclic heteroaryl group as described herein, and the second ring need not be aromatic and need not contain heteroatoms. Thus, bicyclic "heteroaryl" includes, for example, a stable 5- or 6-membered monocyclic aromatic ring (composed of carbon atoms and one to four, preferably at most three heteroatoms, as just defined above) fused to a benzene ring, or a second monocyclic "heteroaryl", or "heterocyclic", "cycloalkyl", or "cycloalkenyl" (as defined above). Examples of heteroaryl groups include, but are not limited to, benzimidazole, benzopyrazole, benzisothiazole, benzisoxazole, benzofuran, isobenzofuran, benzothiazole, benzothiophene, benzotriazole, benzoxazole, furan, furazan, imidazole, indazole, indole, indolizine, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, phthalazine, pteridine, purine, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, pyridone, quinazoline, quinoline, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazine, triazole, benzimidazole, benzothiadiazole, isoindole, pyrrolopyridine, imidazopyridine such as imidazo[1,2-a]pyridine, pyrazolopyridine, pyrrolopyrimidine and their N-oxides.

[0145] The term "oxo" refers to a carbonyl (C=O) group. When a carbon atom is represented as being substituted with an oxo group, it is understood that two hydrogen atoms will be removed from the carbon atom and replaced with =O. Similarly, when a carbon atom is represented as being substituted with two groups and may be substituted with an "oxo" group, the two substituents may together form an oxo group.

[0146] As used herein and unless otherwise indicated, the term "subject" refers to any human or veterinary subject, including mammals such as mice, rats, cows, sheep, pigs, rabbits, goats, horses, monkeys, dogs, cats and humans, including neonates, infants, juveniles, adolescents, adults or geriatric patients.

[0147] The term "thiol" refers to a group having the formula -SH.

[0148] The term "therapeutically effective amount" is an amount sufficient to achieve a beneficial or desired clinical outcome. A therapeutically effective amount may be administered in one or more administrations. A therapeutically effective amount is sufficient to alleviate, ameliorate, stabilize, reverse, slow or delay the progression of a disease state.

[0149] Unless otherwise specified or clearly described, it should be understood that the substitutions present can occur on any atom of an alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl group, provided that the valency permits.

[0150] Unless otherwise clearly specified, when a compound can exist in alternative tautomeric or stereoisomeric forms, all alternative isomers are intended to be covered within the scope of the claimed subject matter. For example, unless otherwise clearly specified, the compounds provided herein can be stereoisomerically pure (e.g., a single enantiomer or diastereomer), or a mixture of stereoisomers, such as a racemic or diastereomeric mixture.

[0151] The terms "treating", "treat" or "treatment" generally refer to controlling, alleviating, ameliorating a disorder, slowing its progression and / or eliminating the disorder once the specified disorder has been established. In addition to its ordinary meaning, the term "preventing", "prevent" or "prevention" also refers to delaying the onset of a specified disorder, or reducing the risk of occurrence of the disorder or recurrence of the processes and / or symptoms of the disorder that can lead to the disorder.

[0152] In the description herein, if there is any discrepancy between the chemical name and the chemical structure, the chemical structure shall prevail.

[0153] B. Compounds

[0154] In certain embodiments, the present invention provides compounds of formula (I):

[0155]

[0156] or a pharmaceutically acceptable salt thereof, wherein:

[0157] R 1 is hydrogen, fluorine, chlorine or methyl;

[0158] X is N or CH;

[0159] Z is NR 2 or CR 2a R 2b ;

[0160] R 2 is alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclic, cycloalkyl, heterocyclic, heteroaryl, -C(O)R 12 、-C(O)NR 13 R 14 or -S(O) t R12 , wherein the alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 substituents;

[0161] R 2a is -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 , wherein the -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted by one, two or three independently selected R 11 substituents;

[0162] and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl, or halo C 1-3 alkyl;

[0163] Or R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl or heterocyclyl, wherein the cycloalkyl or heterocyclyl is optionally substituted by one, two or three independently selected R 11 substituents;

[0164] R 3 is halo, cyano, C 1-3 alkyl, or halo C 1-3 alkyl;

[0165] R 4 is hydrogen, halo, cyano, C 1-3 alkyl or halo C 1-3 alkyl;

[0166] R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy or C 1-3 alkoxy;

[0167] R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo C1-3 Alkyl, C 1-3 Alkoxy or halogenated C 1-3 Alkoxy;

[0168] R 7 is a halogenated alkyl, a deuterated alkyl, -R u -cycloalkyl, -R u -heterocyclic, cycloalkyl, heterocyclic, or heteroaryl, wherein the haloalkyl, deuterated alkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 replace;

[0169] R 8 is hydrogen, deuterium, alkyl, deuterated alkyl or haloalkyl;

[0170] R 9 is a haloalkyl group, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 、-C(O)NR 13 R 14 、-S(O) t R 12 , or -S(O) t NR 13 R 14 , where the -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 replace; or

[0171] R 8 and R 9 Together with the nitrogen atom to which they are attached, they form a heterocyclic or heteroaryl group, wherein the heterocyclic or heteroaryl group is optionally substituted by one, two or three independently selected R 11 replace;

[0172] Each R 11 are independently halo, cyano, oxo, C 1-3 Alkyl, deuterated C 1-3 Alkyl, halogenated C 1-3 Alkyl, cyano C 1-3 Alkyl, hydroxyl C 1-3 Alkyl, C 1-3 Alkoxy C 1-3 Alkyl, halogenated C 1-3 Alkoxy C 1-3 Alkyl, hydroxyl, C 1-3 Alkoxy, halogenated C1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl, or halo C 1-3 alkylsulfinyl; or two R 11 groups together with the carbon atom to which they are attached form a C 3-5 cycloalkyl, 3- to 6-membered heterocyclic group or oxo, wherein the C 3-5 cycloalkyl or 3- to 6-membered heterocyclic group is optionally substituted by one or two independently selected halogens;

[0173] R 12 is alkyl, deuterated alkyl or haloalkyl;

[0174] R 13 and R 14 are each independently hydrogen, alkyl, deuterated alkyl or haloalkyl, or R 13 and R 14 together with the nitrogen atom to which they are attached form a heterocyclic group optionally substituted by one, two or three independently selected R 11 substituents;

[0175] R u is a methylene, ethylene or propylene linker optionally substituted by one to six independently selected halogens;

[0176] k is 0, 1, 2 or 3;

[0177] t is 1 or 2;

[0178] m is 0, 1 or 2; and

[0179] n is 0, 1, or 2, provided that:

[0180] when Z is NR 2 then m is 1 and n is 1 or 2; and

[0181] when Z is CR 2a R 2b and R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl and m is 1, then the cycloalkyl is substituted by at least one R 11 substituent.

[0182] In certain embodiments, provided herein are compounds of formula (I):

[0183]

[0184] or a pharmaceutically acceptable salt thereof, wherein:

[0185] R 1 is hydrogen, fluorine, chlorine or methyl;

[0186] X is N or CH;

[0187] Z is NR 2 or CR 2a R 2b ;

[0188] R 2 is alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 or -S(O) t R 12 wherein the alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 substituents;

[0189] R 2a is -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 -SR 7 or -NR 8 R 9 wherein the -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted by one, two or three independently selected R 11 substituents;

[0190] and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl, or halo C 1-3 alkyl;

[0191] Or R 2a and R 2b together with the carbon atom to which they are attached form cycloalkyl or heterocyclyl, wherein the cycloalkyl or heterocyclyl is optionally substituted by one, two or three independently selected R 11 substituents;

[0192] R 3 is halo, cyano, C1-3 Alkyl or halogenated C 1-3 alkyl;

[0193] R 4 is hydrogen, halo, cyano, C 1-3 Alkyl or halogenated C 1-3 alkyl;

[0194] R 5 Is halogenated, C 1-3 Alkyl, C 3-5 Cycloalkyl, halogenated C 1-3 Alkyl, halogenated C 1-3 Alkoxy or C 1-3 Alkoxy;

[0195] R 6 Is halogenated, cyano, C 1-3 Alkyl, C 3-5 Cycloalkyl, halogenated C 1-3 Alkyl, C 1-3 Alkoxy or halogenated C 1-3 Alkoxy;

[0196] R 7 is a halogenated alkyl, a deuterated alkyl, -R u -cycloalkyl, -R u -heterocyclic, cycloalkyl, heterocyclic, or heteroaryl, wherein the haloalkyl, deuterated alkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 replace;

[0197] R 8 is hydrogen, deuterium, alkyl, deuterated alkyl or haloalkyl;

[0198] R 9 is a haloalkyl group, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 、-C(O)NR 13 R 14 、-S(O) t R 12 , or -S(O) t NR 13 R 14 , where the -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 replace; or

[0199] R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclic group or heteroaryl group, wherein the heterocyclic group or heteroaryl group is optionally substituted by one, two or three independently selected R 11 substituents;

[0200] Each R 11 independently is halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, halo C 1-3 alkoxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl, or halo C 1-3 alkylsulfinyl;

[0201] R 12 is alkyl, deuterated alkyl or haloalkyl;

[0202] R 13 and R 14 each independently is hydrogen, alkyl, deuterated alkyl or haloalkyl, or R 13 and R 14 together with the nitrogen atom to which they are attached form a heterocyclic group optionally substituted by one, two or three independently selected R 11 substituents;

[0203] R u is a methylene, ethylene or propylene linker optionally substituted by one to six independently selected halo;

[0204] k is 0, 1, 2 or 3;

[0205] t is 1 or 2;

[0206] m is 0, 1 or 2; and

[0207] n is 0, 1, or 2, provided that:

[0208] when Z is NR 2 then m is 1 and n is 1 or 2; and

[0209] when Z is CR 2a R2b and R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl group and m is 1, then the cycloalkyl group is substituted with at least one R 11 substituent.

[0210] In certain embodiments, provided herein are compounds of formula (I):

[0211]

[0212] or a pharmaceutically acceptable salt thereof, wherein:

[0213] R 1 is hydrogen, fluorine, chlorine or methyl;

[0214] X is N or CH;

[0215] Z is NR 2 or CR 2a R 2b ;

[0216] R 2 is alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 or -S(O) t R 12 wherein the alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl is optionally substituted with one, two or three independently selected R 11 substituents;

[0217] R 2a is -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 -SR 7 or -NR 8 R 9 wherein the -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one, two or three independently selected R 11 substituents;

[0218] and R 2bis hydrogen, deuterium, a halogen, C 1-3 alkyl, deuterated C 1-3 alkyl, or halogenated C 1-3 alkyl;

[0219] or R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl group substituted by one, two or three independently selected R 11 groups, or form a heterocyclic group optionally substituted by one, two or three independently selected R 11 groups.

[0220] R 3 is halogenated, cyano, C 1-3 alkyl, or halogenated C 1-3 alkyl;

[0221] R 4 is hydrogen, halogenated, cyano, C 1-3 alkyl or halogenated C 1-3 alkyl;

[0222] R 5 is halogenated, C 1-3 alkyl, C 3-5 cycloalkyl, halogenated C 1-3 alkyl, halogenated C 1-3 alkoxy or C 1-3 alkoxy;

[0223] R 6 is halogenated, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halogenated C 1-3 alkyl, C 1-3 alkoxy or halogenated C 1-3 alkoxy;

[0224] R 7 is halogenated alkyl, deuterated alkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, or heteroaryl, wherein the halogenated alkyl, deuterated alkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group or heteroaryl is optionally substituted by one, two or three independently selected R 11 groups;

[0225] R 8 is hydrogen, deuterium, alkyl, deuterated alkyl or halogenated alkyl;

[0226] R 9 is halogenated alkyl, -R u -cycloalkyl, -R u-heterocyclic group, cycloalkyl group, heterocyclic group, heteroaryl group, -C(O)R 12 、-C(O)NR 13 R 14 、-S(O) t R 12 、or -S(O) t NR 13 R 14 wherein the -R u -cycloalkyl group, -R u -heterocyclic group, cycloalkyl group, heterocyclic group or heteroaryl group is optionally substituted by one, two or three independently selected R 11 substituents; or

[0227] R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclic group or heteroaryl group, wherein the heterocyclic group or heteroaryl group is optionally substituted by one, two or three independently selected R 11 substituents;

[0228] Each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, halo C 1-3 alkoxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl, or halo C 1-3 alkylsulfinyl; or two R 11 groups together with the carbon atom to which they are attached form a C 3-5 cycloalkyl group, a 3- to 6-membered heterocyclic group or oxo, wherein the C 3-5 cycloalkyl group or 3- to 6-membered heterocyclic group is optionally substituted by 1 or 2 independently selected halo;

[0229] R 12 is alkyl, deuterated alkyl or haloalkyl;

[0230] R 13 and R 14 are each independently hydrogen, alkyl, deuterated alkyl or haloalkyl, or R 13 and R 14Together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclic group by one, two or three independently selected R 11 substituents;

[0231] R u is a methylene, ethylene or propylene linker optionally substituted by one to six independently selected halogen atoms;

[0232] k is 0, 1, 2 or 3;

[0233] t is 1 or 2;

[0234] m is 0, 1 or 2; and

[0235] n is 0, 1 or 2, provided that when Z is NR 2 , m is 1 and n is 1 or 2.

[0236] In certain embodiments, the present invention provides compounds of formula (I):

[0237]

[0238] or a pharmaceutically acceptable salt thereof, wherein:

[0239] R 1 is hydrogen, fluorine, chlorine or methyl;

[0240] X is N or CH;

[0241] Z is NR 2 or CR 2a R 2b ;

[0242] R 2 is alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, heteroaryl, -C(O)R 12 、-C(O)NR 13 R 14 or -S(O) t R 12 ,wherein the alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group or heteroaryl is optionally substituted by one, two or three independently selected R 11 substituents;

[0243] R 2a is -R u -cycloalkyl, -R u-heterocyclic group, cycloalkyl group, heterocyclic group, aryl group, heteroaryl group, -OR 7 、-SR 7 or -NR 8 R 9 , wherein the -R u -cycloalkyl group, -R u -heterocyclic group, cycloalkyl group, heterocyclic group, aryl group or heteroaryl group is optionally substituted by one, two or three independently selected R 11 substituents;

[0244] And R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl group, deuterated C 1-3 alkyl group, or halogenated C 1-3 alkyl group;

[0245] Or R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl group substituted by one, two or three independently selected R 11 substituents, or form a heterocyclic group optionally substituted by one, two or three independently selected R 11 substituents.

[0246] R 3 is halogenated, cyano, C 1-3 alkyl group, or halogenated C 1-3 alkyl group;

[0247] R 4 is hydrogen, halogenated, cyano, C 1-3 alkyl group or halogenated C 1-3 alkyl group;

[0248] R 5 is halogenated, C 1-3 alkyl group, C 3-5 cycloalkyl group, halogenated C 1-3 alkyl group, halogenated C 1-3 alkoxy group or C 1-3 alkoxy group;

[0249] R 6 is halogenated, cyano, C 1-3 alkyl group, C 3-5 cycloalkyl group, halogenated C 1-3 alkyl group, C 1-3 alkoxy group or halogenated C 1-3 alkoxy group;

[0250] R 7 is halogenated alkyl group, deuterated alkyl group, -R u -cycloalkyl group, -R u -heterocyclic group, cycloalkyl group, heterocyclic group, or heteroaryl group, wherein the halogenated alkyl group, deuterated alkyl group, -Ru -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group or heteroaryl is optionally substituted by one, two or three independently selected R 11 substituted;

[0251] R 8 is hydrogen, deuterium, alkyl, deuterated alkyl or haloalkyl;

[0252] R 9 is haloalkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 -S(O) t R 12 or -S(O) t NR 13 R 14 wherein the -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group or heteroaryl is optionally substituted by one, two or three independently selected R 11 substituted; or

[0253] R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclic group or heteroaryl, wherein the heterocyclic group or heteroaryl is optionally substituted by one, two or three independently selected R 11 substituted;

[0254] each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, halo C 1-3 alkoxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl, or halo C 1-3 alkylsulfinyl;

[0255] R 12 is alkyl, deuterated alkyl or haloalkyl;

[0256] R 13 and R 14 are each independently hydrogen, alkyl, deuterated alkyl, or haloalkyl, or R 13 and R 14 together with the nitrogen atom to which they are attached form a heterocyclic group optionally substituted with one, two, or three independently selected R 11 substituents;

[0257] R u is a methylene, ethylene, or propylene linker optionally substituted with one to six independently selected halo groups;

[0258] k is 0, 1, 2, or 3;

[0259] t is 1 or 2;

[0260] m is 0, 1, or 2; and

[0261] n is 0, 1, or 2, provided that when Z is NR 2 , m is 1 and n is 1 or 2.

[0262] In certain embodiments, the present disclosure provides compounds of formula (I):

[0263]

[0264] or a pharmaceutically acceptable salt thereof, wherein:

[0265] R 1 is hydrogen, fluorine, chlorine, or methyl;

[0266] X is N or CH;

[0267] Z is NR 2 or CR 2a R 2b ;

[0268] R 2 is alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, heteroaryl, -C(O)R 12 , -C(O)NR 13 R 14 or -S(O) t R 12 wherein the alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, or heteroaryl is optionally substituted with one, two, or three independently selected R11 Substituted;

[0269] R 2a is -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 , wherein the -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, aryl or heteroaryl is optionally substituted by one, two or three independently selected R 11 Substituted;

[0270] And R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl, or halo - C 1-3 alkyl;

[0271] Or R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl substituted by one, two or three independently selected R 11 , or form a heterocyclic group optionally substituted by one, two or three independently selected R 11 .

[0272] R 3 is halo, cyano, C 1-3 alkyl, or halo - C 1-3 alkyl;

[0273] R 4 is hydrogen, halo, cyano, C 1-3 alkyl or halo - C 1-3 alkyl;

[0274] R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo - C 1-3 alkyl, halo - C 1-3 alkoxy or C 1-3 alkoxy;

[0275] R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo - C 1-3 alkyl, C 1-3 alkoxy or halo - C 1-3 alkoxy;

[0276] R7 is a haloalkyl, deuterated alkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, or heteroaryl, wherein the haloalkyl, deuterated alkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group or heteroaryl is optionally substituted by one, two or three independently selected R 11 substituents;

[0277] R 8 is hydrogen, deuterium, alkyl, deuterated alkyl or haloalkyl;

[0278] R 9 is -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 -S(O) t R 12 - or -S(O) t NR 13 R 14 wherein the -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group or heteroaryl is optionally substituted by one, two or three independently selected R 11 substituents; or

[0279] R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclic group or heteroaryl, wherein the heterocyclic group or heteroaryl is optionally substituted by one, two or three independently selected R 11 substituents;

[0280] Each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1--3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, halo C 1-3 alkoxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, C 1-3alkylsulfinyl, or halo-C 1-3 alkylsulfinyl;

[0281] R 12 is alkyl, deuterated alkyl or haloalkyl;

[0282] R 13 and R 14 are each independently hydrogen, alkyl, deuterated alkyl or haloalkyl, or R 13 and R 14 together with the nitrogen atom to which they are attached form a heterocyclic group optionally substituted with one, two or three independently selected R 11 substituents;

[0283] R u is a methylene, ethylene or propylene linker optionally substituted with one to six independently selected halogens;

[0284] k is 0, 1, 2 or 3;

[0285] t is 1 or 2;

[0286] m is 0, 1 or 2; and

[0287] n is 0, 1 or 2, provided that when Z is NR 2 then m is 1 and n is 1 or 2.

[0288] In certain embodiments, provided herein are compounds of formula (I) having formula (II):

[0289]

[0290] or a pharmaceutically acceptable salt thereof.

[0291] In certain embodiments, provided herein are compounds of formula (I) having formula (IIa):

[0292]

[0293] or a pharmaceutically acceptable salt thereof, wherein j is 1 or 2, and wherein, when j is 1, the carbon atom attached to R 11 has a single R 11 substituent, and when j is 2, the carbon atom attached to R 11 has two independently selected R 11 substituents.

[0294] In certain embodiments, provided herein are compounds of formula (I) having formula (IIb):

[0295]

[0296] or a pharmaceutically acceptable salt thereof.

[0297] In certain embodiments, provided herein are compounds of formula (I) having formula (IIc):

[0298] or a pharmaceutically acceptable salt thereof.

[0299] In certain embodiments, provided herein are compounds of formula (I) having formula (IId):

[0300] or a pharmaceutically acceptable salt thereof.

[0301] In certain embodiments, provided herein are compounds of formula (I) having formula (IIe):

[0302] or a pharmaceutically acceptable salt thereof.

[0303] In certain embodiments, provided herein are compounds of formula (I) having formula (IIf):

[0304]

[0305] wherein p is 1 or 2; or a pharmaceutically acceptable salt thereof. In certain embodiments, provided herein are compounds of formula (IIf) wherein each R 11 is independently halo, and the other variables are as described elsewhere herein for formula (I) or (IIf). In certain embodiments, provided herein are compounds of formula (IIf) wherein each R 11 is fluorine, and the other variables are as described elsewhere herein for formula (I) or (IIf).

[0306] In certain embodiments, provided herein are compounds of formula (I) having formula (III):

[0307]

[0308] or a pharmaceutically acceptable salt thereof.

[0309] In certain embodiments, provided herein are compounds of formula (I) having formula (IIIa):

[0310]

[0311] or a pharmaceutically acceptable salt thereof, wherein n is 1 or 2.

[0312] In certain embodiments, provided herein are compounds of formula (I) having formula (IV):

[0313] or a pharmaceutically acceptable salt thereof.

[0314] In certain embodiments, provided herein are compounds of formula (IVa):

[0315]

[0316] or a pharmaceutically acceptable salt thereof.

[0317] In certain embodiments, provided herein are compounds of formula (I) having formula (IVb):

[0318]

[0319] wherein j is 1 or 2; or a pharmaceutically acceptable salt thereof, wherein when j is 1, the carbon atom linked to R 11 has a single R 11 substituent, and when j is 2, the carbon atom linked to R 11 has two independently selected R 11 substituents.

[0320] In certain embodiments, provided herein are compounds of formula (I):

[0321]

[0322] or a pharmaceutically acceptable salt thereof, wherein:

[0323] R 1 is hydrogen, fluorine, chlorine or methyl;

[0324] X is N or CH;

[0325] Z is NR 2 or CR 2a R 2b ;

[0326] R 2 is alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 or -S(O) t R 12 wherein the alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u-A heterocyclic group, cycloalkyl group, heterocyclic group or heteroaryl group is optionally substituted by one, two or three independently selected Rs 11 ;

[0327] R 2a is -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl group, heterocyclic group, aryl group, heteroaryl group, -OR 7 , -SR 7 or -NR 8 R 9 , where the -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl group, heterocyclic group, aryl group or heteroaryl group is optionally substituted by one, two or three independently selected Rs 11 ;

[0328] And R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl, or halogenated C 1-3 alkyl;

[0329] R 3 is halogenated, cyano, C 1-3 alkyl, or halogenated C 1-3 alkyl;

[0330] R 4 is hydrogen, halogenated, cyano, C 1-3 alkyl or halogenated C 1-3 alkyl;

[0331] R 5 is halogenated, C 1-3 alkyl, C 3-5 cycloalkyl, halogenated C 1-3 alkyl, halogenated C 1-3 alkoxy or C 1-3 alkoxy;

[0332] R 6 is halogenated, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halogenated C 1-3 alkyl, C 1-3 alkoxy or halogenated C 1-3 alkoxy;

[0333] R 7 is deuterated alkyl, heterocyclic group, or heteroaryl group, where the halogenated alkyl, deuterated alkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl group, heterocyclic group or heteroaryl group is optionally substituted by one, two or three independently selected Rs 11Substituted;

[0334] R 8 is hydrogen, deuterium, alkyl, deuterated alkyl or haloalkyl;

[0335] R 9 is haloalkyl, -R u -cycloalkyl, -R u -heterocycloalkyl, cycloalkyl, heterocycloalkyl, heteroaryl, -C(O)NR 13 R 14 、-S(O) t R 12 、or -S(O) t NR 13 R 14 wherein the -R u -cycloalkyl, -R u -heterocycloalkyl, cycloalkyl, heterocycloalkyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 ; or

[0336] R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocycloalkyl or heteroaryl, wherein the heterocycloalkyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 ;

[0337] Each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, halo C 1-3 alkoxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl, or halo C 1-3 alkylsulfinyl; or two R 11 groups together with the carbon atom to which they are attached form a C 3-5 cycloalkyl, 3- to 6-membered heterocycloalkyl or oxo, wherein the C 3-5 cycloalkyl or 3- to 6-membered heterocycloalkyl is optionally substituted by 1 or 2 independently selected halo;

[0338] R 12is alkyl, deuterated alkyl or halogenated alkyl;

[0339] R 13 and R 14 are each independently hydrogen, alkyl, deuterated alkyl or haloalkyl, or R 13 and R 14 Together with the nitrogen atom to which they are attached, they form an optionally independently selected R 11 substituted heterocyclic group;

[0340] R u is a methylene, ethylene or propylene linker optionally substituted with one to six independently selected halo;

[0341] k is 0, 1, 2, or 3;

[0342] t is 1 or 2;

[0343] m is 0, 1, or 2; and

[0344] n is 0, 1, or 2, provided that:

[0345] When Z is NR 2 When m is 1 and n is 1 or 2.

[0346] In certain embodiments, provided herein are compounds of Formula (I):

[0347]

[0348] or a pharmaceutically acceptable salt thereof, wherein:

[0349] R 1 is hydrogen, fluorine, chlorine or methyl;

[0350] X is N or CH;

[0351] Z is NR 2 or CR 2a R 2b ;

[0352] R 2 is alkyl, halogenated alkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 、-C(O)NR 13 R 14 or -S(O) t R 12 , wherein the alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -Ru - Heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 substituents;

[0353] R 2a is -R u - cycloalkyl, -R u - heterocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -SR 7 or -NR 8 R 9 wherein the -R u - cycloalkyl, -R u - heterocyclyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted by one, two or three independently selected R 11 substituents;

[0354] and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl, or halo C 1-3 alkyl;

[0355] R 3 is halo, cyano, C 1-3 alkyl, or halo C 1-3 alkyl;

[0356] R 4 is hydrogen, halo, cyano, C 1-3 alkyl or halo C 1-3 alkyl;

[0357] R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy or C 1-3 alkoxy;

[0358] R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, C 1-3 alkoxy or halo C 1-3 alkoxy;

[0359] R 7 is haloalkyl, deuterated alkyl, -R u - cycloalkyl, -R u - heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl, wherein the haloalkyl, deuterated alkyl, -R u - cycloalkyl, -R u- Heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 Substituted;

[0360] R 8 Is hydrogen, deuterium, alkyl, deuterated alkyl or haloalkyl;

[0361] R 9 Is haloalkyl, -R u - Cycloalkyl, -R u - Heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)NR 13 R 14 、-S(O) t R 12 、or -S(O) t NR 13 R 14 wherein the -R u - Cycloalkyl, -R u - Heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 Substituted; or

[0362] R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl, wherein the heterocyclyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 Substituted;

[0363] Each R 11 Independently is halo, cyano, oxo, C 1-3 Alkyl, deuterated C 1-3 Alkyl, halo C 1-3 Alkyl, cyano C 1-3 Alkyl, hydroxy C 1-3 Alkyl, C 1-3 Alkoxy C 1-3 Alkyl, halo C 1-3 Alkoxy C 1-3 Alkyl, hydroxy, C 1-3 Alkoxy, halo C 1-3 Alkoxy, C 1-3 Alkylthio, halo C 1-3 Alkylthio, C 1-3 Alkylsulfonyl, C 1-3 Alkylsulfinyl, or halo C 1-3 Alkylsulfinyl; or two R 11 Groups together with the carbon atom to which they are attached form a C 3-5 Cycloalkyl, 3 - to 6 - membered heterocyclyl or oxo, wherein the C 3-5The cycloalkyl or 3- to 6-membered heterocyclic group is optionally substituted by one or two independently selected halo;

[0364] R 12 is alkyl, deuterated alkyl or haloalkyl;

[0365] R 13 and R 14 are each independently hydrogen, alkyl, deuterated alkyl or haloalkyl, or R 13 and R 14 together with the nitrogen atom to which they are attached form a heterocyclic group optionally substituted by one, two or three independently selected R 11 substituents;

[0366] R u is a methylene, ethylene or propylene linker optionally substituted by one to six independently selected halo;

[0367] k is 0, 1, 2 or 3;

[0368] t is 1 or 2;

[0369] m is 0, 1 or 2; and

[0370] n is 0, 1, or 2, provided that:

[0371] when Z is NR 2 , m is 1 and n is 1 or 2.

[0372] In certain embodiments, compounds of formula (IIa) or (IVb) are provided herein, wherein R 11 is halo, cyano, or halo C 1-3 alkyl; and the other variables are as described elsewhere herein for formula (IIa) and (IVb), respectively. In certain embodiments, compounds of formula (IIa) or (IVb) are provided herein, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 is halo, cyano, or halo C 1-3 alkyl; j is 1 or 2; k is 0; and m and n are both 1.

[0373] In certain embodiments, compounds of formula (IIa) or (IVb) are provided herein, wherein R 11 is fluorine, cyano, or fluoro C 1-3 alkyl; and the other variables are as described elsewhere herein for formula (IIa) and (IVb), respectively. In certain embodiments, compounds of formula (IIa) or (IVb) are provided herein, wherein R 1is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 is fluorine, cyano, or fluorinated C 1-3 alkyl; j is 1 or 2; k is 0; and m and n are both 1.

[0374] In certain embodiments, the present disclosure provides compounds of formula (IIa) or (IVb), wherein R 11 is fluorine, cyano, -CHF 2 or -CF 3 ; and the other variables are as described elsewhere herein for formula (IIa) and (IVb), respectively. In certain embodiments, the present disclosure provides compounds of formula (IIa) or (IVb), wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 is fluorine, cyano, -CHF 2 or -CF 3 ; j is 1 or 2; k is 0; and m and n are both 1.

[0375] In certain embodiments, the present disclosure provides compounds of formula (IIa) or (IVb), wherein R 1 is hydrogen, fluorine, chlorine or methyl;

[0376] X is N or CH;

[0377] R 3 is halogenated, cyano, C 1-3 alkyl, or halogenated C 1-3 alkyl;

[0378] R 4 is hydrogen, halogenated, cyano, C 1-3 alkyl or halogenated C 1-3 alkyl;

[0379] R 5 is halogenated, C 1-3 alkyl, C 3-5 cycloalkyl, halogenated C 1-3 alkyl, halogenated C 1-3 alkoxy or C 1-3 alkoxy;

[0380] R 6 is halogenated, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halogenated C 1-3 alkyl, C1-3 Alkoxy or halo C 1-3 Alkoxy;

[0381] R 11 is halo; j is 2; k is 0 or 1; and m and n are both 1. In certain embodiments, provided herein are compounds of formula (IIa) or (IVb), wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 is halo; j is 2; k is 0; and m and n are both 1.

[0382] In certain embodiments, provided herein are compounds of formula (IIa) or (IVb), wherein R 1 is hydrogen, fluorine, chlorine or methyl;

[0383] X is N or CH;

[0384] R 3 is halo, cyano, C 1-3 alkyl, or halo C 1-3 alkyl;

[0385] R 4 is hydrogen, halo, cyano, C 1-3 alkyl or halo C 1-3 alkyl;

[0386] R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy or C 1-3 alkoxy;

[0387] R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, C 1-3 alkoxy or halo C 1-3 alkoxy;

[0388] R 11 is fluorine; j is 2; k is 0 or 1; and m and n are both 1. In certain embodiments, provided herein are compounds of formula (IIa) or (IVb), wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl;11 Fluorine; j is 2; k is 0; and both m and n are 1.

[0389] In certain embodiments, provided herein are compounds of formula (IIa) or (IVb), wherein R 1 is hydrogen, fluorine, chlorine or methyl;

[0390] X is N or CH;

[0391] R 3 is halo, cyano, C 1-3 alkyl, or halo C 1-3 alkyl;

[0392] R 4 is hydrogen, halo, cyano, C 1-3 alkyl or halo C 1-3 alkyl;

[0393] R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy or C 1-3 alkoxy;

[0394] R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, C 1-3 alkoxy or halo C 1-3 alkoxy;

[0395] R 11 is cyano; j is 1; k is 0 or 1; and both m and n are 1. In certain embodiments, provided herein are compounds of formula (IIa) or (IVb), wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 is cyano; j is 1; k is 0; and both m and n are 1.

[0396] In certain embodiments, provided herein are compounds of formula (IIa) or (IVb), wherein R 1 is hydrogen, fluorine, chlorine or methyl;

[0397] X is N or CH;

[0398] R 3 is halo, cyano, C 1-3 alkyl, or halo C1-3 Alkyl;

[0399] R 4 is hydrogen, halo, cyano, C 1-3 alkyl or halo C 1-3 alkyl;

[0400] R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy or C 1-3 alkoxy;

[0401] R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, C 1-3 alkoxy or halo C 1-3 alkoxy;

[0402] R 11 is -CHF 2 or -CF 3 ; j is 1; k is 0 or 1; and m and n are both 1. In certain embodiments, compounds of formula (IIa) or (IVb) are provided herein, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 is -CHF 2 or -CF 3 ; j is 1; k is 0; and m and n are both 1.

[0403] In certain embodiments, compounds of formula (I) having formula (IVc) are provided herein:

[0404]

[0405] or a pharmaceutically acceptable salt thereof.

[0406] In certain embodiments, compounds of formula (I) having formula (IVd) are provided herein:

[0407] or a pharmaceutically acceptable salt thereof.

[0408] In certain embodiments, compounds of formula (I) having formula (IVe) are provided herein:

[0409]

[0410] or a pharmaceutically acceptable salt thereof.

[0411] In certain embodiments, provided herein are compounds of formula (I) having formula (IVf):

[0412]

[0413] or a pharmaceutically acceptable salt thereof.

[0414] In certain embodiments, provided herein are compounds of formula (IIc) or (IVf), wherein each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, halo C 1-3 alkoxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl, or halo C 1-3 alkylsulfinyl; or two R 11 groups together with the carbon atom to which they are attached form a C 3-5 cycloalkyl, 3- to 6-membered heterocyclic group or oxo; and the remaining variables are as described elsewhere herein for formula (IIc) and (IVf), respectively.

[0415] In certain embodiments, provided herein are compounds of formula (IIc) or (IVf), wherein each R 11 is independently halo, cyano, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, halo C 1-3 alkoxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C1-3 alkylsulfonyl, C 1-3 alkylsulfinyl, or halo-C 1-3 alkylsulfinyl; and the remaining variables are as described elsewhere herein for Formulas (IIc) and (IVf), respectively.

[0416] In certain embodiments, provided herein are compounds of Formula (IIc) or (IVf), wherein R 11 is halo, C 1-3 alkyl, halo-C 1-3 alkyl or hydroxy, and the other variables are as described elsewhere herein for Formulas (IIc) and (IVf), respectively. In certain embodiments, provided herein are compounds of Formula (IIc) or (IVf), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; each R 11 is independently halo, C 1-3 alkyl, halo-C 1-3 alkyl or hydroxy. In certain embodiments, provided herein are compounds of Formula (IIc) or (IVf), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; each R 11 is independently halo, C 1-3 alkyl, halo-C 1-3 alkyl or hydroxy.

[0417] In certain embodiments, provided herein are compounds of Formula (IIc) or (IVf), or a pharmaceutically acceptable salt thereof, wherein R 11a is C 1-3 alkyl or halo-C 1-3 alkyl; R 11b is hydroxy, and the remaining variables are as described elsewhere herein for Formulas (IIc) and (IVf).

[0418] In certain embodiments, provided herein are compounds of Formula (IIc) or (IVf), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; each R 11 is independently C 1-3 alkyl, halo-C1-3 is alkyl or hydroxy, and the remaining variables are as described elsewhere herein for formulas (IIc) and (IVf). In certain embodiments, provided herein are compounds of formula (IIc) or (IVf), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; each R 11 is independently C 1-3 alkyl, halo-C 1-3 alkyl or hydroxy.

[0419] In certain embodiments, provided herein are compounds of formula (IIc) or (IVf), or pharmaceutically acceptable salts thereof, wherein R 11a is methyl or trifluoromethyl and R 11b is hydroxy, and the remaining variables are as described elsewhere herein for formulas (IIc) and (IVf). In certain embodiments, provided herein are compounds of formula (IIc) or (IVf), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11a is methyl or trifluoromethyl and R 11b is hydroxy. In certain embodiments, provided herein are compounds of formula (IIc) or (IVf), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11a is methyl or trifluoromethyl and R 11b is hydroxy.

[0420] In certain embodiments, provided herein are compounds of formula (IIc) or (IVf), or pharmaceutically acceptable salts thereof, wherein each R 11 is independently halo; and the remaining variables are as described elsewhere herein for formulas (IIc) and (IVf).

[0421] In certain embodiments, provided herein are compounds of formula (IIc) or (IVf), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen, fluorine, chlorine or methyl;

[0422] X is N or CH;

[0423] R3 is halo, cyano, C 1-3 alkyl, or halo C 1-3 alkyl;

[0424] R 4 is hydrogen, halo, cyano, C 1-3 alkyl or halo C 1-3 alkyl;

[0425] R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy or C 1-3 alkoxy;

[0426] R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, C 1-3 alkoxy or halo C 1-3 alkoxy;

[0427] Each R 11 is independently halo;

[0428] k is 0, 1, 2 or 3;

[0429] m is 0, 1 or 2; and

[0430] n is 0, 1 or 2.

[0431] In certain embodiments, provided herein are compounds of formula (IIc) or (IVf), or pharmaceutically acceptable salts thereof, wherein

[0432] R 1 is hydrogen, fluorine, chlorine or methyl;

[0433] X is N or CH;

[0434] R 3 is halo, cyano, C 1-3 alkyl, or halo C 1-3 alkyl;

[0435] R 4 is hydrogen, halo, cyano, C 1-3 alkyl or halo C 1-3 alkyl;

[0436] R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, halo C1-3 an alkoxy group or C 1-3 an alkoxy group;

[0437] R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, C 1-3 alkoxy or halo C 1-3 alkoxy;

[0438] R 11 is fluorine;

[0439] k is 0, 1, 2 or 3;

[0440] m is 0, 1 or 2; and

[0441] n is 0, 1 or 2. In certain embodiments, provided herein are compounds of formula (IIc) or (IVf) wherein k is 0, m is 1; n is 1; and the other variables are as described elsewhere herein for formulae (IIc) and (IVf), respectively.

[0442] In certain embodiments, provided herein are compounds of formula (IIc) or (IVf), or a pharmaceutically acceptable salt thereof, wherein R 11 is fluorine; and the remaining variables are as described elsewhere herein for formulae (IIc) and (IVf), respectively.

[0443] In certain embodiments, provided herein are compounds of formula (IIc) or (IVf), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl and R 11 is fluorine.

[0444] In certain embodiments, provided herein are compounds of formula (IIc) or (IVf), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; and R 11 is fluorine.

[0445] In certain embodiments, provided herein are compounds of formula (I), (IVb) or (IVc) having formula (IVg):

[0446]

[0447] or a pharmaceutically acceptable salt thereof.

[0448] In certain embodiments, provided herein are compounds of formula (I), (IVb), or (IVc) having formula (IVh):

[0449]

[0450] or a pharmaceutically acceptable salt thereof.

[0451] In certain embodiments, provided herein are compounds of formula (I), (IVb), or (IVc) having formula (IVi):

[0452]

[0453] or a pharmaceutically acceptable salt thereof.

[0454] In certain embodiments, provided herein are compounds of formula (IId), (IVg), (IVh), or (IVi), or a pharmaceutically acceptable salt thereof, wherein R 11 is independently halo, cyano, or haloC 1-3 alkyl; and the remaining variables are as described elsewhere herein for formulae (IId), (IVg), (IVh), and (IVi). In certain embodiments, provided herein are compounds of formula (IId), (IVg), (IVh), or (IVi), or a pharmaceutically acceptable salt thereof, wherein R 11 is cyano or haloC 1-3 alkyl; and the remaining variables are as described elsewhere herein for formulae (IId), (IVg), (IVh), and (IVi), respectively. In certain embodiments, provided herein are compounds of formula (IId), (IVg), (IVh), or (IVi), or a pharmaceutically acceptable salt thereof, wherein R 11 is cyano or fluoroC 1-3 alkyl; and the remaining variables are as described elsewhere herein for formulae (IId), (IVg), (IVh), and (IVi), respectively. In certain embodiments, provided herein are compounds of formula (IId), (IVg), (IVh), or (IVi), or a pharmaceutically acceptable salt thereof, wherein R 11 is cyano, -CHF 2 or -CF 3 ; and the remaining variables are as described elsewhere herein for formulae (IId), (IVg), (IVh), and (IVi), respectively.

[0455] In certain embodiments, provided herein are compounds of formula (IId), (IVg), (IVh), or (IVi), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, fluoro, chloro, or methyl; X is N or CH; R4 is hydrogen, halo, cyano, C 1-3 alkyl or halo C 1-3 alkyl; R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy or C 1-3 alkoxy; R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, C 1-3 alkoxy or halo C 1-3 alkoxy; and R 11 is cyano or halo C 1-3 alkyl. In certain embodiments, provided herein are compounds of formula (IId), (IVg), (IVh) or (IVi), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, fluorine, chlorine or methyl; X is N or CH; R 4 is hydrogen, halo, cyano, C 1-3 alkyl or halo C 1-3 alkyl; R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy or C 1-3 alkoxy; R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, C 1-3 alkoxy or halo C 1-3 alkoxy; and R 11 is cyano or fluoro C 1-3 alkyl. In certain embodiments, provided herein are compounds of formula (IId), (IVg), (IVh) or (IVi), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, fluorine, chlorine or methyl; X is N or CH; R 4 is hydrogen, halo, cyano, C 1-3 alkyl or halo C 1-3 alkyl; R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy or C 1-3 alkoxy; R 6 is halo, cyano, C1-3 alkyl, C 3-5 cycloalkyl, halo-C 1-3 alkyl, C 1-3 alkoxy or halo-C 1-3 alkoxy; and R 11 is cyano, -CHF 2 or -CF 3 。

[0456] In certain embodiments, provided herein are compounds of formula (IId), (IVg), (IVh) or (IVi), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl and R 11 is cyano or halo-C 1-3 alkyl. In certain embodiments, provided herein are compounds of formula (IId), (IVg), (IVh) or (IVi), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl and R 11 is cyano or fluoro-C 1-3 alkyl. In certain embodiments, provided herein are compounds of formula (IId), (IVg), (IVh) or (IVi), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl and R 11 is cyano, -CHF 2 or -CF 3 。

[0457] In certain embodiments, provided herein are compounds of formula (IId), (IVg), (IVh) or (IVi), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; and R 11 is cyano or halo-C 1-3 alkyl.

[0458] In certain embodiments, provided herein are compounds of formula (IId), (IVg), (IVh), or (IVi), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine, or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; and R 11 is cyano or fluoroC 1-3 alkyl.

[0459] In certain embodiments, provided herein are compounds of formula (IId), (IVg), (IVh), or (IVi), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine, or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; and R 11 is cyano, -CHF 2 or -CF 3 .

[0460] In certain embodiments, provided herein are compounds of formula (I), (IVb), or (IVf) having formula (IVj):

[0461]

[0462] or a pharmaceutically acceptable salt thereof. In certain embodiments, provided herein are compounds of formula (IIe) or (IVj), or a pharmaceutically acceptable salt thereof, wherein each R 11 is independently halo; and the remaining variables are as described elsewhere herein for formula (IIe) and (IVj).

[0463] In certain embodiments, provided herein are compounds of formula (IIe) or (IVj), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, fluorine, chlorine, or methyl; X is N or CH; R 4 is hydrogen, halo, cyano, C 1-3 alkyl or haloC 1-3 alkyl; R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, haloC 1-3 alkyl, haloC 1-3 alkoxy, or C 1-3 alkoxy; R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, haloC 1-3 alkyl, C1-3 alkoxy or halo-C 1-3 alkoxy; and each R 11 is independently halo.

[0464] In certain embodiments, provided herein are compounds of formula (IIe) or (IVj), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen, fluorine, chlorine or methyl; X is N or CH; R 4 is hydrogen, halo, cyano, C 1-3 alkyl or halo-C 1-3 alkyl; R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo-C 1-3 alkyl, halo-C 1-3 alkoxy or C 1-3 alkoxy; R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo-C 1-3 alkyl, C 1-3 alkoxy or halo-C 1-3 alkoxy; and R 11 is fluorine.

[0465] In certain embodiments, provided herein are compounds of formula (IIe) or (IVj), or pharmaceutically acceptable salts thereof, wherein R 11 is fluorine; and the remaining variables are as described elsewhere herein for formulae (IIe) and (IVj). In certain embodiments, provided herein are compounds of formula (IIe) or (IVj), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl and R 11 is fluorine.

[0466] In certain embodiments, provided herein are compounds of formula (IIe) or (IVj), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; and R 11 is fluorine.

[0467] In certain embodiments, provided herein are compounds of formula (I) having formula (IVk):

[0468]

[0469] or a pharmaceutically acceptable salt thereof, wherein p is 1 or 2. In certain embodiments, provided herein are compounds of formula (IIf) or (IVk), or a pharmaceutically acceptable salt thereof, wherein each R 11 is independently halo, and the remaining variables are as described for formula (IIf) and (IVk), respectively. In certain embodiments, provided herein are compounds of formula (IIf) or (IVk), or a pharmaceutically acceptable salt thereof, wherein R 11 is fluorine, and the remaining variables are as described for formula (IIf) and (IVk), respectively. In certain embodiments, provided herein are compounds of formula (IIf) or (IVk), or a pharmaceutically acceptable salt thereof, wherein: R 1 is hydrogen, fluorine, chlorine or methyl;

[0470] X is N or CH;

[0471] R 4 is hydrogen, halo, cyano, C 1-3 alkyl or halo C 1-3 alkyl;

[0472] R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy or C 1-3 alkoxy;

[0473] R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, C 1-3 alkoxy or halo C 1-3 alkoxy;

[0474] each R 11 is independently halo;

[0475] and p is 1 or 2. In certain further embodiments, provided herein are compounds of formula (IIf) or (IVk), wherein:

[0476] R 1 is hydrogen, fluorine, chlorine or methyl;

[0477] X is N or CH;

[0478] R 4 is hydrogen, halo, cyano, C 1-3 alkyl or halo C 1-3 alkyl;

[0479] R5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy or C 1-3 alkoxy;

[0480] R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, C 1-3 alkoxy or halo C 1-3 alkoxy;

[0481] R 11 is fluorine;

[0482] and p is 1 or 2.

[0483] In certain embodiments, provided herein are compounds of formula (IIf) or (IVk), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl and R 11 is fluorine. In certain embodiments, provided herein are compounds of formula (IIf) or (IVk), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; and R 11 is fluorine.

[0484] In certain embodiments, provided herein are compounds of formula (I), (IVa), (IVb), (IVf) or (IVj) having formula (IVl):

[0485]

[0486] or a pharmaceutically acceptable salt thereof, wherein R 11a and R 11b are each independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, halo C 1-3 alkoxy C1-3 alkyl, hydroxy, C 1-3 alkoxy, halo-C 1-3 alkoxy, C 1-3 alkylthio, halo-C 1-3 alkylthio, C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl, or halo-C 1-3 alkylsulfinyl; or two R 11 groups together with the carbon atom to which they are attached form a C 3-5 cycloalkyl, 3- to 6-membered heterocyclic group or oxo; and the remaining variables are as described elsewhere herein for formulas (I), (IVa), (IVb), (IVf) and (IVj).

[0487] In certain embodiments, provided herein are compounds of formula (IVl) wherein R 11a is halo, cyano, C 1-3 alkyl, deuterated C 1-3 alkyl, halo-C 1-3 alkyl or cyano-C 1-3 alkyl; R 11b is halo, hydroxy-C 1-3 alkyl, C 1-3 alkoxy-C 1-3 alkyl, halo-C 1-3 alkoxy-C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo-C 1-3 alkoxy, C 1-3 alkylthio, halo-C 1-3 alkylthio, C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl, or halo-C 1-3 alkylsulfinyl; and the remaining variables are as described elsewhere herein for formula (IVl).

[0488] In certain embodiments, provided herein are compounds of formula (IVl) wherein R 11a is halo, C 1-3 alkyl or halo-C 1-3 alkyl and R 11b is halo or hydroxy, and the other variables are as described elsewhere herein for formula (IVl). In certain embodiments, provided herein are compounds of formula (IVl), or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11a is halo, C 1-3alkyl or halo-C 1-3 alkyl and R 11b is halo or hydroxy. In certain embodiments, provided herein are compounds of formula (IVl), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11a is halo, C 1-3 alkyl or halo-C 1-3 alkyl and R 11b is halo or hydroxy.

[0489] In certain embodiments, provided herein are compounds of formula (IVl), or pharmaceutically acceptable salts thereof, wherein R 11a is C 1-3 alkyl or halo-C 1-3 alkyl; R 11b is hydroxy, and the remaining variables are as described elsewhere herein for formula (IVl).

[0490] In certain embodiments, provided herein are compounds of formula (IVl), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11a is C 1-3 alkyl or halo-C 1-3 alkyl and R 11b is hydroxy, and the remaining variables are as described elsewhere herein for formula (IVl). In certain embodiments, provided herein are compounds of formula (IVl), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11a is C 1-3 alkyl or halo-C 1-3 alkyl and R 11b is hydroxy.

[0491] In certain embodiments, provided herein are compounds of formula (IVl), or pharmaceutically acceptable salts thereof, wherein R 11a is methyl or trifluoromethyl and R 11bis a hydroxyl group, and the remaining variables are as described elsewhere herein for formula (IVl). In certain embodiments, provided herein are compounds of formula (IVl), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11a is methyl or trifluoromethyl and R 11b is a hydroxyl group. In certain embodiments, provided herein are compounds of formula (IVl), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11a is methyl or trifluoromethyl and R 11b is a hydroxyl group.

[0492] In certain embodiments, provided herein are compounds of formula (IVl), wherein R 11a is fluorine and R 11b is fluorine, and the other variables are as described elsewhere herein for formula (IVl). In certain embodiments, provided herein are compounds of formula (I), (II), (IIa), (IIc), (IIe), (IV), (IVa), (IVb), (IVf), (IVj), (IVk) or (IVl), wherein each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, halo C 1-3 alkoxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl, or halo C 1-3 alkylsulfinyl, or two R 11 groups together with the carbon atom to which they are attached form a C 3-5cycloalkyl, 3- to 6-membered heterocyclic group, or oxo; and the other variables are as described elsewhere herein for formulas (I), (II), (IIa), (IIc), (IIe), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), and (IVl), respectively. In certain embodiments, provided herein are compounds of formula (I), (II), (IIa), (IIc), (IIe), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), or (IVl), wherein each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy; or two R 11 groups together with the carbon atom to which they are attached form a C 3-5 cycloalkyl, 3- to 6-membered heterocyclic group, or oxo; and the other variables are as described elsewhere herein for formulas (I), (II), (IIa), (IIc), (IIe), (IIf), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), or (IVl), respectively. In certain embodiments, provided herein are compounds of formula (I), (II), (IIa), (IIc), (IIe), (IIf), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), or (IVl), wherein each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, halo C 1-3 alkyl, hydroxy, halo C 1-3 alkoxy; or two R 11 groups together with the carbon atom to which they are attached form a C 3-5 cycloalkyl; and the other variables are as described elsewhere herein for formulas (I), (II), (IIa), (IIc), (IIe), (IIf), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), or (IVl), respectively. In certain embodiments, provided herein are compounds of formula (I), (II), (IIa), (IIc), (IIe), (IIf), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), or (IVl), wherein each R 11 is independently fluoro, cyano, oxo, hydroxy, methyl, -CHF 2 、-CF 3or -OCHF 2 , or two Rs 11 groups together with the carbon atom to which they are attached form cyclobutyl or oxo; and the other variables are as described elsewhere herein for formulas (I), (II), (IIa), (IIc), (IIe), (IIf), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), and (IVl). In certain embodiments, provided herein are compounds of formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl), wherein each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, halo C 1-3 alkyl, hydroxy, or halo C 1-3 alkoxy; and the other variables are as described elsewhere herein for formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl). In certain embodiments, provided herein are compounds of formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl), wherein each R 11 is independently fluorine, cyano, oxo, hydroxy, methyl, -CHF 2 , -CF 3 or -OCHF 2; and the other variables are as described elsewhere herein for Formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), and (IVl). In certain embodiments, provided herein are compounds of Formula (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl), wherein R 11 is halo, cyano, C 1-3 alkyl, deuterated C 1-3 alkyl, or halo C 1-3 alkyl; and the other variables are as described elsewhere herein for Formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), and (IVl). In certain embodiments, provided herein are compounds of Formula (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl), wherein R 11 is halo, cyano, or halo C 1-3 alkyl; and the other variables are as described elsewhere herein for Formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), and (IVl). In certain embodiments, provided herein are compounds of Formula (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl), wherein R 11 is fluoro, cyano, or fluoro C 1-3alkyl; and the other variables are as described elsewhere herein for formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), and (IVl). In certain embodiments, provided herein are compounds of formula (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl), wherein R 11 is fluorine, cyano, -CHF 2 or -CF 3 ; and the other variables are as described elsewhere herein for formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), and (IVl). In certain embodiments, provided herein are compounds of formula (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), and (IVl), wherein R 11 is halo; and the other variables are as described elsewhere herein for formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), and (IVl). In certain embodiments, provided herein are compounds of formula (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl), wherein R 11is fluorine; and the other variables are as described elsewhere herein for formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), and (IVl).

[0493] In certain embodiments, provided herein are compounds of formula (I) having formula (V):

[0494]

[0495] or a pharmaceutically acceptable salt thereof.

[0496] In certain embodiments, provided herein are compounds of formula (I), (II), or (IV) having formula (VI):

[0497]

[0498] or a pharmaceutically acceptable salt thereof. In certain embodiments, provided herein are compounds of formula (VI) wherein R 3 is halo, cyano, alkyl, or haloalkyl; R 4 is hydrogen, halo, C 1-3 alkyl or halo C 1-3 alkyl; R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkoxy or C 1-3 alkoxy; R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, C 1-3 alkoxy or halo C 1-3 alkoxy; R 8 is hydrogen, alkyl, or haloalkyl; R 9 is cycloalkyl or heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally substituted with one, two, or three independently selected R 11 ; or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocycloalkyl or heteroaryl, wherein the heterocycloalkyl or heteroaryl is optionally substituted with one, two, or three independently selected R 11 ; each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3Alkyl, cyano C 1-3 Alkyl, hydroxy C 1-3 Alkyl, C 1-3 Alkoxy C 1-3 Alkyl, halo C 1-3 Alkoxy C 1-3 Alkyl, hydroxy, C 1-3 Alkoxy, halo C 1-3 Alkoxy, C 1-3 Alkylthio, halo C 1-3 Alkylthio, C 1-3 Alkylsulfonyl, halo C 1-3 Alkylsulfonyl, C 1-3 Alkylsulfinyl or halo C 1-3 Alkylsulfinyl; k is 0, 1 or 2; m is 0 or 1; and n is 0, 1 or 2. In certain embodiments, provided herein are compounds of formula (I) or (VI) wherein R 8 is hydrogen, alkyl or haloalkyl; R 9 is haloalkyl, -R u -cycloalkyl or cycloalkyl, wherein the -R u -cycloalkyl or cycloalkyl is optionally substituted by one, two or three R 11 ; each R 11 is independently halo or halo C 1-3 alkyl, and the other variables are as described elsewhere herein for formula (I) and (VI), respectively. In certain embodiments, provided herein are compounds of formula (I) or (VI) wherein R 8 is hydrogen, C 1-3 alkyl or halo C 1-3 alkyl; R 9 is halo C 1-3 alkyl, -R u -C 3-5 cycloalkyl or C 3-5 cycloalkyl, wherein the -R u -C 3-5 cycloalkyl or C 3-5 cycloalkyl is optionally substituted by one, two or three R 11 ; each R 11 is independently halo or halo C 1-3 alkyl, and the remaining variables are as described elsewhere herein for formula (I) and (VI), respectively.

[0499] In certain embodiments, provided herein are compounds of formula (I) or (VI) wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 8is hydrogen, C 1-3 alkyl or halo-C 1-3 alkyl; R 9 is halo-C 1-3 alkyl, -R u -C 3-5 cycloalkyl or C 3-5 cycloalkyl, wherein the -R u -C 3-5 cycloalkyl or C 3-5 cycloalkyl is optionally substituted by one, two or three R 11 substituents; each R 11 is independently halo or halo-C 1-3 alkyl; and the remaining variables are as described elsewhere herein for formulas (I) and (VI), respectively. In certain embodiments, provided herein are compounds of formula (I) or (VI) wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 8 is hydrogen, C 1-3 alkyl or halo-C 1-3 alkyl; R 9 is halo-C 1-3 alkyl, -R u -C 3-5 cycloalkyl or C 3-5 cycloalkyl, wherein the -R u -C 3-5 cycloalkyl or C 3-5 cycloalkyl is optionally substituted by one, two or three R 11 substituents; each R 11 is independently halo or halo-C 1-3 alkyl; and the remaining variables are as described elsewhere herein for formulas (I) and (VI), respectively.

[0500] In certain embodiments, provided herein are compounds of formula (I) or (VI) wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 8 is hydrogen, C 1-3 alkyl or halo-C 1-3 alkyl; R 9 is halo-C 1-3 alkyl, -R u -C 3-5 cycloalkyl or C 3-5 cycloalkyl, wherein the -R u -C3-5 A cycloalkyl group or C 3-5 The cycloalkyl group is optionally substituted by one, two or three R 11 ; each R 11 is independently halo or halo-C 1-3 alkyl; m and n are both 1 and k is 0. In certain embodiments, compounds of formula (I) or (VI) are provided herein, wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 8 is hydrogen, C 1-3 alkyl or halo-C 1-3 alkyl; R 9 is halo-C 1-3 alkyl, -R u -C 3-5 cycloalkyl or C 3-5 cycloalkyl, wherein the -R u -C 3-5 cycloalkyl or C 3-5 cycloalkyl is optionally substituted by one, two or three R 11 ; each R 11 is independently halo or halo-C 1-3 alkyl; m and n are both 1 and k is 0. In certain embodiments, compounds of formula (I) or (VI), or pharmaceutically acceptable salts thereof, are provided herein, wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; and the remaining variables are as described elsewhere herein for formula (I) and (VI), respectively.

[0501] In certain embodiments, compounds of formula (I) or (VI) are provided herein, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 8 is hydrogen; R 9 is -CH 2 CHF 2 , cyclopropylmethyl, cyclobutyl, or bicyclo[1.1.1]pentan-1-yl, or wherein the cyclopropylmethyl, cyclobutyl, or bicyclo[1.1.1]pentan-1-yl is optionally substituted by one, two or three R 11 ; each R 11is independently fluorine or trifluoromethyl; m and n are both 1 and k is 0. In certain embodiments, provided herein are compounds of formula (I) or (VI) wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 8 is hydrogen; R 9 is -CH 2 CHF 2 、cyclopropylmethyl, cyclobutyl, or bicyclo[1.1.1]pentan-1-yl, or wherein the cyclopropylmethyl, cyclobutyl, or bicyclo[1.1.1]pentan-1-yl is optionally substituted with one, two or three R 11 ; each R 11 is independently fluorine or trifluoromethyl; m and n are both 1 and k is 0.

[0502] In certain embodiments, provided herein are compounds of formula (I) or (VI) wherein R 8 is hydrogen, alkyl or haloalkyl; R 9 is -R u -cycloalkyl or cycloalkyl, wherein the -R u -cycloalkyl or cycloalkyl is optionally substituted with one, two or three R 11 ; each R 11 is independently halo or halo-C 1-3 alkyl, and the other variables are as described elsewhere herein for formula (I) and (VI). In certain embodiments, provided herein are compounds of formula (I) or (VI) wherein R 8 is hydrogen, alkyl or haloalkyl; R 9 is -R u -cycloalkyl or cycloalkyl, wherein the -R u -cycloalkyl or cycloalkyl is optionally substituted with one, two or three R 11 ; each R 11 is independently halo or halo-C 1-3 alkyl, and the other variables are as described elsewhere herein for formula (I) and (VI). In certain embodiments, provided herein are compounds of formula (I) or (VI) wherein R 8 is hydrogen, alkyl or haloalkyl; R 9is cyclopropylmethyl or cyclobutyl, wherein the cyclopropylmethyl or cyclobutyl is optionally substituted with one, two or three fluorine or trifluoromethyl groups, and the other variables are as described elsewhere herein for formulas (I) and (VI). In certain embodiments, provided herein are compounds of formula (I) or (VI), wherein k is 0; m is 1; n is 1, and the other variables are as described elsewhere herein for formulas (I) and (VI). In certain embodiments, provided herein are compounds of formula (I) or (VI), wherein R 11 is fluorine, and the other variables are as described elsewhere herein for formulas (I) and (VI). In certain embodiments, provided herein are compounds, provided herein are compounds of formula (I), (II), (IV), (IVa) or (VI) having formula (VIa):

[0503]

[0504] or a pharmaceutically acceptable salt thereof, wherein j is 1 or 2. In certain embodiments, provided herein are compounds of formula (VIa), or a pharmaceutically acceptable salt thereof, wherein each R 11 is independently halo, cyano, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, halo C 1-3 alkoxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, halo C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl or halo C 1-3 alkylsulfinyl; or two R 11 groups together with the carbon atom to which they are attached form a C 3-5 cycloalkyl; j is 1 or 2, and the remaining variables are as described elsewhere herein for formula (VIa). In certain embodiments, provided herein are compounds of formula (VIa), or a pharmaceutically acceptable salt thereof, wherein each R 11 is independently halo, cyano, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3Alkoxy C 1-3 Alkyl, halo C 1-3 Alkoxy C 1-3 Alkyl, hydroxy, C 1-3 Alkoxy, halo C 1-3 Alkoxy, C 1-3 Alkylthio, halo C 1-3 Alkylthio, C 1-3 Alkylsulfonyl, halo C 1-3 Alkylsulfonyl, C 1-3 Alkylsulfinyl or halo C 1-3 Alkylsulfinyl; or two R 11 groups together with the carbon atom to which they are attached form a C 3-5 Cycloalkyl; j is 1; and the remaining variables are as described elsewhere herein for formula (VIa). In certain embodiments, provided herein are compounds of formula (VIa), or pharmaceutically acceptable salts thereof, wherein R 11 is halo C 1-3 alkyl; j is 1; and the remaining variables are as described elsewhere herein for formula (VIa). In certain embodiments, provided herein are compounds of formula (VIa), or pharmaceutically acceptable salts thereof, wherein

[0505] R 1 is hydrogen, fluorine, chlorine or methyl;

[0506] X is N or CH;

[0507] R 3 is halo, cyano, C 1-3 alkyl, or halo C 1-3 alkyl;

[0508] R 4 is hydrogen, halo, cyano, C 1-3 alkyl or halo C 1-3 alkyl;

[0509] R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy or C 1-3 alkoxy;

[0510] R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, C 1-3 alkoxy or halo C 1-3 alkoxy; R 11 is halo C 1-3An alkyl group; j is 1; k is 0; m is 1; and n is 1. In certain embodiments, provided herein are compounds of formula (VIa), or pharmaceutically acceptable salts thereof, wherein

[0511] R 1 is hydrogen, fluorine, chlorine or methyl;

[0512] X is N or CH;

[0513] R 3 is halo, cyano, C 1-3 alkyl, or halo C 1-3 alkyl;

[0514] R 4 is hydrogen, halo, cyano, C 1-3 alkyl or halo C 1-3 alkyl;

[0515] R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy or C 1-3 alkoxy;

[0516] R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, C 1-3 alkoxy or halo C 1-3 alkoxy; R 11 is trifluoromethyl; j is 1; k is 0; m is 1; and n is 1.

[0517] In certain embodiments, provided herein are compounds of formula (VIa), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 is halo C 1-3 alkyl; j is 1; k is 0; m is 1; and n is 1. In certain embodiments, provided herein are compounds of formula (VIa), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 is trifluoromethyl; j is 1; k is 0; m is 1; and n is 1.

[0518] In certain embodiments, provided herein are compounds of formula (VIa), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; each R 11 is independently halo, cyano, haloC 1-3 alkyl, haloC 1-3 alkoxy or C 1-3 alkylsulfonyl; or two R 11 groups together with the carbon atom to which they are attached form a C 3-5 cycloalkyl; j is 1 or 2; k is 0; m is 1; and n is 1.

[0519] In certain embodiments, provided herein are compounds of formula (VIa), or pharmaceutically acceptable salts thereof, wherein each R 11 is independently fluorine, cyano, -CF 3 、-CHF 2 、-OCF 3 or -S(O) 2 CH 3 ,or two R 11 groups together with the carbon atom to which they are attached form cyclopropyl; j is 1 or 2; and the remaining variables are as described elsewhere herein for formula (VIa).

[0520] In certain embodiments, provided herein are compounds of formula (VIa), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; each R 11 is independently fluorine, cyano, -CF 3 、-CHF 2 、-OCF 3 or -S(O) 2 CH 3 ; or two R 11 groups together with the carbon atom to which they are attached form cyclopropyl; j is 1 or 2 and k is 0; m is 1 and n is 1.

[0521] In certain embodiments, provided herein are compounds of formula (VIa), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5is methoxy or cyclopropyl; R 6 is methyl; each R 11 is independently fluorine, cyano, -CF 3 -, -CHF 2 -, -OCF 3 or -S(O) 2 CH 3 ; or two R 11 groups together with the carbon atom to which they are attached form cyclopropyl; j is 1 or 2 and k is 0; m is 1 and n is 1.

[0522] In certain embodiments, provided herein are compounds of formula (I), (II), (IV), (IVa) or (VI) having formula (VIb):

[0523]

[0524] or a pharmaceutically acceptable salt thereof.

[0525] In certain embodiments, provided herein are compounds of formula (I), (II), (IV), (IVa) or (VI) having formula (VIc):

[0526]

[0527] or a pharmaceutically acceptable salt thereof.

[0528] In certain embodiments, provided herein are compounds of formula (VIb) or (VIc), or a pharmaceutically acceptable salt thereof, wherein each R 11 is independently halo, cyano, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, halo C 1-3 alkoxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, halo C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl or halo C 1-3 alkylsulfinyl; or two R 11 groups together with the carbon atom to which they are attached form C 3-5a cycloalkyl group, and the remaining variables are as described elsewhere herein for formulas (VIb) and (VIc), respectively.

[0529] In certain embodiments, provided herein are compounds of formula (VIb) or (VIc), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; each R 11 is independently halo, cyano, haloC 1-3 alkyl, haloC 1-3 alkoxy or C 1-3 alkylsulfonyl; or two R 11 groups together with the carbon atom to which they are attached form a C 3-5 cycloalkyl group; and the remaining variables are as described elsewhere herein for formulas (VIb) and (VIc), respectively.

[0530] In certain embodiments, provided herein are compounds of formula (VIb) or (VIc), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; and each R 11 is independently halo, cyano, haloC 1-3 alkyl, haloC 1-3 alkoxy or C 1-3 alkylsulfonyl; or two R 11 groups together with the carbon atom to which they are attached form a C 3-5 cycloalkyl group.

[0531] In certain embodiments, provided herein are compounds of formula (VIb) or (VIc), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; each R 11 is independently halo, cyano, haloC 1-3 alkyl, haloC 1-3 alkoxy or C 1-3 alkylsulfonyl; or two R 11 groups together with the carbon atom to which they are attached form a C 3-5 cycloalkyl group; and the remaining variables are as described elsewhere herein for formula (VIb) or (VIc).

[0532] In certain embodiments, provided herein are compounds of formula (VIb) or (VIc), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; each R 11 is independently halo, cyano, haloC 1-3 alkyl, haloC 1-3 alkoxy or C 1-3 alkylsulfonyl; or two R 11 groups together with the carbon atom to which they are attached form C 3-5 cycloalkyl; m is 1; n is 1; j is 1 or 2 and k is 0.

[0533] In certain embodiments, provided herein are compounds of formula (VIb) or (VIc), or pharmaceutically acceptable salts thereof, wherein each R 11 is independently fluorine, cyano, -CF 3 , -CHF 2 , -OCF 3 or -S(O) 2 CH 3 , or two R 11 groups together with the carbon atom to which they are attached form cyclopropyl; j is 1 or 2; and the remaining variables are as described elsewhere herein for formula (VIb) and (VIc), respectively.

[0534] In certain embodiments, provided herein are compounds of formula (VIb) or (VIc), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; each R 11 is independently fluorine, cyano, -CF 3 , -CHF 2 , -OCF 3 or -S(O) 2 CH 3 ; or two R 11 groups together with the carbon atom to which they are attached form cyclopropyl; m is 1; n is 1; j is 1 or 2 and k is 0.

[0535] In certain embodiments, provided herein are compounds of formula (VIb) or (VIc), or pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R5 is methoxy or cyclopropyl; R 6 is methyl; each R 11 is independently fluorine, cyano, -CF 3 , -CHF 2 , -OCF 3 or -S(O) 2 CH 3 ; or two R 11 groups together with the carbon atom to which they are attached form cyclopropyl; m is 1; n is 1; j is 1 or 2 and k is 0.

[0536] In certain embodiments, the present disclosure provides compounds of formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb) or (VIc), wherein each R 11 is independently halo, cyano, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, halo C 1-3 alkoxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, halo C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl or halo C 1-3 alkylsulfinyl; or two R 11 groups together with the carbon atom to which they are attached form C 3-5 cycloalkyl or oxo; and the other variables are as described elsewhere herein for formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb) and (VIc).

[0537] In certain embodiments, the present disclosure provides compounds of formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb) or (VIc), wherein each R 11 is independently halo, cyano C 1-3 alkyl, halo C 1-3 alkyl, hydroxy, halo C 1-3 alkoxy, C 1-3 alkylsulfonyl or halo C 1-3 alkylsulfonyl; or two R 11The group, together with the carbon atom to which it is attached, forms a C 3-5 cycloalkyl or oxo; and the other variables are as described elsewhere herein for formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb), and (VIc), respectively.

[0538] In certain embodiments, provided herein are compounds of formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb), or (VIc), wherein each R 11 is independently halo, cyano C 1-3 alkyl, halo C 1-3 alkyl, hydroxy, halo C 1-3 alkoxy, or C 1-3 alkylsulfonyl; or two R 11 groups, together with the carbon atom to which they are attached, form a C 3-5 cycloalkyl or oxo; and the other variables are as described elsewhere herein for formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb), and (VIc), respectively.

[0539] In certain embodiments, provided herein are compounds of formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb), or (VIc), wherein each R 11 is independently halo, cyano, C 1-3 alkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy, or C 1-3 alkylsulfonyl; and the other variables are as described elsewhere herein for formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb), and (VIc), respectively. In certain embodiments, provided herein are compounds of formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb), or (VIc), wherein each R 11 is independently fluoro, cyano, -CHF 2 、-CF 3 、-OCF 3 、-OCHF 2 or -S(O) 2 CH 3 ; or two R 11The group, together with the carbon atom to which it is attached, forms a cyclopropyl; and the other variables are as described elsewhere herein for formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb), and (VIc), respectively. In certain embodiments, provided herein are compounds of formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb), or (VIc), wherein each R 11 is independently fluorine, cyano, -CHF 2 , -CF 3 , -OCF 3 , or -S(O) 2 CH 3 ; or two R 11 groups, together with the carbon atom to which they are attached, form a cyclopropyl, and the other variables are as described elsewhere herein for formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb), and (VIc), respectively. In certain embodiments, provided herein are compounds of formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb), or (VIc), wherein each R 11 is independently fluorine, cyano, -CHF 2 , -CF 3 , -OCF 3 , or -S(O) 2 CH 3 ; and the other variables are as described elsewhere herein for formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb), and (VIc), respectively.

[0540] In certain embodiments, provided herein are compounds of formula (I), (II), (IV), (VI), or (X) having formula (VII):

[0541]

[0542] or a pharmaceutically acceptable salt thereof, wherein q is 0, 1, 2, or 3. In certain embodiments, provided herein are compounds of formula (I), (II), (IV), (VI), or (X) having formula (VIIa):

[0543]

[0544] or a pharmaceutically acceptable salt thereof. In certain embodiments, provided herein are compounds of formula (VII) or (VIIa), wherein each R 11 is independently halo, cyano, haloC 1-3 alkyl, hydroxyC 1-3 alkyl, C 1-3 alkoxyC1-3 alkyl, halo-C 1-3 alkoxy-C 1-3 alkyl, hydroxy, C 1-3 alkoxy or halo-C 1-3 alkoxy; k is 0; X is CH; R 1 is hydrogen; and the other variables are as described respectively for formulas (I), (II), (IV), (VI) and (X). In certain embodiments, provided herein are compounds of formula (VII) or (VIIa), wherein each R 11 is independently halo, cyano, haloalkyl or hydroxy; k is 0; X is CH; R 1 is hydrogen; and the other variables are as described respectively for formulas (I), (II), (IV), (VI) and (X). In certain further embodiments, provided herein are compounds of formula (VII) or (VIIa), wherein each R 11 is independently halo, cyano or halo-C 1-3 alkyl; k is 0; X is CH; R 1 is hydrogen; and the other variables are as described respectively for formulas (I), (II), (IV), (VI) and (X). In certain further embodiments, provided herein are compounds of formula (VII) or (VIIa), wherein R 4 is hydrogen; R 5 is methoxy; R 6 is methyl and X, R 1 , R 11 and k are as described above.

[0545] In certain embodiments, provided herein are compounds of formula (I), (II) or (IV) having formula (VIII):

[0546]

[0547] or a pharmaceutically acceptable salt thereof, wherein Ring A is cycloalkyl, heterocycloalkyl, aryl or heteroaryl; q is 0, 1, 2 or 3; and the other variables are as described for formulas (I), (II) and (IV), respectively. In certain embodiments, provided herein are compounds of formula (VIII) wherein Ring A is heterocycloalkyl or heteroaryl. In certain embodiments, provided herein are compounds of formula (VIII) wherein Ring A is heterocycloalkyl. In certain embodiments, provided herein are compounds of formula (VIII) wherein Ring A is heteroaryl. In certain embodiments, provided herein are compounds of formula (VIII) wherein Ring A is pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazolyl, imidazolyl, thiazolyl, or pyrazolyl. In certain embodiments, provided herein are compounds of formula (VIII) wherein Ring A is pyridyl or pyrazolyl. In certain embodiments, provided herein are compounds of formula (VIII) wherein Ring A is pyridyl. In certain embodiments, provided herein are compounds of formula (VIII) wherein Ring A is pyrazolyl. In certain embodiments, provided herein are compounds of formula (VIII) wherein Ring A is oxazolyl. In certain embodiments, provided herein are compounds of formula (VIII) wherein X is CH, R 1 is hydrogen; R 4 is hydrogen; R 5 is methoxy; R 6 is methyl; each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, halo C 1-3 alkoxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl, or halo C 1-3 alkylsulfinyl; k is 0; q is 0, 1, 2 or 3 and Ring A is as described above.

[0548] In certain embodiments, provided herein are compounds of formula (I) of formula (X):

[0549]

[0550] or a pharmaceutically acceptable salt thereof. In certain embodiments, provided herein are compounds of formula (I) or (X) wherein R2 is alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocycloalkyl, cycloalkyl, heterocycloalkyl or heteroaryl, wherein the alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocycloalkyl, cycloalkyl, heterocycloalkyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 ; and R u and R 11 are as described elsewhere herein for formula (I) and (X), respectively. In certain embodiments, provided herein are compounds of formula (I) or (X) wherein R 2 is C 1-6 alkyl, halo C 1-6 alkyl, deuterated C 1-6 alkyl, hydroxy C 1-6 alkyl, C 1-6 alkoxy C 1-6 alkyl, cyano C 1-6 alkyl, -R u -C 3-6 cycloalkyl, -R u -3- to 7-membered heterocycloalkyl, C 3-6 cycloalkyl, 3- to 7-membered heterocycloalkyl or 5- to 10-membered heteroaryl, wherein the C 1-6 alkyl, halo C 1-6 alkyl, deuterated C 1-6 alkyl, hydroxy C 1-6 alkyl, C 1-6 alkoxy C 1-6 alkyl, cyano C 1-6 alkyl, -R u -C 3-6 cycloalkyl, -R u -3- to 7-membered heterocycloalkyl, C 3-6 cycloalkyl, 3- to 7-membered heterocycloalkyl or 5- to 10-membered heteroaryl is optionally substituted by one, two or three independently selected R 11 ; and R u and R 11 are as described elsewhere herein for formula (I) and (X), respectively. In certain embodiments, provided herein are compounds of formula (I) or (X) wherein R 2 is C 1-3 alkyl, halo C 1-3 alkyl, deuterated C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, cyano C1-3 alkyl, -R u -C 3-6 cycloalkyl, -R u -3- to 6-membered heterocyclic group, C 3-6 cycloalkyl, 3- to 6-membered heterocyclic group or 5- to 6-membered heteroaryl, wherein the C 1-3 alkyl, halo-C 1-3 alkyl, deuterated-C 1-3 alkyl, hydroxy-C 1-3 alkyl, C 1-3 alkoxy-C 1-3 alkyl, cyano-C 1-3 alkyl, -R u -C 3-6 cycloalkyl, -R u -3- to 6-membered heterocyclic group, C 3-6 cycloalkyl, 3- to 6-membered heterocyclic group or 5- to 6-membered heteroaryl is optionally substituted by one, two or three independently selected R 11 groups; and R u and R 11 are as described elsewhere herein for formula (I) and (X), respectively. In certain embodiments, provided herein are compounds of formula (I) or (X), wherein R 2 is alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, cyanoalkyl, -R u -cycloalkyl or -R u -heterocyclic group, wherein the alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, cyanoalkyl, -R u -cycloalkyl or -R u -heterocyclic group is optionally substituted by R 11 and R 11 and the other variables are as described elsewhere herein for formula (I) and (X), respectively. In certain embodiments, provided herein are compounds of formula (I) or (X), wherein R 2 is C 1-3 alkyl, halo-C 1-3 alkyl, deuterated C 1-3 alkyl, hydroxy C 1-3 alkyl, cyano C 1-3 alkyl, -R u -C 3-5 cycloalkyl, -R u -3- to 5-membered heterocyclic group, wherein the C 1-3 alkyl, halo-C 1-3 alkyl, deuterated C 1-3 alkyl, hydroxy C 1-3 alkyl, cyano C 1-3 alkyl, -R u -C 3-5 cycloalkyl, -R u- A 3- to 5-membered heterocyclic group is optionally substituted with independently selected R 11 groups, and R 11 and the other variables are as described elsewhere herein for Formulas (I) and (X), respectively. In certain embodiments, provided herein are compounds of Formula (I) or (X) wherein R 2 is haloalkyl, deuterated alkyl, -R u -cycloalkyl or -R u -heterocyclic group, wherein the haloalkyl, deuterated alkyl, -R u -cycloalkyl or -R u -heterocyclic group is optionally substituted with independently selected R 11 groups, and R 11 and the other variables are as described elsewhere herein for Formulas (I) and (X), respectively. In certain embodiments, provided herein are compounds of Formula (I) or (X) wherein R 2 is halo-C 1-3 alkyl, deuterated C 1-3 alkyl, -R u -C 3-5 cycloalkyl or -R u -a 3- to 5-membered heterocyclic group, wherein the halo-C 1-3 alkyl, deuterated C 1-3 alkyl, -R u -C 3-5 cycloalkyl or -R u -a 3- to 5-membered heterocyclic group is optionally substituted with independently selected R 11 groups, and R 11 and the other variables are as described elsewhere herein for Formulas (I) and (X), respectively. In certain embodiments, provided herein are compounds of Formula (I) or (X) wherein R 2 is haloalkyl or -R u -heterocyclic group, wherein the -R u -heterocyclic group is optionally substituted with independently selected halo; and the other variables are as described elsewhere herein for Formulas (I) and (X), respectively. In certain embodiments, provided herein are compounds of Formula (I) or (X) wherein R 2 is halo-C 1-3 alkyl or -R u -a 3- to 5-membered heterocyclic group, wherein the -R u -a 3- to 5-membered heterocyclic group is optionally substituted with independently selected halo; and the other variables are as described elsewhere herein for Formulas (I) and (X), respectively. In certain embodiments, provided herein are compounds of Formula (I) or (X) wherein R 2is fluoroethyl or (3-fluoroxetane-3-yl)methyl; and the other variables are as described elsewhere herein for formulas (I) and (X), respectively. In certain embodiments, provided herein are compounds of formula (I) or (X) wherein R 2 is fluoroethyl; and the other variables are as described elsewhere herein for formulas (I) and (X), respectively. In certain embodiments, provided herein are compounds of formula (I) or (X) wherein R 2 is (3-fluoroxetane-3-yl)methyl; and the other variables are as described elsewhere herein for formulas (I) and (X), respectively. In certain embodiments, provided herein are compounds of formula (I) or (X) wherein R 2 is alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl or cyanoalkyl, wherein the alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl or cyanoalkyl is optionally substituted by one R 11 substituent, and R 11 are as described elsewhere herein for formulas (I) and (X), respectively. In certain further embodiments, provided herein are compounds of formula (X) wherein X is CH, R 1 is hydrogen, R 4 is hydrogen; R 5 is methoxy; R 6 is methyl; each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, halo C 1-3 alkoxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl, or halo C 1-3 alkylsulfinyl; k is 0; and R 2 is as described above.

[0551] In certain embodiments, provided herein are compounds of formula (III), (IIIa) or formula (V) wherein R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl optionally substituted by one, two or three independently selected R 11 substituents; and each R 11 is independently halo, cyano, oxo, C1-3 alkyl, deuterated C 1-3 alkyl, halogenated C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, C 1-3 alkylthio, halogenated C 1-3 alkylthio, C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl, or halogenated C 1-3 alkylsulfinyl and the other variables are as described elsewhere herein for Formulas (III), (IIIa) and (V), respectively. In certain embodiments, provided herein are compounds of Formula (III), (IIIa) or Formula (V) wherein R 2a and R 2b together with the carbon atom to which they are attached form a C 11 cycloalkyl optionally substituted with one, two or three independently selected R 3-6 and R 11 is as described for Formula (I).

[0552] In certain embodiments, provided herein are compounds of formula (I), (II), (IV), (IVa), (VI), or (X), wherein m is 0 or 1; n is 0, 1, or 2, and the other variables are as described elsewhere herein for formulae (I), (II), (IV), (IVa), (VI), and (X). In certain embodiments, provided herein are compounds of formula (I), (II), (IV), (IVa), (VI), or (X), wherein m is 0 or 1; n is 0 or 1, and the other variables are as described elsewhere herein for formulae (I), (II), (IV), (IVa), (VI), and (X). In certain embodiments, provided herein are compounds of formula (I), (II), (IIa), (IIb), (IIc), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (VI), (VIa), or (X), wherein m is 1; n is 1, and the other variables are as described elsewhere herein for formulae (I), (II), (IIa), (IIb), (IIc), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (VI), (VIa), and (X). In certain embodiments, provided herein are compounds of formula (I), (II), (IIa), (IIb), (IIc), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (VI), (VIa), or (X), wherein k is 0; m is 1; n is 1, and the other variables are as described elsewhere herein for formulae (I), (II), (IIa), (IIb), (IIc), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (VI), (VIa), and (X).

[0553] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl group substituted with one, two, or three independently selected R 11 groups, or form a heterocyclic group optionally substituted with one, two, or three independently selected R 11 groups; and each R 11 is as described elsewhere herein for formulae (I), (II), (III), (IIIa), (IV), (IVa), and (V).

[0554] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl group substituted with one, two, or three independently selected R 11 ; and each R 11 is as described elsewhere herein for formulae (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively.

[0555] In certain embodiments, provided herein are compounds of formula (I), (III), (IIIa), or (V), wherein R 2a and R 2b together with the carbon atom to which they are attached form a C 11 cycloalkyl group optionally substituted with one, two, or three independently selected R 3-6 ; and each R 11 is as described elsewhere herein for formulae (III), (IIIa), and (V), respectively.

[0556] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 , wherein the -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one, two, or three independently selected R 11 , and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halo C 1-3 alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl group substituted with one, two, or three independently selected R 11 , or form a heterocyclyl group optionally substituted with one, two, or three independently selected R 11 ; and R u , R 7 , R 8 , R 9 and R 11Respectively as described elsewhere herein for formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V).

[0557] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 , wherein the cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is optionally substituted with one, two, or three independently selected R 11 substituents, and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl, or halogenated C 1-3 alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl substituted with one, two, or three independently selected R 11 substituents, or form a heterocycloalkyl optionally substituted with one, two, or three independently selected R 11 substituents; and R 7 , R 8 , R 9 and R 11 are respectively as described elsewhere herein for formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V).

[0558] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 , wherein the cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is optionally substituted with one, two, or three independently selected R 11 substituents, and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl, or halogenated C 1-3 alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a C 11 substituted with one, two, or three independently selected R 3-6cycloalkyl, or forms a 4-6 membered heterocyclic group optionally substituted by one, two or three independently selected R 11 ; and R u , R 7 , R 8 , R 9 and R 11 are as described elsewhere herein for formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively.

[0559] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is cycloalkyl, heterocyclic group, -OR 7 , -SR 7 or -NR 8 R 9 , wherein the cycloalkyl or heterocyclic group is optionally substituted by one, two or three independently selected R 11 , and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halo C 1-3 alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a C 11 cycloalkyl substituted by one, two or three independently selected R 3-6 , or forms a 4-6 membered heterocyclic group optionally substituted by one, two or three independently selected R 11 ; and R 7 , R 8 , R 9 and R 11 are as described elsewhere herein for formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively.

[0560] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is cycloalkyl, heterocyclic group, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 , wherein the cycloalkyl, heterocyclic group, aryl or heteroaryl is optionally substituted by one, two or three independently selected R 11 , and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C1-3 alkyl or halo-C 1-3 alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a C 11 cycloalkyl which is substituted by one, two or three independently selected R 3-5 groups, or form a 4- or 5-membered heterocyclic group which is optionally substituted by one, two or three independently selected R 11 groups; and R u , R 7 , R 8 , R 9 and R 11 are as described elsewhere herein for formulae (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively.

[0561] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 , wherein the -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, aryl or heteroaryl is optionally substituted by one, two or three independently selected R 11 groups, and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halo-C 1-3 alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a heterocyclic group which is optionally substituted by one, two or three independently selected R 11 groups; and R u , R 7 , R 8 , R 9 and R 11 are as described elsewhere herein for formulae (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively.

[0562] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2ais cycloalkyl, heterocyclic, aryl, heteroaryl, -OR 7 、-SR 7 or -NR 8 R 9 , wherein the cycloalkyl, heterocyclic, aryl or heteroaryl is optionally substituted by one, two or three independently selected R 11 substituents, and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a heterocyclic group optionally substituted by one, two or three independently selected R 11 substituents; and R u , R 7 , R 8 , R 9 and R 11 are as described elsewhere herein for formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively.

[0563] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is -R u -cycloalkyl or cycloalkyl, wherein the -R u -cycloalkyl or cycloalkyl is optionally substituted by one, two or three independently selected R 11 substituents, and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl; and R 11 are as described elsewhere herein for formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively.

[0564] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is -R u -cycloalkyl, -R u -heterocyclic, cycloalkyl or heterocyclic, wherein the -R u -cycloalkyl, -R u -heterocyclic, cycloalkyl or heterocyclic is optionally substituted by one, two or three independently selected R 11 substituents; R 2bis hydrogen, deuterium, a halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl; and R 11 is as described elsewhere herein for Formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively.

[0565] In certain embodiments, provided herein are compounds of Formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein the cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is optionally substituted with one, two, or three independently selected R 11 substituents, and R 2b is hydrogen, deuterium, a halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a heterocycloalkyl optionally substituted with one, two, or three independently selected R 11 substituents; and R 11 is as described elsewhere herein for Formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively.

[0566] In certain embodiments, provided herein are compounds of Formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein the cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is optionally substituted with one, two, or three independently selected R 11 substituents, and R 2b is hydrogen, deuterium, a halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl; and R 11 is as described elsewhere herein for Formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively.

[0567] In certain embodiments, provided herein are compounds of Formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is heterocycloalkyl or heteroaryl, wherein the heterocycloalkyl or heteroaryl is optionally substituted with one, two, or three independently selected R 11 substituents, and R 2bis hydrogen, deuterium, a halogen, C 1-3 alkyl, deuterated C 1-3 alkyl, or halogenated C 1-3 alkyl; and R 11 is as described elsewhere herein for Formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively.

[0568] In certain embodiments, provided herein are compounds of Formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is heteroaryl, wherein the heteroaryl is optionally substituted with one, two, or three independently selected R 11 ; and R 2b is hydrogen, deuterium, a halogen, C 1-3 alkyl, deuterated C 1-3 alkyl, or halogenated C 1-3 alkyl; and R 11 is as described elsewhere herein for Formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively.

[0569] In certain embodiments, provided herein are compounds of Formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 , or -NR 8 R 9 , wherein the cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one, two, or three independently selected R 11 ; and R 2b is hydrogen, deuterium, a halogen, C 1-3 alkyl, deuterated C 1-3 alkyl, or halogenated C 1-3 alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a 4- to 5-membered heterocyclyl optionally substituted with one, two, or three independently selected R 11 ; and R 7 , R 8 , R 9 and R 11 are as described elsewhere herein for Formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively.

[0570] In certain embodiments, provided herein are compounds of Formula (I), (II), (IV), or (IVa), wherein R2a and R 2b together with the carbon atom to which they are attached form a cyclobutyl group substituted with one, two or three independently selected R 11 groups, or form an oxetanyl group; and R 11 are as described elsewhere herein for formulas (I), (II), (IV) and (IVa), respectively. In certain embodiments, provided herein are compounds of formula (I), (II), (IV) or (IVa), wherein R 2a and R 2b together with the carbon atom to which they are attached form a cyclobutyl group substituted with one or two R 11 groups, or form an oxetanyl group; each R 11 is independently fluorine, cyano, -CHF 2 , -CF 3 , -OCF 3 or -S(O) 2 CH 3 ; or two R 11 groups together with the carbon atom to which they are attached form a cyclopropyl group; m is 1; n is 1; and the other variables are as described elsewhere herein for formulas (I), (II), (IV) and (IVa), respectively.

[0571] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is -OR 7 , -SR 7 or -NR 8 R 9 ; R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl; and R 7 , R 8 , R 9 and R 11 are as described elsewhere herein for formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively.

[0572] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is -R u -cycloalkyl, -OR 7 , -SR 7 or -NR 8 R 9 ; R 2bis hydrogen, deuterium, a halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halo C 1-3 alkyl; R 7 is haloalkyl or cycloalkyl; R 8 is hydrogen; R 9 is -R u -cycloalkyl or cycloalkyl, where the -R u -cycloalkyl or cycloalkyl is optionally substituted by one, two or three independently selected R 11 substituents, and the remaining variables are as described elsewhere herein for formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V). In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is -R u -cycloalkyl, -OR 7 -, -SR 7 or -NR 8 R 9 ; R 2b is hydrogen, deuterium, a halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halo C 1-3 alkyl; R 7 is haloalkyl or cycloalkyl; R 8 is hydrogen; R 9 is -R u -cycloalkyl or cycloalkyl, where the -R u -cycloalkyl or cycloalkyl is optionally substituted by one, two or three independently selected R 11 substituents; each R 11 is independently halo or halo C 1-3 alkyl; and the remaining variables are as described elsewhere herein for formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V). In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is cyclopropylmethyl, -OR 7 -, -SR 7 or -NR 8 R 9 ; R 2b is hydrogen, deuterium, a halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halo C 1-3 alkyl; R 7 is -CH 2 CF 3or cyclobutyl; R 8 is hydrogen; R 9 is cyclopropylmethyl or cyclobutyl, wherein the cyclopropylmethyl or cyclobutyl is optionally substituted with one, two or three R 11 substituents; each R 11 is independently fluorine or trifluoromethyl, and the remaining variables are as described elsewhere herein for formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V). In certain embodiments, R 2b is hydrogen.

[0573] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is -OR 7 , -SR 7 or -NR 8 R 9 ; R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halo C 1-3 alkyl; and R 7 is -CH 2 CF 3 or cyclobutyl; R 9 is cyclopropylmethyl or cyclobutyl, wherein the cyclopropylmethyl or cyclobutyl is optionally substituted with one, two or three R 11 substituents; each R 11 is independently fluorine or trifluoromethyl, and the remaining variables are as described elsewhere herein for formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V).

[0574] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 7 is -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl, wherein the -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl is optionally substituted with one, two or three independently selected R 11 substituents; R 8 is hydrogen, deuterium, alkyl, deuterated alkyl or haloalkyl; R 9 is -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl, wherein the -R u-cycloalkyl, -R u -heterocycloalkyl, cycloalkyl, heterocycloalkyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 , or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocycloalkyl or heteroaryl, wherein the heterocycloalkyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 ; each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, halo C 1-3 alkoxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, halo C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl or halo C 1-3 alkylsulfinyl; and R u is a methylene, ethylene or propylene linker optionally substituted by one to six independently selected halo.

[0575] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 7 is cycloalkyl, heterocycloalkyl or heteroaryl, wherein the cycloalkyl, heterocycloalkyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 ; R 8 is hydrogen, deuterium, alkyl, deuterated alkyl or haloalkyl; R 9 is cycloalkyl, heterocycloalkyl or heteroaryl, wherein the cycloalkyl, heterocycloalkyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 , or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocycloalkyl or heteroaryl, wherein the heterocycloalkyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 , and wherein the heterocycloalkyl is further optionally substituted by oxo, and each R 11 is independently halo, cyano, oxo, C 1-3Alkyl, deuterated C 1-3 Alkyl, halogenated C 1-3 Alkyl, cyano C 1-3 Alkyl, hydroxy C 1-3 Alkyl, C 1-3 Alkoxy C 1-3 Alkyl, halogenated C 1-3 Alkoxy C 1-3 Alkyl, hydroxy, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Alkylthio, halogenated C 1-3 Alkylthio, C 1-3 Alkylsulfonyl, halogenated C 1-3 Alkylsulfonyl, C 1-3 Alkylsulfinyl or halogenated C 1-3 Alkylsulfinyl; and R u is a methylene, ethylene or propylene linker optionally substituted with one to six independently selected halogen atoms.

[0576] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 7 is a cycloalkyl or heterocyclic group optionally substituted with one, two or three independently selected R 11 substituents; R 8 is hydrogen, deuterium, alkyl, deuterated alkyl or halogenated alkyl; R 9 is a cycloalkyl or heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally substituted with one, two or three independently selected R 11 substituents, or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclic group or heteroaryl group, wherein the heterocyclic group or heteroaryl group is optionally substituted with one, two or three independently selected R 11 substituents; R 11 independently is halogen, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halogenated C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, halogenated C 1-3 alkoxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, C 1-3 alkylthio, halogenated C 1-3 alkylthio, C 1-3 alkylsulfonyl, halogenated C1-3 alkylsulfonyl, C 1-3 alkylsulfinyl or halo C 1-3 alkylsulfinyl.

[0577] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 7 is -R u -heterocyclyl or heterocyclyl, wherein the -R u -heterocyclyl or heterocyclyl is optionally substituted with one, two, or three independently selected R 11 ; and each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, halo C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl or halo C 1-3 alkylsulfinyl.

[0578] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 7 is haloalkyl; R 8 is hydrogen, deuterium, alkyl, deuterated alkyl, or haloalkyl; and R 9 is haloalkyl.

[0579] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is -NR 8 R 9 ; R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl, or halo C 1-3 alkyl; and R 8 , R 9 and R 11 are as described respectively for formula (I), (II), (III), (IIIa), (IV), (IVa), and (V).

[0580] In certain embodiments, provided herein are compounds of Formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is -NR 8 R 9 ; R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl, or halogenated C 1-3 alkyl; and R 9 is -R 11 -cycloalkyl optionally substituted with one, two, or three R u , and R 11 are as described elsewhere herein for Formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively. In certain embodiments, provided herein are compounds of Formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is -NR 8 R 9 ; R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl, or halogenated C 1-3 alkyl; and R 9 is cycloalkyl optionally substituted with one, two, or three independently selected R 11 , and R 11 are as described elsewhere herein for Formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively. In certain embodiments, provided herein are compounds of Formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is -NR 8 R 9 ; R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl, or halogenated C 1-3 alkyl; and R 9 is cyclopropyl optionally substituted with one, two, or three fluorines, and the remaining variables are as described elsewhere herein for Formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively.

[0581] In certain embodiments, provided herein are compounds of Formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 8is hydrogen, deuterium, alkyl, deuterated alkyl or haloalkyl; R 9 is haloalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl or heterocyclyl, wherein the haloalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl or heterocyclyl is optionally substituted by one, two or three independently selected R 11 ; and each R 11 is independently halo, cyano, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, halo C 1-3 alkoxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, halo C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl or halo C 1-3 alkylsulfinyl, respectively for formula (I), (II), (III), (IIIa), (IV), (IVa), and (V).

[0582] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 8 is hydrogen, deuterium, alkyl, deuterated alkyl or haloalkyl; R 9 is haloalkyl, -R u -heterocyclyl or heterocyclyl, wherein the haloalkyl, -R u -heterocyclyl or heterocyclyl is optionally substituted by one, two or three independently selected R 11 ; and R 11 is as described respectively for formula (I), (II), (III), (IIIa), (IV), (IVa), and (V).

[0583] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2a is -OR 7 ; R 7 is haloalkyl, -Ru -cycloalkyl, -R u -heterocyclic group, cycloalkyl or heterocyclic group, wherein the haloalkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl or heterocyclic group is optionally substituted by one, two or three independently selected R 11 ; and R 11 is as defined for formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) respectively.

[0584] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2b is hydrogen or methyl. In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V), wherein R 2b is hydrogen. In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2b is hydrogen, and the other variables are as defined elsewhere herein for formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V) respectively.

[0585] In certain embodiments, provided herein are compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein m is 0, and the other variables are as defined elsewhere herein for formulas (I), (II), (IV), (IVa), (VI) and (X) respectively. In certain embodiments, provided herein are compounds of formula (I), (II), (IV), (IVa), (VI) or (X), wherein m is 0, n is 0 or 1, and the other variables are as defined elsewhere herein for formulas (I), (II), (IV), (VI) and (X) respectively.

[0586] In certain embodiments, provided herein are compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C1-3 alkylthio, halo-C 1-3 alkylthio, C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl or halo-C 1-3 alkylsulfinyl, and the other variables are as described herein for formulas (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X), respectively. In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X), wherein each R 11 is independently halo, cyano, C 1-3 alkyl or halo-C 1-3 alkyl, and the other variables are as described herein for formulas (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X), respectively. In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X), wherein each R 11 is independently halo, cyano, or halo-C 1-3 alkyl, and the other variables are as described herein for formulas (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X), respectively. In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X), wherein each R 11 is independently halo, cyano, halo-C 1-3 alkyl, hydroxy-C 1-3 alkyl, C 1-3 alkoxy-C 1-3 alkyl, halo-C 1-3 alkoxy-C 1-3 alkyl, hydroxy, C 1-3 alkoxy or halo-C 1-3an alkoxy group, and the other variables are as described herein for formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X), respectively. In certain embodiments, each R 11 is independently halo, cyano, halo C 1-3 alkyl, or hydroxy.

[0587] In certain embodiments, provided herein are compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X), wherein each R 11 is independently halo, cyano, or halo C 1-3 alkyl, and the other variables are as described herein for formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X), respectively. In certain embodiments, each R 11 is independently halo or cyano.

[0588] In certain embodiments, provided herein are compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X), wherein each R 11 is independently fluorine, chlorine, bromine, cyano, -CHF 2 or -CF 3 , and the other variables are as described elsewhere herein for formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X), respectively. In certain embodiments, each R 11 is independently Cl or cyano.

[0589] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein the nitrogen of the indole is protected by a protecting group and the other variables are as described elsewhere herein for formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) and (X), respectively. In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein the nitrogen of the indole is protected by Boc or tosylamide and the other variables are as described elsewhere herein for formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) and (X), respectively.

[0590] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein k is 0 and the other variables are as described elsewhere herein for formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) and (X), respectively. In certain embodiments, provided herein are compounds of formula (I), (II), (IIa), (IIb), (IIc), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein k is 0 and the other variables are as described elsewhere herein for formula (I), (II), (IIa), (IIb), (IIc), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (V), (VI), (VII), (VIIa), (VIII), (IX) and (X), respectively.

[0591] In certain embodiments, provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein R3 is halogenated, methyl or -CF 3 , and the other variables are as described elsewhere herein for formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) and (X), respectively. In certain embodiments, provided herein are compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein R 3 is methyl, and the other variables are as described elsewhere herein for formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) and (X), respectively.

[0592] In certain embodiments, provided herein are compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein R 4 is hydrogen, halogenated, C 1-3 alkyl or halogenated C 1-3 alkyl, and the other variables are as described elsewhere herein for formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) and (X), respectively. In certain other embodiments, R 4 is hydrogen, fluorine, chlorine, methyl or -CF 3 . In certain other embodiments, R 4 is hydrogen, fluorine, chlorine or methyl. In certain other embodiments, R 4 is hydrogen.

[0593] In certain embodiments, provided herein are compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein R 5 is halogenated, C 1-3 alkyl, C 3-5 cycloalkyl or C 1-3 alkoxy; and the other variables are as described elsewhere herein for formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) and (X), respectively. In certain embodiments, R 5is chlorine, bromine, methyl, cyclopropyl or methoxy.

[0594] In certain embodiments, provided herein are compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl or C 1-3 alkoxy; and the other variables are as described elsewhere herein for formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) and (X), respectively. In certain embodiments, R 6 is chlorine, bromine, cyano, methyl, cyclopropyl or methoxy.

[0595] In certain embodiments, provided herein are compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein R 4 is hydrogen or methyl; R 5 is methoxy; R 6 is methyl, and the other variables are as described elsewhere herein for formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) and (X), respectively. In certain other embodiments, R 4 is hydrogen; R 5 is methoxy and R 6 is methyl. In certain embodiments, provided herein are compounds of formula (I), (Il), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX) or (X), wherein R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6is methyl, and the other variables are as described elsewhere herein for formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), and (X). In certain embodiments, provided herein are compounds of formula (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), or (X), wherein R 1 is hydrogen, fluorine, or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine, or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl, and the other variables are as described elsewhere herein for formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), and (X). In certain embodiments, provided herein are compounds of formula (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), or (X), wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, chlorine, or methyl; R 5is methoxy or cyclopropyl; R 6 is methyl, and the other variables are as described elsewhere herein for formulas (I), (Il), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), and (X). In certain embodiments, provided herein are compounds of formula (I), (Il), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), or (X), wherein R 1 is hydrogen or fluorine; X is CH; R 4 is hydrogen, fluorine, or chlorine; R 5 is methoxy; R 6 is methyl, and the other variables are as described elsewhere herein for formulas (I), (Il), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), and (X).

[0596] In certain embodiments, provided herein are compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X), wherein R 1is hydrogen; X is CH, and the other variables are as described elsewhere herein for formulas (I), (Il), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X).

[0597] In certain embodiments, provided herein are compounds of formula (I), (Il), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), or (X), wherein R 1 is hydrogen; X is CH, and the other variables are as described elsewhere herein for formulas (I), (Il), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), and (X).

[0598] In certain embodiments, provided herein are pharmaceutical compositions that comprise any one of the compounds described herein (e.g., a compound of formula (I), (I), (Il), (IIa), (IIb), (IIc), (III), (IIIa), (IV), (IVa), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (IVm), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), or (X)), or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

[0599] In certain embodiments, provided herein is a compound of formula (I), wherein the compound is selected from:

[0600] 4-((2S,4S)-4-(4-Fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 1)

[0601] 4-((2R,4R)-4-(4-Fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0602] 4-((2S,4R)-4-(4-Fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0603] 4-((2R,4S)-4-(4-Fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0604] 4-(4-(4-Fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0605] (±)-trans-4-(4-(4-Bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 2)

[0606] 4-((2S,4S)-(4-(4-Bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0607] 4-((2R,4R)-(4-(4-Bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0608] 4-((2S,4R)-(4-(4-Bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0609] 4-((2R,4S)-(4-(4-Bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0610] 4-(4-(4-Bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0611] (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; (Example 3)

[0612] 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid;

[0613] 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid;

[0614] 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid;

[0615] 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid;

[0616] 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid;

[0617] 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; (Example 4)

[0618] 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid;

[0619] 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid;

[0620] 4-((2R,4S)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid;

[0621] 4-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid;

[0622] (±)-trans-4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; (Example 5)

[0623] 4-((2S,4S)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid;

[0624] 4-((2R,4R)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid;

[0625] 4-((2S,4R)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid;

[0626] 4-((2R,4S)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid;

[0627] 4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid;

[0628] (±)-trans-4-(4-(2H-Indazol-2-yl)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 6)

[0629] 4-((2S,4S)-(4-(2H-Indazol-2-yl)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0630] 4-((2R,4R)-4-(2H-indazol-2-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0631] 4-((2S,4R)-(4-(2H-indazol-2-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0632] 4-((2R,4S)-(4-(2H-indazol-2-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0633] 4-(4-(2H-indazol-2-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0634] (±)-trans-4-(4-(4-(difluoromethyl)-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 7)

[0635] 4-((2S,4S)-(4-(4-(difluoromethyl)-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0636] 4-((2R,4R)-(4-(4-(difluoromethyl)-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0637] 4-((2S,4R)-(4-(4-(difluoromethyl)-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0638] 4-((2R,4S)-(4-(4-(difluoromethyl)-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0639] 4-(4-(4-(difluoromethyl)-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0640] 4-((2S,4S)-4-chloro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 8)

[0641] 4-((2R,4R)-4-chloro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0642] 4-((2S,4R)-4-chloro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0643] 4-((2R,4S)-4-chloro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0644] 4-(4-chloro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0645] (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; (Example 9)

[0646] 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid;

[0647] 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid;

[0648] 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid;

[0649] 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid;

[0650] 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid;

[0651] 4-((2S,4S)-4-(4-Cyano-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid (Example 10)

[0652] 4-((2R,4R)-4-(4-Cyano-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0653] 4-((2S,4R)-4-(4-Cyano-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0654] 4-((2R,4S)-4-(4-Cyano-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0655] 4-(4-(4-Cyano-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0656] (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; (Example 11)

[0657] 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid;

[0658] 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid;

[0659] 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid;

[0660] 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid;

[0661] 4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid;

[0662] (±)-trans-4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2-oxopyrrolidin-1-yl)piperidin-2-yl)benzoic acid; (Example 12)

[0663] 4-((2S,4S)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2-oxopyrrolidin-1-yl)piperidin-2-yl)benzoic acid; (Example 13)

[0664] 4-((2R,4R)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2-oxopyrrolidin-1-yl)piperidin-2-yl)benzoic acid;

[0665] 4-((2S,4R)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2-oxopyrrolidin-1-yl)piperidin-2-yl)benzoic acid;

[0666] 4-((2R,4S)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2-oxopyrrolidin-1-yl)piperidin-2-yl)benzoic acid;

[0667] 4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2-oxopyrrolidin-1-yl)piperidin-2-yl)benzoic acid;

[0668] (±)-trans-4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidin-2-yl)benzoic acid; (Example 14)

[0669] 4-((2S,4S)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidin-2-yl)benzoic acid; (Example 15)

[0670] 4-((2R,4R)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidin-2-yl)benzoic acid;

[0671] 4-((2S,4R)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidin-2-yl)benzoic acid;

[0672] 4-((2R,4S)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidin-2-yl)benzoic acid;

[0673] 4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidin-2-yl)benzoic acid;

[0674] (±)-trans-4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(sulfamoylamino)piperidin-2-yl)benzoic acid; (Example 16)

[0675] 4-((2S,4S)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(sulfamoylamino)piperidin-2-yl)benzoic acid;

[0676] 4-((2R,4R)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(sulfamoylamino)piperidin-2-yl)benzoic acid;

[0677] 4-((2S,4R)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(sulfamoylamino)piperidin-2-yl)benzoic acid;

[0678] 4-((2R,4S)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(sulfamoylamino)piperidin-2-yl)benzoic acid;

[0679] 4-(-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(sulfamoylamino)piperidin-2-yl)benzoic acid;

[0680] (±)-trans-4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylamino)piperidin-2-yl)benzoic acid; (Example 17)

[0681] 4-((2S,4S)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylamino)piperidin-2-yl)benzoic acid; (Example 18)

[0682] 4-((2R,4R)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylamino)piperidin-2-yl)benzoic acid;

[0683] 4-((2S,4R)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylamino)piperidin-2-yl)benzoic acid;

[0684] 4-((2R,4S)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylamino)piperidin-2-yl)benzoic acid;

[0685] 4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylamino)piperidin-2-yl)benzoic acid;

[0686] 4-((2S,4S)-4-((3,3-Difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 19)

[0687] 4-((2R,4R)-4-((3,3-Difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0688] 4-((2S,4R)-4-((3,3-Difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0689] 4-((2R,4S)-4-((3,3-Difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0690] 4-((3,3-Difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0691] 4-((2S,4S)-4-(Cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 20)

[0692] 4-((2R,4R)-4-(Cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0693] 4-((2S,4R)-4-(Cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0694] 4-((2R,4S)-4-(Cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0695] 4-(4-(Cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0696] 4-((2S,4S)-4-(Bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 21)

[0697] 4-((2R,4R)-4-(Bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0698] 4-((2S,4R)-4-(Bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0699] 4-((2R,4S)-4-(Bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0700] 4-(4-(Bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0701] 4-((2S,4S)-4-((2,2-Difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 22)

[0702] 4-((2R,4R)-4-((2,2-Difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0703] 4-((2S,4R)-4-((2,2-difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0704] 4-((2R,4S)-4-((2,2-difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0705] 4-(4-((2,2-difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0706] 4-((2S,4S)-4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 23)

[0707] 4-((2R,4R)-4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0708] 4-((2S,4R)-4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0709] 4-((2R,4S)-4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0710] 4-(4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0711] 4-((2S,4S)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 24)

[0712] 4-((2R,4R)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0713] 4-((2S,4R)-4-((3,3-Difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0714] 4-((2R,4S)-4-((3,3-Difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0715] 4-(4-((3,3-Difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0716] 4-((2S,4S)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidin-2-yl)benzoic acid; (Example 25)

[0717] 4-((2R,4R)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidin-2-yl)benzoic acid;

[0718] 4-((2S,4R)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidin-2-yl)benzoic acid;

[0719] 4-((2R,4S)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidin-2-yl)benzoic acid;

[0720] 4-(1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidin-2-yl)benzoic acid;

[0721] 4-((2S,4S)-4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 26)

[0722] 4-((2R,4R)-4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0723] 4-((2S,4R)-4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0724] 4-((2R,4S)-4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0725] 4-(4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0726] 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidin-2-yl)benzoic acid; (Example 27)

[0727] 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidin-2-yl)benzoic acid;

[0728] 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidin-2-yl)benzoic acid;

[0729] 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidin-2-yl)benzoic acid;

[0730] 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidin-2-yl)benzoic acid;

[0731] 4-((2S,4S)-4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 28)

[0732] 4-((2R,4R)-4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 29)

[0733] 4-((2S,4R)-4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0734] 4-((2R,4S)-4-(Difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0735] 4-(4-(Difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0736] 4-((3R,5S)-1,1-Difluoro-6-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid; (Example 30)

[0737] 4-((3S,5S)-1,1-Difluoro-6-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid (or Example 30)

[0738] 4-((3S,5R)-1,1-Difluoro-6-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid;

[0739] 4-((3R,5R)-1,1-Difluoro-6-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid;

[0740] 4-(1,1-Difluoro-6-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid;

[0741] (±)-4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 31)

[0742] (S)-4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 32)

[0743] (R)-4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0744] 4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0745] 4-((5S,7S)-8-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]dec-7-yl)benzoic acid; (Example 33)

[0746] 4-((5R,7S)-8-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]dec-7-yl)benzoic acid; (or Example 33)

[0747] 4-((5R,7R)-8-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]dec-7-yl)benzoic acid;

[0748] 4-((5S,7R)-8-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]dec-7-yl)benzoic acid;

[0749] 4-(8-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]dec-7-yl)benzoic acid;

[0750] 4-((5S,7S)-8-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-8-azaspiro[4.5]dec-7-yl)benzoic acid; (Example 34)

[0751] 4-((5R,7S)-8-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-8-azaspiro[4.5]dec-7-yl)benzoic acid; (or Example 34)

[0752] 4-((5R,7R)-8-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-8-azaspiro[4.5]dec-7-yl)benzoic acid;

[0753] 4-((5S,7R)-8-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-8-azaspiro[4.5]dec-7-yl)benzoic acid;

[0754] 4-(8-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-8-azaspiro[4.5]dec-7-yl)benzoic acid;

[0755] 4-(5R,7S)-2,2-Difluoro-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azaspiro[4.5]decan-7-yl)benzoic acid; (Example 35 or 36)

[0756] 4-(5S,7S)-(2,2-Difluoro-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azaspiro[4.5]decan-7-yl)benzoic acid; (or Example 36 or 35)

[0757] 4-(5S,7R)-(2,2-Difluoro-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azaspiro[4.5]decan-7-yl)benzoic acid;

[0758] 4-(5R,7R)-(2,2-Difluoro-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azaspiro[4.5]decan-7-yl)benzoic acid;

[0759] 4-(2,2-Difluoro-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azaspiro[4.5]decan-7-yl)benzoic acid;

[0760] (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-phenylpiperidin-2-yl)benzoic acid; (Example 37)

[0761] 4-((2S,4S)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-phenylpiperidin-2-yl)benzoic acid;

[0762] 4-((2R,4R)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-phenylpiperidin-2-yl)benzoic acid;

[0763] 4-((2S,4R)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-phenylpiperidin-2-yl)benzoic acid;

[0764] 4-((2R,4S)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-phenylpiperidin-2-yl)benzoic acid;

[0765] 4-(4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-phenylpiperidin-2-yl)benzoic acid;

[0766] 4-((2S,4S)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(pyridin-2-yl)piperidin-2-yl)benzoic acid; (Example 38)

[0767] 4-((2R,4R)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(pyridin-2-yl)piperidin-2-yl)benzoic acid;

[0768] 4-((2S,4R)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(pyridin-2-yl)piperidin-2-yl)benzoic acid;

[0769] 4-((2R,4S)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(pyridin-2-yl)piperidin-2-yl)benzoic acid;

[0770] 4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(pyridin-2-yl)piperidin-2-yl)benzoic acid;

[0771] 4-(2-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azaspiro[3.4]octan-1-yl)benzoic acid; (Example 39)

[0772] (S)-4-(2-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azaspiro[3.4]octan-1-yl)benzoic acid;

[0773] (R)-4-(2-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azaspiro[3.4]octan-1-yl)benzoic acid;

[0774] (R)-4-(2-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azaspiro[3.3]heptan-1-yl)benzoic acid; (Example 40)

[0775] (S)-4-(2-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azaspiro[3.3]heptan-1-yl)benzoic acid;

[0776] 4-(2-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azaspiro[3.3]heptan-1-yl)benzoic acid;

[0777] 4-((2S,4S)-4-Cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 41)

[0778] 4-((2R,4R)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0779] 4-((2S,4R)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0780] 4-((2R,4S)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0781] 4-(4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0782] 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidin-2-yl)benzoic acid; (Example 42)

[0783] 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidin-2-yl)benzoic acid;

[0784] 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidin-2-yl)benzoic acid;

[0785] 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidin-2-yl)benzoic acid;

[0786] 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidin-2-yl)benzoic acid;

[0787] 4-((2S,4S)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0788] 4-((2S,4R)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0789] 4-((2R,4R)-4-Cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0790] 4-((2R,4S)-4-Cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0791] 4-(4-Cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 43)

[0792] 4-((2S,4S)-4-(Cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 44)

[0793] 4-((2R,4R)-4-(Cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0794] 4-((2S,4R)-4-(Cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0795] 4-((2R,4S)-4-(Cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0796] 4-(4-(Cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0797] (S)-4-(2,2-Difluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 45)

[0798] (R)-4-(2,2-Difluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0799] 4-(2,2-Difluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0800] 4-((2R,4S,6S)-2-(Difluoromethyl)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 46 or 47)

[0801] 4-((2S,4R,6S)-2-(Difluoromethyl)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 47 or 46)

[0802] 4-((2S,4S,6R)-2-(Difluoromethyl)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0803] 4-((2R,4R,6R)-2-(Difluoromethyl)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0804] 4-(2-(Difluoromethyl)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0805] 4-((2R,4S,6S)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 48 or 49)

[0806] 4-((2S,4R,6S)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 49 or 48)

[0807] 4-((2S,4S,6R)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0808] 4-((2R,4R,6R)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0809] 4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0810] (S)-4-(2,2-Difluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)-2-fluorobenzoic acid; (Example 50)

[0811] (R)-4-(2,2-Difluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)-2-fluorobenzoic acid;

[0812] 4-(2,2-Difluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)-2-fluorobenzoic acid;

[0813] (S)-4-(8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azaspiro[2.1.5 5 .1 3 undecan-7-yl)benzoic acid; (Example 51)

[0814] (R)-4-(8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azaspiro[2.1.5 5 .1 3 undecan-7-yl)benzoic acid;

[0815] 4-(8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azaspiro[2.1.5 5 .1 3 undecan-7-yl)benzoic acid;

[0816] (S)-4-(7-((3-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2,2-difluoro-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 53)

[0817] (R)-4-(7-((3-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2,2-difluoro-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0818] 4-(7-((3-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2,2-difluoro-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0819] (S)-4-(2,2-Difluoro-7-((3-fluoro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 54)

[0820] (R)-4-(2,2-difluoro-7-((3-fluoro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0821] 4-(2,2-difluoro-7-((3-fluoro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0822] 4-((2R,4s,6S)-2-cyano-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 52 or 55)

[0823] 4-((2S,4r,6S)-2-cyano-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 55 or 52)

[0824] 4-((2S,4s,6R)-2-cyano-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0825] 4-((2R,4r,6R)-2-cyano-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0826] 4-(2-cyano-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0827] 4-((2R,4s,6S)-2-(difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 56 or 57)

[0828] 4-((2S,4r,6S)-2-(difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 57 or 56)

[0829] 4-((2S,4s,6R)-2-(difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0830] 4-((2R,4r,6R)-2-(Difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0831] 4-(2-(Difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0832] (S)-4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxo-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 58)

[0833] (R)-4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxo-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0834] 4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxo-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0835] 4-((2R,4s,6S)-2-Hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-methyl-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 59 or 60)

[0836] 4-((2S,4r,6S)-2-Hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-methyl-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 60 or 59)

[0837] 4-((2S,4s,6R)-2-Hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-methyl-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0838] 4-((2R,4r,6R)-2-Hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-methyl-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0839] 4-(2-Hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-methyl-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0840] 4-((2S)-2-Fluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 61)

[0841] 4-((2R,4s,6S)-2-Fluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 62 or 63)

[0842] 4-((2S,4r,6S)-2-Fluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 62 or 63)

[0843] 4-((2S,4s,6R)-2-Fluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0844] 4-((2R,4r,6R)-2-Fluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0845] 4-(2-Fluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0846] 4-((2R,4s,6S)-4-(2-Hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 64)

[0847] 4-((2S,4r,6S)-2-Hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 64)

[0848] 4-((2S,4s,6R)-2-Hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0849] 4-((2R,4r,6R)-2-Hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0850] 4-(2-Hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0851] (R)-4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethyl)piperazin-2-yl)benzoic acid; (Example 65)

[0852] (S)-4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethyl)piperazin-2-yl)benzoic acid;

[0853] 4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethyl)piperazin-2-yl)benzoic acid;

[0854] (R)-4-(4-(2,2-Difluoroethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (Example 66)

[0855] (S)-4-(4-(2,2-Difluoroethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid;

[0856] 4-(4-(2,2-Difluoroethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid;

[0857] (R)-4-(4-((3,3-Difluorocyclobutyl)methyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (Example 67)

[0858] (S)-4-(4-((3,3-Difluorocyclobutyl)methyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid;

[0859] 4-(4-((3,3-Difluorocyclobutyl)methyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid;

[0860] (R)-4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperazin-2-yl)benzoic acid; (Example 68)

[0861] (S)-4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperazin-2-yl)benzoic acid;

[0862] 4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperazin-2-yl)benzoic acid;

[0863] (R)-4-(4-((3-Fluorooxetan-3-yl)methyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (Example 69)

[0864] (S)-4-(4-((3-Fluorooxetan-3-yl)methyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid;

[0865] 4-(4-((3-Fluorooxetan-3-yl)methyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid;

[0866] (R)-4-(4-(2-Fluoroethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (Example 70)

[0867] (S)-4-(4-(2-Fluoroethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid;

[0868] 4-(4-(2-Fluoroethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid;

[0869] (±)-trans-4-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; (Example 71)

[0870] 4-((2S,4S)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; (Example 81)

[0871] 4-((2R,4R)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0872] 4-((2S,4R)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0873] 4-((2R,4S)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0874] 4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0875] 4-((2S,4S)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidin-1-yl)piperidin-2-yl)benzoic acid; (Example 72)

[0876] 4-((2R,4R)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0877] 4-((2S,4R)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0878] 4-((2R,4S)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0879] 4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0880] 4-((2S,4S)-4-(3-Cyanoazetidin-1-yl)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 73)

[0881] 4-((2R,4R)-4-(3-Cyanoazetidin-1-yl)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0882] 4-((2S,4R)-4-(3-Cyanoazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0883] 4-((2R,4S)-4-(3-Cyanoazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0884] 4-(4-(3-Cyanoazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0885] 4-((2S,4S)-4-(3-(Difluoromethyl)azetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 74)

[0886] 4-((2R,4R)-4-(3-(Difluoromethyl)azetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0887] 4-((2S,4R)-4-(3-(Difluoromethyl)azetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0888] 4-((2R,4S)-4-(3-(Difluoromethyl)azetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0889] 4-(4-(3-(Difluoromethyl)azetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0890] 4-((2S,4S)-1-((3-Chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; (Example 75)

[0891] 4-((2R,4R)-1-((3-Chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0892] 4-((2S,4R)-1-((3-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0893] 4-((2R,4S)-1-((3-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0894] 4-(1-((3-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0895] 4-((2S,4S)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; (Example 76)

[0896] 4-((2R,4R)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0897] 4-((2S,4R)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0898] 4-((2R,4S)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0899] 4-(1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0900] 4-((2S,4S)-4-(3-cyanoazetidin-1-yl)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 77)

[0901] 4-((2R,4R)-4-(3-cyanoazetidin-1-yl)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0902] 4-((2S,4R)-4-(3-cyanoazetidin-1-yl)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0903] 4-((2R,4S)-4-(3-cyanoazetidin-1-yl)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0904] 4-(4-(3-cyanoazetidin-1-yl)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0905] 4-((2S,4S)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(5-azaspiro[2.3]hexan-5-yl)piperidin-2-yl)benzoic acid; (Example 78)

[0906] 4-((2R,4R)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(5-azaspiro[2.3]hexan-5-yl)piperidin-2-yl)benzoic acid;

[0907] 4-((2S,4R)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(5-azaspiro[2.3]hexan-5-yl)piperidin-2-yl)benzoic acid;

[0908] 4-((2R,4S)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(5-azaspiro[2.3]hexan-5-yl)piperidin-2-yl)benzoic acid;

[0909] 4-(1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(5-azaspiro[2.3]hexan-5-yl)piperidin-2-yl)benzoic acid;

[0910] 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(methylsulfonyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; (Example 79)

[0911] 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(methylsulfonyl)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0912] 4-((2S,4R)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(methylsulfonyl)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0913] 4-((2R,4S)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(methylsulfonyl)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0914] 4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(methylsulfonyl)azetidin-1-yl)piperidin-2-yl)benzoic acid;

[0915] 4-((2S,4S)-4-(3-Fluoroazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 80)

[0916] 4-((2R,4R)-4-(3-Fluoroazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0917] 4-((2S,4R)-4-(3-Fluoroazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0918] 4-((2R,4S)-4-(3-Fluoroazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0919] 4-(4-(3-Fluoroazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0920] 4-((2S,4S)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-yloxy)piperidin-2-yl)benzoic acid; (Example 82)

[0921] 4-((2R,4R)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-yloxy)piperidin-2-yl)benzoic acid;

[0922] 4-((2S,4R)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-yloxy)piperidin-2-yl)benzoic acid;

[0923] 4-((2R,4S)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-yloxy)piperidin-2-yl)benzoic acid;

[0924] 4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-yloxy)piperidin-2-yl)benzoic acid;

[0925] 4-((2S,4S)-4-(2,2-Difluoroethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 83)

[0926] 4-((2R,4R)-4-(2,2-Difluoroethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0927] 4-((2S,4R)-4-(2,2-Difluoroethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0928] 4-((2R,4S)-4-(2,2-Difluoroethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0929] 4-(4-(2,2-Difluoroethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0930] 4-((2S,4S)-4-Cyclobutoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 84)

[0931] 4-((2R,4R)-4-Cyclobutoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0932] 4-((2S,4R)-4-Cyclobutoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0933] 4-((2R,4S)-4-Cyclobutoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0934] 4-(4-Cyclobutoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[0935] 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethoxy)piperidin-2-yl)benzoic acid; (Example 85)

[0936] 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethoxy)piperidin-2-yl)benzoic acid;

[0937] 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethoxy)piperidin-2-yl)benzoic acid;

[0938] 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethoxy)piperidin-2-yl)benzoic acid; and

[0939] 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethoxy)piperidin-2-yl)benzoic acid.

[0940] In certain embodiments, provided herein are compounds of formula (I), wherein the compound is selected from the group consisting of: the compounds in Table A below and their pharmaceutically acceptable salts:

[0941]

[0942]

[0943]

[0944]

[0945]

[0946]

[0947]

[0948]

[0949]

[0950]

[0951]

[0952]

[0953]

[0954]

[0955]

[0956]

[0957]

[0958]

[0959]

[0960] In certain embodiments, provided herein are compounds of formula (I), wherein the compounds are selected from the group consisting of: the compounds in Table B below and pharmaceutically acceptable salts thereof:

[0961]

[0962]

[0963]

[0964]

[0965]

[0966]

[0967]

[0968]

[0969]

[0970]

[0971]

[0972]

[0973] In certain embodiments, provided herein are compounds of formula (I), wherein the compounds are selected from the group consisting of: the compounds in Table C below and their pharmaceutically acceptable salts:

[0974]

[0975]

[0976]

[0977]

[0978]

[0979]

[0980]

[0981]

[0982]

[0983]

[0984] In certain embodiments, provided herein are compounds of formula (I), wherein the compounds are selected from the group consisting of: the compounds in Table D below and their pharmaceutically acceptable salts:

[0985]

[0986]

[0987]

[0988]

[0989]

[0990]

[0991]

[0992]

[0993]

[0994]

[0995] In some embodiments, the compounds of formula (I) are not compounds selected from the following list of compounds:

[0996] 4-(7-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0997] 4-(7-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[0998] 4-(8-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decane-7-yl)benzoic acid;

[0999] 4-(9-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-9-azaspiro[5.5]undecane-8-yl)benzoic acid;

[1000] 4-(1,1-Difluoro-6-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid;

[1001] 4-(1-Methoxy-6-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid;

[1002] 4-(1,1-Difluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[1003] 4-(2,2-Difluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[1004] 4-(1-Methoxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[1005] 4-(2-Methoxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[1006] 4-(2-Ethoxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[1007] 4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(trifluoromethyl)piperidin-2-yl)benzoic acid;

[1008] 4-(4-(Difluoromethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1009] 4-(4-Fluoro-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-methylpiperidin-2-yl)benzoic acid;

[1010] 4-(4-Ethyl-4-fluoro-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1011] 4-(4-Fluoro-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-propylpiperidin-2-yl)benzoic acid;

[1012] 4-((1R,3S,5S)-3-Ethoxy-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azabicyclo[3.2.1]octan-1-yl)benzoic acid;

[1013] 4-((2R,8R)-8-Ethoxy-3-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-3-azabicyclo[3.2.1]octan-2-yl)benzoic acid;

[1014] 4-((1R,4R,5R)-5-Ethoxy-2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azabicyclo[2.2.2]octan-1-yl)benzoic acid;

[1015] 4-((3R,5R)-5-Ethoxy-2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azabicyclo[2.2.2]octan-3-yl)benzoic acid;

[1016] 4-((2R,4R)-4-Cyclopropoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1017] 4-((2R,4R)-4-Cyclobutoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1018] 4-((2R,4R)-4-(Cyclopentyloxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1019] 4-((2R,4R)-4-(Cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1020] 4-((2R,4R)-4-(Cyclobutylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1021] 4-((2R,4R)-4-(Cyclopentylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1022] 4-((2R,4R)-4-(Cyclohexylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1023] 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylmethoxy)piperidin-2-yl)benzoic acid;

[1024] 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((tetrahydrofuran-3-yl)methoxy)piperidin-2-yl)benzoic acid;

[1025] 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-2-ylmethoxy)piperidin-2-yl)benzoic acid;

[1026] 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((tetrahydrofuran-2-yl)methoxy)piperidin-2-yl)benzoic acid;

[1027] 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((tetrahydro-2H-pyran-2-yl)methoxy)piperidin-2-yl)benzoic acid;

[1028] 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((tetrahydro-2H-pyran-3-yl)methoxy)piperidin-2-yl)benzoic acid;

[1029] 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((tetrahydro-2H-pyran-4-yl)methoxy)piperidin-2-yl)benzoic acid;

[1030] 4-((2R,4R)-1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(trifluoromethoxy)piperidin-2-yl)benzoic acid;

[1031] 4-((2R,4R)-4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1032] 4-(3-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-3-azabicyclo[4.1.0]heptan-2-yl)benzoic acid;

[1033] 4-(3-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-3-azabicyclo[4.1.0]heptan-4-yl)benzoic acid;

[1034] 4-(6-Ethoxy-3-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-3-azabicyclo[4.1.0]heptan-2-yl)benzoic acid;

[1035] 4-(6-Ethoxy-3-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-3-azabicyclo[4.1.0]heptan-4-yl)benzoic acid;

[1036] 4-((2R,4R)-4-(2,2-difluorocyclopropoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1037] 4-((2R,4R)-4-(2-fluoro-2-methylcyclopropoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1038] 4-((2R,4R)-4-(2,2-dimethylcyclopropoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1039] 4-((2R,4R)-4-(3,3-difluorocyclobutoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1040] 4-(4-Acetamido-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1041] 4-((2R,4R)-4-((2,2-difluorocyclopropyl)methoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1042] 4-((2R,4R)-4-((2-fluoro-2-methylcyclopropyl)methoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1043] 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2-methylcyclopropyl)methoxy)piperidin-2-yl)benzoic acid;

[1044] 4-((2R,4R)-4-((2,2-dimethylcyclopropyl)methoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1045] 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1-methylcyclopropoxy)piperidin-2-yl)benzoic acid;

[1046] 4-(5-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)octahydrofuro[3,2-c]pyridin-4-yl)benzoic acid;

[1047] 4-((6S)-5-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)octahydrofuro[3,2-c]pyridin-6-yl)benzoic acid;

[1048] 4-(6-(((5S)-5-methoxy-7-methyloctahydro-1H-indol-4-yl)methyl)-2H-6H4-pyrano[3,2-c]pyridin-5-yl)benzoic acid;

[1049] 4-(6-(((7S)-5-methoxy-7-methyloctahydro-1H-indol-4-yl)methyl)-2H-6H4-pyrano[3,2-c]pyridin-7-yl)benzoic acid;

[1050] 4-((1R)-2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1,2,3,4-tetrahydro-2H4-isoquinolin-1-yl)benzoic acid;

[1051] (S)-4-(5-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-5-azaspiro[2.5]octan-4-yl)benzoic acid;

[1052] 4-((2R,4R)-4-Ethoxy-1-((6-fluoro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1053] 4-((2R,4R)-1-((6-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-ethoxypiperidin-2-yl)benzoic acid;

[1054] 4-((2R,4R)-4-Ethoxy-1-((5-methoxy-6,7-dimethyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1055] 4-((2R,4R)-1-((7-cyclopropyl-5-methoxy-1H-indol-4-yl)methyl)-4-ethoxypiperidin-2-yl)benzoic acid;

[1056] 4-((2R,4R)-1-((7-cyano-5-methoxy-1H-indol-4-yl)methyl)-4-ethoxypiperidin-2-yl)benzoic acid;

[1057] 4-((2R,4R)-4-Ethoxy-1-((5-methoxy-7-(trifluoromethyl)-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1058] 4-((2R,4R)-1-((7-(difluoromethyl)-5-methoxy-1H-indol-4-yl)methyl)-4-ethoxypiperidin-2-yl)benzoic acid;

[1059] rac-4-((2R,4S)-4-(Cyclopropylmethoxy)-1-((5-methoxy-7-(methyl-d3)-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1060] 4-((2R,4R)-4-(Cyclopropylmethoxy)-1-((3-fluoro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1061] 4-((2R,4R)-4-Ethoxy-1-(4-methyl-3,7,8,9-tetrahydropyrano[3,2-e]indol-9-yl)piperidin-2-yl)benzoic acid;

[1062] 4-((2R,4R)-4-Ethoxy-1-(4-methyl-6,7,8,9-tetrahydro-3H-benzo[e]indol-9-yl)piperidin-2-yl)benzoic acid;

[1063] 4-((2R,4R)-4-Ethoxy-1-(5-methyl-1,6-dihydro-2H-furo[3,2-e]indol-1-yl)piperidin-2-yl)benzoic acid;

[1064] 4-((2R,4R)-4-Ethoxy-1-(4-methyl-3,6,7,8-tetrahydrocyclopenta[e]indol-8-yl)piperidin-2-yl)benzoic acid;

[1065] 4-((2R,4R)-4-Ethoxy-1-(4-methyl-3,7,8,9-tetrahydrothiopyrano[3,2-e]indol-9-yl)piperidin-2-yl)benzoic acid;

[1066] 4-((2R,4R)-4-Ethoxy-1-(4-methyl-6,6-dioxo-3,7,8,9-tetrahydrothiopyrano[3,2-e]indol-9-yl)piperidin-2-yl)benzoic acid;

[1067] 4-((2R,4R)-4-Ethoxy-1-(6-methoxy-8-methyl-1,3,4,5-tetrahydrobenzo[cd]indol-5-yl)piperidin-2-yl)benzoic acid;

[1068] 4-((2R,4R)-4-Ethoxy-1-(6-methoxy-8-methyl-4,5-dihydro-1H-pyrano[2,3,4-cd]indol-5-yl)piperidin-2-yl)benzoic acid;

[1069] 4-((2R,4R)-4-(Cyclopropylmethoxy)-1-(4-methyl-3,7,8,9-tetrahydropyrano[3,2-e]indol-9-yl)piperidin-2-yl)benzoic acid;

[1070] 4-((2R,4R)-4-(Cyclopropylmethoxy)-1-(4-methyl-6,7,8,9-tetrahydro-3H-benzo[e]indol-9-yl)piperidin-2-yl)benzoic acid;

[1071] 4-((2R,4R)-4-(Cyclopropylmethoxy)-1-(5-methyl-1,6-dihydro-2H-furo[3,2-e]indol-1-yl)piperidin-2-yl)benzoic acid;

[1072] 4-((2R,4R)-4-(Cyclopropylmethoxy)-1-(4-methyl-3,6,7,8-tetrahydrocyclopenta[e]indol-8-yl)piperidin-2-yl)benzoic acid;

[1073] 4-((2R,4R)-4-(Cyclopropylmethoxy)-1-(4-methyl-3,7,8,9-tetrahydrothiopyrano[3,2-e]indol-9-yl)piperidin-2-yl)benzoic acid;

[1074] 4-((2R,4R)-4-(Cyclopropylmethoxy)-1-(4-methyl-6,6-dioxido-3,7,8,9-tetrahydrothieno[3,2-e]indol-9-yl)piperidin-2-yl)benzoic acid;

[1075] 4-((2R,4R)-4-(Cyclopropylmethoxy)-1-(6-methoxy-8-methyl-1,3,4,5-tetrahydrobenzo[cd]indol-5-yl)piperidin-2-yl)benzoic acid;

[1076] 4-((2R,4R)-4-(Cyclopropylmethoxy)-1-(6-methoxy-8-methyl-4,5-dihydro-1H-pyrano[2,3,4-cd]indol-5-yl)piperidin-2-yl)benzoic acid;

[1077] 4-((2R,4R)-4-(Cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-1-naphthoic acid;

[1078] 5-((2R,4R)-4-(Cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)quinoline-8-carboxylic acid;

[1079] 8-((2R,4R)-4-(Cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)quinoline-5-carboxylic acid;

[1080] 8-((2R,4R)-4-(Cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)imidazo[1,2-a]pyridine-5-carboxylic acid;

[1081] 5-((2R,4R)-4-(Cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-6-oxo-1,6-dihydropyridine-2-carboxylic acid;

[1082] 6-((2R,4R)-4-(Cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid;

[1083] 4-((2R,4R)-4-(Cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-5,6,7,8-tetrahydronaphthalene-1-carboxylic acid;

[1084] rac-7-((2R,4S)-4-(Cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-2,3-dihydro-1H-indene-4-carboxylic acid;

[1085] 7-((2R,4R)-4-(Cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-2,3-dihydrobenzofuran-4-carboxylic acid;

[1086] (S)-3-(4-(Cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1,2,3,4-tetrahydroquinolin-7-yl)propanoic acid;

[1087] (S)-2-((4-(Cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1,2,3,4-tetrahydroquinolin-7-yl)oxy)acetic acid;

[1088] 4-(9-((5-methoxy-7-(methyl-d3)-1H-indol-4-yl)methyl)-1-oxa-9-azaspiro[5.5]undecan-8-yl)benzoic acid;

[1089] 4-(7-((5-methoxy-7-(methyl-d3)-1H-indol-4-yl)methyl)-1-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[1090] 4-(8-((5-methoxy-7-(methyl-d3)-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decane-7-yl)benzoic acid;

[1091] (4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)phenyl)phosphonic acid;

[1092] rac-4-((2R,4S)-4-Ethoxy-1-((5-methoxy-7-(methyl-d3)-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1093] 4-((2R,4R)-4-Ethoxy-1-((5-ethyl-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1094] N-Hydroxy-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzamide;

[1095] (4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)phenyl)boronic acid;

[1096] Imino(4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)phenyl)(methyl)-l6-thianone;

[1097] (S)-4-(4,4-Difluoro-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1098] 4-(5-Ethoxy-2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azabicyclo[4.1.0]heptan-1-yl)benzoic acid;

[1099] 4-(5-Ethoxy-2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azabicyclo[4.1.0]heptan-3-yl)benzoic acid;

[1100] 4-(1-Ethoxy-6-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid;

[1101] 4-(1-Ethoxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid;

[1102] Methyl 4-(4-(ethylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoate;

[1103] 7-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-2,3-dihydrobenzofuran-4-carboxylic acid;

[1104] 8-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)imidazo[1,2-a]pyridine-5-carboxylic acid;

[1105] 4-((2S)-3-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-3-azabicyclo[4.1.0]heptan-2-yl)benzoic acid;

[1106] 4-(((2R,4R)-2-(4-(2H-Tetrazol-5-yl)phenyl)-4-(cyclopropylmethoxy)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole;

[1107] 5-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-6-oxo-1,6-dihydropyridine-2-carboxylic acid;

[1108] 4-(8-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-2,2-dimethyl-1-oxa-8-azaspiro[4.5]dec-7-yl)benzoic acid;

[1109] 4-((2S)-4-(Cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-2-fluorobenzoic acid; and

[1110] 4-[4-(Ethylamino)-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-2-piperidinyl]-2-fluorobenzoic acid; or a stereoisomer and a pharmaceutically acceptable salt thereof.

[1111] In some embodiments, the compounds of formula (I) are not the compounds disclosed in PCT Publication No. WO 2022 / 028527, which is incorporated herein by reference for the purpose of excluding the compounds disclosed therein.

[1112] Any combination of groups of the various variables described above is contemplated herein. Throughout the specification, the groups and their substituents are selected by those skilled in the art to provide stable moieties and compounds.

[1113] The compounds of the present disclosure include the compounds themselves and their salts. The salts for the purposes of the present disclosure are preferably pharmaceutically acceptable salts of the compounds according to the present disclosure. Also included are salts that are not suitable for pharmaceutical use but can be used, for example, for the isolation or purification of the compounds according to the present disclosure. For example, salts can be formed between anions and positively charged substituents (e.g., amino groups) on the compounds described herein. Suitable anions include chloride, bromide, iodide, sulfate, nitrate, phosphate, citrate, methanesulfonate, trifluoroacetate, and acetate. Similarly, salts can be formed between cations and negatively charged substituents (e.g., carboxylate groups) on the compounds described herein. Suitable cations include sodium ion, potassium ion, magnesium ion, calcium ion, and ammonium cations (such as tetramethylammonium ion).

[1114] As used herein, "pharmaceutically acceptable salts" refers to acid or base addition salts, including but not limited to base addition salts formed by a compound of formula (I) having an acidic moiety with a pharmaceutically acceptable cation (e.g., sodium, potassium, magnesium, calcium, aluminum, lithium, and ammonium). A list of suitable salts can be found in: Remington’s Pharmaceutical Sciences, 17th Edition, Mack Publishing Company, Easton, Pennsylvania, 1985, page 1418; S.M. Berge et al., "Pharmaceutical Salts", J. Pharm. Sci. 1977, 66, 1-19; and "Pharmaceutical Salts: Properties, Selection, and Use. A Handbook"; Wermuth, C.G. and Stahl, P.H. (Eds.) Verlag Helvetica Chimica Acta, Zurich, 2002 [ISBN 3-906390-26-8]; each of which is incorporated herein by reference in its entirety.

[1115] This disclosure also encompasses all suitable isotopic variants of the compounds according to this disclosure, whether or not radioactive. Isotopic variants of the compounds according to this disclosure are understood to mean such compounds in which at least one atom within the compounds according to this disclosure has been exchanged for another atom having the same atomic number but an atomic mass different from the atomic mass usually or predominantly present in nature.

[1116] Examples of isotopes that can be incorporated into the compounds according to this disclosure are those of hydrogen, carbon, nitrogen, oxygen, fluorine, chlorine, bromine, and iodine, such as 2 H (deuterium), 3 H (tritium), 13 C, 14 C, 15 N, 17 O, 18 O, 18 F, 36 Cl, 82 Br, 123 I, 124 I, 125 I, 129 I and 131 I. Specific isotopic variants of the compounds according to this disclosure, especially those in which one or more radioactive isotopes have been incorporated, may be useful, for example, for examining the mechanism of action or the distribution of the active compound in the body. With3 H, 14 C and / or 18 F isotope-labeled compounds are suitable for this purpose. In addition, the incorporation of isotopes (e.g., deuterium) can confer specific therapeutic benefits due to the higher metabolic stability of the compound, such as an extended half-life in the body or a reduced required active dose.

[1117] Accordingly, certain embodiments provide isotope-enriched analogs of the compounds disclosed herein, such as deuterated analogs, to improve the pharmacokinetic (PK), pharmacodynamic (PD), and toxicity profiles of the compounds.

[1118] In some embodiments, the hydrogen atoms of the compounds described herein can be replaced by deuterium atoms. In certain embodiments, as applied to chemical groups and unless otherwise indicated, "deuterated" refers to a chemical group that is isotope-enriched in deuterium in an amount far greater than its natural abundance, e.g., at least 90% deuterium is present at the designated position.

[1119] Isotope variants of the compounds according to the present disclosure can be prepared by various methods, including, for example, the methods described below and in the working examples, by using the appropriate isotope modifications of the specific reagents and / or starting compounds therein.

[1120] C. Formulations

[1121] As used herein, the term "pharmaceutical composition" is intended to cover products that contain an active ingredient and inert ingredients that constitute carriers, as well as any product directly or indirectly produced by the combination, compounding, or aggregation of any two or more of these ingredients, or by the dissociation of one or more of these ingredients, or by other types of reactions or interactions of one or more of these ingredients. Accordingly, the pharmaceutical compositions of the present disclosure cover any composition prepared by mixing a compound of the present disclosure or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable carrier.

[1122] The term "pharmaceutically acceptable carrier" refers to a carrier or adjuvant that can be administered to a patient together with a compound of the present disclosure or a pharmaceutically acceptable salt thereof, and that is non-toxic and does not destroy the pharmacological activity of the compound when administered in a dose sufficient to deliver a therapeutically effective amount of the compound.

[1123] The amount administered depends on the compound formulation, route of administration, etc. and is generally determined empirically and will necessarily vary depending on the target, host, route of administration, etc. Generally, for a particular application, the amount of the active compound in a unit dose formulation can vary or be adjusted between about 1 milligram (mg) to about 100 mg or about 1 mg to about 1000 mg. For convenience, the total daily dose can be administered in divided portions and at different times of the day.

[1124] Solid dosage forms of the pharmaceutical compositions of the invention for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is admixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or calcium phosphate dibasic and / or: a) fillers or extenders such as starch, lactose, sucrose, glucose, mannitol, and silicic acid, b) binders such as carboxymethyl cellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrants such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarders such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as cetyl alcohol and glycerol monostearate, h) adsorbents such as kaolin and bentonite clays, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. For capsules, tablets, and pills, the dosage form may also contain buffering agents.

[1125] Excipients such as lactose (lactose or milk sugar) and high molecular weight polyethylene glycols can also be used, and solid pharmaceutical compositions of a similar type can be used as fillers in soft and hard gelatin capsules.

[1126] Solid dosage forms of the pharmaceutical compositions of the invention are tablets, dragees, capsules, pills, and granules, which can be prepared with coatings and shells such as enteric coatings and other pharmaceutical coatings. They can optionally contain opacifying agents and can also be formulations that release the active ingredient optionally in a delayed manner only in or preferably in a certain part of the intestine. Examples of embedding pharmaceutical compositions that can be used include polymeric substances and waxes.

[1127] The active compound can also, if appropriate, be in microencapsulated form together with one or more of the above excipients.

[1128] Liquid dosage forms of the pharmaceutical compositions of the invention for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs. In addition to the active compound, the liquid dosage forms may also contain inert diluents commonly used in the art such as water or other solvents, solubilizing agents, and emulsifying agents such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butanediol, dimethylformamide, oils (especially cottonseed oil, groundnut oil, corn oil, germ oil, olive oil, castor oil, and sesame oil), glycerol, tetrahydrofurfuryl alcohol, fatty acid esters of polyethylene glycol and sorbitan anhydride, and mixtures thereof.

[1129] In addition to the active compound, the suspension of the compounds of the present invention may also contain suspending agents, for example, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof.

[1130] The pharmaceutical compositions of the present disclosure for injection comprise pharmaceutically acceptable sterile aqueous or non-aqueous solutions, dispersions, suspensions or emulsions, and sterile powders for reconstitution into sterile injectable solutions or dispersions only immediately prior to use. Examples of suitable aqueous and non-aqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, etc.) and suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters (such as ethyl oleate). Proper fluidity can be maintained, for example, by the use of coating materials such as lecithin, by maintaining the required particle size in the case of dispersions, and by the use of surfactants.

[1131] In addition to the inert diluent, these pharmaceutical compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents, dispersing agents, sweetening agents, flavoring agents and perfuming agents. Prevention of the action of microorganisms may be ensured by including various antibacterial and antifungal agents (for example, parabens, chlorobutanol, phenol, sorbic acid, etc.). It may also be necessary to include isotonic agents such as sugars, sodium chloride, etc. Prolonged absorption of injectable pharmaceutical forms may be achieved by including agents that delay absorption such as aluminum monostearate and gelatin. These compounds may be incorporated into sustained release or targeted delivery systems such as polymer matrices, liposomes and microspheres. Such formulations may provide a more effective distribution of the compounds.

[1132] The pharmaceutical compositions as injectable formulations may be sterilized, for example, by filtration through a bacteria-retaining filter or by incorporating a sterilizing agent in the form of a sterile solid pharmaceutical composition which can be dissolved or dispersed in sterile water or other sterile injectable medium immediately prior to use.

[1133] Dosage forms for topical administration of the compounds or pharmaceutical compositions of the present disclosure include powders, patches, sprays, ointments and inhalants. The active compound is mixed under sterile conditions with a pharmaceutically acceptable carrier and any preservatives, buffers or propellants that may be required.

[1134] The compounds and compositions described herein can be administered, for example, orally, parenterally (e.g., subcutaneously, intradermally, intravenously or intramuscularly), topically, rectally, nasally, sublingually or buccally, in a dosage range of from about 0.01 milligrams per kilogram (mg / kg) to about 1000 mg / kg (e.g., about 0.01 to about 100 mg / kg, about 0.1 to about 100 mg / kg) every 4 to 120 hours, or as required according to the particular drug, dosage form, and / or route of administration. Other routes of administration include enteral, intraarterial, intraperitoneal, and intrathecal administration. The interrelationship of dosages (in mg per square meter of body surface) for animals and man is described in Freireich et al., Cancer Chemother. Rep. [Cancer Chemotherapy Reports], 50, 219-244 (1966). The body surface area can be approximately determined from the height and weight of the patient. See, e.g., Scientific Tables [Scientific Tables], Geigy Pharmaceuticals, Ardsley, N.Y., 537 (1970). In certain embodiments, the composition is administered orally or by injection. The methods herein contemplate administering a therapeutically effective amount of the compound or compound composition to achieve the desired or specified effect. Generally, the pharmaceutical compositions of the present disclosure will be administered about 1 to about 6 times per day, or alternatively as a continuous infusion. Such administration can be used as a chronic or acute therapy.

[1135] Lower or higher doses than those described above may be required. The specific dosage and treatment regimen for any particular patient will depend on a variety of factors, including the activity of the particular compound employed, age, weight, general health, sex, diet, time of administration, rate of excretion, drug combination, the severity and course of the disease, condition or symptom, the patient's susceptibility to the disease, and the judgment of the treating physician.

[1136] Dosage forms include from about 0.001 mg to about 2,000 mg (including from about 0.001 mg to about 1,000 mg, from about 0.001 mg to about 500 mg, from about 0.01 mg to about 250 mg) of a compound of formula (I) or a salt thereof (e.g., a pharmaceutically acceptable salt) as defined anywhere herein. The dosage form may further include a pharmaceutically acceptable carrier and / or an additional therapeutic agent.

[1137] An appropriate dosage level can be determined by any suitable method. Preferably, for topical administration, the active substance is administered at a frequency of 1 to 4 times per day, or less frequently if a drug delivery system is used. However, the actual dosage level and the schedule of administration of the active ingredient in the pharmaceutical compositions of the present disclosure can be varied so as to obtain an amount of the active ingredient that effectively achieves the desired therapeutic response for a particular patient, composition, and mode of administration without imposing intolerable toxicity on the patient. In certain cases, the dosage may deviate from the specified amount, particularly, the specified amount will vary depending on the patient's age, sex, weight, diet, and general health, the route of administration, the individual response to the active ingredient, the nature of the formulation, and the time or interval at which the administration is carried out. Thus, in some cases, administration in amounts lower than the aforementioned minimum amount may be satisfactory, while in other cases, the specified upper limit may be exceeded. If larger amounts are administered, it is recommended that these amounts be divided into multiple individual doses and spread throughout the day.

[1138] D. Method of Use

[1139] Provided herein are methods of treating, preventing, or ameliorating a disease or disorder mediated by or otherwise affected by the alternative complement pathway using a compound or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, disclosed herein. In certain additional embodiments, provided herein are methods of treating, preventing, or ameliorating a disease or disorder mediated by or otherwise affected by complement factor B (CFB) using a compound or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, disclosed herein. In certain additional embodiments, provided herein are methods of treating, preventing, or ameliorating a disease or disorder mediated by or otherwise affected by inhibition of the alternative complement pathway using a compound or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, disclosed herein. In certain additional embodiments, provided herein are methods of treating, preventing, or ameliorating a disease or disorder mediated by or otherwise affected by inhibition of complement factor B using a compound or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, disclosed herein.

[1140] Examples of known complement-related diseases or disorders include: neurological disorders, multiple sclerosis, stroke, Guillain-Barré syndrome, traumatic brain injury, Parkinson's disease, disorders of inappropriate or poor complement activation, hemodialysis complications, hyperacute allograft rejection, xenograft rejection, interleukin-2-induced toxicity during IL-2 therapy, inflammatory disorders, inflammation in autoimmune diseases, Crohn's disease, adult respiratory distress syndrome, thermal injury (including burns or frostbite), myocarditis, post-ischemic reperfusion conditions, myocardial infarction, balloon angioplasty, post-pump syndromes in cardiopulmonary bypass or renal bypass, atherosclerosis, hemodialysis, renal ischemia, mesenteric artery reperfusion after aortic reconstruction, infectious diseases or sepsis, immune complex disorders and autoimmune diseases, rheumatoid arthritis, systemic lupus erythematosus (SLE), SLE nephritis, proliferative nephritis, liver fibrosis, hemolytic anemia, myasthenia gravis, tissue regeneration and nerve regeneration. In addition, other known complement-related diseases are lung diseases and disorders such as dyspnea, hemoptysis, ARDS, asthma, chronic obstructive pulmonary disease (COPD), emphysema, pulmonary embolism and infarction, pneumonia, fibrosing dust diseases, inert dusts and minerals (e.g., silica, coal dust, beryllium, and asbestos), pulmonary fibrosis, organic dust diseases, chemical injuries (caused by irritant gases and chemicals such as chlorine, phosgene, sulfur dioxide, hydrogen sulfide, nitrogen dioxide, ammonia, and hydrochloric acid), smoke injury, thermal injury (e.g., burns, frostbite), asthma, allergy, bronchoconstriction, hypersensitivity pneumonitis, parasitic diseases, Goodpasture's syndrome, pulmonary vasculitis, pauci-immune vasculitis, immune complex-related inflammation; eye diseases including age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, macular edema, Behçet's uveitis, multifocal choroiditis, Vogt-Koyanagi-Harada syndrome, intermediate uveitis, birdshot retinochoroiditis, sympathetic ophthalmia, ocular cicatricial pemphigoid, ocular pemphigoid, non-arteritic ischemic optic neuropathy, postoperative inflammation, and uveitis associated with retinal vein occlusion (including uveitis of Behçet's disease and other subtypes), antiphospholipid syndrome.

[1141] In certain embodiments, provided herein are methods of treating kidney disease, chronic kidney disease, diabetic nephropathy, glomerular kidney disease, complement C3 glomerulopathy (C3G), IgA nephropathy (IgAN), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome (aHUS), dense deposit disease (DDD), minimal change disease (MCD), paroxysmal nocturnal hemoglobinuria (PNH), ANCA-associated vasculitis, lupus nephritis, or polycystic kidney disease (PKD).

[1142] E. Examples

[1143] Example 1: A compound of formula (I):

[1144]

[1145] or a pharmaceutically acceptable salt thereof, wherein:

[1146] R 1 is hydrogen, fluorine, chlorine or methyl;

[1147] X is N or CH;

[1148] Z is NR 2 or CR 2a R 2b ;

[1149] R 2 is alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocycloalkyl, cycloalkyl, heterocycloalkyl, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 or -S(O) t R 12 , wherein the alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocycloalkyl, cycloalkyl, heterocycloalkyl or heteroaryl is optionally substituted by one, two or three independently selected R 11 ;

[1150] R 2a is haloalkyl, -R u -cycloalkyl, -R u -heterocycloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -OR 7 -SR 7 or -NR 8 R 9 , wherein the -R u -cycloalkyl, -R u -heterocycloalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted by one, two or three independently selected R 11 ;

[1151] and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl, or halo C 1-3 alkyl;

[1152] Or R 2a and R 2bform a cycloalkyl or heterocyclic group together with the carbon atoms to which they are attached, wherein the cycloalkyl or heterocyclic group is optionally substituted by one, two or three independently selected R 11 substituents;

[1153] R 3 is halo, cyano, C 1-3 alkyl, or halo C 1-3 alkyl;

[1154] R 4 is hydrogen, halo, cyano, C 1-3 alkyl or halo C 1-3 alkyl;

[1155] R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy or C 1-3 alkoxy;

[1156] R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, C 1-3 alkoxy or halo C 1-3 alkoxy;

[1157] R 7 is haloalkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, or heteroaryl, wherein the haloalkyl, deuterated alkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group or heteroaryl is optionally substituted by one, two or three independently selected R 11 substituents;

[1158] R 8 is hydrogen, deuterium, alkyl, deuterated alkyl or haloalkyl;

[1159] R 9 is haloalkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, heteroaryl, -C(O)R 12 、-C(O)NR 13 R 14 、-S(O) t R 12 、or -S(O) t NR 13 R 14, wherein -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group or heteroaryl is optionally substituted by one, two or three independently selected R 11 ; or

[1160] R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclic group or heteroaryl, wherein the heterocyclic group or heteroaryl is optionally substituted by one, two or three independently selected R 11 ;

[1161] Each R 11 independently is halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, C 1-3 alkoxy C 1-3 alkyl, halo C 1-3 alkoxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl, or halo C 1-3 alkylsulfinyl; or

[1162] Two R 11 groups together with the carbon atom to which they are attached form C 3-5 cycloalkyl, 3- to 6-membered heterocyclic group or oxo, wherein the C 3-5 cycloalkyl or 3- to 6-membered heterocyclic group is optionally substituted by 1 or 2 independently selected halo;

[1163] R 12 is alkyl, deuterated alkyl or haloalkyl;

[1164] R 13 and R 14 are each independently hydrogen, alkyl, deuterated alkyl or haloalkyl, or R 13 and R 14 together with the nitrogen atom to which they are attached form a heterocyclic group optionally substituted by one, two or three independently selected R 11 ;

[1165] R u is a methylene, ethylene or propylene linker optionally substituted by one to six independently selected halo;

[1166] k is 0, 1, 2 or 3;

[1167] t is 1 or 2;

[1168] m is 0, 1 or 2; and

[1169] n is 0, 1, or 2, provided that:

[1170] when Z is NR 2 then m is 1 and n is 1 or 2; and

[1171] when Z is CR 2a R 2b and R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl and m is 1, then the cycloalkyl is substituted with at least one R 11 .

[1172] Example 2: A compound as described in Example 1, wherein m is 0 or 1; n is 0, 1 or 2, provided that when Z is NR 2 then m is 1 and n is 1 or 2.

[1173] Example 3: A compound as described in Example 1, wherein m is 0 or 1; and n is 0 or 1, provided that when Z is NR 2 then m is 1 and n is 1.

[1174] Example 4: A compound as described in any one of Examples 1 to 3, the compound having the formula (II):

[1175]

[1176] or a pharmaceutically acceptable salt thereof, wherein m is 0 or 1; n is 0 or 1; and X, R 1 , R 2a , R 2b , R 3 , R 4 , R 5 , R 6 and k are as described in Example 1.

[1177] Example 5: A compound as described in any one of Examples 1 to 4, the compound having the formula (III):

[1178]

[1179] or a pharmaceutically acceptable salt thereof, wherein X, R 1 , R 2a , R 2b , R 3 , R4 , R 5 , R 6 and k are as described in Example 1.

[1180] Example 6: A compound as described in any one of Examples 1 to 4, the compound having formula (IV):

[1181]

[1182] or a pharmaceutically acceptable salt thereof, wherein m is 0 or 1; n is 0 or 1; and X, R 1 , R 2a , R 2b , R 3 , R 4 , R 5 , R 6 , k, m, and n are as described in Example 1.

[1183] Example 7: A compound as described in any one of Examples 1 to 4, the compound having formula (IVa):

[1184]

[1185] or a pharmaceutically acceptable salt thereof.

[1186] Example 8: A compound as described in any one of Examples 1 to 4, the compound having formula (V):

[1187]

[1188] or a pharmaceutically acceptable salt thereof, wherein X, R 1 , R 2a , R 2b , R 3 , R 4 , R 5 , R 6 and k are as described in Example 1.

[1189] Example 9: A compound as described in any one of Examples 1 to 8, wherein R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl group substituted by one, two, or three independently selected R 11 groups, or form a heterocyclic group optionally substituted by one, two, or three independently selected R 11 groups.

[1190] Example 10: A compound as described in any one of Examples 1 to 8, wherein R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl group substituted by one, two, or three independently selected R11 Substituted cycloalkyl

[1191] Example 11: A compound as described in Example 5 or 8, wherein R 2a and R 2b together with the carbon atom to which they are attached form a C 11 cycloalkyl optionally substituted with one, two or three independently selected R 3-6 groups

[1192] Example 12: A compound as described in any one of Examples 1 to 8, wherein R 2a is -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 ; wherein the -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, aryl or heteroaryl is optionally substituted with one, two or three independently selected R 11 groups, and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl substituted with one, two or three independently selected R 11 groups, or form a heterocyclic group optionally substituted with one, two or three independently selected R 11 groups

[1193] Example 13: A compound as described in any one of Examples 1 to 8, wherein R 2a is cycloalkyl, heterocyclic group, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 ; wherein the cycloalkyl, heterocyclic group, aryl or heteroaryl is optionally substituted with one, two or three independently selected R 11 groups, and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl substituted with one, two or three independently selected R 11A substituted cycloalkyl group, or forms an optionally mono-, di- or tri-substituted R 11 substituted heterocyclic group.

[1194] Example 14: A compound according to any one of Examples 1 to 8, wherein R 2a is cycloalkyl, heterocyclic, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 , wherein the cycloalkyl, heterocyclic, aryl or heteroaryl group is optionally mono-, di- or tri-substituted by independently selected R 11 , and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a C 11 cycloalkyl group substituted by one, two or three independently selected R 3-6 , or form a 4- to 6-membered heterocyclic group optionally substituted by one, two or three independently selected R 11 .

[1195] Example 15: A compound according to any one of Examples 1 to 8, wherein R 2a is cycloalkyl, heterocyclic, -OR 7 , -SR 7 or -NR 8 R 9 , wherein the cycloalkyl or heterocyclic group is optionally mono-, di- or tri-substituted by independently selected R 11 , and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a C 11 cycloalkyl group substituted by one, two or three independently selected R 3-6 , or form a 4- to 6-membered heterocyclic group optionally substituted by one, two or three independently selected R 11 .

[1196] Example 16: A compound according to any one of Examples 1 to 8, wherein R 2a is cycloalkyl, heterocyclic, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8R 9 wherein the cycloalkyl, heterocyclic group, aryl or heteroaryl is optionally substituted by one, two or three independently selected R 11 groups, and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a C 11 cycloalkyl substituted by one, two or three independently selected R 3-5 groups, or form a 4- to 5-membered heterocyclic group optionally substituted by one, two or three independently selected R 11 groups.

[1197] Example 17: A compound according to any one of Examples 1 to 8, wherein R 2a is -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 , wherein the -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, aryl or heteroaryl is optionally substituted by one, two or three independently selected R 11 groups, and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a heterocyclic group optionally substituted by one, two or three independently selected R 11 groups.

[1198] Example 18: A compound according to any one of Examples 1 to 8, wherein R 2a is cycloalkyl, heterocyclic group, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 , wherein the cycloalkyl, heterocyclic group, aryl or heteroaryl is optionally substituted by one, two or three independently selected R 11 groups, and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a heterocyclic group optionally substituted with one, two or three independently selected R 11 substituents.

[1199] Example 19: A compound according to any one of Examples 1 to 8, wherein R 2a is -R u -cycloalkyl or cycloalkyl, wherein the -R u -cycloalkyl or cycloalkyl is optionally substituted with one, two or three independently selected R 11 substituents, and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halo C 1-3 alkyl.

[1200] Example 20: A compound according to any one of Examples 1 to 8, wherein R 2a is -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl or heterocyclic group, wherein the -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl or heterocyclic group is optionally substituted with one, two or three independently selected R 11 substituents; R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halo C 1-3 alkyl.

[1201] Example 21: A compound according to any one of Examples 1 to 8, wherein R 2a is cycloalkyl, heterocyclic group, aryl or heteroaryl, wherein the cycloalkyl, heterocyclic group, aryl or heteroaryl is optionally substituted with one, two or three independently selected R 11 substituents, and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halo C 1-3 alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a heterocyclic group optionally substituted with one, two or three independently selected R 11 substituents.

[1202] Example 22: A compound according to any one of Examples 1 to 8, wherein R 2ais a cycloalkyl, heterocyclic group, aryl or heteroaryl, wherein the cycloalkyl, heterocyclic group, aryl or heteroaryl is optionally substituted by one, two or three independently selected Rs 11 and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl.

[1203] Example 23: The compound according to any one of Examples 1 to 8, wherein R 2a is a heterocyclic group or heteroaryl, wherein the heterocyclic group or heteroaryl is optionally substituted by one, two or three independently selected Rs 11 and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl.

[1204] Example 24: The compound according to any one of Examples 1 to 8, wherein R 2a is heteroaryl, wherein the heteroaryl is optionally substituted by one, two or three independently selected Rs 11 and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl.

[1205] Example 25: The compound according to any one of Examples 1 to 8, wherein R 2a is a cycloalkyl, heterocyclic group, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 , wherein the cycloalkyl, heterocyclic group, aryl or heteroaryl is optionally substituted by one, two or three independently selected Rs 11 and R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a 4- to 5-membered heterocyclic group optionally substituted by one, two or three independently selected Rs 11 and R 7 , R 8 , R 9 and R 11 are as described in Example 1.

[1206] Example 26: A compound according to any one of Examples 1 to 8, wherein R 2a is -OR 7 , -SR 7 or -NR 8 R 9 ; R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl; and R 7 , R 8 , R 9 and R 11 are as in Example 1.

[1207] Example 27: A compound according to any one of Examples 1 to 8, wherein R 2a is -R u -cycloalkyl, -OR 7 , -SR 7 or -NR 8 R 9 ; R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl; R 7 is halogenated alkyl or cycloalkyl; R 8 is hydrogen; R 9 is -R u -cycloalkyl or cycloalkyl, wherein the -R u -cycloalkyl or cycloalkyl is optionally substituted by one, two or three independently selected R 11 ; and each R 11 is independently halogenated or halogenated C 1-3 alkyl.

[1208] Example 28: A compound according to any one of Examples 1 to 8, 12 to 18, 25 and 26, wherein R 7 is -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, or heteroaryl, wherein the -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group or heteroaryl is optionally substituted by one, two or three independently selected R 11 , the cycloalkyl or heterocyclic group is optionally substituted by one, two or three independently selected R 11 ; R 8 is hydrogen, deuterium, alkyl, deuterated alkyl or halogenated alkyl; R 9 is -R u -cycloalkyl, -Ru - Heterocyclic group, cycloalkyl group, heterocyclic group or heteroaryl group, wherein said -R u - Cycloalkyl group, -R u - Heterocyclic group, cycloalkyl group, heterocyclic group or heteroaryl group is optionally substituted by one, two or three independently selected R 11 substituents, or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclic group or heteroaryl group, wherein the heterocyclic group or heteroaryl group is optionally substituted by one, two or three independently selected R 11 substituents; each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, halo C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl or halo C 1-3 alkylsulfinyl; and R u is a methylene, ethylene or propylene linker optionally substituted by one to six independently selected halo.

[1209] Example 29: A compound according to any one of Examples 1 to 8, 12 to 18, 25 and 26, wherein R 7 is a cycloalkyl group, heterocyclic group or heteroaryl group, wherein the cycloalkyl group, heterocyclic group or heteroaryl group is optionally substituted by one, two or three independently selected R 11 substituents; R 8 is hydrogen, deuterium, alkyl, deuterated alkyl or haloalkyl; R 9 is a cycloalkyl group, heterocyclic group or heteroaryl group, wherein the cycloalkyl group, heterocyclic group or heteroaryl group is optionally substituted by one, two or three independently selected R 11 substituents, or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclic group or heteroaryl group, wherein the heterocyclic group or heteroaryl group is optionally substituted by one, two or three independently selected R 11 substituents, and wherein the heterocyclic group is further optionally substituted by oxo, and each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3Alkyl, hydroxy, C 1-3 Alkoxy, halo C 1-3 Alkoxy, C 1-3 Alkylthio, halo C 1-3 Alkylthio, C 1-3 Alkylsulfonyl, halo C 1-3 Alkylsulfonyl, C 1-3 Alkylsulfinyl or halo C 1-3 Alkylsulfinyl; and R u is a methylene, ethylene or propylene linker optionally substituted with one to six independently selected halogens.

[1210] Example 30: A compound according to any one of Examples 1 to 8, 12 to 18, 25 and 26, wherein R 7 is a cycloalkyl or heterocyclic group optionally substituted with one, two or three independently selected R 11 ; R 8 is hydrogen, deuterium, alkyl, deuterated alkyl or haloalkyl; R 9 is a cycloalkyl or heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally substituted with one, two or three independently selected R 11 ; or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclic group or heteroaryl group, wherein the heterocyclic group or heteroaryl group is optionally substituted with one, two or three independently selected R11; each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, halo C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl or halo C 1-3 alkylsulfinyl.

[1211] Example 31: A compound according to any one of Examples 1 to 8, 12 to 18, 25 and 26, wherein R 7 is -R u -heterocyclic group or heterocyclic group, wherein the -R u -heterocyclic group or heterocyclic group is optionally substituted with one, two or three independently selected R 11 ; and each R 11 is independently halo, cyano, oxo, C 1-3Alkyl, deuterated C 1-3 Alkyl, halogenated C 1-3 Alkyl, cyano C 1-3 Alkyl, hydroxy, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, C 1-3 Alkylthio, halogenated C 1-3 Alkylthio, C 1-3 Alkylsulfonyl, halogenated C 1-3 Alkylsulfonyl, C 1-3 Alkylsulfinyl or halogenated C 1-3 Alkylsulfinyl.

[1212] Example 32: A compound according to any one of Examples 1 to 8, 12 to 18, 25 and 26, wherein R 7 is a haloalkyl; R 8 is hydrogen, deuterium, alkyl, deuterated alkyl or haloalkyl; and R 9 is a haloalkyl.

[1213] Example 33: A compound according to any one of Examples 1 to 8, 12 to 18, 25 and 26, wherein R 2a is -NR 8 R 9 ; R 2b is hydrogen, deuterium, halogen, C 1-3 alkyl, deuterated C 1-3 alkyl or halogenated C 1-3 alkyl.

[1214] Example 34: A compound according to Example 33, wherein R 8 is hydrogen, deuterium, alkyl, deuterated alkyl or haloalkyl; R 9 is a haloalkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl or heterocyclic group, wherein the haloalkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl or heterocyclic group is optionally substituted by one, two or three independently selected R 11 and each R 11 is independently halogen, cyano, C 1-3 alkyl, deuterated C 1-3 alkyl, halogenated C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halogenated C 1-3 alkoxy, C 1-3 alkylthio, halogenated C 1-3 alkylthio, C 1-3 alkylsulfonyl, halogenated C 1-3Alkylsulfonyl, C 1-3 Alkylsulfinyl or halo C 1-3 Alkylsulfinyl.

[1215] Example 35: The compound according to Example 33, wherein R 8 is hydrogen, deuterium, alkyl, deuterated alkyl or haloalkyl; R 9 is haloalkyl, -R u -heterocyclyl or heterocyclyl, wherein the haloalkyl, -R u -heterocyclyl or heterocyclyl is optionally substituted by one, two or three independently selected R 11 substituents.

[1216] Example 36: The compound according to any one of Examples 1 to 8, 12 to 18, 25 and 26, wherein R 2a is -OR 7 ; R 7 is haloalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl or heterocyclyl, wherein the haloalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl or heterocyclyl is optionally substituted by one, two or three independently selected R 11 substituents; and R 11 is as described in Example 1.

[1217] Example 37: The compound according to any one of Examples 1 to 8, 12 to 36, wherein R 2b is hydrogen or methyl.

[1218] Example 38: The compound according to any one of Examples 1 to 8, 12 to 37, wherein R 2b is hydrogen.

[1219] Example 39: The compound according to Example 1, 4, or 6, which has the formula (VI):

[1220]

[1221] or a pharmaceutically acceptable salt thereof, wherein X, R 1 , R 3 , R 4 , R 5 , R 6 , R 8 , R 9 and k are as described in Examples 1, 4 and 6, respectively.

[1222] Example 40: The compound according to Example 39, wherein R 3is halo, cyano, alkyl, or haloalkyl; R 4 is hydrogen, halo, C 1-3 alkyl or halo C 1-3 alkyl; R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkoxy or C 1-3 alkoxy; R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, C 1-3 alkoxy or halo C 1-3 alkoxy; R 8 is hydrogen, deuterium, alkyl or haloalkyl; R 9 is cycloalkyl or heterocyclic group, wherein the cycloalkyl or heterocyclic group is optionally substituted by one, two or three independently selected R 11 ; or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclic group or heteroaryl, wherein the heterocyclic group or heteroaryl is optionally substituted by one, two or three independently selected R 11 ; each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 alkylthio, halo C 1-3 alkylthio, C 1-3 alkylsulfonyl, halo C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl or halo C 1-3 alkylsulfinyl; k is 0, 1 or 2; m is 0 or 1; and n is 0, 1 or 2.

[1223] Example 41: A compound as described in Example 1, 4, 6, or 39, the compound having the formula (VIa):

[1224]

[1225] or a pharmaceutically acceptable salt thereof, wherein j is 1 or 2, and X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11, k, m, and n are as described in Examples 1, 4, 6, and 39, respectively.

[1226] Example 42: A compound as described in Example 1 or 4, the compound having formula (VII):

[1227]

[1228] or a pharmaceutically acceptable salt thereof, wherein q is 0, 1, 2, or 3, and X, R 1 , R 3 , R 4 , R 5 , R 6 and k are as described in Example 1 or 4, respectively.

[1229] Example 43: A compound as described in Example 42, the compound having formula (VIIa):

[1230]

[1231] or a pharmaceutically acceptable salt thereof.

[1232] Example 44: A compound as described in Example 1, 4, or 6, the compound having formula (VIII):

[1233]

[1234] or a pharmaceutically acceptable salt thereof, wherein ring A is cycloalkyl, heterocyclic, aryl, or heteroaryl; q is 0, 1, 2, or 3, and X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 and k are as described in Examples 1, 4, and 6, respectively.

[1235] Example 45: A compound as described in Example 44, wherein ring A is heterocyclic or heteroaryl.

[1236] Example 46: A compound as described in Example 44, wherein ring A is heteroaryl.

[1237] Example 47: A compound as described in Example 44, wherein ring A is pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazolyl, imidazolyl, thiazolyl, or pyrazolyl.

[1238] Example 48: A compound as described in Example 44, wherein ring A is pyridyl or pyrazolyl; q is 0, 1, 2, or 3, and X, R 1 , R 3 , R 4 , R 5, R 6 , R 11 and k are as described in Example 44.

[1239] Example 49: A compound as described in Example 44, wherein ring A is pyridyl; q is 0, 1, 2, or 3, and X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 and k are as described in Example 44.

[1240] Example 50: A compound as described in Example 44, wherein ring A is pyrazolyl; q is 0, 1, 2, or 3, and X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 and k are as described in Example 44.

[1241] Example 51: A compound as described in Example 44, wherein ring A is oxazolyl; q is 0, 1, 2, or 3, and X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 and k are as described in Example 44.

[1242] Example 52: A compound as described in Example 1, 4, or 6, the compound having formula (IX):

[1243]

[1244] or a pharmaceutically acceptable salt thereof, wherein q is 0, 1, 2, or 3, and R 1 , R 3 , R 4 , R 5 , R 6 and k are as described in Examples 1, 4, and 6, respectively.

[1245] Example 53: A compound as described in Example 1, the compound having formula (X):

[1246]

[1247] or a pharmaceutically acceptable salt thereof, wherein m is 1; n is 1 or 2, and X, R 1 , R 2 , R 3 , R 4 , R5 , R 6 , k, m, and n are as described in Example 1.

[1248] Example 54: A compound as described in Example 53, wherein R 2 is alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, or heteroaryl, wherein the alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclic group, cycloalkyl, heterocyclic group, or heteroaryl is optionally substituted by one, two, or three independently selected R 11 ; and R u and R 11 are as described in Example 1.

[1249] Example 55: A compound as described in Example 53, wherein R 2 is alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, or cyanoalkyl, wherein the alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, or cyanoalkyl is optionally substituted by R 11 ; R 1 , R 3 , R 4 , R 5 , R 6 , R 11 , R 11 , k, m, and n are as described in Example 1.

[1250] Example 56: A compound as described in Example 53, wherein R 2 is C 1-6 alkyl, halo-C 1-6 alkyl, deuterated-C 1-6 alkyl, hydroxy-C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, cyano-C 1-6 alkyl, -R u -C 3-6 cycloalkyl, -R u -3- to 7-membered heterocyclic group, C 3-6 cycloalkyl, 3- to 7-membered heterocyclic group, or 5- to 10-membered heteroaryl, wherein the C 1-6 alkyl, halo-C 1-6 alkyl, deuterated-C 1-6 alkyl, hydroxy-C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, cyano-C 1-6Alkyl, -R u -C 3-6 Cycloalkyl, -R u -3- to 7-membered heterocyclic group, C 3-6 Cycloalkyl, 3- to 7-membered heterocyclic group or 5- to 10-membered heteroaryl is optionally substituted by one, two or three independently selected R 11 ; R 1 , R 3 , R 4 , R 5 , R 6 , R 11 , k, m and n are as described in Example 1.

[1251] Example 57: The compound as described in Example 53, wherein R 2 is halo C 1-3 alkyl or -R u -3- to 5-membered heterocyclic group, wherein the -R u -3- to 5-membered heterocyclic group is optionally substituted by independently selected halo; and R 1 , R 3 , R 4 , R 5 , R 6 , k, m and n are as described in Example 1.

[1252] Example 58: The compound as described in Example 53, wherein R 2 is fluoroethyl or (3-fluoroxetan-3-yl)methyl; and R 1 , R 3 , R 4 , R 5 , R 6 , k, m and n are as described in Example 1.

[1253] Example 59: The compound as described in Example 1, 4, or 6, the compound having formula (IIa):

[1254]

[1255] or a pharmaceutically acceptable salt thereof, wherein j is 1 or 2; X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 , k, m and n are as described in Examples 1, 4 and 6, respectively.

[1256] Example 60: The compound as described in Example 1, 4, or 6, the compound having formula (IIc):

[1257]

[1258] or a pharmaceutically acceptable salt thereof, wherein X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 , k, m and n are as described in Examples 1, 4 and 6 respectively.

[1259] Example 61: A compound as described in Example 1, 4, 6, or 59, the compound having formula (IVb):

[1260]

[1261] or a pharmaceutically acceptable salt thereof, wherein j is 1 or 2; X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 and k are as described in Examples 1, 4, 6 and 59 respectively.

[1262] Example 62: A compound as described in Example 1, 4, 6, or 59, the compound having formula (IIe):

[1263]

[1264] or a pharmaceutically acceptable salt thereof, wherein X, R 1 , R 4 , R 5 , R 6 and R 11 are as described in Examples 1, 4, 6 and 59 respectively.

[1265] Example 63: A compound as described in Example 1, 4, or 6, the compound having formula (IIf):

[1266]

[1267] or a pharmaceutically acceptable salt thereof, wherein p is 1 or 2; and X, R 1 , R 4 , R 5 , R 6 and R 11 are as described in Examples 1, 4 and 6 respectively.

[1268] Example 64: A compound as described in Example 1, 4, or 6, the compound having formula (IVk):

[1269]

[1270] or a pharmaceutically acceptable salt thereof, wherein p is 1 or 2; and X, R 1 , R 4 , R 5 , R 6 and R 11 are as described in Examples 1, 4, and 6, respectively.

[1271] Example 65: A compound as described in Examples 1, 4, 6, 59, or 60, the compound having the formula (IVf):

[1272]

[1273] or a pharmaceutically acceptable salt thereof, wherein X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 and k are as described in Examples 1, 4, 6, 59, and 60, respectively.

[1274] Example 66: A compound as described in Examples 1, 4, 6, 59, or 60, the compound having the formula (IVj):

[1275]

[1276] or a pharmaceutically acceptable salt thereof, wherein X, R 1 , R 4 , R 5 , R 6 and R 11 are as described in Examples 1, 4, 6, 59, and 60, respectively.

[1277] Example 67: A compound as described in Examples 1, 4, 6, or 59, the compound having the formula (IIb):

[1278]

[1279] or a pharmaceutically acceptable salt thereof.

[1280] Example 68: A compound as described in Example 67, wherein m is 1; n is 1; and wherein X, R 1 , R 4 , R 5 , R 6 and R 11 are as described in Examples 1, 4, 6, and 59, respectively, or a pharmaceutically acceptable salt thereof.

[1281] Example 69: A compound as described in Examples 1, 4, 6, or 59, the compound having the formula (IId):

[1282]

[1283] or a pharmaceutically acceptable salt thereof, wherein X, R 1 , R 4 , R 5 , R 6 and R 11 are as described in Examples 1, 4, 6, and 59, respectively.

[1284] Example 70: A compound as described in Example 1, 4, 6, or 59, which compound has the formula (IVc):

[1285]

[1286] or a pharmaceutically acceptable salt thereof, wherein X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 , k, m, and n are as described in Examples 1, 4, 6, and 59, respectively.

[1287] Example 71: A compound as described in Example 1, 4, 6, or 59, which compound has the formula (IVg):

[1288]

[1289] or a pharmaceutically acceptable salt thereof, wherein X, R 1 , R 4 , R 5 , R 6 and R 11 are as described in Examples 1, 4, 6, and 59, respectively.

[1290] Example 72: A compound as described in Example 1, 4, 6, or 59, which compound has the formula (IVd):

[1291]

[1292] or a pharmaceutically acceptable salt thereof, wherein X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 , k, m, and n are as described in Examples 1, 4, 6, and 59, respectively.

[1293] Example 73: A compound as described in Example 1, 4, 6, or 59, which compound has the formula (IVe):

[1294]

[1295] or a pharmaceutically acceptable salt thereof, wherein X, R 1 、R 3 、R 4 、R 5 、R 6 、R 11 、k, m and n are as described in Examples 1, 4, 6, and 59, respectively.

[1296] Example 74: A compound as described in Example 1, 4, 6, or 59, the compound having the formula (IVh):

[1297]

[1298] or a pharmaceutically acceptable salt thereof, wherein X, R 1 、R 4 、R 5 、R 6 and R 11 are as described in Examples 1, 4, 6, and 59, respectively.

[1299] Example 75: A compound as described in Example 1, 4, 6, or 59, the compound having the formula (IVi):

[1300]

[1301] or a pharmaceutically acceptable salt thereof, wherein X, R 1 、R 4 、R 5 、R 6 and R 11 are as described in Examples 1, 4, 6, and 59, respectively.

[1302] Example 76: A compound as described in any one of Examples 1 to 75, wherein each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, deuterated C 1-3 alkyl, halo C 1-3 alkyl, cyano C 1-3 alkyl, hydroxy C 1-3 alkyl, hydroxy, C 1-3 alkoxy, halo C 1-3 alkoxy; or two R 11 groups together with the carbon atom to which they are attached form C 3-5 cycloalkyl or oxo.

[1303] Example 77: A compound as described in any one of Examples 1 to 75, wherein each R 11Independently is fluorine, cyano, oxo, hydroxy, methyl, -CHF 2 , -CF 3 or -OCHF 2 , or two R 11 groups together with the carbon atom to which they are attached form cyclobutyl or oxo.

[1304] Example 78: A compound according to any one of Examples 1 to 75, wherein each R 11 is independently halo, cyano, haloC 1-3 alkyl, haloC 1-3 alkoxy or C 1-3 alkylsulfonyl; or two R 11 groups together with the carbon atom to which they are attached form C 3-5 cycloalkyl.

[1305] Example 79: A compound according to any one of Examples 1 to 75, wherein each R 11 is independently fluorine, cyano, -CF 3 , -CHF 2 , -OCF 3 or -S(O) 2 CH 3 , or two R 11 groups together with the carbon atom to which they are attached form cyclopropyl.

[1306] Example 80: A compound according to any one of Examples 1 to 75, wherein each R 11 is independently halo, cyano, oxo, C 1-3 alkyl, haloC 1-3 alkyl, cyanoC 1-3 alkyl, hydroxy, C 1-3 alkoxy, haloC 1-3 alkoxy, C 1-3 alkylthio, haloC 1-3 alkylthio, C 1-3 alkylsulfonyl, C 1-3 alkylsulfinyl, or haloC 1-3 alkylsulfinyl.

[1307] Example 81: A compound according to any one of Examples 1 to 75, wherein each R 11 is independently halo, cyano, haloC 1-3 alkyl, hydroxyC 1-3 alkyl, C 1-3 alkoxyC 1-3 alkyl, haloC 1-3 alkoxyC 1-3 alkyl, hydroxy, C 1-3 alkoxy or haloC1-3 Alkoxy group.

[1308] Example 82: A compound as described in any one of Examples 1 to 75, wherein each R 11 is independently halo, cyano, or halo C 1-3 alkyl or hydroxy.

[1309] Example 83: A compound as described in any one of Examples 1 to 75, wherein each R 11 is independently halo, cyano or halo C 1-3 alkyl.

[1310] Example 84: A compound as described in any one of Examples 1 to 75, wherein each R 11 is independently F, Cl, Br, cyano, -CHF 2 or -CF 3 .

[1311] Example 85: A compound as described in any one of Examples 1 to 75, wherein each R 11 is independently halo or cyano.

[1312] Example 86: A compound as described in any one of Examples 1 to 75, wherein each R 11 is independently chloro or cyano.

[1313] Example 87: A compound as described in any one of Examples 1 to 76, 78, 80 to 83, or 85, wherein R 11 is halo.

[1314] Example 88: A compound as described in any one of Examples 1 to 76, 78, 80 to 83, or 85, wherein R 11 is fluoro.

[1315] Example 89: A compound as described in any one of Examples 1 - 76, 78, or 80 to 83, wherein R 11 is cyano or halo C 1-3 alkyl.

[1316] Example 90: A compound as described in any one of Examples 1 - 76, 78, 80, or 89, wherein R 11 is halo C 1-3 alkyl.

[1317] Example 91: A compound as described in any one of Examples 1 - 76, 78, 80, or 89, wherein R 11 is fluoro C 1-3 alkyl.

[1318] Example 92: A compound according to any one of Examples 1 - 76, 78, or 80 to 83, wherein R 11 is cyano, -CHF 2 or -CF 3 .

[1319] Example 93: A compound according to any one of Examples 1 - 76, 78, 80, or 89, wherein R 11 is -CF 3 .

[1320] Example 94: A compound according to any one of Examples 1 to 53, 59, 60, 61, 65, 67, 69, 70, 72, or 73, wherein k is 0.

[1321] Example 95: A compound according to any one of Examples 1 to 53, 59, 60, 61, 65, 67, 69, 70, 72, or 73, wherein k is 1.

[1322] Example 96: A compound according to any one of Examples 1, 4, 6, 7, 39, 41, 53, 59, 60, 61, 65, 67, 70, 72 or 73, wherein m is 1 and n is 1.

[1323] Example 97: A compound according to Example 96, wherein R 3 is halo, methyl or -CF 3 .

[1324] Example 98: A compound according to Example 97, wherein R 3 is methyl.

[1325] Example 99: A compound according to any one of Examples 1 to 98, wherein R 4 is hydrogen, halo, C 1-3 alkyl or halo C 1-3 alkyl.

[1326] Example 100: A compound according to any one of Examples 1 to 99, wherein R 4 is hydrogen, fluorine, chlorine, methyl or -CF 3 .

[1327] Example 101: A compound according to any one of Examples 1 to 100, wherein R 4 is hydrogen, fluorine, chlorine or methyl.

[1328] Example 102: A compound according to any one of Examples 1 to 101, wherein R 4 is hydrogen.

[1329] Example 103: The compound according to any one of Examples 1 to 102, wherein R 5 is halogenated, C 1-3 alkyl, C 3-5 cycloalkyl or C 1-3 alkoxy.

[1330] Example 104: The compound according to any one of Examples 1 to 103, wherein R 5 is chlorine, bromine, methyl, cyclopropyl or methoxy.

[1331] Example 105: The compound according to any one of Examples 1 to 104, wherein R 6 is halogenated, cyano, C 1-3 alkyl, C 3-5 cycloalkyl or C 1-3 alkoxy.

[1332] Example 106: The compound according to any one of Examples 1 to 105, wherein R 6 is chlorine, bromine, cyano, methyl, cyclopropyl or methoxy.

[1333] Example 107: The compound according to any one of Examples 1 to 106, wherein R 4 is hydrogen or methyl; R 5 is methoxy and R 6 is methyl.

[1334] Example 108: The compound according to any one of Examples 1 to 107, wherein R 4 is hydrogen; R 5 is methoxy and R 6 is methyl.

[1335] Example 109: The compound according to any one of Examples 1 to 108, wherein R 1 is hydrogen and X is CH.

[1336] Example 110: The compound according to Example 1, wherein the compound is selected from the group consisting of:

[1337] 4-((2S,4S)-4-(4-Fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 1)

[1338] 4-((2R,4R)-4-(4-Fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1339] 4-((2S,4R)-4-(4-Fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1340] 4-((2R,4S)-4-(4-Fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1341] 4-(4-(4-Fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1342] (±)-trans-4-(4-(4-Bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 2)

[1343] 4-((2S,4S)-(4-(4-Bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1344] 4-((2R,4R)-(4-(4-Bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1345] 4-((2S,4R)-(4-(4-Bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1346] 4-((2R,4S)-(4-(4-Bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1347] 4-(4-(4-Bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;

[1348] (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; (Example 3)

[1349] 4-((2S,4S)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid;

[1350] 4-((2R,4R)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid;

[1351] 4-((2S,4R)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid;

[1352] 4-((2R,4S)-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid;

[1353] 4-(1-((5-Methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid;

[1354] 4-((2S,4S)-1-((5-Methoxy-7-...

Claims

1. A compound of formula (IVf): or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, fluorine, chlorine or methyl; X is N or CH; R 3 is halo, cyano, C 1-3 alkyl, or halo C 1-3 alkyl; R 4 is hydrogen, halogenated, cyano, C 1-3 alkyl or halogenated C 1-3 alkyl; R 5 is halo, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, halo C 1-3 alkoxy or C 1-3 alkoxy; R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, halo C 1-3 alkyl, C 1-3 alkoxy or halo C 1-3 alkoxy; R 11 Each is independently halo-; k is 0, 1, 2 or 3; m is 0, 1 or 2; and n is 0, 1, or 2.

2. The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R 1 is hydrogen, fluorine, chlorine or methyl; X is N or CH; R 3 is halogenated, cyano, C 1-3 alkyl, or halogenated C 1-3 alkyl; R 4 is hydrogen, halogenated, cyano, C 1-3 alkyl or halogenated C 1-3 alkyl; R 5 is halogenated, C 1-3 alkyl, C 3-5 cycloalkyl, halogenated C 1-3 alkyl, halogenated C 1-3 alkoxy or C 1-3 alkoxy; R 6 is halo, cyano, C 1-3 alkyl, C 3-5 cycloalkyl, haloC 1-3 alkyl, C 1-3 alkoxy or haloC 1-3 alkoxy; R 11 is fluorine; k is 0, 1, 2 or 3; m is 0, 1 or 2; and n is 0, 1, or 2.

3. The compound or a pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein k is 0; m is 1; and n is 1.

4. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 - 3, wherein R 1 is hydrogen, fluorine or chlorine; X is CH; R 4 is hydrogen, fluorine, chlorine or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; and R 11 is fluorine.

5. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 - 4, which has the formula (IVl) 6. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 - 5, wherein the compound is 7. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 - 5, wherein the compound is 8. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 - 5, wherein the compound is 9. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 - 5, wherein the compound is

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