Amino acid compounds with nitrogen linkers and uses thereof

Abstract

The present disclosure relates generally to compounds of formula (I): or a pharmaceutically acceptable salt thereof, wherein R1, R2, Q, L1, L2, L3, X, and Y are as described herein. Compounds of formula (I) and pharmaceutical compositions thereof are inhibitors of αvβ1, αvβ6, and / or αvβ8 integrins that are useful for treating fibrosis such as idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP), and for treating cancer, for example, in combination with a checkpoint inhibitor.

Description

AMINO ACID COMPOUNDS WITH NITROGEN LINKERS AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority benefit of United States Provisional Patent Application Nos. 63 / 586,843, filed September 29, 2023, 63 / 586,987, filed September 29, 2023, 63 / 587,033, filed September 29, 2023, and 63 / 587,011, filed September 29, 2023, the contents of each of which are hereby incorporated herein in its entirety. FIELD

[0002] This disclosure relates generally to therapeutic agents that may be useful as inhibitors of one or more of αVβ1, αVβ6, and αVβ8integrins. The therapeutic agents may be used in the treatment or prophylactic treatment of diseases, e.g., fibrosis such as idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP), and cancer. BACKGROUND

[0003] Fibrosis, a pathologic feature of many diseases, is caused by a dysfunction in the body’s natural ability to repair damaged tissues. If left untreated, fibrosis can result in scarring of vital organs causing irreparable damage and eventual organ failure.

[0004] Patients with nonalcoholic fatty liver disease (NAFLD) may progress from simple steatosis to nonalcoholic steatohepatitis (NASH) and then fibrosis. While liver fibrosis is reversible in its initial stages, progressive liver fibrosis can lead to cirrhosis.

[0005] Fibrosis in the kidney, characterized by glomerulosclerosis and tubulointerstitial fibrosis, is the final common manifestation of a wide variety of chronic kidney diseases (CKD). Irrespective of the initial causes, progressive CKD often results in widespread tissue scarring that leads to destruction of kidney parenchyma and end-stage renal failure, a devastating condition that requires dialysis or kidney replacement.

[0006] Scleroderma encompasses a spectrum of complex and variable conditions primarily characterized by fibrosis, vascular alterations, and autoimmunity. The scleroderma spectrum of disorders share the common feature of fibrosis, resulting in hardening or thickening of the skin. For some patients, this hardening occurs only in limited areas, but for others, it can spread to other major organs.

[0007] Following myocardial infarction, cardiac structural remodeling is associated with an inflammatory reaction, resulting in scar formation at the site of the infarction. This scar formation is a result of fibrotic tissue deposition which may lead to reduced cardiac function and disruption of electrical activity within the heart.

[0008] Crohn’s Disease is a chronic disease of unknown etiology tending to progress even in the setting of medical or surgical treatment. Intestinal fibrosis is among the most common complications of Crohn’s disease, resulting in stricture formation in the small intestine and colon.

[0009] Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing disease of unknown etiology, occurring in adults and limited to the lungs. In IPF, the lung tissue becomes thickened, stiff, and scarred. As lung fibrosis progresses, it becomes more difficult for the lungs to transfer oxygen into the bloodstream and the organs do not receive the oxygen needed to function properly. IPF currently affects approximately 200,000 people in the U.S., resulting in 40,000 deaths per year. Patients diagnosed with IPF experience progressive breathlessness and eventually, complete respiratory failure.

[0010] Primary biliary cholangitis (PBC), also known as primary biliary cirrhosis, is a chronic disease of the liver that causes damage and fibrosis in the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to build up in the liver, a condition called cholestasis. Over time, this leads to scarring and fibrosis in both the liver and biliary tract.

[0011] Primary sclerosing cholangitis (PSC) involves bile duct inflammation, and fibrosis that obliterates the bile ducts. The resulting impediment to the flow of bile to the intestines can lead to cirrhosis of the liver and subsequent complications such as liver failure and liver cancer. Expression of αVβ6is elevated in liver and bile duct of PSC patients.

[0012] Nonspecific interstitial pneumonia (NSIP) is a rare disorder that affects the tissue that surrounds and separates the tiny air sacs of the lungs. These air sacs, called the alveoli, are where the exchange of oxygen and carbon dioxide takes place between the lungs and the bloodstream. Interstitial pneumonia is a disease in which the mesh-like walls of the alveoli become inflamed. The pleura (a thin covering that protects and cushions the lungs and the individual lobes of the lungs) might become inflamed as well. There are two primary forms of NSIP - cellular and fibrotic. The cellular form is defined mainly by inflammation of the cells of the interstitium. The fibrotic form is defined by thickening and scarring of lung tissue. This scarring is known as fibrosis. When the lung tissue thickens or becomes scarred, it does not function as effectively. Breathing becomes less efficient, and there are lower levels of oxygen in the blood (Kim et al., Proc. Am. Thorac. Soc. (2006) 3:285-292; Lynch, D., Radiology (2001) 221:583-584; Kinder et al., Am. J. Respir. Crit. Care Med. (2007) 176:691-697).

[0013] Available courses of treatment are scarce, as there are currently no options on the market proven to have an effect on long-term patient survival or symptomatology. There remains a need for treatment of fibrotic diseases.

[0014] The αVβ6integrin is expressed in epithelial cells, and binds to the latency-associated peptide of transforming growth factor-β1 (TGFβ1) and mediates TGFβ1 activation. Its expression level is significantly increased after injury to lung and cholangiocytes, and plays a critical in vivo role in tissue fibrosis. Increased levels are also associated with increased mortality in IPF and NSIP patients.

[0015] The αVβ1, αVβ6, and αVβ8integrins bind to the latency-associated peptide of transforming growth factor-β1 (TGFβ1) and mediate TGFβ1 activation. For example, the αVβ1integrin is expressedon liver and pancreatic cells. The αVβ6integrin is expressed in epithelial cells, for example airway epithelial cells. The αVβ8integrin is expressed in epithelial cells, for example airway epithelial cells, and cancer cells. Integrin expression levels can be significantly increased upon injury or disease, for example, after injury to lung and cholangiocytes. Accordingly, such integrins can play a critical in vivo role in injury or disease, e.g. tissue fibrosis. Increased levels are also associated with increased mortality in subjects with such diseases, such as IPF and NSIP patients.

[0016] Cancer cells may be modulated by TGFβ1 signaling in various ways. For example, cancer cells may express one or more of αVβ1, αVβ6, and αVβ8integrins, for example, αVβ8. Immune cells may express latent TGFβ1, which may be activated by such integrins. Antibodies to each of αVβ8and TGFβ1 have been developed to disrupt TGFβ1 signaling. However, efficacy against cancer for such antibodies has been limited. SUMMARY

[0017] Disclosed are amino acid compounds that are inhibitors of one or more of αVβ1, αVβ6, and αVβ8, compositions containing these compounds and methods for treating diseases mediated by one or more of αVβ1, αVβ6, and αVβ8such as a fibrotic disease or cancer.

[0018] In one aspect, provided is a compound of formula (I), or any variation thereof, or a salt thereof (e.g., a pharmaceutically acceptable salt thereof), as detailed herein.

[0019] Further provided is a pharmaceutical composition comprising a compound of formula (I), or any variation thereof detailed herein, or a salt thereof (e.g., a pharmaceutically acceptable salt thereof), and a pharmaceutically acceptable carrier or excipient.

[0020] Also provided is a pharmaceutical composition comprising a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof (e.g., a pharmaceutically acceptable salt thereof), a checkpoint inhibitor, and a pharmaceutically acceptable carrier or excipient.

[0021] In another aspect, provided is a method of treating a fibrotic disease or condition in an individual (such as a human) in need thereof comprising administering to the individual a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing. In some embodiments, an effective amount of a compound of formula (I) or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing, is administered. In some embodiments, the effective amount is a therapeutically effective amount. In some embodiments, the fibrotic disease or condition is pulmonary, liver, renal, cardiac, dermal, or gastrointestinal fibrosis. In other embodiments the fibrotic disease or condition is idiopathic pulmonary fibrosis, interstitial lung disease, radiation-induced pulmonary fibrosis, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), alcoholic liver disease induced fibrosis, Alport syndrome, primary sclerosing cholangitis, primarily biliary cholangitis (also known as primarybiliary cirrhosis), systemic sclerosis associated interstitial lung disease, scleroderma (also known as systemic sclerosis) , diabetic nephropathy, diabetic kidney disease, focal segmental glomerulosclerosis, chronic kidney disease, or Crohn’s Disease.

[0022] In another aspect, provided is a method of delaying the onset and / or development of a fibrotic disease or condition in an individual (such as a human) who is at risk for developing a fibrotic disease or condition comprising administering to the individual a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing. In some embodiments, an effective amount of a compound of formula (I) or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing, is administered. In some embodiments, the effective amount is a therapeutically effective amount. In some embodiments, the disease or condition is pulmonary, liver, renal, cardiac, dermal, or gastrointestinal fibrosis. In other embodiments the fibrotic disease or condition is idiopathic pulmonary fibrosis, interstitial lung disease, radiation-induced pulmonary fibrosis, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), alcoholic liver disease induced fibrosis, Alport syndrome, primary sclerosing cholangitis, primarily biliary cholangitis (also known as primary biliary cirrhosis), systemic sclerosis associated interstitial lung disease, scleroderma (also known as systemic sclerosis), diabetic nephropathy, diabetic kidney disease, focal segmental glomerulosclerosis, chronic kidney disease, or Crohn’s Disease.

[0023] Further provided is a kit comprising a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing. In some embodiments, the kit comprises instructions for use according to a method described herein, such as a method of treating a fibrotic disease in an individual. In some embodiments, the kit comprises instructions for use according to a method described herein, such as a method of treating a cancer in an individual.

[0024] Also provided is a kit comprising a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof, and a checkpoint inhibitor. In some embodiments, the kit comprises instructions for use according to a method described herein, such as a method of treating a fibrotic disease in an individual. In some embodiments, the kit comprises instructions for use according to a method described herein, such as a method of treating a cancer in an individual.

[0025] Further provided is a method of inhibiting αVβ6integrin in an individual comprising administering a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof.

[0026] Also provided is a method of inhibiting one or more of αVβ1, αVβ6, and αVβ8integrin in an individual in need thereof, comprising administering to the individual a compound of formula (I), orany variation thereof detailed herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0027] Further provided is a method of inhibiting TGFβ activation in a cell comprising contacting the cell with a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0028] Also provided is a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutical composition thereof, for the treatment of a fibrotic disease.

[0029] Also provided is use of a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment of a fibrotic disease.

[0030] Further provided is use of a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for the treatment of a disease mediated by cells that express one or more of: αVβ1, αVβ6, and αVβ8.

[0031] Also provided is use of a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, in the manufacture of a medicament for the treatment of a disease mediated by cells that express one or more of: αVβ1, αVβ6, and αVβ8.

[0032] Further provided is use of a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for treatment of a cancer.

[0033] Also provided is use of a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, in the manufacture of a medicament for the treatment of a cancer.

[0034] Further provided is a method of treating a subject in need thereof. In some embodiments, the method comprises providing the subject. In some embodiments, the subject comprises at least one tissue in need of therapy. In some embodiments, the at least one tissue can be characterized by at least one value that is elevated compared to a healthy value in a healthy state of the tissue. In some embodiments, the tissue comprises an elevated value of αVβ1integrin activity and / or expression. In some embodiments, the tissue comprises an elevated value of αVβ6integrin activity and / or expression. In some embodiments, the tissue comprises an elevated value of αVβ8integrin activity and / or expression. In some embodiments, the tissue comprises an elevated value of a pSMAD / SMAD ratio. In some embodiments, the tissue comprises an elevated value of new collagen formation or accumulation. In some embodiments, the tissue comprises an elevated value of total collagen. In some embodiments, the tissue comprises an elevated value of Type I Collagen gene Col1a1 expression. In some embodiments, the tissue comprises an elevated value of perforin. In some embodiments, the tissue comprises an elevated value of Granzyme B. In some embodiments, the tissue comprises an elevated value of interferon γ. In some embodiments, the method comprises administering to thesubject an effective amount of a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In some embodiments, the method comprises administering to the subject a therapeutically effective amount of a compound of formula (I), or any variation thereof detailed herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0035] Also provided is a method of characterizing anticancer activity of a small molecule inhibitor in a subject. In some embodiments, the method comprises providing a first live cell sample from the subject. In some embodiments, the first live cell sample can be characterized by the presence of at least one integrin capable of activating transforming growth factor β (TGF-β) from latency associated peptide-TGF-β. In some embodiments, the method comprises determining a first value in the first live cell sample. In some embodiments, the first value can be a pSMAD2 / SMAD2 ratio. In some embodiments, the first value can be a pSMAD3 / SMAD3 ratio. In some embodiments, the first value can be a perforin level. In some embodiments, the first value can be a granzyme B level. In some embodiments, the first value can be an interferon γ level. In some embodiments, the method comprises administering the small molecule to the subject. In some embodiments, the method comprises providing a second live cell sample from the subject. In some embodiments, the second live cell sample can be drawn from the same tissue in the subject as the first live cell sample. In some embodiments, the method comprises determining a second value in the second live cell sample. In some embodiments, the second value can correspond to the pSMAD2 / SMAD2 ratio, pSMAD3 / SMAD3 ratio, perforin level, granzyme B level, or interferon γ level of the first value. In some embodiments, the method comprises characterizing the anticancer activity of the small molecule in the subject by comparing the second value to the first value.

[0036] In another aspect, provided is a method of making a compound of formula (I) or any variation thereof. Also provided are compound intermediates useful in synthesis of a compound of formula (I), or any variation thereof.

[0037] It is understood that aspects and variations described herein also include “consisting” and / or “consisting essentially of” aspects and variations. BRIEF DESCRIPTION OF THE FIGURES

[0038] FIG. 1 is a diagram illustrating aspects of integrin-mediated TGF-β activation in tumor adaptive immunity.

[0039] FIG.2A is a diagram illustrating an initial experiment in mice.

[0040] FIG.2B is a graph showing that EMT6 cell proliferation was not affected by anti-αVβ8or IgG control in vitro.

[0041] FIG.3A is a graph showing tumor volume as a function of time for the short arm of the study of Example B3.

[0042] FIG.3B is a graph showing tumor volume as a function of time for the long arm of the study of Example B3.

[0043] FIG.4A is a graph showing tumor volume versus time for mice in Group 1.

[0044] FIG.4B is a graph showing tumor volume versus time for mice in Group 2.

[0045] FIG.4C is a graph showing tumor volume versus time for mice in Group 3.

[0046] FIG.4D is a graph showing tumor volume versus time for mice in Group 4.

[0047] FIG.4E is a graph showing tumor volume versus time for mice in Group 5.

[0048] FIG.5 is a graph of percent survival versus time over 5 weeks, showing that long term survival was significantly improved by the combination of the anti-PD1 and anti-αVβ8antibodies in Group 4.

[0049] FIG. 6A is a graph showing that inhibiting αVβ8significantly reduced SMAD3 phosphorylation in Groups 3 and 4, consistent with significantly reduced TGFβ signaling inside the tumor cells.

[0050] FIG.6B is a graph showing that inhibiting αVβ8significantly reduced integrin αVβ1expression in myofibroblasts.

[0051] FIG. 7A is a bar graph showing that Granzyme B expression, assessed by immunohistochemistry staining with an anti-granzyme B antibody was significantly enhanced in Groups 3 and 4 with the anti-αVβ8antibody.

[0052] FIG.7B is a graph showing that CD8+ cytotoxic T cells were increased in Group 3, containing the anti αVβ8antibody alone, and significantly increased in Group 4, containing the anti PD-1 and anti αVβ8antibodies together.

[0053] FIG.8A is a graph showing that αVβ8inhibition results in cytotoxic T cell activation 14 days post treatment for perforin (PRF1).

[0054] FIG. 8B is a graph showing that αVβ8inhibition results in cytotoxic T cell activation 14 days post treatment for granzyme B (GZMB).

[0055] FIG.8C is a graph showing that αVβ8inhibition results in cytotoxic T cell activation 14 days post treatment for interferon γ (IFNg).

[0056] FIG.8D is a graph showing that αVβ8inhibition results in cytotoxic T cell activation 14 days post treatment for Fas ligand (FASL).

[0057] FIG. 9A is a graph of cell profiling analysis showing that CD8 T cells were upregulated by αVβ8inhibition.

[0058] FIG.9B is a graph of cell profiling analysis showing that NK cells were upregulated by αVβ8inhibition.

[0059] FIG. 9C is a graph of cell profiling analysis showing that cytotoxic T cells were upregulated by αVβ8inhibition.

[0060] FIG. 10A shows tumor antibody concentration (left axis) and pSMAD3 / SMAD3 ratio (right axis), indicating a clear, dose-responsive relationship for treatment with the anti-αVβ8antibody at 0.4, 2, and 10 mg / kg in combination with the anti-PD-1 antibody.

[0061] FIG.10B shows a clear, dose-responsive relationship for the anti-αVβ8antibody at 0.4, 2, and 10 mg / kg in combination with the anti-PD-1 antibody versus Granzyme B (pg / mL, left axis) and interferon γ (IFNγ, pg / mL, right axis).

[0062] FIG.11 shows the results of combinations of the anti-αVβ8antibody with anti-PD1, anti-PDL1 or anti-CTLA-4 resulted in similar T cell activation.

[0063] FIG.12 is a diagram illustrating an experiment in mice.

[0064] FIG. 13A shows the results of Group 2, 10 mg / kg of an anti-PD1 antibody (RMP1-14) at 0-, 3-, and 7-days post-treatment.

[0065] FIG. 13B shows the results of Group 5, the high dose of the small molecule αVβ8inhibitor at 0-, 3-, and 7-days post-treatment.

[0066] FIG. 13C shows the results of Group 8, 10 mg / kg of the anti-PD1 antibody and 1 mg / kg of the ALK5 inhibitor at 0-, 3-, and 7-days post-treatment.

[0067] FIG.13D shows the results of Group 4, including 10 mg / kg of the anti-PD1 antibody and the high dose of small molecule αVβ8inhibitor at 0-, 3-, and 7-days post-treatment.

[0068] FIG. 14A shows the change in tumor volume for individual mice subjects (data points) and the median change in tumor volume among all subjects (bars) in each Group.

[0069] FIG. 14B shows pSMAD3 / SMAD3 ratios for the corresponding Groups, a marker of TGFβ signaling.

[0070] FIG.15A is a graph showing scores for interferon γ signaling for various treatment Groups as range (boxes) and median (line in each box).

[0071] FIG. 15B is a graph showing scores for Granzyme B concentration for various treatment Groups as range (boxes) and median (line in each box).

[0072] FIG.15C is a graph showing scores for T cell activation for various treatment Groups as range (boxes) and median (line in each box). DETAILED DESCRIPTION

[0073] The following description sets forth exemplary methods, parameters and the like. It should be recognized, however, that such description is not intended as a limitation on the scope of the present disclosure but is instead provided as a description of exemplary embodiments. Definitions

[0074] For use herein, unless clearly indicated otherwise, use of the terms “a”, “an” and the like refers to one or more.

[0075] Reference to “about” a value or parameter herein includes (and describes) embodiments that are directed to that value or parameter per se. For example, description referring to “about X” includes description of “X”. Likewise, reference to a value “X” also includes description of “about X”.

[0076] “Alkyl” as used herein refers to and includes, unless otherwise stated, a saturated linear (i.e., unbranched) or branched univalent hydrocarbon chain or combination thereof, having the number ofcarbon atoms designated (i.e., C1-C10means one to ten carbon atoms). Particular alkyl groups are those having 1 to 20 carbon atoms (a “C1-C20alkyl”), having 1 to 10 carbon atoms (a “C1-C10alkyl”), having 6 to 10 carbon atoms (a “C6-C10alkyl”), having 1 to 6 carbon atoms (a “C1-C6alkyl”), having 2 to 6 carbon atoms (a “C2-C6alkyl”), or having 1 to 4 carbon atoms (a “C1-C4alkyl”). Examples of alkyl groups include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, and the like.

[0077] “Alkylene” as used herein refers to the same residues as alkyl, but having bivalency. Particular alkylene groups are those having 1 to 20 carbon atoms (a “C1-C20alkylene”), having 1 to 10 carbon atoms (a “C1-C10alkylene”), having 6 to 10 carbon atoms (a “C6-C10alkylene”), having 1 to 6 carbon atoms (a “C1-C6alkylene”), 1 to 5 carbon atoms (a “C1-C5alkylene”), 1 to 4 carbon atoms (a “C1-C4alkylene”) or 1 to 3 carbon atoms (a “C1-C3alkylene”). Examples of alkylene include, but are not limited to, groups such as methylene (-CH2-), ethylene (-CH2CH2-), propylene (-CH2CH2CH2-), isopropylene (-CH2CH(CH3)-), butylene (-CH2(CH2)2CH2-), isobutylene (-CH2CH(CH3)CH2-), pentylene (-CH2(CH2)3CH2-), hexylene (-CH2(CH2)4CH2-), heptylene (-CH2(CH2)5CH2-), octylene (-CH2(CH2)6CH2-), and the like. It is understood that when alkylene is substituted (for example with a cycloalkyl group), the substituent is not one of the sites of bivalency. For example, propylene substitution with cyclopropyl may providebut does not provide, wherein the wavy line denotes a site of bivalency.

[0078] “n-Alkylene” as used herein refers to the same residues as alkylene, but having a straight chain of carbon atoms, wherein the two sites of bivalency are on the two ends of the straight chain of carbon atoms. For example, a “C3n-alkylene” or “n-propylene” refers to -CH2CH2CH2-, wherein each of the -CH2- is optionally substituted, but “C3n-alkylene” does not encompass -CH2-CH(CH3)- or -C (CH3)2-. For another example, a “C4n-alkylene” or “n-butylene” refers to, wherein each of the -CH2- is optionally substituted, but does not encompass,, wherein the wavy line denotes a site of bivalency. Particular n-alkylene groups are those having 1 to 20 carbon atoms (a “C1-C20n-alkylene”), having 1 to 10 carbon atoms (a “C1-C10n-alkylene”), having 6 to 10 carbon atoms (a “C6-C10n- alkylene”), having 1 to 6 carbon atoms (a “C1-C6n-alkylene”), 1 to 5 carbon atoms (a “C1-C5n- alkylene”), 1 to 4 carbon atoms (a “C1-C4n-alkylene”) or 1 to 3 carbon atoms (a “C1-C3n-alkylene”).It is understood that when n-alkylene is substituted (for example with a cycloalkyl group), the substituent is not one of the sites of bivalency. For example, n-propylene substitution with cyclopropyl may providebut does not provide, wherein the wavy line denotes a site of bivalency.

[0079] “Alkenyl” as used herein refers to and includes, unless otherwise stated, an unsaturated linear (i.e., unbranched) or branched univalent hydrocarbon chain or combination thereof, having at least one site of olefinic unsaturation (i.e., having at least one moiety of the formula C=C) and having the number of carbon atoms designated (i.e., C2-C10means two to ten carbon atoms). An alkenyl group may have “cis” or “trans” configurations, or alternatively have “E” or “Z” configurations. Particular alkenyl groups are those having 2 to 20 carbon atoms (a “C2-C20alkenyl”), having 6 to 10 carbon atoms (a “C6-C10alkenyl”), having 2 to 8 carbon atoms (a “C2-C8alkenyl”), having 2 to 6 carbon atoms (a “C2-C6alkenyl”), or having 2 to 4 carbon atoms (a “C2-C4alkenyl”). Examples of alkenyl groups include, but are not limited to, groups such as ethenyl (or vinyl), prop-1-enyl, prop-2- enyl (or allyl), 2-methylprop-1-enyl, but-1-enyl, but-2-enyl, but-3-enyl, buta-1,3-dienyl, 2- methylbuta-1,3-dienyl, pent-1-enyl, pent-2-enyl, hex-1-enyl, hex-2-enyl, hex-3-enyl, and the like.

[0080] “Alkenylene” as used herein refers to the same residues as alkenyl, but having bivalency. Particular alkenylene groups are those having 2 to 20 carbon atoms (a “C2-C20alkenylene”), having 2 to 10 carbon atoms (a “C2-C10alkenylene”), having 6 to 10 carbon atoms (a “C6-C10alkenylene”), having 2 to 6 carbon atoms (a “C2-C6alkenylene”), 2 to 4 carbon atoms (a “C2-C4alkenylene”) or 2 to 3 carbon atoms (a “C2-C3alkenylene”). Examples of alkenylene include, but are not limited to, groups such as ethenylene (or vinylene) (-CH=CH-), propenylene (-CH=CHCH2-), 1,4-but-1-enylene (-CH=CH-CH2CH2-), 1,4-but-2-enylene (-CH2CH=CHCH2-), 1,6-hex-1-enylene (-CH=CH- (CH2)3CH2-), and the like.

[0081] “Alkynyl” as used herein refers to and includes, unless otherwise stated, an unsaturated linear (i.e., unbranched) or branched univalent hydrocarbon chain or combination thereof, having at least one site of acetylenic unsaturation (i.e., having at least one moiety of the formula C≡C) and having the number of carbon atoms designated (i.e., C2-C10means two to ten carbon atoms). Particular alkynyl groups are those having 2 to 20 carbon atoms (a “C2-C20alkynyl”), having 6 to 10 carbon atoms (a “C6-C10alkynyl”), having 2 to 8 carbon atoms (a “C2-C8alkynyl”), having 2 to 6 carbon atoms (a “C2-C6alkynyl”), or having 2 to 4 carbon atoms (a “C2-C4alkynyl”). Examples of alkynyl group include, but are not limited to, groups such as ethynyl (or acetylenyl), prop-1-ynyl, prop-2-ynyl (or propargyl), but-1-ynyl, but-2-ynyl, but-3-ynyl, and the like.

[0082] “Alkynylene” as used herein refers to the same residues as alkynyl, but having bivalency. Particular alkynylene groups are those having 2 to 20 carbon atoms (a “C2-C20alkynylene”), having 2 to 10 carbon atoms (a “C2-C10alkynylene”), having 6 to 10 carbon atoms (a “C6-C10alkynylene”),having 2 to 6 carbon atoms (a “C2-C6alkynylene”), 2 to 4 carbon atoms (a “C2-C4alkynylene”) or 2 to 3 carbon atoms (a “C2-C3alkynylene”). Examples of alkynylene include, but are not limited to, groups such as ethynylene (or acetylenylene) (-C≡C-), propynylene (-C≡CCH2-), and the like.

[0083] “Cycloalkyl” as used herein refers to and includes, unless otherwise stated, saturated cyclic univalent hydrocarbon structures, having the number of carbon atoms designated (i.e., C3-C10means three to ten carbon atoms). Cycloalkyl can consist of one ring, such as cyclohexyl, or multiple rings, such as adamantyl. A cycloalkyl comprising more than one ring may be fused, spiro or bridged, or combinations thereof. Particular cycloalkyl groups are those having from 3 to 12 annular carbon atoms. A preferred cycloalkyl is a cyclic hydrocarbon having from 3 to 8 annular carbon atoms (a "C3-C8cycloalkyl"), having 3 to 6 annular carbon atoms (a “C3-C6cycloalkyl”), or having from 3 to 4 annular carbon atoms (a "C3-C4cycloalkyl"). Examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl, and the like.

[0084] “Cycloalkylene” as used herein refers to the same residues as cycloalkyl, but having bivalency. Cycloalkylene can consist of one ring or multiple rings which may be fused, spiro or bridged, or combinations thereof. Particular cycloalkylene groups are those having from 3 to 12 annular carbon atoms. A preferred cycloalkylene is a cyclic hydrocarbon having from 3 to 8 annular carbon atoms (a "C3-C8cycloalkylene"), having 3 to 6 carbon atoms (a “C3-C6cycloalkylene”), or having from 3 to 4 annular carbon atoms (a "C3-C4cycloalkylene"). Examples of cycloalkylene include, but are not limited to, cyclopropylene, cyclobutylene, cyclopentylene, cyclohexylene, cycloheptylene, norbornylene, and the like. A cycloalkylene may attach to the remaining structures via the same ring carbon atom (e.g., 1,1-cyclopropylene) or different ring carbon atoms (e.g., 1,2- cyclopropylene). When a cycloalkylene attaches to the remaining structures via two different ring carbon atoms, the connecting bonds may be cis or trans to each other (e.g., cis-1,2-cyclopropylene or trans-1,2-cyclopropylene). If points of attachment are not specified, the moiety can include any chemically possible attachments. For example, cyclopropylene can indicate 1,1-cyclopropylene or 1,2-cyclopropylene (e.g., cis-1,2-cyclopropylene, trans-1,2-cyclopropylene, or a mixture thereof), or a mixture thereof.

[0085] “Cycloalkenyl” refers to and includes, unless otherwise stated, an unsaturated cyclic non- aromatic univalent hydrocarbon structure, having at least one site of olefinic unsaturation (i.e., having at least one moiety of the formula C=C) and having the number of carbon atoms designated (i.e., C3- C10means three to ten carbon atoms). Cycloalkenyl can consist of one ring, such as cyclohexenyl, or multiple rings, such as norbornenyl. A preferred cycloalkenyl is an unsaturated cyclic hydrocarbon having from 3 to 8 annular carbon atoms (a “C3-C8cycloalkenyl”). Examples of cycloalkenyl groups include, but are not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, norbornenyl, and the like.

[0086] “Cycloalkenylene” as used herein refers to the same residues as cycloalkenyl, but having bivalency.

[0087] “Aryl” or “Ar” as used herein refers to an unsaturated aromatic carbocyclic group having a single ring (e.g., phenyl) or multiple condensed rings (e.g., naphthyl or anthryl) which condensed rings are carbocyclic and may or may not be aromatic, provided at least one ring in the multiple condensed ring structure is aromatic. Particular aryl groups are those having from 6 to 14 annular carbon atoms (a “C6-C14aryl”). An aryl group having more than one ring where at least one ring is non-aromatic may be connected to the parent structure at either an aromatic ring position or at a non- aromatic ring position. In one variation, an aryl group having more than one ring where at least one ring is non-aromatic is connected to the parent structure at an aromatic ring position.

[0088] “Arylene” as used herein refers to the same residues as aryl, but having bivalency. Particular arylene groups are those having from 6 to 14 annular carbon atoms (a “C6-C14arylene”).

[0089] “Heteroaryl” as used herein refers to an unsaturated aromatic cyclic group having from 1 to 14 annular carbon atoms and at least one annular heteroatom, including but not limited to heteroatoms such as nitrogen, oxygen and sulfur. A heteroaryl group may have a single ring (e.g., pyridyl, furyl) or multiple condensed rings (e.g., indolizinyl, benzothienyl) which condensed rings may be carbocyclic or may contain one or more annular heteroatom and which may or may not be aromatic, provided at least one ring in the multiple condensed ring structure is both aromatic and contains at least one annular heteroatom. Particular heteroaryl groups are 5 to 14-membered rings having 1 to 12 annular carbon atoms and 1 to 6 annular heteroatoms independently selected from nitrogen, oxygen and sulfur, 5 to 10-membered rings having 1 to 8 annular carbon atoms and 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen and sulfur, or 5, 6 or 7-membered rings having 1 to 5 annular carbon atoms and 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen and sulfur. In one variation, particular heteroaryl groups are monocyclic aromatic 5-, 6- or 7- membered rings having from 1 to 6 annular carbon atoms and 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen and sulfur. In another variation, particular heteroaryl groups are polycyclic aromatic rings having from 1 to 12 annular carbon atoms and 1 to 6 annular heteroatoms independently selected from nitrogen, oxygen and sulfur. A heteroaryl group having more than one ring where at least one ring is non-aromatic may be connected to the parent structure at either an aromatic ring position or at a non-aromatic ring position. In one variation, a heteroaryl group having more than one ring where at least one ring is non-aromatic is connected to the parent structure at an aromatic ring position. A heteroaryl group may be connected to the parent structure at a ring carbon atom or a ring heteroatom.

[0090] “Heteroarylene” as used herein refers to the same residues as heteroaryl, but having bivalency.

[0091] “Heterocycle”, “heterocyclic”, or “heterocyclyl” as used herein refers to a saturated or an unsaturated non-aromatic cyclic group having from 1 to 14 annular carbon atoms and from 1 to 6 annular heteroatoms, such as nitrogen, sulfur or oxygen, and the like. A heterocyclic group may have a single ring (e.g., pyrrolidinyl) or multiple condensed rings (e.g., decahydroisoquinolin-1-yl), whichcondensed rings which may be carbocylic or contain one or more annular heteroatoms, but which excludes aryl and heteroaryl rings. A heterocycle comprising more than one ring may be fused, bridged or spiro, or any combination thereof. In fused ring systems, one or more of the fused rings can be cycloalkyl or aryl, but excludes heteroaryl groups. The heterocyclyl group may be optionally substituted independently with one or more substituents described herein. Particular heterocyclyl groups are 3 to 14-membered rings having 1 to 13 annular carbon atoms and 1 to 6 annular heteroatoms independently selected from nitrogen, oxygen and sulfur, 3 to 12-membered rings having 1 to 11 annular carbon atoms and 1 to 6 annular heteroatoms independently selected from nitrogen, oxygen and sulfur, 3 to 10-membered rings having 1 to 9 annular carbon atoms and 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen and sulfur, 3 to 8-membered rings having 1 to 7 annular carbon atoms and 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen and sulfur, or 3 to 6-membered rings having 1 to 5 annular carbon atoms and 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen and sulfur. In one variation, heterocyclyl includes monocyclic 3-, 4-, 5-, 6- or 7-membered rings having from 1 to 2, 1 to 3, 1 to 4, 1 to 5, or 1 to 6 annular carbon atoms and 1 to 2, 1 to 3, or 1 to 4 annular heteroatoms independently selected from nitrogen, oxygen and sulfur. In another variation, heterocyclyl includes polycyclic non-aromatic rings having from 1 to 12 annular carbon atoms and 1 to 6 annular heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0092] “Heterocyclylene” as used herein refers to the same residues as heterocyclyl, but having bivalency.

[0093] “Halo” or “halogen” refers to elements of the Group 17 series having atomic number 9 to 85. Preferred halo groups include the radicals of fluorine, chlorine, bromine and iodine. Where a residue is substituted with more than one halogen, it may be referred to by using a prefix corresponding to the number of halogen moieties attached, e.g., dihaloaryl, dihaloalkyl, trihaloaryl etc. refer to aryl and alkyl substituted with two (“di”) or three (“tri”) halo groups, which may be but are not necessarily the same halogen; thus 4-chloro-3-fluorophenyl is within the scope of dihaloaryl. An alkyl group in which each hydrogen is replaced with a halo group is referred to as a “perhaloalkyl.” A preferred perhaloalkyl group is trifluoromethyl (-CF3). Similarly, “perhaloalkoxy” refers to an alkoxy group in which a halogen takes the place of each H in the hydrocarbon making up the alkyl moiety of the alkoxy group. An example of a perhaloalkoxy group is trifluoromethoxy (–OCF3).

[0094] “Carbonyl” refers to the group C=O.

[0095] “Thiocarbonyl” refers to the group C=S.

[0096] “Oxo” refers to the moiety =O.

[0097] “D” refers to deuterium (2H).

[0098] “Boc” refers to tert-butyloxycarbonyl.

[0099] “Cbz” refers to carboxybenzyl.

[0100] “HATU” refers to 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3- oxide hexafluorophosphate.

[0101] “BOP” refers to benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate.

[0102] “PyBOP” refers to benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate.

[0103] “Optionally substituted” unless otherwise specified means that a group may be unsubstituted or substituted by one or more (e.g., 1, 2, 3, 4 or 5) of the substituents listed for that group in which the substituents may be the same or different. In one embodiment, an optionally substituted group has one substituent. In another embodiment, an optionally substituted group has two substituents. In another embodiment, an optionally substituted group has three substituents. In another embodiment, an optionally substituted group has four substituents. In some embodiments, an optionally substituted group has 1 to 2, 1 to 3, 1 to 4, 1 to 5, 2 to 3, 2 to 4, or 2 to 5 substituents. In one embodiment, an optionally substituted group is unsubstituted.

[0104] Unless clearly indicated otherwise, “an individual” as used herein intends a mammal, including but not limited to a primate, human, bovine, horse, feline, canine, or rodent. In one variation, the individual is a human.

[0105] As used herein, “treatment” or “treating” is an approach for obtaining beneficial or desired results including clinical results. For purposes of this invention, beneficial or desired results include, but are not limited to, one or more of the following: decreasing one more symptoms resulting from the disease, diminishing the extent of the disease, stabilizing the disease (e.g., preventing or delaying the worsening of the disease), preventing or delaying the spread of the disease, delaying the occurrence or recurrence of the disease, delay or slowing the progression of the disease, ameliorating the disease state, providing a remission (whether partial or total) of the disease, decreasing the dose of one or more other medications required to treat the disease, enhancing effect of another medication, delaying the progression of the disease, increasing the quality of life, and / or prolonging survival. Also encompassed by “treatment” is a reduction of pathological consequence of fibrosis. The methods of the invention contemplate any one or more of these aspects of treatment.

[0106] As used herein, the term “effective amount” intends such amount of a compound of the invention which should be effective in a given therapeutic form. As is understood in the art, an effective amount may be in one or more doses, i.e., a single dose or multiple doses may be required to achieve the desired treatment endpoint. An effective amount may be considered in the context of administering one or more therapeutic agents (e.g., a compound, or pharmaceutically acceptable salt thereof), and a single agent may be considered to be given in an effective amount if, in conjunction with one or more other agents, a desirable or beneficial result may be or is achieved. Suitable doses of any of the co-administered compounds may optionally be lowered due to the combined action (e.g., additive or synergistic effects) of the compounds.

[0107] A “therapeutically effective amount” refers to an amount of a compound or salt thereof sufficient to produce a desired therapeutic outcome.

[0108] As used herein, “unit dosage form” refers to physically discrete units, suitable as unit dosages, each unit containing a predetermined quantity of active ingredient calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. Unit dosage forms may contain a single or a combination therapy.

[0109] As used herein, the term “controlled release” refers to a drug-containing formulation or fraction thereof in which release of the drug is not immediate, i.e., with a “controlled release” formulation, administration does not result in immediate release of the drug into an absorption pool. The term encompasses depot formulations designed to gradually release the drug compound over an extended period of time. Controlled release formulations can include a wide variety of drug delivery systems, generally involving mixing the drug compound with carriers, polymers or other compounds having the desired release characteristics (e.g., pH-dependent or non-pH-dependent solubility, different degrees of water solubility, and the like) and formulating the mixture according to the desired route of delivery (e.g., coated capsules, implantable reservoirs, injectable solutions containing biodegradable capsules, and the like).

[0110] As used herein, by “pharmaceutically acceptable” or “pharmacologically acceptable” is meant a material that is not biologically or otherwise undesirable, e.g., the material may be incorporated into a pharmaceutical composition administered to a patient without causing any significant undesirable biological effects or interacting in a deleterious manner with any of the other components of the composition in which it is contained. Pharmaceutically acceptable carriers or excipients have preferably met the required standards of toxicological and manufacturing testing and / or are included on the Inactive Ingredient Guide prepared by the U.S. Food and Drug Administration, herein incorporated by reference in its entirety.

[0111] “Pharmaceutically acceptable salts” are those salts which retain at least some of the biological activity of the free (non-salt) compound and which can be administered as drugs or pharmaceuticals to an individual. Exemplary pharmaceutically acceptable salts are found in, e.g., Remington: The Science and Practice of Pharmacy, Lippincott Williams & Wilkins, 23rded. (2020), which is hereby incorporated by reference in its entirety. Such salts, for example, include: (1) acid addition salts, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or formed with organic acids such as acetic acid, oxalic acid, propionic acid, and the like; (2) salts formed when an acidic proton present in the parent compound either is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base. Acceptable organic bases include ethanolamine, diethanolamine, triethanolamine and the like. Acceptable inorganic bases which can be used to prepared salts include aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, sodium hydroxide, and the like. Pharmaceutically acceptable salts can be prepared in situ in the manufacturing process,or by separately reacting a purified compound of the invention in its free acid or base form with a suitable organic or inorganic base or acid, respectively, and isolating the salt thus formed during subsequent purification.

[0112] The term “excipient” as used herein means an inert or inactive substance that may be used in the production of a drug or pharmaceutical, such as a tablet containing a compound of the invention as an active ingredient. Various substances may be embraced by the term excipient, including without limitation any substance used as a binder, disintegrant, coating, compression / encapsulation aid, cream or lotion, lubricant, solutions for parenteral administration, materials for chewable tablets, sweetener or flavoring, suspending / gelling agent, or wet granulation agent. Exemplary excipients are found in, e.g., Handbook of Pharmaceutical Excipients, Pharmaceutical Press, 9thed. (2020), which is hereby incorporated by reference in its entirety. Binders include, e.g., carbomers, povidone, xanthan gum, etc.; coatings include, e.g., cellulose acetate phthalate, ethylcellulose, gellan gum, maltodextrin, enteric coatings, etc.; compression / encapsulation aids include, e.g., calcium carbonate, dextrose, fructose dc (dc = “directly compressible”), honey dc, lactose (anhydrate or monohydrate; optionally in combination with aspartame, cellulose, or microcrystalline cellulose), starch dc, sucrose, etc.; disintegrants include, e.g., croscarmellose sodium, gellan gum, sodium starch glycolate, etc.; creams or lotions include, e.g., maltodextrin, carrageenans, etc.; lubricants include, e.g., magnesium stearate, stearic acid, sodium stearyl fumarate, etc.; materials for chewable tablets include, e.g., dextrose, fructose dc, lactose (monohydrate, optionally in combination with aspartame or cellulose), etc.; suspending / gelling agents include, e.g., carrageenan, sodium starch glycolate, xanthan gum, etc.; sweeteners include, e.g., aspartame, dextrose, fructose dc, sorbitol, sucrose dc, etc.; and wet granulation agents include, e.g., calcium carbonate, maltodextrin, microcrystalline cellulose, etc.

[0113] Unless otherwise stated, "substantially pure" intends a composition that contains no more than 10% impurity, such as a composition comprising less than about 9%, 7%, 5%, 3%, 1%, 0.5% impurity.

[0114] It is understood that aspects and embodiments described herein as “comprising” include “consisting of” and “consisting essentially of” embodiments.

[0115] When a composition is described as “consisting essentially of” the listed components, the composition contains the components expressly listed, and may contain other components which do not substantially affect the disease or condition being treated such as trace impurities. However, the composition either does not contain any other components which do substantially affect the disease or condition being treated other than those components expressly listed; or, if the composition does contain extra components other than those listed which substantially affect the disease or condition being treated, the composition does not contain a sufficient concentration or amount of those extra components to substantially affect the disease or condition being treated. When a method is described as “consisting essentially of” the listed steps, the method contains the steps listed, and may contain other steps that do not substantially affect the disease or condition being treated, but the method doesnot contain any other steps which substantially affect the disease or condition being treated other than those steps expressly listed.

[0116] When a moiety is indicated as substituted by “at least one” substituent, this also encompasses the disclosure of exactly one substituent.

[0117] When a moiety is indicated as substituted by “at least two” substituents, this also encompasses the disclosure of exactly two substituents.

[0118] When a moiety is indicated as substituted by “at least three” substituents, this also encompasses the disclosure of exactly three substituents. Compounds

[0119] Provided herein is a compound of formula (I):or a pharmaceutically acceptable salt thereof, wherein: R1is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl optionally substituted by one or more R4, 1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl optionally substituted by one or more R4, 6-aminopyridin-2- yl optionally substituted by one or more R4, or (pyridin-2-yl)amino optionally substituted by one or more R4; Q is H or C1-C6alkyl; R2is: (i) RB2, wherein: RB2is C1-C6alkyl optionally substituted by one or more RB2a, C3-C8cycloalkyl optionally substituted by one or more RB2b, 3- to 12- membered saturated heterocyclyl optionally substituted by one or more RB2cwherein a carbon atom of the 3- to 12-membered saturated heterocyclyl is bonded to the –C(O), or C2-C6alkenyl optionally substituted by one or more RB2d; wherein each RB2a, RB2b, RB2c, and RB2dis, where possible, independently oxo, deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2- C6alkynyl, C3-C8cycloalkyl, 3- to 12-membered saturated heterocyclyl, -CN, -OR5, -SR5, -NR6R7, -NO2, -C=NH(OR5), -C(O)R5, -OC(O)R5, -C(O)OR5, -C(O)NR6R7, -NR5C(O)R6, -NR5C(O)OR6, -NR5C(O)NR6R7, -S(O)R5, -S(O)2R5, -NR5S(O)R6, -NR5S(O)2R6, -S(O)NR6R7, -S(O)2NR6R7, or -P(O)(OR5)(OR6), wherein the C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, 3- to 12-membered saturated heterocyclyl of RB2a, RB2b, RB2c, and RB2dare independently optionally substituted by one or more R4a, or (ii) RC2, wherein: RC2is C6-C12aryl optionally substituted by one or more RC2a, 5- to 12-membered heteroaryl optionally substituted by one or more RC2b, C3-C10cycloalkenyl optionally substituted by one or more RC2c, 3- to 12- membered partially unsaturated heterocyclyl optionally substituted by one or more RC2d, C1-C6alkyl substituted by one or more RC2e, C2-C6alkenyl substituted by one or more RC2f, C3-C8cycloalkyl substituted by one or more RC2g, or 3- to 12-membered fully saturated heterocyclyl substituted by one or more RC2h; wherein at least one RC2egroup, when present, is 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl, wherein the 3- to 12-membered partially unsaturated heterocyclyl, C6- C14aryl, and 5- to 10-membered heteroaryl of RC2eare independently optionally substituted by one or more R4a; and each of the other RC2egroups, when present, is independently R4; at least one RC2fgroup, when present, is 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl, wherein the 3- to 12-membered partially unsaturated heterocyclyl, C6- C14aryl, and 5- to 10-membered heteroaryl of RC2fare independently optionally substituted by one or more R4a; and each of the other RC2fgroups, when present, is independently R4; at least one RC2ggroup, when present, is 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl, wherein the 3- to 12-membered partially unsaturated heterocyclyl, C6- C14aryl, and 5- to 10-membered heteroaryl of RC2gare independently optionally substituted by one or more R4a; and each of the other RC2ggroups, when present, is independently R4; at least one RC2hgroup, when present, is 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl, wherein the 3- to 12-membered partially unsaturated heterocyclyl, C6- C14aryl, and 5- to 10-membered heteroaryl of RC2hare independently optionally substituted by one or more R4a; and each of the other RC2hgroups, when present, is independently oxo or R4; and each RC2a, RC2b, RC2c, and RC2dis, where possible, independently oxo or R4;(iii) RD2, wherein RD2is -NRD3(C1-C6alkyl), -NRD3(C3-C8cycloalkyl), -NRD3(3- to 12- membered saturated heterocyclyl) such that a carbon atom of the 3- to 12- membered saturated heterocyclyl of -NRD3(3- to 12-membered saturated heterocyclyl) is bonded to the N of -NRD3, 3- to 12-membered N-containing saturated heterocyclyl such that a nitrogen atom of the 3- to 12-membered N- containing saturated heterocyclyl is bonded to the carbon of -C(O)-, or 5- to 10-membered heteroaryl such that a nitrogen atom of the 5- to 10-membered heteroaryl is bonded to the carbon of -C(O)-, wherein the C1-C6alkyl of the -NRD3(C1-C6alkyl) of RD2is optionally substituted by one or more RD2a, the C3-C8cycloalkyl of the - NRD3(C3-C8cycloalkyl) of RD2is optionally substituted by one or more RD2b, the 3- to 12-membered saturated heterocyclyl of the -NRD3(3- to 12- membered saturated heterocyclyl) of RD2is optionally substituted by one or more RD2c, the 3- to 12-membered N-containing saturated heterocyclyl of RD2is optionally substituted by one or more RD2d, and the 5- to 10-membered heteroaryl is optionally substituted by one or more RD2e; RD3is H, deuterium, C1-C6alkyl, C3-C8cycloalkyl, or 3- to 12- membered saturated heterocyclyl, wherein the C1-C6alkyl of RD3is optionally substituted by one or more RD3a, the C3-C8cycloalkyl of RD3is optionally substituted by one or more RD3b, and the 3- to 12-membered saturated heterocyclyl of RD3is optionally substituted by one or more RD3c-; and each RD2a, RD2b, RD2c, RD2d, RD2e, RD3a, RD3b, and RD3cis, where possible, independently oxo or R4, or (iv) RE2, wherein RE2is -O(C1-C6alkyl), -O(C3-C8cycloalkyl), -O(3- to 12-membered saturated heterocyclyl) such that a carbon atom of the 3- to 12-membered saturated heterocyclyl of -O(3- to 12-membered saturated heterocyclyl) is bonded to the -OC(O)-, -O(5- to 10-membered aryl) such that a carbon atom of the 5- to 10-membered aryl of -O(C6-C14aryl) is bonded to the -OC(O)-, or -O(5- to 10-membered heteroaryl) such that a carbon atom of the 5- to 10- membered heteroaryl of -O(5- to 10-membered heteroaryl) is bonded to the - OC(O)-, wherein the C1-C6alkyl of -O(C1-C6alkyl) of RE2is optionally substituted by one or more RE2a, the C3-C8cycloalkyl -O(C3-C8cycloalkyl) of RE2is optionally substituted by one or more RE2b, the 3- to 12-memberedsaturated heterocyclyl of -O(3- to 12-membered saturated heterocyclyl) of RE2is optionally substituted by one or more RE2c, the 5- to 10-membered heteroaryl of -O(C6-C14aryl) of RE2is optionally substituted by one or more RE2d, the 5- to 10-membered heteroaryl of -O(5- to 10-membered heteroaryl) of RE2eis optionally substituted by one or more RE2e; and each RE2a, RE2b, RE2c, RE2d, and RE2eis, where possible, independently oxo or R4, L1is C2-C4alkylene optionally substituted by one or more by R4; L2is a bond or C1-C6alkylene optionally substituted by one or more R4; L3is C2-C4alkylene optionally substituted by one or more R4; Y is a bond or C3-C5cycloalkylene optionally substituted by one or more Ya; X is -N(Rx)-; Rxis unsubstituted C3-C8alkyl, C1-C8alkyl substituted by one or more Rxa, C3-C6cycloalkyl optionally substituted by one or more Rxb, 3- to 12-membered heterocyclyl optionally substituted by one or more Rxc, C6-C14aryl optionally substituted by one or more Rxd, 5- to 10-membered heteroaryl optionally substituted by one or more Rxe, or -S(O)2Rxf; each Rxais independently halogen, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, 3- to 12- membered heterocyclyl, C6-C14aryl, 5- to 10-membered heteroaryl, oxo, -CN, -OR5, -SR5, -NR6R7, -NO2, -N3, -C=NH(OR5), -C(O)R5, -OC(O)R5, -C(O)OR5, -C(O)NR6R7, -NR5C(O)R6, -NR5C(O)OR6, -NR5C(O)NR6R7, -S(O)R5, -S(O)2R5, -NR5S(O)R6, -NR5S(O)2R6, -S(O)NR6R7, -S(O)2NR6R7, or -P(O)(OR5)(OR6), wherein the C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of Rxaare independently optionally substituted by one or more R4a; Rxfis C1-C6alkyl optionally substituted by one or more Rxgor C3-C5cycloalkyl optionally substituted by one or more Rxh; each Rxb, Rxc, Rxd, Rxe, Rxg, Rxh, and Yais independently oxo or R4; each R4is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3- C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, 5- to 10-membered heteroaryl, -CN, -OR5, -SR5, -NR6R7, -NO2, -N3, -C=NH(OR5), -C(O)R5, -OC(O)R5, -C(O)OR5, -C(O)NR6R7, -NR5C(O)R6, -NR5C(O)OR6, -NR5C(O)NR6R7, -S(O)R5, -S(O)2R5, -S(O)2OH, -NR5S(O)R6, -NR5S(O)2R6, -S(O)NR6R7, -S(O)2NR6R7, or -P(O)(OR5)(OR6), wherein the C1-C6alkyl, C2- C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of R4are independently optionally substituted by one or more R4a; each R4ais independently deuterium, halogen, oxo, -OR8, -NR8R9, -C(O)R8, -C(O)OR8, -NR8C(O)OR10, -CN, -S(O)R8, -S(O)2R8, -P(O)(OR8)(OR9), C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, 5- to 10-membered heteroaryl, C6-C14aryl, or C1-C6alkyl, wherein the 3- to 12-membered heterocyclyl, 5- to 10-membered heteroaryl, C6-C14aryl, and C1-C6alkyl of R4aare independently optionally substituted by one or more R4b; each R4bis independently deuterium, oxo, -OH, -O-C1-C6alkyl, -O(2H), halogen, or C1-C6alkyl optionally substituted by one or more deuterium, halogen, -OH, -O(2H), or oxo; each R5is independently hydrogen, deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3- C6cycloalkyl, C6-C14aryl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocyclyl, wherein the C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C14aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocyclyl of R5are each independently optionally substituted by one or more R5a; each R5ais independently halogen, deuterium, oxo, -CN, -OR10, -NR11R12, -P(O)(OR11)(OR12), C3-C6cycloalkyl, 3- to 12-membered heterocyclyl, or C1-C6alkyl optionally substituted by one or more deuterium, halogen, -OH, -O(2H), or oxo; each R6is independently hydrogen, deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3- C6cycloalkyl, C6-C14aryl, 5- to 10-membered heteroaryl, or 3- to 6-membered heterocyclyl, wherein the C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C14aryl, 5- to 10-membered heteroaryl, and 3- to 6-membered heterocyclyl of R6are independently optionally substituted by one or more deuterium, halogen, oxo, -CN, -OR10, -NR11R12, or C1-C6alkyl optionally substituted by one or more deuterium, halogen, -OH, -O(2H), or oxo; each R7is independently hydrogen, deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3- C6cycloalkyl, C6-C14aryl, 5- to 10-membered heteroaryl, or 3- to 6-membered heterocyclyl, wherein the C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C14aryl, 5- to 10-membered heteroaryl, and 3- to 6-membered heterocyclyl of R7are independently optionally substituted by one or more deuterium, halogen, oxo, -CN, -OR10, -NR11R12, or C1-C6alkyl optionally substituted by one or more deuterium, halogen, -OH, -O(2H), or oxo; or R6and R7are taken together with the atom to which they are attached to form a 3- to 10- membered heterocyclyl optionally substituted by one or more deuterium, halogen, oxo, -OR10, -NR11R12, or C1-C6alkyl optionally substituted by one or more deuterium, halogen, oxo, -OH, or - O(2H); each R8, R9, and R10is independently hydrogen, deuterium, C1-C6alkyl, C2-C6alkenyl, or C2- C6alkynyl, wherein the C1-C6alkyl, C2-C6alkenyl and C2-C6alkynyl are optionally substituted by one or more deuterium, halogen, or oxo; and each R11and R12is independently hydrogen, deuterium, C1-C6alkyl, C2-C6alkenyl, or C2- C6alkynyl, wherein the C1-C6alkyl, C2-C6alkenyl and C2-C6alkynyl are optionally substituted by one or more deuterium, halogen, or oxo; or R11and R12are taken together with the atom to which they are attached to form a 3-6 membered heterocyclyl optionally substituted by one or more deuterium, halogen, oxo, or C1-C6alkyl optionally substituted by one or more deuterium, oxo, or halogen.

[0120] In one embodiment of a compound of formula (I), or a pharmaceutically acceptable salt thereof, when R1is unsubstituted 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl; Q is H or -CH3; and the moiety -R2is: RB2wherein RB2is C1-C6alkyl optionally substituted by one or more RB2a; RC2wherein RC2is C1-C6alkyl substituted by one or more RC2eor C2-C6alkenyl substituted by one or more RC2f; RD2is -NRD3(C1-C6alkyl), -NRD3(C3-C8cycloalkyl), -NRD3(3- to 12-membered saturated heterocyclyl) such that a carbon atom of the 3- to 12-membered saturated heterocyclyl of -NRD3(3- to 12-membered saturated heterocyclyl) is bonded to the N of -NRD3; or

[0121] In one embodiment of a compound of formula (I), or a pharmaceutically acceptable salt thereof, when R1is unsubstituted 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl; Q is H or -CH3; and the moiety -R2is: RB2wherein RB2is C1-C6alkyl optionally substituted by one or more RB2a; RC2wherein RC2is C1-C6alkyl substituted by one or more RC2eor C2-C6alkenyl substituted by one or more RC2f; RD2is -NRD3(C1-C6alkyl), -NRD3(C3-C8cycloalkyl), -NRD3(3- to 12-membered saturated heterocyclyl) such that a carbon atom of the 3- to 12-membered saturated heterocyclyl of -NRD3(3- to 12-membered saturated heterocyclyl) is bonded to the N of -NRD3, orRE2; provided that RB2aand RC2eare not selected from the group consisting of unsubstituted phenyl, unsubstituted pyridinyl, methyl, and fluorine.

[0122] In one embodiment of a compound of formula (I), or a pharmaceutically acceptable salt thereof, when R1is unsubstituted 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl; Q is H or -CH3; and the moiety -; then R2is RE2.

[0123] In one embodiment of a compound of formula (I), or a pharmaceutically acceptable salt thereof, the compound is not: (S)-4-((2-methoxyethyl)(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)amino)-2- pivalamidobutanoic acid; (S)-4-((2-methoxyethyl)(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)amino)-2- (tetrahydro-2H-pyran-4-carboxamido)butanoic acid; (S)-2-(4,4-difluorocyclohexane-1-carboxamido)-4-((2-methoxyethyl)(4-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)butyl)amino)butanoic acid; (S)-2-(2,3-dihydro-1H-indene-2-carboxamido)-4-((2-methoxyethyl)(4-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)butyl)amino)butanoic acid; (S)-4-((2-methoxyethyl)(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)amino)-2-(2- methyl-2-phenylpropanamido)butanoic acid; (S)-4-((2-methoxyethyl)(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)amino)-2-(1- phenylcyclopropane-1-carboxamido)butanoic acid; (S)-4-((2-methoxyethyl)(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)amino)-2-(1- phenylcyclobutane-1-carboxamido)butanoic acid; (S)-2-((S)-3-hydroxypyrrolidine-1-carboxamido)-4-((2-methoxyethyl)(4-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)butyl)amino)butanoic acid; or (S)-2-((R)-3-hydroxypyrrolidine-1-carboxamido)-4-((2-methoxyethyl)(4-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)butyl)amino)butanoic acid.

[0124] In one variation is provided a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R1is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl optionally substituted by one or more R4or 1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl optionally substituted by one or more R4; Q is H; R2is RB2wherein RB2is C1-C6alkyl, C3-C8cycloalkyl, or 3- to 12-membered saturated heterocyclyl, such that a carbon atom of the 3- to 12-membered saturated heterocyclyl is bonded to the –C(O),wherein the C1-C6alkyl is optionally substituted by one or more RB2a, the C3-C8cycloalkyl is optionally substituted by one or more RB2b, and the 3- to 12-membered saturated heterocyclyl is optionally substituted by one or more RB2c; L1is C2-C4n-alkylene optionally substituted by one or more by R4; L2is a bond or C1-C3n-alkylene optionally substituted by one or more by R4; L3is C2-C4n-alkylene optionally substituted by one or more by R4; X is -N(Rx)-; Rxis C1-C8alkyl substituted by one or more Rxa, C3-C6cycloalkyl optionally substituted by one or more Rxb, or 5- to 10-membered heteroaryl optionally substituted by one or more Rxe; each Rxais independently halogen, C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6- C14aryl, 5- to 10-membered heteroaryl, -CN, -OR5, -C(O)OR5, or -S(O)2R5, wherein the C3- C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of Rxaare independently optionally substituted by one or more R4a; Y is a bond or C3-C5cycloalkylene optionally substituted by one or more Ya; each RB2ais, where possible, independently halogen, C1-C6alkyl, C3-C8cycloalkyl, 3- to 12- membered saturated heterocyclyl, -CN, -OR5, -NR6R7, or -NR5C(O)OR6, wherein the C1-C6alkyl, C3- C8cycloalkyl and 3- to 12-membered saturated heterocyclyl of RB2aare independently optionally substituted by one or more R4a; each RB2bis, where possible, independently halogen or C1-C6alkyl, wherein the C1-C6alkyl of RB2bis independently optionally substituted by one or more R4a; each RB2cis, where possible, independently halogen, C1-C6alkyl, -C(O)R5, or -C(O)OR5, wherein the C1-C6alkyl of RB2cis independently optionally substituted by one or more R4a; each Rxb, Rxe, and Yais, where possible, independently R4; each R4is independently C1-C6alkyl, wherein the C1-C6alkyl of R4is independently optionally substituted by one or more R4a; each R4ais independently halogen, oxo, -OR8, -NR8R9, -CN, C3-C8cycloalkyl, 5- to 10- membered heteroaryl, or C1-C6alkyl, wherein the C3-C8cycloalkyl, 5- to 10-membered heteroaryl and C1-C6alkyl of R4aare independently optionally substituted by one or more R4b; each R4bis independently halogen; each R5is independently hydrogen, C1-C6alkyl, C3-C6cycloalkyl, C6-C14aryl, or 5- to 10- membered heteroaryl, wherein the C1-C6alkyl, C3-C6cycloalkyl, C6-C14aryl, and 5- to 10-membered heteroaryl of R5are each independently optionally substituted by one or more R5a; each R5ais independently halogen, deuterium, -OR10, or C1-C6alkyl optionally substituted by one or more deuterium, halogen, -OH, -O(2H), or oxo; each R6is independently hydrogen or C1-C6alkyl, wherein the C1-C6alkyl of R6is independently optionally substituted by one or more deuterium, halogen, oxo, -CN, -OR10, -NR11R12, or C1-C6alkyl optionally substituted by one or more deuterium, halogen, -OH, -O(2H), or oxo;each R7is hydrogen; each R8is independently hydrogen or C1-C6alkyl optionally substituted by one or more deuterium, halogen, or oxo; each R9is hydrogen; each R10is independently C1-C6alkyl optionally substituted by one or more deuterium, halogen, or oxo; each R11is independently hydrogen, deuterium, C1-C6alkyl optionally substituted by one or more deuterium, halogen, or oxo, C2-C6alkenyl optionally substituted by one or more deuterium, halogen, or oxo, or C2-C6alkynyl optionally substituted by one or more deuterium, halogen, or oxo; and each R12is independently hydrogen, deuterium, C1-C6alkyl optionally substituted by one or more deuterium, halogen, or oxo, C2-C6alkenyl optionally substituted by one or more deuterium, halogen, or oxo, or C2-C6alkynyl optionally substituted by one or more deuterium, halogen, or oxo; or R11and R12are taken together with the atom to which they are attached to form a 3-6 membered heterocyclyl optionally substituted by one or more deuterium, halogen, oxo or C1-C6alkyl optionally substituted by one or more deuterium, oxo, or halogen.

[0125] In one variation is provided a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein: R1is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl optionally substituted by one or more R4or 1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl; Q is H; R2is RB2wherein RB2is C1-C6alkyl, C3-C8cycloalkyl, or 3- to 12-membered saturated heterocyclyl, such that a carbon atom of the 3- to 12-membered saturated heterocyclyl is bonded to the –C(O), wherein the C1-C6alkyl is optionally substituted by one or more RB2a, the C3-C8cycloalkyl is optionally substituted by one or more RB2b, and the 3- to 12-membered saturated heterocyclyl is optionally substituted by one or more RB2c; L1is C2-C4n-alkylene; L2is a bond or C1-C3n-alkylene; L3is C2-C4n-alkylene; X is -N(Rx)-; Rxis C1-C8alkyl substituted by one or more Rxa, C3-C6cycloalkyl optionally substituted by one or more Rxb, or 5- to 10-membered heteroaryl; each Rxais independently halogen, C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6- C14aryl, 5- to 10-membered heteroaryl, -CN, -OR5, -C(O)OR5, or -S(O)2R5, wherein the C3- C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of Rxaare independently optionally substituted by one or more R4a;Y is a bond or C3-C5cycloalkylene; each RB2ais, where possible, independently halogen, C1-C6alkyl, C3-C8cycloalkyl, 3- to 12- membered saturated heterocyclyl, -CN, -OR5, -NR6R7, or -NR5C(O)OR6, wherein the C1-C6alkyl, C3- C8cycloalkyl and 3- to 12-membered saturated heterocyclyl of RB2aare independently optionally substituted by one or more R4a; each RB2bis, where possible, independently halogen or C1-C6alkyl, wherein the C1-C6alkyl of RB2bis independently optionally substituted by one or more R4a; each RB2cis, where possible, independently halogen, C1-C6alkyl, -C(O)R5, or -C(O)OR5, wherein the C1-C6alkyl of RB2cis independently optionally substituted by one or more R4a; each Rxbis, where possible, independently R4; each R4is independently C1-C6alkyl, wherein the C1-C6alkyl of R4is independently optionally substituted by one or more R4a; each R4ais independently halogen, oxo, -OR8, -NR8R9, -CN, C3-C8cycloalkyl, 5- to 10- membered heteroaryl, or C1-C6alkyl, wherein the C1-C6alkyl of R4ais independently optionally substituted by one or more R4b; each R4bis independently halogen; each R5is independently hydrogen, C1-C6alkyl, C3-C6cycloalkyl, C6-C14aryl, or 5- to 10- membered heteroaryl, wherein the C1-C6alkyl, C3-C6cycloalkyl, C6-C14aryl, and 5- to 10-membered heteroaryl of R5are each independently optionally substituted by one or more R5a; each R5ais independently halogen, deuterium, -OR10, or C1-C6alkyl; each R6is independently hydrogen or C1-C6alkyl; each R7is hydrogen; each R8is independently hydrogen or C1-C6alkyl; each R9is hydrogen; and each R10is independently C1-C6alkyl.

[0126] In one variation is provided a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein: R1is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl optionally substituted by one or more R4or 1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl; Q is H; R2is RB2wherein RB2is C1-C6alkyl, C3-C8cycloalkyl, or 4- to 6-membered saturated heterocyclyl, such that a carbon atom of the 4- to 6-membered saturated heterocyclyl is bonded to the –C(O), wherein the C1-C6alkyl is optionally substituted by one or more RB2a, the C3-C8cycloalkyl is optionally substituted by one or more RB2b, and the 4- to 6-membered saturated heterocyclyl is optionally substituted by one or more RB2c; L1is C2n-alkylene;L2is a bond or C1-C3n-alkylene; L3is C2-C4n-alkylene; X is -N(Rx)-; Rxis C1-C5alkyl substituted by one or more Rxa, C3cycloalkyl optionally substituted by one or more Rxb, or 5-membered heteroaryl; each Rxais independently halogen, C3-C4cycloalkyl, 5- to 6-membered heterocyclyl, C6aryl, 5-membered heteroaryl, -CN, -OR5, -C(O)OR5, or -S(O)2R5, wherein the C3-C4cycloalkyl, 5- to 6- membered heterocyclyl, C6aryl, and 5-membered heteroaryl of Rxaare independently optionally substituted by one or more R4a; Y is a bond or C3-C5cycloalkylene; each RB2ais, where possible, independently halogen, C1-C5alkyl, C3-C6cycloalkyl, 4- to 6- membered saturated heterocyclyl, -CN, -OR5, -NR6R7, or -NR5C(O)OR6, wherein the C1-C5alkyl, C3- C6cycloalkyl, and 4- to 6-membered saturated heterocyclyl of RB2aare independently optionally substituted by one or more R4a; each RB2bis, where possible, independently halogen or C1alkyl, wherein the C1alkyl of RB2bis independently optionally substituted by one or more R4a; each RB2cis, where possible, independently halogen, C1-C5alkyl, -C(O)R5, or -C(O)OR5, wherein the C1-C5alkyl of RB2cis independently optionally substituted by one or more R4a; each Rxbis, where possible, independently R4; each R4is independently C1alkyl, wherein the C1alkyl of R4is independently optionally substituted by one or more R4a; each R4ais independently halogen, oxo, -OR8, -NR8R9, -CN, C3cycloalkyl, 6-membered heteroaryl, or C1-C3alkyl, wherein the C1-C3alkyl of R4ais independently optionally substituted by one or more R4b; each R4bis independently halogen; each R5is independently hydrogen, C1-C4alkyl, C3-C5cycloalkyl, C6aryl, or 5- to 6- membered heteroaryl, wherein the C1-C6alkyl, C3-C5cycloalkyl, C6aryl, and 5- to 6-membered heteroaryl of R5are each independently optionally substituted by one or more R5a; each R5ais independently halogen, deuterium, -OR10, or C1alkyl; each R6is independently hydrogen or C1alkyl; each R7is hydrogen; each R8is independently hydrogen or C1alkyl; each R9is hydrogen; and each R10is C1alkyl.

[0127] In one variation is provided a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein: R1is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl optionally substituted by one or more R4;Q is H; R2is RC2wherein RC2is C6-C12aryl optionally substituted by one or more RC2a, 5- to 12- membered heteroaryl optionally substituted by one or more RC2b, such that a carbon atom of the 5- to 12-membered heteroaryl is bonded to the –C(O), 3- to 12-membered partially unsaturated heterocyclyl optionally substituted by one or more RC2d, C1-C6alkyl substituted by one or more RC2e, C3-C8cycloalkyl substituted by one or more RC2g, or 3- to 12-membered fully saturated heterocyclyl substituted by one or more RC2h; L1is C2-C4n-alkylene optionally substituted by one or more R4; L2is a bond or C1-C3n-alkylene optionally substituted by one or more R4; L3is C2-C4n-alkylene optionally substituted by one or more R4; X is -N(Rx)-; Rxis unsubstituted C3-C8alkyl, C1-C8alkyl substituted by one or more Rxa, C3-C6cycloalkyl optionally substituted by one or more Rxb, 3- to 12-membered heterocyclyl optionally substituted by one or more Rxc, 5- to 10-membered heteroaryl optionally substituted by one or more Rxe, or -S(O)2Rxf; each Rxais independently halogen, C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6- C14aryl, 5- to 10-membered heteroaryl, -CN, -OR5, or -S(O)2R5, wherein the C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of Rxaare independently optionally substituted by one or more R4a; Rxfis C1-C6alkyl optionally substituted by one or more Rxg; Y is a bond or C3-C5cycloalkylene optionally substituted by one or more Ya; at least one RC2egroup, when present, is 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl, wherein the 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of RC2eare independently optionally substituted by one or more R4a; and each of the other RC2egroups, when present, is independently R4; at least one RC2ggroup, when present, is 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl, wherein the 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of RC2gare independently optionally substituted by one or more R4a; and each of the other RC2ggroups, when present, is independently R4; at least one RC2hgroup, when present, is C6-C14aryl or 5- to 10-membered heteroaryl, wherein the C6-C14aryl and 5- to 10-membered heteroaryl of RC2hare independently optionally substituted by one or more R4a; and each of the other RC2hgroups, when present, is independently oxo or R4; each RC2a, RC2b, RC2d, Rxb, Rxc, Rxd, Rxe, Rxg, and Yais, where possible, independently oxo or R4; each R4is independently halogen, C1-C6alkyl, 5- to 10-membered heteroaryl, -CN, -OR5, -S(O)2R5, or -S(O)2OH, wherein the C1-C6alkyl and 5- to 10-membered heteroaryl of R4are independently optionally substituted by one or more R4a;each R4ais independently halogen, oxo, -OR8, -CN, -S(O)2R8, or C1-C6alkyl, wherein the C1- C6alkyl of R4aare independently optionally substituted by one or more R4b; each R4bis independently halogen; each R5is independently hydrogen, C1-C6alkyl, C3-C6cycloalkyl, C6-C14aryl, or 5- to 10- membered heteroaryl, wherein the C1-C6alkyl, C3-C6cycloalkyl, C6-C14aryl, and 5- to 10-membered heteroaryl of R5are each independently optionally substituted by one or more R5a; each R5ais independently halogen, -OR10, C3-C6cycloalkyl, or C1-C6alkyl optionally substituted by one or more deuterium, halogen, -OH, -O(2H), or oxo; each R8is independently hydrogen or C1-C6alkyl optionally substituted by one or more deuterium, halogen, or oxo; and each R10is independently C1-C6alkyl optionally substituted by one or more deuterium, halogen, or oxo.

[0128] In one variation is provided a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein: R1is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl optionally substituted by one or more R4; Q is H; R2is RC2wherein RC2is C6-C12aryl optionally substituted by one or more RC2a, 5- to 12- membered heteroaryl optionally substituted by one or more RC2b, such that a carbon atom of the 5- to 12-membered heteroaryl is bonded to the –C(O), 3- to 12-membered partially unsaturated heterocyclyl optionally substituted by one or more RC2d, C1-C6alkyl substituted by one or more RC2e, C3-C8cycloalkyl substituted by one or more RC2g, or 3- to 12-membered fully saturated heterocyclyl substituted by one or more RC2h; L1is C2-C4n-alkylene; L2is a bond or C1-C3n-alkylene; L3is C2-C4n-alkylene; X is -N(Rx)-; Rxis unsubstituted C3-C8alkyl, C1-C8alkyl substituted by one or more Rxa, C3-C6cycloalkyl optionally substituted by one or more Rxb, 3- to 12-membered heterocyclyl, 5- to 10-membered heteroaryl, or -S(O)2Rxf; each Rxais independently halogen, C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6- C14aryl, 5- to 10-membered heteroaryl, -CN, -OR5or -S(O)2R5, wherein the C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of Rxaare independently optionally substituted by one or more R4a; Rxfis C1-C6alkyl; Y is a bond or C3-C5cycloalkylene; at least one RC2egroup, when present, is 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl, wherein the 3- to 12-membered partially unsaturatedheterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of RC2eare independently optionally substituted by one or more R4a; and each of the other RC2egroups, when present, is independently R4; at least one RC2ggroup, when present, is 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl, wherein the 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of RC2gare independently optionally substituted by one or more R4a; and each of the other RC2ggroups, when present, is independently R4; at least one RC2hgroup, when present, is C6-C14aryl or 5- to 10-membered heteroaryl, wherein the C6-C14aryl and 5- to 10-membered heteroaryl of RC2hare independently optionally substituted by one or more R4a; and each of the other RC2hgroups, when present, is independently oxo or R4; each RC2a, RC2b, RC2d, and Rxbis, where possible, independently oxo or R4; each R4is independently halogen, C1-C6alkyl, 5- to 10-membered heteroaryl, -CN, -OR5, -S(O)2R5, or -S(O)2OH, wherein the C1-C6alkyl and 5- to 10-membered heteroaryl of R4are independently optionally substituted by one or more R4a; each R4ais independently halogen, oxo, -OR8, -CN, -S(O)2R8, or C1-C6alkyl, wherein the C1- C6alkyl of R4aare independently optionally substituted by one or more R4b; each R4bis independently halogen; each R5is independently hydrogen, C1-C6alkyl, C3-C6cycloalkyl, C6-C14aryl, or 5- to 10- membered heteroaryl, wherein the C1-C6alkyl, C3-C6cycloalkyl, and 5- to 10-membered heteroaryl of R5are each independently optionally substituted by one or more R5a; each R5ais independently halogen, -OR10, C3-C6cycloalkyl, or C1-C6alkyl ; each R8is independently hydrogen or C1-C6alkyl optionally substituted by one or more halogen; and each R10is independently C1-C6alkyl optionally substituted by one or more deuterium, halogen, or oxo.

[0129] In one variation is provided a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein: R1is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl optionally substituted by one or more R4; Q is H; R2is RC2wherein RC2is C6-C9aryl optionally substituted by one or more RC2a, 5- to 9- membered heteroaryl optionally substituted by one or more RC2b, such that a carbon atom of the 5- to 12-membered heteroaryl is bonded to the –C(O), 3- to 10-membered partially unsaturated heterocyclyl optionally substituted by one or more RC2d, C1-C4alkyl substituted by one or more RC2e, C3-C4cycloalkyl substituted by one or more RC2g, or 4- to 6-membered fully saturated heterocyclyl substituted by one or more RC2h; L1is C2n-alkylene; L2is a bond or C1-C3n-alkylene; L3is C2-C4n-alkylene;X is -N(Rx)-; Rxis unsubstituted C3alkyl, C1-C5alkyl substituted by one or more Rxa, C3-C4cycloalkyl optionally substituted by one or more Rxb, 4-membered heterocyclyl, 5-membered heteroaryl, or -S(O)2Rxf; each Rxais independently halogen, C3cycloalkyl, 4- to 6-membered heterocyclyl, C6aryl, 5- membered heteroaryl, -CN, -OR5or -S(O)2R5, wherein the C3cycloalkyl, 4- to 6-membered heterocyclyl, C6aryl, and 5-membered heteroaryl of Rxaare independently optionally substituted by one or more R4a; Rxfis C1-C6alkyl; Y is a bond or C3cycloalkylene; at least one RC2egroup, when present, is 6- to 10-membered partially unsaturated heterocyclyl, C6aryl, or 5- to 6-membered heteroaryl, wherein the 6- to 10-membered partially unsaturated heterocyclyl, C6aryl, and 5- to 6-membered heteroaryl of RC2eare independently optionally substituted by one or more R4a; and each of the other RC2egroups, when present, is independently R4; at least one RC2ggroup, when present, is 6-membered partially unsaturated heterocyclyl, C6aryl, or 5- to 10-membered heteroaryl, wherein the 6-membered partially unsaturated heterocyclyl, C6aryl, and 5- to 10-membered heteroaryl of RC2gare independently optionally substituted by one or more R4a; and each of the other RC2ggroups, when present, is independently R4; at least one RC2hgroup, when present, is C6aryl or 5-membered heteroaryl, wherein the C6aryl and 5-membered heteroaryl of RC2hare independently optionally substituted by one or more R4a; and each of the other RC2hgroups, when present, is independently oxo or R4; each RC2a, RC2b, RC2d, and Rxbis, where possible, independently oxo or R4; each R4is independently halogen, C1-C6alkyl, 5- to 10-membered heteroaryl, -CN, -OR5, -S(O)2R5, or -S(O)2OH, wherein the C1-C6alkyl and 5- to 10-membered heteroaryl of R4are independently optionally substituted by one or more R4a; each R4ais independently halogen, oxo, -OR8, -CN, -S(O)2R8, or C1alkyl, wherein the C1alkyl of R4aare independently optionally substituted by one or more R4b; each R4bis independently halogen; each R5is independently hydrogen, C1-C4alkyl, C3-C5cycloalkyl, C6aryl, or 6-membered heteroaryl, wherein the C1-C4alkyl, C3-C5cycloalkyl, and 6-membered heteroaryl of R5are each independently optionally substituted by one or more R5a; each R5ais independently halogen, -OR10, C3cycloalkyl, or C1alkyl ; each R8is independently hydrogen or C1alkyl optionally substituted by one or more halogen; and each R10is independently C1alkyl optionally substituted by one or more deuterium, halogen, or oxo.

[0130] In some variations, the compound of formula (I) or salt thereof, is a compound wherein:R2is RD2wherein each RD2ais independently halogen, C1-C6alkoxy, C3-C8cycloalkyl, 3- to 12-membered saturated or partially unsaturated heterocyclyl, C6-C14membered aryl, or 5- to 10- membered heteroaryl, wherein the 3- to 12-membered saturated or partially unsaturated heterocyclyl of RD2ais optionally substituted by halogen or C1-C6haloalkyl, wherein the C3-C8cycloalkyl of RD2ais optionally substituted by halogen, and wherein the C6-C14membered aryl of RD2ais optionally substituted by halogen, CN, C1-C6haloalkyl or C1-C6haloalkoxy; each RD2bis -OH; and each RD2cis halogen, -OH, C1-C6alkyl, C1-C6haloalkyl, or -C(O)OR5, wherein the C1-C6alkyl of RD2cis optionally substituted by halogen, -OH, or C1-C6alkoxy.

[0131] In some variations, the compound of formula (I) or salt thereof, is a compound wherein: R2is RE2wherein each RE2ais independently halogen, C1-C6alkoxy, C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14membered aryl, or 5- to 12-membered heteroaryl, wherein the 3- to 12-membered heterocyclyl of RE2ais optionally substituted by C1-C6alkyl, wherein the C3-C8cycloalkyl of RE2ais optionally substituted by halogen, and wherein the C6-C14membered aryl of RE2ais optionally substituted by halogen, CN, C1-C6haloalkyl or C1-C6haloalkoxy; each RE2bis halogen, C1-C6alkyl; and each RE2dis halogen.

[0132] In some embodiments, the compound is a compound of formula (I) wherein (i) when R1is unsubstituted 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl, L1is unsubstituted C2alkylene, Rxis 2-methoxyethyl, -L2-Y-L3- is C4alkylene, and Q is methyl, then RE2is not - O(pentan-3-yl), -O(neopentyl, or -O(2,2-difluorobutyl); (ii) when R1is unsubstituted 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl, L1is unsubstituted C2alkylene, -L2-Y-L3- is C4alkylene, Q is methyl, and RE2is -O(tert-butyl), then Rxis not methyl, cyclopropyl, or methylsulfonyl; (iii) when R1is unsubstituted 1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl, L1is unsubstituted C2alkylene, Rxis cyclopropyl, -L2-Y-L3- is C4alkylene, and Q is methyl, then RE2is not -O(tert- butyl); and (iv) when R1is unsubstituted 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl, L1is unsubstituted C2alkylene, Y is unsubstituted C3-C4cycloalkyl, and Q is methyl, then RE2is not -O(tert-butyl).

[0133] In some embodiments, the compound is a compound of formula (I) wherein (i) when R1is unsubstituted 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl, L1is unsubstituted C2alkylene, Rxis 2-methoxyethyl, -L2-Y-L3- is C4alkylene, and Q is methyl, then RE2is not - O(pentan-3-yl), -O(neopentyl), or -O(2,2-difluorobutyl);(ii) when R1is unsubstituted 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl, L1is unsubstituted C2alkylene, -L2-Y-L3- is C4alkylene, Q is methyl, and RE2is -O(tert-butyl), then Rxis not methyl, cyclopropyl, or methylsulfonyl; (iii) when R1is unsubstituted 1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl, L1is unsubstituted C2alkylene, Rxis cyclopropyl, -L2-Y-L3- is C4alkylene, and Q is methyl, then RE2is not -O(tert- butyl); and (iv) when R1is unsubstituted 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl, L1is unsubstituted C2alkylene, Q is methyl, and RE2is -O(tert-butyl), then Y is not unsubstituted C3-C4cycloalkyl.

[0134] In some embodiments, the compound is a compound of formula (I) wherein when Q is not H, then RE2is not -O(tert-butyl).

[0135] In one variation is provided a compound of the formula (I), or a pharmaceutically acceptable salt thereof, wherein the carbon bearing the C(O)OQ and N(H)C(O)R2moieties is in the “S” configuration. In another variation is provided a compound of the formula (I), or a pharmaceutically acceptable salt thereof, wherein the carbon bearing the C(O)OQ and N(H)C(O)R2moieties is in the “R” configuration. Mixtures of a compound of the formula (I) are also embraced, including racemic or non-racemic mixtures of a given compound, and mixtures of two or more compounds of different chemical formulae.

[0136] In the descriptions herein, it is understood that every description, variation, embodiment or aspect of a moiety may be combined with every description, variation, embodiment or aspect of other moieties the same as if each and every combination of descriptions is specifically and individually listed. For example, every description, variation, embodiment or aspect provided herein with respect to R2of formula (I) may be combined with every description, variation, embodiment or aspect of L1, X, L2, Y, L3and / or R1the same as if each and every combination were specifically and individually listed. It is also understood that all descriptions, variations, embodiments or aspects of formula (I), where applicable, apply equally to other formulae detailed herein, and are equally described, the same as if each and every description, variation, embodiment or aspect were separately and individually listed for all formulae. For example, all descriptions, variations, embodiments or aspects of formula (I), where applicable, apply equally to any of formulae (II-A-1), (II-B-1), (II-B-1-a), (II-B-1-b), (II-C- 1), (II-D-1), (II-E-1), (III-A-1), (IV-A-1), (IV-B-1), (IV-B-1-a), (IV-B-1-b), (V-A-1), (V-B-1), (V-B- 1-a), (V-B-1-b), (VI-A-1), (VI-A-2), (VI-B-1), (VI-B-1-a), (VI-B-1-b), (VII-A-1), (VII-B-1), (VII-B- 1-a), (VII-B-1-b), (VIII-A-1), (VIII-B-1), (VIII-B-1-a), (VIII-B-1-b), (IX-A-1), (IX-B-1), (IX-B-1-a), (IX-B-1-b), (X-A-1), (X-B-1), (X-B-1-a), (X-B-1-b), (XI-A-1), (XI-B-1), (XI-B-1-a), (XI-B-1-b), (XII-A-1), (XII-B-1), (XII-B-1-a), and (XII-B-1-b) detailed herein, and are equally described, the same as if each and every description, variation, embodiment or aspect were separately and individually listed for all formulae.

[0137] In some embodiments of the compound of formula (I), or a pharmaceutically acceptable salt thereof, at least one of RB2a, RB2b, RB2c, RB2d, RC2a, RC2b, RC2c, RC2d, RC2e, RC2f, RC2g, RC2h, RD2a, RD2b,RD2c, RD2d, RD2e, RD3, RD3a, RD3b, RD3c, RE2a, RE2b, RE2c, RE2d, RE2e,Rxb, Rxc, Rxd, Rxe, Rxg, Rxh, R4a, R4b, R5, R5a, R6, R7, R8, R9, R10, R11, or R12is deuterium.

[0138] In some embodiments of the compound of formula (I), or a pharmaceutically acceptable salt thereof, L1is unsubstituted C2-C4n-alkylene. In a particular variation, L1is –CH2–CH2–, –CH2–CH2– CH2–, or –CH2–CH2–CH2–CH2–. In another variation, L1is –CH2–CH2–.

[0139] In some embodiments of the compound of formula (I), or a pharmaceutically acceptable salt thereof, L1is C2-C4n-alkylene substituted by 1-3 R4groups. In one variation, each R4on L1is independently selected from halogen, deuterium, and C1-C6alkyl.

[0140] In some embodiments of the compound of formula (I), or a pharmaceutically acceptable salt thereof, L2is a bond.

[0141] In some embodiments of the compound of formula (I), or a pharmaceutically acceptable salt thereof, L2is –CH2–.

[0142] In some embodiments of the compound of formula (I), or a pharmaceutically acceptable salt thereof, L2is C1-C3n-alkylene substituted by 1-3 R4groups. In one variation, each R4group on L2is independently selected from the group consisting of halogen, deuterium, and C1-C6alkyl.

[0143] In some embodiments of the compound of formula (I), or a pharmaceutically acceptable salt thereof, L3is unsubstituted C2-C4n-alkylene. In one variation, L3is –(CH2)4-. In another variation, L3is –(CH2)2-.

[0144] In some embodiments of the compound of formula (I), or a pharmaceutically acceptable salt thereof, L3is C2-C4n-alkylene substituted by 1-3 R4groups. In one variation, each R4group on L3is independently selected from the group consisting of halogen, deuterium, and C1-C6alkyl. In one variation, L3is –CH2–CF2–CH2–CH2–. In another variation, L3is –CH2–CHF–CH2–CH2–. In another variation, L3is –CH2–CHF–CH2–CHF–. In another variation, L3is –CH2–CH2–CHF–CHF–.

[0145] In some embodiments of the compound of formula (I), or a pharmaceutically acceptable salt thereof, Y is a bond.

[0146] In some embodiments of the compound of formula (I), or a pharmaceutically acceptable salt thereof, Y is unsubstituted C3-C5cycloalkylene. In one variation, Y is unsubstituted cyclopropylene. In another variation, Y is unsubstituted cyclobutylene.

[0147] In some embodiments of the compound of formula (I), or a pharmaceutically acceptable salt thereof, Y is C3-C5cycloalkylene substituted by 1-3 Yagroups. In one variation, each Yais independently selected from the group consisting of halogen, deuterium, and C1-C6alkyl.

[0148] In some embodiments of the compound of formula (I), or a pharmaceutically acceptable salt thereof, Y is a C3-C4cycloalkylene. In one aspect, Y is a cyclopropylene. In another aspect, Y is a cyclobutylene. In one variation, the point of attachment of the C3-C4cycloalkylene to L2and L3areof the C3-C4cycloalkylene to L2and L3are via two different carbon atoms (e.g.,,). In another variation, when the point of attachment of the C3-C4cycloalkylene to L2and L3are via two different carbon atoms, the stereochemistry introduced at the C3-C4cycloalkylene is trans (e.g.,, , ). In another variation, when the point of attachment of the C3-C4cycloalkylene to L2and L3are via two different carbon atoms, the stereochemistry introduced at the C3-C4cycloalkylene is cis (e.g.,, ,

[0149] In some embodiments of the compound of formula (I), or a pharmaceutically acceptable salt thereof, -L2-Y-L3- are taken together to form a moiety selected from the group consisting of: -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2-, -CH2(CH2)2CH2-, -CH2(CH2)3CH2-,denote attachmentpoints to the parent molecule.

[0150] In some embodiments of the compound of formula (I), or a pharmaceutically acceptable salt thereof, -L1-X-L2-Y-L3- are taken together to form a moiety selected from the group consisting of: Rxn-aln-alkylene C -kyleneN C -C(i).2C4 2 7, wherein the C2-C4n-alkylene and the C2-C7n-alkylene are each independently optionally substituted by one or more R4, n-alkyleneRxNC n-alkyln-alkylene C2-C4 0-Cene3AC2-C4(ii). , wherein the C2-C4n-alkylene to the left of the -N(Rx)- moiety is optionally substituted by one Aor more R4, the C0-C3n-alkylene is optionally substituted by one or more R4, the moiety is a C3-C5cycloalkylene optionally substituted by one or more Ya, and the C2-C4n-alkylene to the right of A the moiety is optionally substituted by one or more R4; and x n-alkylenRACe N C n-alkylene C n-alkyle2-C4-C -Cne(iii).0 3 2 4,wherein the C2-C4n-alkylene to the left of the -N(Rx)- moiety is optionally substituted by one 4 03stituted by one or more R4A or more R , the C -C n-alkylene is optionally sub , the moiety is a C3-C5cycloalkylene optionally substituted by one or more Ya, and the C2-C4n-alkylene to the right of A the moiety is optionally substituted by one or more R4.

[0151] In some embodiments of the compound of formula (I), or a pharmaceutically acceptable salt thereof, -L1-X-L2-Y-L3- are taken together to form a moiety selected from the group consisting of:variation, -L1-X-L2-Y-L3- are taken together to form a moiety selected from the group consisting of:

[0152] In some embodiments of the compound of formula (I), or a pharmaceutically acceptable salt thereof, -L1-X-L2-Y-L3- are taken together to form a moiety with the formula of:.

[0153] In some embodiments of the compound of formula (I), or a pharmaceutically acceptable salt thereof, Q is H. In some embodiments, Q is C1-C6alkyl. In some embodiments, Q is C1-C2alkyl. In some embodiments, Q is methyl. In some embodiments, Q is ethyl.

[0154] In some embodiments, the compound of formula (I) is of the formula (II-A-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0155] In some embodiments, the compound of formula (I) is of the formula (II-B-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0156] In some embodiments, the compound of formula (I) is of the formula (II-B-1-a):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0157] In some embodiments, the compound of formula (I) is of the formula (II-B-1-b):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0158] In some embodiments, the compound of formula (I) is of the formula (II-C-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0159] In some embodiments, the compound of formula (I) is of the formula (II-D-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0160] In some embodiments, the compound of formula (I) is of the formula (II-E-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0161] In some embodiments, the compound of formula (I) is of the formula (III-A-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0162] In some embodiments, the compound of formula (I) is of the formula (IV-A-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0163] In some embodiments, the compound of formula (I) is of the formula (IV-B-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0164] In some embodiments, the compound of formula (I) is of the formula (IV-B-1-a):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0165] In some embodiments, the compound of formula (I) is of the formula (IV-B-1-b):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0166] In some embodiments, the compound of formula (I) is of the formula (V-A-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0167] In some embodiments, the compound of formula (I) is of the formula (V-B-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0168] In some embodiments, the compound of formula (I) is of the formula (V-B-1-a):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0169] In some embodiments, the compound of formula (I) is of the formula (V-B-1-b):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0170] In some embodiments, the compound of formula (I) is of the formula (VI-A-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0171] In some embodiments, the compound of formula (I) is of the formula (VI-A-2):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0172] In some embodiments, the compound of formula (I) is of the formula (VI-B-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0173] In some embodiments, the compound of formula (I) is of the formula (VI-B-1-a):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0174] In some embodiments, the compound of formula (I) is of the formula (VI-B-1-b):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0175] In some embodiments, the compound of formula (I) is of the formula (VII-A-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0176] In some embodiments, the compound of formula (I) is of the formula (VII-B-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0177] In some embodiments, the compound of formula (I) is of the formula (VII-B-1-a):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0178] In some embodiments, the compound of formula (I) is of the formula (VII-B-1-b):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0179] In some embodiments, the compound of formula (I) is of the formula (VIII-A-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0180] In some embodiments, the compound of formula (I) is of the formula (VIII-B-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0181] In some embodiments, the compound of formula (I) is of the formula (VIII-B-1-a):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0182] In some embodiments, the compound of formula (I) is of the formula (VIII-B-1-b):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0183] In some embodiments, the compound of formula (I) is of the formula (IX-A-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0184] In some embodiments, the compound of formula (I) is of the formula (IX-B-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0185] In some embodiments, the compound of formula (I) is of the formula (IX-B-1-a):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0186] In some embodiments, the compound of formula (I) is of the formula (IX-B-1-b):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0187] In some embodiments, the compound of formula (I) is of the formula (X-A-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0188] In some embodiments, the compound of formula (I) is of the formula (X-B-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0189] In some embodiments, the compound of formula (I) is of the formula (X-B-1-a):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0190] In some embodiments, the compound of formula (I) is of the formula (X-B-1-b):

[0191] or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0192] In some embodiments, the compound of formula (I) is of the formula (XI-A-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0193] In some embodiments, the compound of formula (I) is of the formula (XI-B-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0194] In some embodiments, the compound of formula (I) is of the formula (XI-B-1-a):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0195] In some embodiments, the compound of formula (I) is of the formula (XI-B-1-b):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0196] In some embodiments, the compound of formula (I) is of the formula (XII-A-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0197] In some embodiments, the compound of formula (I) is of the formula (XII-B-1):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0198] In some embodiments, the compound of formula (I) is of the formula (XII-B-1-a):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0199] In some embodiments, the compound of formula (I) is of the formula (XII-B-1-b):or a pharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), wherein the stereochemistry at the amino acid alpha-carbon can be R, S, or a mixture of R and S.

[0200] When R, S, or a mixture of R and S is indicated for the alpha-carbon of the amino acid, the structures are intended to encompass the following variations, which are illustrated forpharmaceutically acceptable salt thereof, wherein R2and Rxare as defined for formula (I), or any applicable variation thereof, and the alpha- carbon of the amino acid or ester can have either R or S absolute stereochemistry as indicated. In one such embodiment, the alpha-carbon of the amino acid or ester is in the S absolute stereochemistry. When the alpha-carbon of the amino acid or ester is in the S absolute stereochemical configuration, in some embodiments such a compound is substantially isolated from the corresponding compound in which the amino acid or ester is in the R absolute stereochemical configuration, such as when a composition comprising the compound in the S absolute stereochemical configuration comprises no more than about 5% or about 3% or about 1% or about 0.5% or about 0.1% by weight of the corresponding compound having the R absolute stereochemical configuration. In another such embodiment, the alpha-carbon of the amino acid or ester is in the R absolute stereochemistry. When the alpha-carbon of the amino acid or ester is in the R absolute stereochemical configuration, in some embodiments such a compound is substantially isolated from the corresponding compound in which the amino acid or ester is in the S absolute stereochemical configuration, such as when a composition comprising the compound in the R absolute stereochemical configuration comprises no more than about 5% or about 3% or about 1% or about 0.5% or about 0.1% by weight of the corresponding compound having the S absolute stereochemical configuration. In another embodiment is provided a composition comprising a foregoing compound, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In one such embodiment is provided a composition comprising a mixture of a compound in which the alpha-carbon of the amino acid or ester is in the S stereochemical configuration and a compound in which the alpha-carbon of the amino acid or ester is in the R stereochemical configuration.

[0201] Also provided in another embodiment is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Rxis unsubstituted C3-C8alkyl. In some embodiments, Rxis unsubstituted C3-C8alkyl optionally substituted by 1-5 Rxagroups. In some embodiments, Rxisunsubstituted C3-C6alkyl. In some embodiments, Rxis unsubstituted C3-C6alkyl optionally substituted by 1-5 Rxagroups. In some embodiments, C1-C8alkyl substituted by 1-5 Rxagroups. In another aspect of the foregoing embodiment, Rxis C1-C6alkyl substituted by 1-5 Rxagroups, wherein each Rxais independently selected from the group consisting of halogen, C3-C8cycloalkyl, 3- to 12- membered heterocyclyl, C6-C14aryl, 5- to 10-membered heteroaryl, -CN, -OR5, -C(O)OR5, and -S(O)2R5, wherein the C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, and 5- to 10- membered heteroaryl of Rxaare independently optionally substituted by R4a. In some embodiments, Rxis C1-C6alkyl substituted by 1-5 Rxagroups, wherein each Rxais independently selected from the group consisting of halogen, C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, 5- to 10- membered heteroaryl, -CN, -OR5, and -S(O)2R5, and wherein the C3-C8cycloalkyl, 3- to 12- membered heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of Rxaare independently optionally substituted by one or more R4a. In another aspect of the foregoing embodiment, Rxis C1-C4alkyl substituted by 1-5 Rxagroups, wherein at least one of the Rxagroups is halogen (e.g., Rxis – CH2CH2F or –CH2CH2CH2F), or wherein at least two of the Rxagroups are halogen (e.g., Rxis – CH2CHF2or –CH2CH2CHF2), or wherein at least three of the Rxagroups are halogen (e.g., Rxis – CH2CF3or –CH2CH2CF3). In another aspect of the foregoing embodiment, Rxis C1-C4alkyl (e.g., methyl and ethyl) substituted by 1-5 Rxagroups, wherein at least one of the Rxagroups is C3- C6cycloalkyl, wherein the C3-C6cycloalkyl is substituted by 0-5 groups selected from the group consisting of halogen, -OH,–CN, and C1-C6alkyl substituted by 0-5 -OH. (e.g., Rxais cyclopropyl substituted by –OH or –CN or Rxais cyclobutyl substituted by fluoro). In some embodiments, Rxis C1-C4alkyl substituted by 1-5 Rxagroups, wherein at least one Rxagroup is C3-C6cycloalkyl, and wherein the C3-C6cycloalkyl is optionally substituted by 1-5 groups selected from the group consisting of -OH, and –CN. In some embodiments, Rxis C1-C4alkyl substituted by 1-5 Rxagroups, wherein at least one Rxagroup is 4- to 6-membered heterocyclyl, and wherein the 4- to 6-membered heterocyclyl is optionally substituted by 1-5 oxo groups. In another aspect of the foregoing embodiment, Rxis C1-C3alkyl (e.g., C2alkyl) substituted by 1-5 Rxagroups, wherein at least one of the Rxagroups is 4- to 6-membered heterocyclyl, wherein the 4- to 6-membered heterocyclyl is substituted by 0-5 oxo groups (e.g., Rxais oxetanyl or pyrrolidinonyl). In another aspect of the foregoing embodiment, Rxis C1-C4alkyl substituted by 1-5 Rxagroups, wherein at least one of the Rxagroups is phenyl, wherein the phenyl is substituted by 0-5 groups selected from the group consisting of halogen and -OR8, wherein each R8is independently C1-C3alkyl (e.g., Rxais unsubstituted phenyl, phenyl substituted by fluoro, or phenyl substituted by –OCH3). In some embodiments, Rxis C1-C4alkyl substituted by 1-5 Rxagroups, and wherein at least one Rxagroup is unsubstituted phenyl or phenyl substituted by 1-3 halogen. In another aspect of the foregoing embodiment, Rxis C1-C4alkyl substituted by 1-5 Rxagroups, and wherein at least one Rxagroup is unsubstituted phenyl. In another aspect of the foregoing embodiment, Rxis C1-C4alkyl (e.g., ethyl) substituted by 1-5 Rxagroups, wherein at least one of the Rxagroups is 5- to 6-membered heteroaryl, wherein the 5- to 6-memberedheteroaryl is optionally substituted by 1-5 C1-C3alkyl groups (e.g., Rxais unsubstituted pyrazolyl or pyrazolyl substituted by two –CH3groups). In another aspect of the foregoing embodiment, Rxis C1- C5alkyl substituted by 1-5 Rxagroups, wherein at least one of the Rxagroups is –CN, - COOH, -C(O)OR5, or -S(O)2R5, wherein each R5is independently C1-C4alkyl or C6-C14aryl (e.g., Rxais –CN, -C(O)O-tert-butyl, or -S(O)2CH3). In some embodiments, Rxis C1-C4alkyl substituted by 1-5 Rxagroups, wherein at least one Rxagroup is –CN or -S(O)2R5, and wherein each R5is independently C1-C4alkyl or phenyl. In some embodiments, Rxis C1-C4alkyl substituted by 1-5 Rxagroups, wherein at least one Rxagroup is halogen, or wherein at least two Rxagroups are halogen, or wherein at least three of Rxagroups are halogen.

[0202] Also provided in another embodiment is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Rxis C1-C5alkyl substituted by 1-5 Rxagroups, wherein at least one of the Rxagroups is -OR5, wherein R5is selected from the group consisting of hydrogen, C1-C6alkyl, C3-C6cycloalkyl, C6-C14aryl, or 5- to 10-membered heteroaryl, wherein the C1-C6alkyl, C3-C6cycloalkyl, C6-C14aryl, and 5- to 10-membered heteroaryl of R5are each independently optionally substituted by R5a. In another aspect of the foregoing embodiment, R5is hydrogen. In some embodiments, R5is C1-C4alkyl optionally substituted by 1-5 halogen groups. In another aspect of the foregoing embodiment, R5is C1-C3alkyl substituted by 0-5 halogen groups (e.g., R5is –CH3, - CH2CH3, isopropyl, –CHF2, –CF3,or –CH2F3). In another aspect of the foregoing embodiment, R5is C1-C3alkyl optionally substituted by one C3-C6cycloalkyl group. In another aspect of the foregoing embodiment, R5is C3-C6cycloalkyl (e.g., cyclopropyl) optionally substituted by 1-5 halogen or C1-C3alkyl groups (e.g., R5is cyclopropyl substituted by 2 fluoro groups). In some embodiments, R5is cyclopropyl optionally substituted by 1-5 C1-C3alkyl. In another aspect of the foregoing embodiment, R5is C6-C10aryl substituted by 0-5 halogen or C1-C3alkyl groups (e.g., R5is unsubstituted phenyl, phenyl substituted by one fluoro group, or phenyl substituted by two fluoro groups). In another aspect of the foregoing embodiment, R5is phenyl substituted by 0-5 halogen groups. In some embodiments, R5is unsubstituted phenyl. In another aspect of the foregoing embodiment, R5is 6-membered heteroaryl substituted by 0-5 groups selected from the group consisting of halogen and C1-C3alkyl (e.g., R5is unsubstituted pyridinyl, pyridinyl substituted by fluoro, or pyridinyl substituted by –CH3).

[0203] In another aspect of the foregoing embodiment, Rxis C1-C5alkyl substituted by 2-5 Rxagroups, wherein at least one Rxagroup is halogen, wherein at least one Rxagroup is -OR5, and wherein R5is selected from the group consisting of hydrogen and C1-C3alkyl substituted by 0-5 halogen groups (e.g., Rxis C3-C5alkyl substituted by 1-2 fluoro groups and one –OCH3group or Rxis C3-C5alkyl substituted by 1-2 fluoro groups and 1 –OH group). In some embodiments, Rxis C1-C5alkyl substituted by 2-5 Rxagroups, wherein at least one Rxagroup is halogen, and at least one Rxagroup is -OR5, and wherein R5is selected from the group consisting of hydrogen and unsubstituted C1-C3alkyl. In some embodiments, Rxis C1-C5alkyl substituted by 2-3 Rxagroups, wherein at least one Rxagroup is halogen, and at least one Rxagroup is -OR5, and wherein R5is selected from the group consisting of hydrogen and -CH3.

[0204] Also provided in another embodiment is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Rxis C3-C6cycloalkyl optionally substituted by 1-5 Rxbgroups. In another aspect of the foregoing embodiment, Rxis unsubstituted C3-C6cycloalkyl (e.g., cyclopropyl). In another aspect of the foregoing embodiment, Rxis C3-C6cycloalkyl substituted by 1-5 Rxbgroups, wherein each Rxbis independently selected from halogen and C1-C3alkyl, and wherein the C1-C3alkyl of Rxbis independently and optionally substituted by one –OH group (e.g., Rxis cyclopropyl or cyclobutyl, each of which is substituted by one –CH2OH group or two fluoro groups). In some embodiments, Rxis unsubstituted C3-C6cycloalkyl.

[0205] Also provided in another embodiment is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Rxis 3- to 12-membered heterocyclyl optionally substituted by 1-5 Rxcgroups. In another aspect of the foregoing embodiment, Rxis unsubstituted 4- to 6-membered heterocyclyl (e.g., oxetanyl).

[0206] Also provided in another embodiment is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Rxis 5- to 10-membered heteroaryl optionally substituted by 1-5 Rxegroups. In another aspect of the foregoing embodiment, Rxis unsubstituted 5-membered heteroaryl (e.g., thiazolyl). In some embodiments, Rxis unsubstituted thiazolyl. In another aspect of the foregoing embodiment, Rxis unsubstituted 6-membered heteroaryl.

[0207] Also provided in another embodiment is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Rxis -S(O)2Rxf, wherein Rxfis C1-C6alkyl optionally substituted by Rxg(e.g., Rxis -S(O)2CH3). In some embodiments, Rxis -S(O)2Rxf, and wherein Rxfis unsubstituted C1-C6alkyl.

[0208] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, Rxis selected from the group consisting of:

[0209] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, Rxis selected from the group consisting of:

[0210] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, Rxis selected from the group consisting of:, , , , ,

[0211] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, Rxis selected from the group consisting of.

[0212] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof,

[0213] Also provided is a compound of formula (I), or a salt thereof, wherein the compound is selected from the group consisting of:,, ,

[0214] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting

[0215] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof,.

[0216] Also provided in another embodiment is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R2is RB2. In one aspect of the foregoing embodiment, RB2is C1-C6alkyl optionally substituted by 1-5 RB2agroups. In one aspect of the foregoing embodiment, RB2is unsubstituted C1-C6alkyl (e.g., unsubstituted C4-C6alkyl). In one aspect of the foregoing embodiment, the C1-C6alkyl of RB2is straight-chain alkyl (e.g., n-butyl). In another aspect of the foregoing embodiment, the C1-C6alkyl of RB2is branched alkyl (e.g., iso-butyl). In another aspect of the foregoing embodiment, RB2is In another aspect of the foregoing embodiment, the RB2is. In another aspect of the foregoing embodiment, RB2is C1-C6alkyl substituted by 1-5 RB2agroups, wherein each RB2ais independently selected from of halogen, C1-C6alkyl, C3-C8cycloalkyl, 3- to 12-membered saturated heterocyclyl, -CN, -OR5, -NR6R7, -NR5C(O)OR6, and -S(O)2R5, wherein the C1-C6alkyl, C3-C8cycloalkyl, and 3- to 12-membered saturated heterocyclyl of RB2aare independently optionally substituted by one or more R4a. In some embodiments, RB2is C1-C6alkyl substituted by 1-5 RB2agroups, wherein each RB2ais independently selected from the group consisting of halogen, C1-C6alkyl, C3-C8cycloalkyl, 3- to 12-membered saturated heterocyclyl, -CN, -OR5, -NR6R7, and -NR5C(O)OR6, wherein the C1-C6alkyl, C3-C8cycloalkyl, and 3- to 12-membered saturated heterocyclyl of RB2aare independently optionally substituted by one or more R4a. In another aspect of the foregoing embodiment, RB2is C1-C6alkyl (e.g., C2-C5alkyl) substituted by 1-5 RB2agroups, wherein at least one of the RB2agroups is halogen (e.g., RB2is C4-C5alkyl substituted by 2-3 fluoro groups) or C1-C6alkyl optionally substituted with 1-3 -OH. In another aspect of the foregoing embodiment, RB2is C1-C6alkyl (e.g., C1-C3alkyl) substituted by 1-5 RB2agroups, wherein at least one of the RB2agroups is C3-C8cycloalkyl (e.g., cyclopropyl, cyclobutyl, and cyclohexyl). In another aspect of the foregoing embodiment, RB2is C1-C3alkyl substituted by C3-C6cycloalkyl, wherein the C3-C6cycloalkyl is optionally substituted by 1-5 groups selected from the group consisting of halogen (e.g., fluoro) and C1-C6alkyl (e.g., -CH3) optionally substituted with 1-3 halogen. In another aspect of the foregoing embodiment, RB2is C1-C3alkyl substituted by 1-5 C3-C6cycloalkyl (e.g., one C3- C6cycloalkyl, two C3-C6cycloalkyl, or 3-5 C3-C6cycloalkyl), wherein the C3-C6cycloalkyl is unsubstituted (e.g., RB2is methyl substituted by cyclobutyl, wherein the cyclobutyl is unsubstituted or RB2is methyl substituted by cyclohexyl, wherein the cyclohexyl is unsubstituted). In another aspect of the foregoing embodiment, RB2is C1-C3alkyl substituted by 1-5 C3-C6cycloalkyl (e.g., one C3- C6cycloalkyl, two C3-C6cycloalkyl, or 3-5 C3-C6cycloalkyl), wherein the C3-C6cycloalkyl is substituted by 1-5 C1-C3alkyl groups (e.g., RB2is methyl substituted by cyclopropyl, wherein the cyclopropyl is substituted by one –CH3group or RB2is methyl substituted by cyclohexyl, wherein the cyclohexyl is substituted by two –CH3groups). In another aspect of the foregoing embodiment, RB2is C1-C3alkyl substituted by 1-5 C3-C6cycloalkyl, wherein the C3-C6cycloalkyl is substituted with 1-5 C1-C3alkyl optionally substituted with 1-5 halogen. In another aspect of the foregoing embodiment, RB2is C1-C3alkyl substituted by C3-C6cycloalkyl, wherein the C3-C6cycloalkyl is substituted with 1- 5 halogen. In another aspect of the foregoing embodiment, RB2is C1-C5alkyl substituted by 1-5 RB2agroups, wherein at least one of the RB2agroups is 3- to 12-membered saturated heterocyclyl (e.g. RB2is C1alkyl substituted by 6-membered saturated heterocyclyl, such as tetrahydro-2H-pyranyl). In some embodiments, RB2is C1-C3alkyl substituted by 1-54- to 6-membered saturated heterocyclyl. In another aspect of the foregoing embodiment, RB2is C1-C3alkyl substituted by 1-54- to 6-membered saturated heterocyclyl, wherein the 4- to 6-membered saturated heterocyclyl is unsubstituted. Inanother aspect, RB2is C1-C3alkyl substituted by 1-54- to 6-membered saturated heterocyclyl, wherein the 4- to 6-membered saturated heterocyclyl is substituted with one or more groups selected from the group consisting of C1-C6alkyl, halogen and oxo. In another aspect, RB2is C1-C3alkyl substituted by 1-54- to 6-membered saturated heterocyclyl, wherein the 4- to 6-membered saturated heterocyclyl is substituted with one or more groups selected from the group consisting of C1-C6alkyl and oxo. In another aspect of the foregoing embodiment, RB2is C1-C5alkyl substituted by 1-5 RB2agroups, wherein at least one of the RB2agroups is -OR5, wherein each R5is independently selected from hydrogen, C1-C6alkyl, C3-C6cycloalkyl, and C6-C14aryl (e.g., R5is C6-C14aryl substituted by 0-5 halogen). In another aspect of the foregoing embodiment, RB2is C1-C5alkyl substituted by 1-5 RB2agroups, wherein at least one of the RB2agroups is -OR5, wherein each R5is independently selected from hydrogen, C1-C6alkyl and C6-C14aryl (e.g., R5is C6-C14aryl substituted by 0-5 halogen). In some embodiments, RB2is C1-C5alkyl substituted by 1-5 RB2agroups, wherein at least one of the RB2agroups is -OR5, wherein each R5is independently selected from hydrogen, C1-C6alkyl, and C6-C14aryl, wherein the C1-C6alkyl is optionally substituted with 1-5 halogen, and wherein the C6-C14aryl is optionally substituted with 1-5 halogen. In another aspect of the foregoing embodiment, RB2is C1-C5alkyl substituted by -OR5, wherein R5is hydrogen or C1-C4alkyl (e.g., R5is –CH3or isopropyl). In another aspect of the foregoing embodiment, RB2is C1-C4alkyl substituted by -OR5, wherein R5is C1-C3alkyl optionally substituted with 1-5 halogen. In another aspect of the foregoing embodiment, RB2is C1-C4alkyl substituted 1-5 by -OR5, wherein R5is unsubstituted C1-C3alkyl. In another aspect of the foregoing embodiment, RB2is C1-C4alkyl substituted by -OR5, wherein R5is unsubstituted C1-C3alkyl. In another aspect of the foregoing embodiment, RB2is C1-C3alkyl substituted by -OR5, wherein R5is C6-C14aryl (e.g., phenyl) optionally substituted by 1-5 halogen (e.g., R5is phenyl substituted by two fluoro groups). In another aspect of the foregoing embodiment, RB2is C1-C4alkyl substituted by 1-5 -OR5, wherein R5is phenyl optionally substituted by 1-5 halogen. In another aspect of the foregoing embodiment, RB2is C1-C5alkyl substituted by 1-5 RB2agroups, wherein at least one of the RB2agroups is -CN, -NR6R7, -NR5C(O)OR6, or -S(O)2R5(e.g., RB2ais –CN, -NH2, or -NHC(O)OCH3). In another aspect of the foregoing embodiment, RB2is C1-C5alkyl substituted by 2-5 RB2agroups, wherein each RB2ais independently selected from halogen, C1- C6alkyl, C3-C8cycloalkyl, 3- to 6-membered saturated heterocyclyl, -CN, -OR5, -NR6R7, and -NR5C(O)OR6. In another aspect of the foregoing embodiments, RB2is C1-C4alkyl substituted by 2-5 RB2agroups, wherein at least one RB2agroup is selected from the group consisting of halogen and C1-C6alkyl, and at least one RB2agroup is –OR5, wherein each R5is independently selected from the group consisting of hydrogen and C1-C6alkyl optionally substituted with 1-5 halogen. In another aspect of the foregoing embodiment, RB2is C1-C5alkyl (e.g., C1-C4alkyl, such as isobutyl) substituted by 2-5 RB2agroups, wherein at least one RB2agroup is halogen (e.g., RB2ais fluoro) and at least one RB2agroup is –OR5, wherein each R5is independently selected from hydrogen and C1-C6alkyl optionally substituted with 1-5 halogen (e.g., RB2ais –OH). In another aspect of the foregoingembodiment, RB2is C1-C5alkyl (e.g., C1alkyl) substituted by 2-5 RB2agroups, wherein at least one RB2agroup is C3-C6cycloalkyl (e.g., RB2ais cyclohexyl) and at least one RB2agroup is –OR5, wherein each R5is independently selected from hydrogen and C1-C6alkyl optionally substituted with 1-5 halogen (e.g., RB2ais –OH or –OCH3). In some embodiments, RB2is C1-C4alkyl substituted by 2-5 RB2agroups, wherein at least one RB2agroup is C3-C6cycloalkyl, and at least one RB2agroup is -OR5, wherein each R5is independently selected from the group consisting of hydrogen and C1-C6alkyl optionally substituted with 1-5 halogen. In another aspect of the foregoing embodiments, RB2is unsubstituted C1-C6alkyl. In another aspect of the foregoing embodiments, RB2is.

[0217] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, RB2aB2awherein RB2is selected from the group consisting of:, , , ,wherein each RB2ais independently as defined for formula (I).

[0218] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RB2is, wherein each RB2ais C2-C5alkyl or C3-C6cycloalkyl, wherein the C2-C5alkyl is optionally substituted by 1-5 halogen (e.g., F), and wherein the C3-C6cycloalkyl of RB2ais optionally substituted by C1-C3alkyl or halogen.

[0219] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RB2is selected from the g,

[0221] Also provided in another embodiment is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RB2is C3-C8cycloalkyl optionally substituted by 1-5 RB2bgroups. In another aspect of the foregoing embodiment, the C3-C8cycloalkyl of RB2is monocyclic. In anotheraspect, the C3-C8cycloalkyl of RB2is bicyclic (e.g., fused, spiro, or bridged). In another aspect, RB2is unsubstituted C3-C8cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl, and spiro[2.5]octanyl). In another aspect of the foregoing embodiment, RB2is C3-C8cycloalkyl substituted by 1-5 RB2bgroups, wherein each RB2bis independently selected from halogen, C1-C6alkyl, 3- to 12-membered saturated heterocyclyl, and -OR5, wherein the C1-C6alkyl, and 3- to 12-membered saturated heterocyclyl of RB2bare optionally substituted by 1-5 R4agroups. In another aspect of the foregoing embodiment, RB2is C3-C8cycloalkyl substituted by 1-5 RB2bgroups, wherein each RB2bis independently selected from the group consisting of halogen and C1-C6alkyl, wherein the C1-C6alkyl of RB2bare optionally substituted by 1-5 R4agroups. In another aspect of the foregoing embodiment, RB2is C3-C6cycloalkyl (e.g., cyclopropyl or cyclohexyl) substituted by 1-5 RB2bgroups, wherein at least one of the RB2bgroups is halogen (e.g., fluoro). In another aspect of the foregoing embodiment, RB2is C3-C6cycloalkyl substituted by 1-5 RB2bgroups, wherein at least one of the RB2bgroups is C1-C3alkyl, wherein the C1-C3alkyl of RB2bis optionally substituted by 1-5 R4agroups (e.g., RB2bis C1-C2alkyl substituted by 1-5 R4agroups, wherein each R4agroups is independently selected from halogen and 6- membered heteroaryl substituted by 0-5 halogen). In another aspect of the foregoing embodiment, RB2is C3-C6cycloalkyl substituted by 1-5 RB2bgroups, wherein at least one of the RB2bgroups is C1- C3alkyl optionally substituted by 1-5 halogen or 5- to 6-membered heteroaryl. In another aspect of the foregoing embodiment, RB2is C3-C6cycloalkyl substituted by 1-5 RB2bgroups, wherein at least one of the RB2bgroups is unsubstituted C1-C3alkyl (e.g., RB2is cyclohexyl substituted by two –CH3groups). In another aspect of the foregoing embodiment, RB2is C3-C6cycloalkyl substituted by 1-5 RB2bgroups, wherein at least one of the RB2bgroups is 3- to 12-membered saturated heterocyclyl (e.g., tetrahydro-2H-pyranyl or benzodioxolyl). In another aspect of the foregoing embodiment, RB2is C3- C6cycloalkyl substituted by 2-5 RB2bgroups, wherein each RB2bis independently selected from halogen (e.g., fluoro), C1-C6alkyl, and -OR5(e.g., -OH). In another aspect of the foregoing embodiment, RB2is C3-C6cycloalkyl substituted by 2-5 RB2bgroups, wherein at least one RB2bgroup is halogen (e.g., fluoro) and at least one RB2bgroup is C1-C6alkyl (e.g., -CH3). In another aspect of the foregoing embodiment, RB2is C3-C6cycloalkyl (e.g., cyclobutyl) substituted by 2-5 RB2bgroups, wherein at least one RB2bgroup is -OH and at least one RB2bgroup is C1-C6alkyl. In another aspect, RB2unsubstituted C3-C8cycloalkyl.

[0222] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RB2is selected from the group consisting of:formula (I), and n is 0, 1, 2, or 3. In one variation, n is 0. In another variation, n is 1. In another variation, n is 2. In yet another variation, n is 3.

[0223] Also provided in another embodiment is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RB2is selected from the group consisting of:, ,

[0224] Also provided in another embodiment is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RB2is 3- to 12-membered saturated heterocyclyl optionally substituted by 1-5 RB2cgroups, such that the atom of the 3- to 12-membered heterocyclyl that is bonded to the –C(O) is a carbon. In another aspect of the foregoing embodiment, the 3- to 12- membered saturated heterocyclyl of RB2is monocyclic. In another aspect of the foregoing embodiment, the 3- to 12-membered saturated heterocyclyl of RB2is bicyclic (e.g., fused, spiro, or bridged). In another aspect of the foregoing embodiment, RB2is unsubstituted 3- to 12-membered saturated heterocyclyl (e.g., pyrrolidinyl, tetrahydropyranyl, or morpholinyl). In another aspect of the foregoing embodiment, RB2is unsubstituted 4- to 10-membered saturated heterocyclyl. In another aspect of the foregoing embodiment, RB2is unsubstituted 4- to 6-membered saturated heterocyclyl. In another aspect of the foregoing embodiment, RB2is 3- to 12-membered saturated heterocyclyl substituted by 1-5 RB2cgroups, wherein each RB2cis independently selected from oxo, halogen, C1- C6alkyl, -CN, -OR5, -C(O)R5, -C(O)OR5, and -S(O)2R5. In another aspect of the foregoing embodiment, RB2is 3- to 12-membered saturated heterocyclyl substituted by 1-5 RB2cgroups, wherein each RB2cis independently selected from halogen, C1-C6alkyl, -C(O)R5, and -C(O)OR5, wherein the C1-C6alkyl is optionally substituted by 1-5 R4agroups. In another aspect of the foregoing embodiment, RB2is 4- to 6-membered saturated heterocyclyl substituted by 1-5 RB2cgroups, wherein at least one of the RB2cgroups is halogen (e.g., fluoro). In another aspect of the foregoing embodiment, RB2cis C1-C2alkyl substituted by 1-5 R4agroups, wherein each R4agroups is independently selected from halogen, phenyl, 6-membered heteroaryl, and -NR8C(O)OR10(e.g. –NHC(O)O-t-butyl), wherein the phenyl and 6-membered heteroaryl of R4aare each independently optionally substituted by 1-5 halogen (e.g., R4ais unsubstituted phenyl, unsubstituted pyridinyl, or unsubstituted pyrimidinyl). In another aspect of the foregoing embodiment, RB2is 4- to 6-membered saturated heterocyclyl (e.g., oxetanyl, pyrrolidinyl, tetrahydropyranyl, or azetidinyl) substituted by 1-5 RB2cgroups, wherein at least one of the RB2cgroups is C1-C6alkyl optionally substituted by 1-5 R4agroups, wherein each R4ais selected from the group consisting of halogen and 5- to 6-membered heteroaryl groups. In another aspect of the foregoing embodiment, RB2cis C1-C2alkyl substituted by 1-5 R4agroups, wherein each R4ais 6-membered heteroaryl optionally substituted by 1-5 halogen. In another aspect of the foregoing embodiment, RB2is 4- to 6-membered saturated heterocyclyl (e.g., 4- membered heterocyclyl, such as oxetanyl) substituted by 1-5 RB2cgroups, wherein at least one of the RB2cgroups is C1-C6alkyl, wherein the C1-C6alkyl of RB2cis optionally substituted by 1-5 R4agroups. In some embodiments, RB2is 4- to 6-membered saturated heterocyclyl substituted by 1-5 RB2cgroups, wherein at least one of the RB2cgroups is C1-C6alkyl, wherein the C1-C6alkyl of RB2cis substituted by 1-5 halogen. In another aspect of the foregoing embodiment, RB2is 4- to 6-membered saturated heterocyclyl (e.g., 5-membered heterocyclyl) substituted by 1-5 RB2cgroups, wherein at least one of the RB2cgroups is unsubstituted C1-C6alkyl. In another aspect of the foregoing embodiment, RB2is 4- to 6-membered saturated heterocyclyl (e.g., 5- to 6-membered saturated heterocyclyl, such as pyrrolidinyl or piperidinyl) substituted by 1-5 RB2cgroups, wherein at least one RB2cgroup is -OR5, -C(O)R5, or -C(O)OR5, wherein each R5is independently hydrogen or C1-C6alkyl (e.g., RB2cis –OH, -C(O)(CH2)3CH3, or -C(O)OCH3). In another aspect of the foregoing embodiment, RB2is 4- to 6-membered saturated heterocyclyl (e.g., 5- to 6-membered saturated heterocyclyl, such as pyrrolidinyl or piperidinyl) substituted by 1-5 RB2cgroups, wherein at least one RB2cgroup is -C(O)R5, or -C(O)OR5, wherein each R5is C1-C6alkyl (e.g., RB2cis –OH, -C(O)(CH2)3CH3, or -C(O)OCH3). In another aspect of the foregoing embodiment, RB2is 4- to 6-membered saturated heterocyclyl (e.g., 1,2-dihydropyridinyl) substituted by 1-5 RB2cgroups, wherein at least one RB2cgroup is oxo. In another aspect of the foregoing embodiment, RB2is 4- to 6-membered saturated heterocyclyl (e.g., 6- membered heterocyclyl, such as piperidinyl) substituted by 2-5 RB2cgroups, wherein each RB2cis independently selected from halogen, C1-C6alkyl, -C(O)R5, and -C(O)OR5, wherein each R5is independently C1-C6alkyl (e.g., RB2cis independently selected from fluoro and –C(O)O-tert-butyl). In some embodiments, RB2is 4- to 6-membered saturated heterocyclyl substituted by 2-5 RB2cgroups, wherein each RB2cis independently selected from halogen and -C(O)OR5, wherein each R5is independently C1-C6alkyl. In another aspect of the foregoing embodiment, RB2is 4- to 6-membered heterocyclyl substituted by 2-5 RB2cgroups, wherein at least one RB2cgroup is C1-C6alkyl optionally substituted by 1-5 halogen and at least one RB2cgroup is -C(O)R5or -C(O)OR5(e.g., RB2cis independently selected from –CF3, -C(O)CH3, and –C(O)O-tert-butyl). In another aspect of the foregoing embodiment, RB2is 4- to 6-membered saturated heterocyclyl (e.g., 6-membered heterocyclyl, such as piperidinyl) substituted by 2-5 RB2cgroups, wherein each RB2cis independentlyselected from halogen and -C(O)OR5, wherein each R5is independently C1-C6alkyl. In another aspect of the foregoing embodiment, RB2is azetidinyl, pyrrolidinyl, piperidinyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxabicyclohexanyl, oxabicyclooctanyl, tetrahydro-2H-thiopyranyl, or morpholinyl, each of which is independently optionally substituted by 1-5 RB2cgroups. In another aspect of the foregoing embodiment, RB2is pyrrolidinyl, piperidinyl, oxetanyl, tetrahydropyranyl, or morpholinyl, each of which is independently and optionally substituted by 1-5 RB2cgroups. In another aspect of the foregoing embodiment, RB2is pyrrolidinyl, piperidinyl, oxetanyl, or tetrahydropyranyl, each of which is independently and optionally substituted by 1-5 RB2cgroups.

[0225] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof,3. In one variation, n is 0. In another variation, n is 1. In another variation, n is 2. In yet another variation, n is 3. In the above structures that depict an -N(H)- moiety and n is 1, 2, or 3, it is understood that one of the RB2cgroups can replace the hydrogen atom of the -N(H)- moiety (e.g., n is

[0226] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof,

[0227] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof,

[0228] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RB2is selected from the group consisting of:,

[0229] Also provided in another embodiment is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R2is RC2. In one aspect of the foregoing embodiment, RC2is C1-C6alkyl substituted by 1-5 RC2egroups. In one aspect of the foregoing embodiment, the C1-C6alkyl of RC2is straight-chain alkyl (e.g., n-butyl) substituted by 1-5 RC2egroups. In another aspect of the foregoing embodiment, the C1-C6alkyl of RC2is branched alkyl (e.g., iso-butyl)substituted by 1-5 RC2egroups. In another aspect of the foregoing embodiment, RC2is C1-C5alkyl substituted by 1-5 RC2egroups, wherein at least one RC2egroup is 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl, and each of the other RC2egroups, when present, is independently selected from halogen, C1-C6alkyl, C3-C8cycloalkyl, 3- to 12- membered heterocyclyl, C6-C14aryl, 5- to 10-membered heteroaryl, -CN, -OR5, -NR6R7, -NR5C(O)OR6, and -S(O)2R5, wherein the 3- to 12-membered partially unsaturated heterocyclyl, C1- C6alkyl, C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of RC2aare independently optionally substituted by one or more R4a. In some embodiments, RC2is C1-C5alkyl substituted by 1-5 RC2egroups, wherein at least one RC2egroup is 3- to 12- membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl, and each of the other RC2egroups, when present, is independently selected from the group consisting of halogen, C1-C6alkyl, -CN, and -OR5, and wherein the 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, 5- to 10-membered heteroaryl, and C1-C6alkyl of RC2eare independently optionally substituted by one or more R4a. In another aspect of the foregoing embodiment, RC2is C1-C5alkyl substituted by 1-5 RC2egroups, wherein at least one of the RC2egroups is C6-C14aryl, wherein the C6-C14aryl is independently optionally substituted by 1-5 R4agroups. In another aspect of the foregoing embodiment, RC2is C1-C4alkyl substituted by 1-5 RC2egroups, and wherein at least one RC2egroup is unsubstituted phenyl. In another aspect of the foregoing embodiment, RC2is C1-C4alkyl substituted by phenyl, wherein the phenyl is unsubstituted. In some embodiments, RC2is C1-C4alkyl substituted by 1-5 RC2egroups, wherein at least one RC2egroup is phenyl substituted by 1-5 R4agroups, and wherein at least one R4agroup is selected from the group consisting of halogen, -CN, - OR8, and C1-C6alkyl optionally substituted by 1-5 halogen. In another aspect of the foregoing embodiment, RC2is C1-C4alkyl (e.g., C1-C3alkyl) substituted by 1-5 RC2e, wherein at least one RC2egroup is phenyl substituted by 1-5 R4agroups, wherein at least one R4agroup is selected from halogen and C1-C6alkyl substituted by 0-5 halogen (e.g., RC2eis phenyl substituted by one fluoro group). In some embodiments, RC2is C1-C4alkyl substituted by 1-5 RC2egroups, wherein at least one RC2egroup is phenyl substituted by 2-5 R4agroups, wherein at least one R4agroup is halogen or -CN, and wherein at least one R4agroup is -OR8or C1-C6alkyl optionally substituted by 1-5 halogen. In some embodiments, RC2is C1-C4alkyl substituted by 2-5 RC2egroups, wherein at least one RC2egroup is phenyl substituted by 1-5 R4agroups, and wherein at least one RC2eis selected from the group consisting of halogen, -CN, and -OR5. In another aspect of the foregoing embodiment, RC2is C1-C4alkyl substituted by 1-5 RC2egroups, wherein at least one RC2egroup is phenyl substituted by 2-5 R4agroups, wherein at least two R4agroups are halogen (e.g., RC2eis phenyl substituted by two fluoro groups or RC2eis phenyl substituted by one fluoro group and one chloro group). In another aspect of the foregoing embodiment, RC2is C1-C4alkyl substituted by 1-5 RC2egroups , wherein at least one RC2egroup is phenyl substituted by 2-5 R4agroups, wherein at least one R4agroup is halogen and at least one R4agroup is C1-C6alkyl substituted by 0-5 halogen (e.g., RC2eis phenyl substituted by onefluoro group and one –CF3group). In another aspect of the foregoing embodiment, RC2is C1-C4alkyl substituted by 2-5 RC2egroups , wherein at least one RC2egroup is phenyl substituted by 1-5 R4agroups, and wherein at least one RC2eis selected from the group consisting of halogen, -CN, and -OR5.

[0230] In another aspect, RC2is C1-C5alkyl (e.g., C1-C3alkyl) substituted by 1-5 RC2egroups, wherein at least one of the RC2egroups is 5- to 10-membered heteroaryl, and wherein the 5- to 10- membered heteroaryl is optionally substituted by 1-5 R4agroups (e.g., RC2eis unsubstituted pyridinyl). In some embodiments, RC2is C1-C5alkyl substituted by 1-5 RC2egroups, wherein at least one RC2egroup is 5- to 10-membered heteroaryl, and wherein the 5- to 10-membered heteroaryl is optionally substituted by 1-5 R4agroups. In some embodiments, RC2is C1-C5alkyl substituted by 1-5 RC2egroups, wherein at least one RC2egroup is 5- to 10-membered heteroaryl, wherein the 5- to 10- membered heteroaryl is substituted by 1-5 R4agroups, and wherein at least one R4agroup is selected from the group consisting of halogen, -CN, -OR8, and C1-C6alkyl optionally substituted by 1-5 halogen. In another aspect of the foregoing embodiment, RC2is C1-C5alkyl substituted by 1-5 RC2egroups, wherein at least one RC2egroup is 5- to 10-membered heteroaryl, wherein the 5- to 10- membered heteroaryl is substituted by 1-5 R4agroups, and wherein at least one R4agroup is selected from the group consisting of halogen, -CN, -OH, and C1-C6alkyl substituted by 0-5 halogen. In some embodiments, RC2eis pyridyl optionally substituted by 1-5 R4agroups, and wherein at least one R4agroup, when present, is selected from the group consisting of halogen, -CN, -OR8, and C1-C6alkyl optionally substituted by 1-5 halogen. In another aspect of the foregoing embodiment, RC2is pyridyl substituted by 0-5 R4agroups, and wherein at least one R4agroup, when present, is selected from the group consisting of halogen, -CN, -OH, and C1-C6alkyl substituted by 0-5 halogen. In another aspect of the foregoing embodiment, RC2is unsubstituted pyridyl. In another aspect of the foregoing embodiment, RC2is C1-C5alkyl substituted by 2-5 RC2egroups, wherein at least one RC2egroup is 5- to 10-membered heteroaryl, and wherein at least one RC2eis selected from the group consisting of halogen, -CN, and -OR5.

[0231] In another aspect, RC2is C1-C5alkyl substituted by 1-5 RC2egroups, wherein at least one RC2egroup is 5- to 10-membered partially unsaturated heterocyclyl, wherein the 5- to 10-membered partially unsaturated heterocyclyl is optionally substituted by 1-5 R4agroups, and wherein at least one R4agroup is oxo.

[0232] In another aspect, RC2is C1-C5alkyl (e.g., C1-C3alkyl) substituted by 2-5 RC2egroups, wherein at least one RC2egroup is phenyl substituted by 0-5 halogen (e.g., RC2eis unsubstituted phenyl, RC2eis phenyl substituted by one fluoro group, or RC2eis phenyl substituted by one chloro group) and at least one RC2egroup is –OR5, wherein each R5is independently selected from hydrogen and C1-C6alkyl (e.g., RC2eis –OH or –OCH3). In another aspect of the foregoing embodiment, RC2is C1-C5alkyl (e.g., C1-C3alkyl) substituted by 2-5 RC2egroups, wherein at least one RC2egroup is phenyl substituted by 0-5 halogen (e.g., RC2eis unsubstituted phenyl or RC2eis phenyl substituted by one fluoro group) and at least one RC2egroup is halogen (e.g., RC2eis fluoro).

[0233] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, RC2ewherein RC2is selected from the group consisting of:, , , , wheC2erein each R is independently as defined for formula (I).

[0234] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RC2isC2e, wherein each R is C6-C14aryl or 5- to 10-membered heteroaryl, wherein the C6-C14aryl and 5- to 10-membered heteroaryl of RC2eis optionally substituted by C1-C3alkyl, halogen, or -OR5.

[0235] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof,or 3, m is 0, 1, or 2, and RC2eand R4are each independently defined as formula (I).

[0236] Also provided in another embodiment is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RC2is C3-C8cycloalkyl substituted by 1-5 RC2ggroups. In another aspect of the foregoing embodiment, the C3-C8cycloalkyl of RC2is monocyclic. In another aspect, the C3-C8cycloalkyl of RC2is bicyclic (e.g., fused, spiro, or bridged). In another aspect, In another aspect of the foregoing embodiment, RC2is C3-C8cycloalkyl substituted by 1-5 RC2ggroups, wherein at least one RC2ggroup is selected from the group consisting of C6-C14aryl, 5- to 10-membered heteroaryl, and 3- to 10 membered partially unsaturated heterocyclyl, wherein each of the other RC2ggroups, when present, is independently selected from the group consisting of halogen, C1-C6alkyl, and -OR5, and wherein the C1-C6alkyl, 3- to 10-membered partially unsaturated heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of RC2gare substituted by 0-5 R4agroups. In some embodiments, RC2is C3-C8cycloalkyl substituted by 1-5 RC2ggroups, wherein at least one RC2ggroup is selected from thegroup consisting of C6-C14aryl, 5- to 10-membered heteroaryl, and 3- to 10 membered partially unsaturated heterocyclyl, and each of the other RC2ggroups, when present, is independently -OR5, and wherein the 3- to 10-membered partially unsaturated heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of RC2gare optionally substituted by 1-5 R4agroups. In another aspect of the foregoing embodiment, RC2is C3-C4cycloalkyl substituted by 1-5 RC2ggroups, wherein at least one of the RC2ggroups is C6-C14aryl (e.g., phenyl) substituted by 0-5 R4agroups, wherein each R4ais independently selected from halogen, C1-C6alkyl, and -OR5(e.g., RC2gis unsubstituted phenyl or RC2gis phenyl substituted by fluoro, methyl, tert-butyl, or –OCF3). In some embodiments, RC2is C3-C6cycloalkyl substituted by 1-5 RC2ggroups, and wherein at least one RC2ggroup is C6-C14aryl. In some embodiments, RC2is C3-C6cycloalkyl substituted by 1-5 RC2ggroups, wherein at least one RC2ggroup is phenyl optionally substituted by 1-5 R4agroups, and wherein each R4ais independently selected from the group consisting of halogen, -OR8, -CN, and -S(O)2R8. In another aspect of the foregoing embodiment, RC2is C3-C6cycloalkyl substituted by 1-5 RC2bgroups, wherein at least one of the RC2ggroups is 5- to 10-membered heteroaryl (e.g., pyridinyl or isoquinolinyl). In some embodiments, RC2is C3-C6cycloalkyl substituted by 1-5 RC2ggroups, wherein at least one RC2ggroup is 5- to 10- membered heteroaryl, wherein the 5- to 10-membered heteroaryl of RC2gis optionally substituted by 1-5 R4agroups, wherein each R4ais independently selected from the group consisting of halogen, C1- C6alkyl, -OR8, and -CN, wherein the C1-C6alkyl of R4ais optionally substituted with 1-5 groups selected from the group consisting of halogen and -O-C1-C6alkyl. In another aspect of the foregoing embodiment, RC2is C3-C6cycloalkyl substituted by 1-5 RC2ggroups, wherein at least one RC2ggroup is pyridyl substituted by 0-5 R4agroups, and wherein each R4ais independently selected from the group consisting of halogen, C1-C6alkyl, and -OR8. In some embodiments, RC2is C3-C6cycloalkyl substituted by 1-5 RC2ggroups, wherein at least one RC2ggroup is pyridyl optionally substituted by 1-5 R4agroups, and wherein each R4ais independently selected from the group consisting of halogen, C1- C6alkyl, and -OR8, wherein the C1-C6alkyl of R4ais optionally substituted with 1-5 halogen. In another aspect of the foregoing embodiment, RC2is C3-C8cycloalkyl substituted by 1-5 RC2ggroups, and wherein at least one RC2ggroup is 3- to 10-membered partially unsaturated heterocyclyl optionally substituted by 1-5 R4agroups. In some embodiments, RC2is C3-C8cycloalkyl substituted by 1-5 RC2ggroups, wherein at least one RC2ggroup is 3- to 10-membered partially unsaturated heterocyclyl optionally substituted by 1-5 R4agroups, and wherein each R4ais independently selected from the group consisting of halogen, C1-C6alkyl, and oxo. In another aspect of the foregoing embodiment, RC2is C3-C6cycloalkyl substituted by 1-5 RC2ggroups, wherein at least one RC2ggroup is 5- to 10- membered partially unsaturated heterocyclyl, and wherein the 5- to 10-membered partially unsaturated heterocyclyl is substituted by oxo. In another aspect of the foregoing embodiment, RC2is C3-C6cycloalkyl substituted by 2-5 RC2ggroups, wherein at least one RC2ggroup is halogen (e.g., fluoro) and at least one RC2ggroup is phenyl substituted by 0-5 C1-C6alkyl (e.g., -CH3). In anotheraspect of the foregoing embodiment, RC2is C3-C6cycloalkyl (e.g., cyclobutyl) substituted by 2-5 RC2ggroups, wherein at least one RC2ggroup is -OH and at least one RC2ggroup is phenyl.

[0237] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, (RC2g)nwherein RC2is selected from the group consisting of: ,, ,defined for formula (I), and n is 1, 2, or 3. In one variation, n is 1. In another variation, n is 2. In yet another variation, n is 3.

[0238] Also provided in another embodiment is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RC2is unsubstituted C3-C10cycloalkenyl. In some embodiments, RC2is unsubstituted bicyclic C9-C12cycloalkenyl. In another aspect of the foregoing embodiment, RC2is C3-C10cycloalkenyl substituted by 1-5 RC2cgroups, and wherein each RC2cis independently selected from the group consisting of oxo, halogen, C1-C6alkyl, -CN, -OR5, -C(O)R5, -C(O)OR5, and -S(O)2R5. In another aspect of the foregoing embodiment, RC2is C3-C10cycloalkenyl substituted by oxo.

[0239] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein, wherein RC2care each defined as Formula (I) and can be on any of the annular atoms, and wherein n is 0, 1, 2, or 3.

[0240] Also provided in another embodiment is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RC2is 3- to 12-membered partially unsaturated heterocyclyl substituted by 1-5 RC2dgroups, such that the atom of the 3- to 12-membered partially unsaturated heterocyclyl that is bonded to the –C(O) is a carbon. In another aspect of the foregoing embodiment, the 3- to 12-membered partially unsaturated heterocyclyl of RC2is monocyclic. In another aspect of the foregoing embodiment, the 3- to 12-membered partially unsaturated heterocyclyl of RC2is bicyclic (e.g., fused, spiro, or bridged). In some embodiments, RC2is 4- to 10-membered partially unsaturated heterocyclyl comprising at least one annular N atom. In another aspect of the foregoing embodiment, RC2is unsubstituted 4- to 10-membered partially unsaturated heterocyclyl (e.g., 2H-pyridyl). In another aspect of the foregoing embodiment, RC2is 3- to 12-membered partially unsaturated heterocyclyl substituted by 1-5 RC2dgroups, wherein each RC2dis independently selected from thegroup consisting of oxo, halogen, C1-C6alkyl, C6-C14aryl, 5- to 10-membered heteroaryl, -CN, -OR5, -C(O)R5, -C(O)OR5, and -S(O)2R5. In another aspect of the foregoing embodiment, RC2is 3- to 12- membered partially unsaturated heterocyclyl substituted by 1-5 RC2dgroups, wherein each RC2dis independently selected from the group consisting of oxo, halogen, C1-C6alkyl, -CN, -OR5, -C(O)R5, -C(O)OR5, and -S(O)2R5. In some embodiments, RC2is 3- to 12-membered partially unsaturated heterocyclyl substituted by 1-5 RC2dgroups, such that the atom of the 3- to 12-membered partially unsaturated heterocyclyl that is bonded to the –C(O) is a carbon, and wherein each RC2dis independently selected from the group consisting of oxo and C1-C6alkyl. In another aspect of the foregoing embodiment, RC2is 4- to 6-membered partially unsaturated heterocyclyl substituted by 1-5 RC2dgroups, wherein at least one of the RC2dgroups is halogen (e.g., fluoro). In some embodiments, RC2is 4- to 10-membered partially unsaturated heterocyclyl substituted by 1-5 RC2dgroups, and wherein at least one RC2dgroup is oxo. In another aspect of the foregoing embodiment, RC2is 4- to 6- membered partially unsaturated heterocyclyl substituted by 1-5 RC2dgroups, wherein at least one of the RC2dgroups is C1-C6alkyl, wherein the C1-C6alkyl of RC2dis optionally substituted by 1-5 R4agroups. In another aspect of the foregoing embodiment, RC2dis C1-C2alkyl substituted by 1-5 R4agroups, wherein each R4agroups is independently selected from halogen, phenyl, 6-membered heteroaryl, and -NR8C(O)OR10(e.g. –NHC(O)O-t-butyl), wherein the phenyl and 6-membered heteroaryl of R4aare each independently substituted by 0-5 halogen (e.g., R4ais unsubstituted phenyl, unsubstituted pyridinyl, or unsubstituted pyrimidinyl). In another aspect of the foregoing embodiment, RC2is 4- to 6-membered partially unsaturated heterocyclyl (e.g., 4-membered heterocyclyl, such as oxetanyl) substituted by 1-5 RC2dgroups, wherein at least one of the RC2cgroups is oxo.

[0241] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RC2is selected from the group consisting of:, wherein RC2dare each defined as Formula (I) and can be on any of the annular atoms, and wherein n is 0, 1, 2, or 3.

[0242] Also provided in another embodiment is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RC2is C6-C12aryl optionally substituted by 1-5 RC2agroups. In another aspect of the foregoing embodiment, the C6-C12aryl of RC2is monocyclic (e.g., phenyl). In another aspect of the foregoing embodiment, the C6-C12aryl of RC2is bicyclic (e.g., naphthalenyl). In another aspect of the foregoing embodiment, RC2is unsubstituted C6-C12aryl (e.g., unsubstitutedphenyl). In some embodiments, RC2is unsubstituted phenyl. In another aspect of the foregoing embodiment, RC2is C6-C12aryl substituted by 1-5 RC2agroups, wherein each RC2agroup is independently selected from the group consisting of halogen, C1-C6alkyl, C6-C14aryl, 5- to 10- membered heteroaryl, -CN, -OR5, -C(O)R5, -C(O)OR5, -S(O)2R5, and -S(O)2OH, and wherein the C1- C6alkyl, C6-C14aryl, and 5- to 10-membered heteroaryl are independently substituted by 0-5 R4a. In some embodiments, RC2is C6-C12aryl substituted by 1-5 RC2agroups, wherein each RC2agroup is independently selected from the group consisting of halogen, C1-C6alkyl, 5- to 10-membered heteroaryl, -CN, -OR5, -S(O)2R5, and -S(O)2OH, and wherein the C1-C6alkyl and 5- to 10-membered heteroaryl are independently and optionally substituted by 1-5 R4a. In another aspect of the foregoing embodiment, RC2is C6-C12aryl substituted by 1-5 RC2agroups, and wherein at least one RC2agroup is halogen or -CN. In another aspect of the foregoing embodiment, RC2is C6-C12aryl substituted by 1-5 RC2agroups, and wherein at least one RC2agroup is C1-C6alkyl substituted by 0-5 halogen. In some embodiments, RC2is C6-C12aryl substituted by 1-5 RC2agroups, wherein at least one RC2agroup is C1- C6alkyl, and wherein the C1-C6alkyl of RC2ais optionally substituted by 1-5 halogen. In another aspect of the foregoing embodiment, RC2is phenyl substituted by 1-5 RC2agroups, wherein at least one RC2agroup is C1-C6alkyl, and wherein the C1-C6alkyl is substituted by 1-5 halogen. In some embodiments, RC2is phenyl substituted by 1-5 RC2agroup, wherein at least one RC2agroup is -CF3. In another aspect of the foregoing embodiment, RC2is phenyl substituted by at least one -CF3. In another aspect of the foregoing embodiment, RC2is phenyl substituted by 1-5 RC2agroups, wherein at least one RC2agroup is -OR5, and wherein R5is C1-C6alkyl substituted with 0-5 halogen. In some embodiments, RC2is phenyl substituted by 1-5 RC2agroups, wherein at least one RC2agroup is -OR5, and wherein R5is C1-C6alkyl optionally substituted with 1-5 R5agroups, wherein at least one R5agroup is halogen or - O-C1-C6alkyl. In some embodiments, R5is unsubstituted C1-C3alkyl. In another aspect of the foregoing embodiment, RC2is phenyl substituted by 1-5 RC2agroups, wherein at least one RC2agroup is -OR5, and wherein R5is unsubstituted C1-C3alkyl. In another aspect of the foregoing embodiment, RC2is C6-C12aryl substituted by 2-5 RC2agroups, wherein at least one RC2agroup is C1-C6alkyl optionally substituted by 1-5 halogen, and wherein at least one RC2agroup is selected from the group consisting of halogen, -CN, and -OR5. In another aspect of the foregoing embodiment, RC2is C6-C12aryl substituted by 1-5 RC2agroups, and wherein at least one RC2agroup is 5- to 10-membered heteroaryl optionally substituted by 1-5 C1-C6alkyl.

[0243] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RC2is selected from the group consisting of:, wherein RC2ais as defined for formula (I), and n is 0, 1, 2, or 3. In one variation, n is 0. In another variation, n is 1. In another variation, n is 2. In yet another variation, n is 3.

[0244] Also provided in another embodiment is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RC2is 5- to 12-membered heteroaryl optionally substituted by 1-5 RC2bgroups. In another aspect of the foregoing embodiment, the 5- to 12-membered heteroaryl of RC2is monocyclic (e.g., pyridyl, pyridazinyl, pyrimidinyl, and pyrazinyl). In another aspect of the foregoing embodiment, the 5- to 12-membered heteroaryl of RC2is bicyclic (e.g., indazole). In another aspect of the foregoing embodiment, the 5- to 12-membered heteroaryl of RC2has one heteroatom selected from N, O, and S. In another aspect of the foregoing embodiment, the 5- to 12-membered heteroaryl of RC2has two heteroatoms selected from N, O, and S. In another aspect of the foregoing embodiment, the 5- to 12-membered heteroaryl of RC2has three heteroatoms selected from N, O, and S. In another aspect of the foregoing embodiment, RC2is unsubstituted 5- to 12-membered heteroaryl (e.g., unsubstituted pyridyl). In some embodiments, RC2is unsubstituted pyridyl. In another aspect of the foregoing embodiment, RC2is 5- to 12-membered heteroaryl substituted by 1-5 RC2bgroups, wherein each RC2bgroup is independently selected from the group consisting of halogen, C1-C6alkyl, -CN, -OR5, -C(O)R5, -C(O)OR5, and -S(O)2R5, and wherein the C1-C6alkyl is independently substituted by 0-5 R4a. In some embodiments, RC2is 5- to 12-membered heteroaryl substituted by 1-5 RC2bgroups, wherein each RC2bgroup is independently selected from the group consisting of halogen, C1-C6alkyl, and -OR5, and wherein the C1-C6alkyl is independently and optionally substituted by 1-5 R4a. In another aspect of the foregoing embodiment, RC2is C6-C12aryl substituted by 1-5 RC2agroups, and wherein at least one RC2agroup is halogen or -CN. In another aspect of the foregoing embodiment, RC2is 5- to 12-membered heteroaryl substituted by 1-5 RC2bgroups, and wherein at least one RC2bgroup is halogen. In another aspect of the foregoing embodiment, RC2is 5- to 12-membered heteroaryl substituted by 1-5 RC2bgroups, and wherein at least one RC2bgroup is C1-C6alkyl optionally substituted by 1-5 halogen. In another aspect of the foregoing embodiment, RC2is pyridyl substituted by 1-5 RC2bgroups, and wherein at least one RC2bgroup is C1-C6alkyl substituted by 0-5 halogen. In some embodiments, RC2is pyridyl substituted by 1-5 RC2bgroups, and wherein at least one RC2bgroup is C1-C6alkyl optionally substituted by 1-5 halogen. In another aspect of the foregoing embodiment, RC2is pyridyl substituted by 1-5 RC2bgroups, and wherein at least one RC2bgroup is -CF3. In another aspect of the foregoing embodiment, RC2is 5- to 12-membered heteroaryl substituted by 1-5 RC2bgroups, and wherein at least one RC2bgroup is -OR5, and wherein R5is C1-C6alkyl substituted with 0- 5 halogen. In another aspect of the foregoing embodiment, RC2is 5- to 12-membered heteroaryl substituted by 2-5 RC2bgroups, wherein at least one RC2bgroup is C1-C6alkyl substituted by 0-5 halogen, and wherein at least one RC2bgroup is selected from the group consisting of halogen, -CN, and -OR5. In another aspect of the foregoing embodiment, RC2is 5- to 12-membered heteroaryl substituted by 2-5 RC2bgroups, wherein at least one RC2bgroup is C1-C6alkyl substituted by 0-5 halogen, and wherein at least one RC2bgroup is halogen.

[0245] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RC2is selected from the group consisting of:, wherein RC2bare each defined as Formula (I) and can be on any of the annular atoms, and n is 0, 1, 2, or 3. In one variation, n is 0. In another variation, n is 1. In another variation, n is 2. In yet another variation, n is 3. In the above structures that depict an -N(H)- moiety, it is understood that one of the RC2bgroups can replace the hydrogen atom of the -N(H)- moiety (e.g., n is

[0246] Also provided in another embodiment is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RC2is 3- to 12-membered fully saturated heterocyclyl substituted by 1-5 RC2hgroups, such that the atom of the 3- to 12-membered fully saturated heterocyclyl that is bonded to the –C(O) is a carbon. In another aspect of the foregoing embodiment, the 3- to 12- membered fully saturated heterocyclyl of RC2is monocyclic. In another aspect of the foregoing embodiment, the 3- to 12-membered fully saturated heterocyclyl of RC2is bicyclic (e.g., fused, spiro, or bridged). In another aspect of the foregoing embodiment, RC2is 3- to 12-membered fully saturated heterocyclyl substituted by 1-5 RC2hgroups, wherein at least one RC2hgroup is 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl, wherein the 3- to 12- membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl of RC2hare independently optionally substituted by one or more R4a; and each of the other RC2hgroups, when present, is independently oxo or R4. In another aspect of the foregoing embodiment, RC2is 3- to 12- membered fully saturated heterocyclyl substituted by 1-5 RC2hgroups, wherein at least one RC2hgroupis C6-C14aryl optionally substituted by one or more R4a; and each of the other RC2hgroups, when present, is independently oxo or R4. In another aspect of the foregoing embodiment, RC2is 3- to 12- membered fully saturated heterocyclyl substituted by 1-5 RC2hgroups, wherein at least one RC2hgroup is phenyl.

[0247] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RC2is selected from the group consisting of:, , , , ,defined for formula (I), and n is 1, 2, or 3. In one variation, n is 1. In another variation, n is 2. In yet another variation, n is 3. In the above structures that depict an -N(H)- moiety, it is understood that one of the RC2hgroups can replace the hydrogen atom of the -N(H)- moiety

[0248] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof,

[0249] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein RC2is selected from the group consisting of:

[0250] Also provided in another embodiment is a compound of formula (I), or a salt thereof, wherein R2is RD2. In one aspect of the foregoing embodiment, RD2is -NRD3(C1-C6alkyl) substituted by 0-5 RD2agroups. In one aspect of the foregoing embodiment, RD2is -NRD3(unsubstituted C1-C6alkyl) (e.g., unsubstituted C4-C6alkyl). In one aspect of the foregoing embodiment, the C1-C6alkyl of -NRD3(C1-C6alkyl) of RD2is straight-chain alkyl (e.g., n-butyl). In another aspect of the foregoing embodiment, the C1-C6alkyl of -NRD3(C1-C6alkyl) of RD2is branched alkyl (e.g., iso- butyl). In another aspect of the foregoing embodiment, RD2is -NRD3(C1-C5alkyl) wherein the C1-C5alkyl of -NRD3(C1-C5alkyl) is substituted by 1-5 RD2agroups, wherein each RD2ais independently selected from halogen, C1-C6alkyl, C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, 5- to 10-membered heteroaryl, -CN, -OR5, -NR6R7, -NR5C(O)OR6, and -S(O)2R5, wherein the C1-C6alkyl, C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, and 5- to 10- membered heteroaryl of RD2aare independently optionally substituted by R4a. In another aspect of the foregoing embodiment, RD2is -NRD3(C1-C5alkyl) wherein the C1-C5alkyl of -NRD3(C1-C5alkyl) is substituted by 1-5 RD2agroups, wherein at least one of the RD2agroups is halogen (e.g., RD2is C4-C5alkyl substituted by 2-3 fluoro groups). In another aspect of the foregoing embodiment, RD2is - NRD3(C1-C5alkyl) wherein the C1-C5alkyl of -NRD3(C1-C5alkyl) is substituted by 1-5 RD2agroups, wherein at least one of the RD2agroups is C3-C8cycloalkyl (e.g., cyclopropyl, cyclobutyl, and cyclohexyl). In another aspect of the foregoing embodiment, RD2is -NRD3(C1-C3alkyl) wherein the C1-C3alkyl of -NRD3(C1-C3alkyl) is substituted by C3-C6cycloalkyl, wherein the C3-C6cycloalkyl is substituted by 0-5 groups selected from the group consisting of halogen (e.g., fluoro), C1-C6alkyl (e.g., -CH3), and -OR5(e.g., -OH and –OCH3). In another aspect of the foregoing embodiment, RD2is -NRD3(C1-C3alkyl) wherein the C1-C3alkyl of -NRD3(C1-C3alkyl) is substituted by C3-C6cycloalkyl, wherein the C3-C6cycloalkyl is unsubstituted (e.g., RD2is -NRD3(C1alkyl) substituted by cyclobutyl, wherein the cyclobutyl is unsubstituted or RD2is -NRD3(C1alkyl) substituted by cyclohexyl, wherein the cyclohexyl is unsubstituted). In another aspect of the foregoing embodiment, RD2is - NRD3(C1-C3alkyl) wherein the C1-C3alkyl of -NRD3(C1-C3alkyl) is substituted by C3-C6cycloalkyl, wherein the C3-C6cycloalkyl is substituted by 1-2 C1-C3alkyl groups (e.g., RD2is -NRD3(C1alkyl) substituted by cyclopropyl, wherein the cyclopropyl is substituted by one –CH3group or RD2is -NRD3(C1alkyl) substituted by cyclohexyl, wherein the cyclohexyl is substituted by two –CH3groups). In another aspect of the foregoing embodiment, RD2is -NRD3(C1-C5alkyl) wherein the C1-C5alkyl of - NRD3(C1-C5alkyl) is substituted by 1-5 RD2agroups, wherein at least one of the RD2agroups is 3- to 12-membered heterocyclyl (e.g. RD2is -NRD3(C1alkyl) substituted by 6-membered heterocyclyl, such as tetrahydro-2H-pyranyl). In another aspect of the foregoing embodiment, RD2is -NRD3(C1-C5alkyl) wherein the C1-C5alkyl of -NRD3(C1-C5alkyl) is substituted by 1-5 RD2agroups, wherein at least one of the RD2agroups is C6-C14aryl, wherein the C6-C14aryl is independently substituted by 0-5 R4agroups. In another aspect of the foregoing embodiment, RD2is -NRD3(C1-C4alkyl) wherein the C1-C4alkyl of -NRD3(C1-C4alkyl) is substituted by phenyl, wherein the phenyl is unsubstituted. In another aspect of the foregoing embodiment, RD2is -NRD3(C1-C4alkyl) (e.g., C1-C3alkyl) wherein the C1-C4alkyl of -NRD3(C1-C4alkyl) is substituted by RD2a, wherein RD2ais phenyl substituted by 1-5 R4agroups, wherein at least one R4agroup is selected from halogen and C1-C6alkyl substituted by 0-5 halogen (e.g., RD2ais phenyl substituted by one fluoro group). In another aspect of the foregoing embodiment, RD2is -NRD3(C1-C4alkyl) (e.g., C1-C3alkyl) wherein the C1-C4alkyl of - NRD3(C1-C4alkyl) is substituted by RD2a, wherein RD2ais phenyl substituted by 2-5 R4agroups, wherein at least two R4agroups are halogen (e.g., RD2ais phenyl substituted by two fluoro groups or RD2ais phenyl substituted by one fluoro group and one chloro group). In another aspect of the foregoing embodiment, RD2is -NRD3(C1-C4alkyl) (e.g., C1-C3alkyl) wherein the C1-C4alkyl of - NRD3(C1-C4alkyl) is substituted by RD2a, wherein RD2ais phenyl substituted by 2-5 R4agroups, wherein at least one R4agroup is halogen and at least one R4agroup is C1-C6alkyl substituted by 0-5 halogen (e.g., RD2ais phenyl substituted by one fluoro group and one –CF3group). In another aspect of the foregoing embodiment, RD2is -NRD3(C1-C5alkyl) (e.g., C1-C3alkyl) wherein the C1-C5alkyl of -NRD3(C1-C5alkyl) is substituted by 1-5 RD2agroups, wherein at least one of the RD2agroups is 5- to 10-membered heteroaryl, wherein the 5- to 10-membered heteroaryl is substituted by substituted by 0- 5 R4agroups (e.g., RD2ais unsubstituted pyridinyl). In another aspect of the foregoing embodiment, RD2is -NRD3(C1-C5alkyl) (e.g., C1-C3alkyl) wherein the C1-C5alkyl of -NRD3(C1-C5alkyl) is substituted by 1-5 RD2agroups, wherein at least one of the RD2agroups is -OR5, wherein each R5is independently selected from hydrogen, C1-C6alkyl, and C6-C14aryl (e.g., R5is C6-C14aryl substituted by 0-5 halogen). In another aspect of the foregoing embodiment, RD2is -NRD3(C1-C5alkyl) wherein the C1-C5alkyl of -NRD3(C1-C5alkyl) is substituted by -OR5, wherein R5is hydrogen or C1-C3alkyl (e.g., R5is –CH3or isopropyl). In another aspect of the foregoing embodiment, RD2is - NRD3(C1-C2alkyl) wherein the C1-C2alkyl of -NRD3(C1-C2alkyl) is substituted by -OR5, wherein R5is C6-C14aryl (e.g., phenyl) substituted by 0-5 halogen (e.g., R5is phenyl substituted by two fluoro groups). In another aspect of the foregoing embodiment, RD2is -NRD3(C1-C5alkyl) wherein the C1-C5alkyl of -NRD3(C1-C5alkyl) is substituted by 1-5 RD2agroups, wherein at least one of the RD2agroups is -CN, -NR6R7, -NR5C(O)OR6, or -S(O)2R5(e.g., RD2ais –CN, -NH2, or -NHC(O)OCH3). In another aspect of the foregoing embodiment, RD2is -NRD3(C1-C5alkyl) wherein the C1-C5alkyl of -NRD3(C1-C5alkyl) is substituted by 2-5 RD2agroups, wherein each RD2ais independently selected from halogen, C1-C6alkyl, C3-C8cycloalkyl, 5- to 10-membered heteroaryl, C6-C14aryl, -CN, -OR5, and -NR5C(O)OR6. In another aspect of the foregoing embodiment, RD2is -NRD3(C1-C5alkyl) (e.g., C1-C3alkyl) wherein the C1-C5alkyl of -NRD3(C1-C5alkyl) is substituted by 2-5 RD2agroups, wherein at least one RD2agroup is phenyl substituted by 0-5 halogen (e.g., RD2ais unsubstituted phenyl, RD2ais phenyl substituted by one fluoro group, or RD2ais phenyl substituted by one chloro group) and at least one RD2agroup is –OR5, wherein each R5is independently selected from hydrogen and C1-C6alkyl (e.g., RD2ais –OH or –OCH3). In another aspect of the foregoing embodiment, RD2is - NRD3(C1-C5alkyl) (e.g., C1-C3alkyl) wherein the C1-C5alkyl of -NRD3(C1-C5alkyl) is substituted by 2-5 RD2agroups, wherein at least one RD2agroup is phenyl substituted by 0-5 halogen (e.g., RD2ais unsubstituted phenyl or RD2ais phenyl substituted by one fluoro group) and at least one RD2agroup is halogen (e.g., RD2ais fluoro). In another aspect of the foregoing embodiment, RD2is - NRD3(C1-C5alkyl) (e.g., C1-C4alkyl, such as isobutyl) wherein the C1-C5alkyl of -NRD3(C1-C5alkyl) is substituted by 2-5 RD2agroups, wherein at least one RD2agroup is halogen (e.g., RD2ais fluoro) and at least one RD2agroup is –OR5, wherein each R5is independently selected from hydrogen and C1-C6alkyl (e.g., RD2ais –OH). In another aspect of the foregoing embodiment, RD2is -NRD3(C1-C5alkyl) (e.g., C1alkyl) wherein the C1-C5alkyl of -NRD3(C1-C5alkyl) is substituted by 2-5 RD2agroups, wherein at least one RD2agroup is C3-C6cycloalkyl (e.g., RD2ais cyclohexyl) and at least one RD2agroup is –OR5, wherein each R5is independently selected from hydrogen and C1-C6alkyl (e.g., RD2ais –OH or –OCH3).

[0251] Also provided is a compound of formula (I), or a salt thereof, wherein RD2is - NRD3(C1-C6alkyl) substituted by RD2a, and the C1-C6alkyl of -NRD3(C1-C6alkyl) is selected from the group consisting of:, wherein each RD2ais independently as defined for formula (I).

[0252] Also provided is a compound of formula (I), or a salt thereof, wherein RD2is - NRD3(C1-C6alkyl) substituted by RD2a, and the C1-C6alkyl of -NRD3(C1-C6alkyl) iswherein each RD2ais C4-C5alkyl or C3-C6cycloalkyl, wherein the C3-C6cycloalkyl of RD2ais optionally substituted by C1-C3alkyl.

[0253] Also provided is a compound of formula (I), or a salt thereof, wherein RD2is - NRD3(C1-C6alkyl) optionally substituted by RD2a, and the C1-C6alkyl optionally substituted by RD2aisselected from the group consisting of:, , , , , , ,

[0254] Also provided in another embodiment is a compound of formula (I), or a salt thereof, wherein RD2is -NRD3(C3-C8cycloalkyl) wherein the C3-C8cycloalkyl of -NRD3(C3-C8cycloalkyl) is substituted by 0-5 RD2bgroups. In another aspect of the foregoing embodiment, the C3-C8cycloalkyl of -NRD3(C3-C8cycloalkyl) of RD2is monocyclic. In another aspect, the C3-C8cycloalkyl of - NRD3(C3-C8cycloalkyl) of RD2is bicyclic (e.g., fused, spiro, or bridged). In another aspect, RD2is - NRD3(unsubstituted C3-C8cycloalkyl) (e.g., cyclopropyl, cyclobutyl, cyclohexyl, and spiro[2.5]octanyl). In another aspect of the foregoing embodiment, RD2is -NRD3(C3-C8cycloalkyl) wherein the C3-C8cycloalkyl of -NRD3(C3-C8cycloalkyl) is substituted by 1-5 RD2bgroups, wherein each RD2bis independently selected from halogen, C1-C6alkyl, 3- to 12-membered heterocyclyl, C6- C14aryl, 5- to 10-membered heteroaryl, and -OR5, wherein the C1-C6alkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of RD2bare substituted by 0-5 R4agroups. In another aspect of the foregoing embodiment, RD2is -NRD3(C3-C6cycloalkyl) (e.g., cyclopropyl or cyclohexyl) wherein the C3-C6cycloalkyl of -NRD3(C3-C6cycloalkyl) is substituted by 1-5 RD2bgroups, wherein at least one of the RD2bgroups is halogen (e.g., fluoro). In another aspect of the foregoing embodiment, RD2is -NRD3(C3-C6cycloalkyl) wherein the C3-C6cycloalkyl of - NRD3(C3-C6cycloalkyl) is substituted by 1-5 RD2bgroups, wherein at least one of the RD2bgroups is C1-C6alkyl, wherein the C1-C6alkyl of RD2bis substituted by 0-5 R4agroups (e.g., RD2bis C1-C2alkyl substituted by 1-5 R4agroups, wherein each R4agroups is independently selected from phenyl substituted by 0-5 halogen and 6-membered heteroaryl substituted by 0-5 halogen). In another aspect of the foregoing embodiment, RD2is -NRD3(C3-C6cycloalkyl) wherein the C3-C6cycloalkyl of - NRD3(C3-C6cycloalkyl) is substituted by 1-5 RD2bgroups, wherein at least one of the RD2bgroups is C1-C3alkyl (e.g., RD2is cyclohexyl substituted by two –CH3groups). In another aspect of the foregoing embodiment, RD2is -NRD3(C3-C6cycloalkyl) wherein the C3-C6cycloalkyl of - NRD3(C3-C6cycloalkyl) is substituted by 1-5 RD2bgroups, wherein at least one of the RD2bgroups is 3- to 12-membered heterocyclyl (e.g., tetrahydro-2H-pyranyl or benzodioxolyl). In another aspect of the foregoing embodiment, RD2is -NRD3(C3-C4cycloalkyl) wherein the C3-C4cycloalkyl of - NRD3(C3-C4cycloalkyl) is substituted by 1-5 RD2bgroups, wherein at least one of the RD2bgroups is C6-C14aryl (e.g., phenyl) substituted by 0-5 R4agroups, wherein each R4ais independently selected from halogen, C1-C6alkyl, and -OR8(e.g., RD2bis unsubstituted phenyl or RD2bis phenyl substituted by fluoro, methyl, tert-butyl, or –OCF3). In another aspect of the foregoing embodiment, RD2is -NRD3(C3-C7cycloalkyl) wherein the C3-C7cycloalkyl of -NRD3(C3-C7cycloalkyl) is substituted by 1-5 RD2bgroups, wherein at least one of the RD2bgroups is 5- to 10-membered heteroaryl (e.g., pyridinyl or isoquinolinyl). In another aspect of the foregoing embodiment, RD2is -NRD3(C3-C6cycloalkyl) wherein the C3-C6cycloalkyl of -NRD3(C3-C6cycloalkyl) is substituted by 2-5 RD2bgroups, wherein each RD2bis independently selected from halogen (e.g., fluoro), C1-C6alkyl, C6-C14aryl (e.g., phenyl), and -OR5(e.g., -OH). In another aspect of the foregoing embodiment, RD2is -NRD3(C3-C6cycloalkyl) wherein the C3-C6cycloalkyl of -NRD3(C3-C6cycloalkyl) is substituted by 2-5 RD2bgroups, wherein at least one RD2bgroup is halogen (e.g., fluoro) and at least one RD2bgroup is phenyl substituted by 0-5 C1-C6alkyl (e.g., -CH3). In another aspect of the foregoing embodiment, RD2is - NRD3(C3-C6cycloalkyl) (e.g., cyclobutyl) wherein the C3-C6cycloalkyl of -NRD3(C3-C6cycloalkyl) is substituted by 2-5 RD2bgroups, wherein at least one RD2bgroup is -OH and at least one RD2bgroup is phenyl.

[0255] Also provided is a compound of formula (I), or a salt thereof, wherein RD2is - NRD3(C3-C8cycloalkyl) optionally substituted by RD2band the C3-C8cycloalkyl optionally substituted by RD2bis selected from the group consisting of:wherein RD2bis as defined for formula (I), and n is 0, 1, 2, or 3. In one variation, n is 0. In another variation, n is 1. In another variation, n is 2. In yet another variation, n is 3.

[0256] Also provided in another embodiment is a compound of formula (I), or a salt thereof, wherein RD2is -NRD3(3- to 12-membered heterocyclyl) such that a carbon atom of the 3- to 12- membered saturated heterocyclyl of -NRD3(3- to 12-membered saturated heterocyclyl) is bonded to the N of -NRD3, wherein the 3- to 12-membered heterocyclyl of -NRD3(3- to 12-membered heterocyclyl) is substituted by 0-5 RD2cgroups. In another aspect of the foregoing embodiment, the 3- to 12-membered heterocyclyl of -NRD3(3- to 12-membered heterocyclyl) of RD2is monocyclic. In another aspect of the foregoing embodiment, the 3- to 12-membered heterocyclyl of -NRD3(3- to 12- membered heterocyclyl) of RD2is bicyclic (e.g., fused, spiro, or bridged). In another aspect of the foregoing embodiment, RD2is -NRD3(unsubstituted 4- to 10-membered heterocyclyl) (e.g., pyrrolidinyl, tetrahydropyranyl, or morpholinyl). In another aspect of the foregoing embodiment, RD2is -NRD3(3- to 12-membered heterocyclyl) wherein the 3- to 12-membered heterocyclyl of -NRD3(3- to 12-membered heterocyclyl) is substituted by 1-5 RD2cgroups, wherein each RD2cis independently selected from oxo, halogen, C1-C6alkyl, C6-C14aryl, 5- to 10-membered heteroaryl, -CN, -OR5, -C(O)R5, -C(O)OR5, and -S(O)2R5. In another aspect of the foregoing embodiment, RD2is -NRD3(4- to 6-membered heterocyclyl) wherein the 4- to 6-membered heterocyclyl of -NRD3(4- to 6-membered heterocyclyl) is substituted by 1-5 RD2cgroups, wherein at least one of the RD2cgroups is halogen (e.g., fluoro). In another aspect of the foregoing embodiment, RD2is -NRD3(4- to 6-memberedheterocyclyl) (e.g., oxetanyl, pyrrolidinyl, tetrahydropyranyl, or azetidinyl) wherein the 4- to 6- membered heterocyclyl of -NRD3(4- to 6-membered heterocyclyl) is substituted by 1-5 RD2cgroups, wherein at least one of the RD2cgroups is C1-C6alkyl, wherein the C1-C6alkyl of RD2cis substituted by 0-5 R4agroups. In another aspect of the foregoing embodiment, RD2cis C1-C2alkyl substituted by 1-5 R4agroups, wherein each R4agroups is independently selected from halogen, phenyl 6-membered heteroaryl, and -NR8C(O)OR10(e.g. –NHC(O)O-t-butyl), wherein the phenyl and 6-membered heteroaryl of R4aare each independently substituted by 0-5 halogen (e.g., R4ais unsubstituted phenyl, unsubstituted pyridinyl, or unsubstituted pyrimidinyl). In another aspect of the foregoing embodiment, RD2is -NRD3(4- to 6-membered heterocyclyl) (e.g., 4-membered heterocyclyl, such as oxetanyl) wherein the 4- to 6-membered heterocyclyl of -NRD3(4- to 6-membered heterocyclyl) is substituted by 1-5 RD2cgroups, wherein at least one of the RD2cgroups is unsubstituted C6-C14aryl (e.g., C6- C10aryl, such as phenyl). In another aspect of the foregoing embodiment, RD2is -NRD3(4- to 6- membered heterocyclyl) (e.g., 5-membered heterocyclyl) wherein the 4- to 6-membered heterocyclyl of -NRD3(4- to 6-membered heterocyclyl) is substituted by 1-5 RD2cgroups, wherein at least one of the RD2cgroups is 5- to 10-membered heteroaryl substituted by 0-5 C1-C6alkyl (e.g., RD2cis pyrazolyl substituted by –CH3). In another aspect of the foregoing embodiment, RD2is -NRD3(4- to 6-membered heterocyclyl) (e.g., 5- to 6-membered heterocyclyl, such as pyrrolidinyl or piperidinyl) wherein the 4- to 6-membered heterocyclyl of -NRD3(4- to 6-membered heterocyclyl) is substituted by 1-5 RD2cgroups, wherein at least one RD2cgroup is -OR5, -C(O)R5, or -C(O)OR5, wherein each R5is independently hydrogen or C1-C6alkyl (e.g., RD2cis –OH, -C(O)(CH2)3CH3, or -C(O)OCH3). In another aspect of the foregoing embodiment, RD2is -NRD3(4- to 6-membered heterocyclyl) (e.g., 1,2- dihydropyridinyl) wherein the 4- to 6-membered heterocyclyl of -NRD3(4- to 6-membered heterocyclyl) is substituted by 1-5 RD2cgroups, wherein at least one RD2cgroup is oxo. In another aspect of the foregoing embodiment, RD2is -NRD3(4- to 6-membered heterocyclyl) (e.g., 6-membered heterocyclyl, such as piperidinyl) wherein the 4- to 6-membered heterocyclyl of -NRD3(4- to 6- membered heterocyclyl) is substituted by 2-5 RD2cgroups, wherein each RD2cis independently selected from halogen, C1-C6alkyl, -C(O)R5, and -C(O)OR5, wherein each R5is independently C1-C6alkyl (e.g., RD2cis independently selected from fluoro and –C(O)O-tert-butyl). In another aspect of the foregoing embodiment, RD2is -NRD3(4- to 6-membered heterocyclyl) wherein the 4- to 6-membered heterocyclyl of -NRD3(4- to 6-membered heterocyclyl) is substituted by 2-5 RD2cgroups, wherein at least one RD2cgroup is C1-C6alkyl substituted by 0-5 halogen and at least one RD2cgroup is -C(O)R5or -C(O)OR5(e.g., RD2cis independently selected from –CF3, -C(O)CH3, and –C(O)O-tert-butyl). In another aspect of the foregoing embodiment, the 3- to 12-membered heterocyclyl of -NRD3(3- to 12- membered heterocyclyl) of RD2is azetidinyl, pyrrolidinyl, piperidinyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxabicyclohexanyl, oxabicyclooctanyl, tetrahydro-2H-thiopyranyl, morpholinyl, or benzodioxanyl, each of which is independently substituted by 0-5 RD2cgroups.

[0257] Also provided is a compound of formula (I), or a salt thereof, wherein RD2is -NRD3(3- to 12-membered saturated heterocyclyl) and the 3- to 12-membered saturated heterocyclyl optionallywherein RD2cis as defined for formula (I), and n is 0, 1, 2, or 3. In one variation, n is 0. In another variation, n is 1. In another variation, n is 2. In yet another variation, n is 3. In the above structures that depict an -N(H)- moiety and n is 1, 2, or 3, it is understood that one of the RD2cgroups can replace the hydrogen atom of the -N(H)- moiety (e.g., n is 1 and the 3- to 12-membered saturated heterocyclyl of -NRD3(3- to 12-membered saturated heterocyclyl)

[0258] In embodiment is a compound of formula (I), or a salt thereof, RD3is hydrogen, deuterium, C1-C6alkyl optionally substituted by one or more RD3a, or C3-C8cycloalkyl optionally substituted by one or more RD3b. In one embodiment, RD3is hydrogen. In one embodiment, RD3is unsubstituted C1- C6alkyl. In one embodiment, RD3is methyl, ethyl, propyl, isopropyl, isobutyl, or tert-butyl. In one embodiment, RD3is unsubstituted C3-C8cycloalkyl. In one embodiment, RD3is cyclopropyl, cyclobutyl, or cyclopentyl. In one embodiment, RD3is cyclobutyl. In one embodiment, RD3is selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, isobutyl, and cyclobutyl.

[0259] Also provided in another embodiment is a compound of formula (I), or a salt thereof, wherein RD2is 3- to 12-membered N-containing saturated or partially saturated heterocyclyl substituted by 0-5 RD2dgroups, such that a nitrogen atom of the 3- to 12-membered N-containing saturated or partially saturated heterocyclyl is bonded to the carbon of -C(O)-. In another aspect of the foregoing embodiment, 3- to 12-membered N-containing saturated or partially saturated heterocyclyl of RD2is monocyclic. In another aspect of the foregoing embodiment, 3- to 12-membered N- containing saturated or partially saturated heterocyclyl of RD2is bicyclic (e.g., fused, spiro, or bridged). In another aspect of the foregoing embodiment, 3- to 12-membered N-containing saturated or partially saturated heterocyclyl of RD2is unsubstituted. In another aspect of the foregoing embodiment, RD2is 3- to 12-membered N-containing saturated or partially saturated heterocyclyl substituted by 1-5 RD2dgroups, wherein each RD2dis independently selected from oxo, halogen, C1- C6alkyl, C6-C14aryl, 5- to 10-membered heteroaryl, -CN, -OR5, -C(O)R5, -C(O)OR5, and -S(O)2R5. In another aspect of the foregoing embodiment, RD2is 4- to 8-membered N-containing saturated or partially saturated heterocyclyl substituted by 1-5 RD2dgroups, wherein at least one of the RD2dgroups is halogen (e.g., fluoro). In another aspect of the foregoing embodiment, RD2is 4- to 6-membered N- containing saturated heterocyclyl (e.g., oxetanyl, pyrrolidinyl, tetrahydropyranyl, or azetidinyl)substituted by 1-5 RD2dgroups, wherein at least one of the RD2dgroups is C1-C6alkyl, wherein the C1- C6alkyl of RD2dis substituted by 0-5 R4agroups. In another aspect of the foregoing embodiment, RD2dis C1-C2alkyl substituted by 1-5 R4agroups, wherein each R4agroups is independently selected from halogen, phenyl 6-membered heteroaryl, and -NR8C(O)OR10(e.g. –NHC(O)O-t-butyl), wherein the phenyl and 6-membered heteroaryl of R4aare each independently substituted by 0-5 halogen (e.g., R4ais unsubstituted phenyl, unsubstituted pyridinyl, or unsubstituted pyrimidinyl).

[0260] Also provided is a compound of formula (I), or a salt thereof, wherein RD2is 3- to 12- membered N-containing saturated or partially saturated heterocyclyl substituted by 0-5 RD2dgroups, and the 3- to 12-membered N-containing saturated or partially saturated heterocyclyl is selected fromis 0, 1, 2, or 3. In one variation, n is 0. In another variation, n is 1. In another variation, n is 2. In yet another variation, n is 3.

[0261] Also provided is a compound of formula (I), or a salt thereof, wherein and RD2is, wherein RD2eis as defined for formula (I), and n is 0, 1, 2, or 3. In one variation, n is 0. In another variation, n is 1. In another variation, n is 2. In yet another variation, n is 3.

[0262] Also provided is a compound of formula (I), or a salt thereof, wherein RD2is selected from

[0263] Also provided in another embodiment is a compound of formula (I), or a salt thereof, wherein R2is RE2and RE2is -O(C1-C6alkyl) wherein the C1-C6alkyl of -O(C1-C6alkyl) is substituted by 0-5 RE2agroups. In one aspect of the foregoing embodiment, RE2is -O(unsubstituted C1-C6alkyl) (e.g., unsubstituted C4-C6alkyl). In one aspect of the foregoing embodiment, the C1-C6alkyl of - O(C1-C6alkyl) of RE2is straight-chain alkyl (e.g., n-butyl). In another aspect of the foregoing embodiment, the C1-C6alkyl of -O(C1-C6alkyl) of RE2is branched alkyl (e.g., iso-butyl). In another aspect of the foregoing embodiment, RE2is -O(C1-C5alkyl) wherein the C1-C5alkyl of - O(C1-C5alkyl) is substituted by 1-5 RE2agroups, wherein each RE2ais independently selected from halogen, C1-C6alkyl, C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, 5- to 10- membered heteroaryl, -CN, -OR5, -NR6R7, -NR5C(O)OR6, and -S(O)2R5, wherein the C1-C6alkyl, C3- C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of RE2aare independently optionally substituted by R4a. In another aspect of the foregoing embodiment, RE2is -O(C1-C5alkyl) wherein the C1-C5alkyl of -O(C1-C5alkyl) is substituted by 1-5 RE2agroups, whereinat least one of the RE2agroups is halogen (e.g., RE2is C4-C5alkyl substituted by 2-3 fluoro groups). In another aspect of the foregoing embodiment, RE2is -O(C1-C5alkyl) wherein the C1-C5alkyl of - O(C1-C5alkyl) is substituted by 1-5 RE2agroups, wherein at least one of the RE2agroups is C3- C8cycloalkyl (e.g., cyclopropyl, cyclobutyl, and cyclohexyl). In another aspect of the foregoing embodiment, RE2is -O(C1-C3alkyl) wherein the C1-C3alkyl of -O(C1-C3alkyl) is substituted by C3- C6cycloalkyl, wherein the C3-C6cycloalkyl is substituted by 0-5 groups selected from the group consisting of halogen (e.g., fluoro), C1-C6alkyl (e.g., -CH3), and -OR5(e.g., -OH and –OCH3). In another aspect of the foregoing embodiment, RE2is -O(C1-C3alkyl) wherein the C1-C3alkyl of - O(C1-C3alkyl) is substituted by C3-C6cycloalkyl, wherein the C3-C6cycloalkyl is unsubstituted (e.g., RE2is -O(C1alkyl) substituted by cyclobutyl, wherein the cyclobutyl is unsubstituted or RE2is -O(C1alkyl) substituted by cyclohexyl, wherein the cyclohexyl is unsubstituted). In another aspect of the foregoing embodiment, RE2is -O(C1-C3alkyl) wherein the C1-C3alkyl of -O(C1-C3alkyl) is substituted by C3-C6cycloalkyl, wherein the C3-C6cycloalkyl is substituted by 1-2 C1-C3alkyl groups (e.g., RE2is -O(C1alkyl) substituted by cyclopropyl, wherein the cyclopropyl is substituted by one – CH3group or RE2is -O(C1alkyl) substituted by cyclohexyl, wherein the cyclohexyl is substituted by two –CH3groups). In another aspect of the foregoing embodiment, RE2is -O(C1-C5alkyl) wherein the C1-C5alkyl of -O(C1-C5alkyl) is substituted by 1-5 RE2agroups, wherein at least one of the RE2agroups is 3- to 12-membered heterocyclyl (e.g. RE2is -O(C1alkyl) substituted by 6-membered heterocyclyl, such as tetrahydro-2H-pyranyl). In another aspect of the foregoing embodiment, RE2is - O(C1-C5alkyl) wherein the C1-C5alkyl of -O(C1-C5alkyl) is substituted by 1-5 RE2agroups, wherein at least one of the RE2agroups is C6-C14aryl, wherein the C6-C14aryl is independently substituted by 0-5 R4agroups. In another aspect of the foregoing embodiment, RE2is -O(C1-C4alkyl) wherein the C1-C4alkyl of -O(C1-C4alkyl) is substituted by phenyl, wherein the phenyl is unsubstituted. In another aspect of the foregoing embodiment, RE2is -O(C1-C4alkyl) (e.g., C1-C3alkyl) wherein the C1-C4alkyl of -O(C1-C4alkyl) is substituted by RE2a, wherein RE2ais phenyl substituted by 1-5 R4agroups, wherein at least one R4agroup is selected from halogen and C1-C6alkyl substituted by 0-5 halogen (e.g., RE2ais phenyl substituted by one fluoro group). In another aspect of the foregoing embodiment, RE2is -O(C1-C4alkyl) (e.g., C1-C3alkyl) wherein the C1-C4alkyl of -O(C1-C4alkyl) is substituted by RE2a, wherein RE2ais phenyl substituted by 2-5 R4agroups, wherein at least two R4agroups are halogen (e.g., RE2ais phenyl substituted by two fluoro groups or RE2ais phenyl substituted by one fluoro group and one chloro group). In another aspect of the foregoing embodiment, RE2is - O(C1-C4alkyl) (e.g., C1-C3alkyl) wherein the C1-C4alkyl of -O(C1-C4alkyl) is substituted by RE2a, wherein RE2ais phenyl substituted by 2-5 R4agroups, wherein at least one R4agroup is halogen and at least one R4agroup is C1-C6alkyl substituted by 0-5 halogen (e.g., RE2ais phenyl substituted by one fluoro group and one –CF3group). In another aspect of the foregoing embodiment, RE2is - O(C1-C5alkyl) (e.g., C1-C3alkyl) wherein the C1-C5alkyl of -O(C1-C5alkyl) is substituted by 1-5 RE2agroups, wherein at least one of the RE2agroups is 5- to 10-membered heteroaryl, wherein the 5- to 10-membered heteroaryl is substituted by substituted by 0-5 R4agroups (e.g., RE2ais unsubstituted pyridinyl). In another aspect of the foregoing embodiment, RE2is -O(C1-C5alkyl) (e.g., C1-C3alkyl) wherein the C1-C5alkyl of -O(C1-C5alkyl) is substituted by 1-5 RE2agroups, wherein at least one of the RE2agroups is -OR5, wherein each R5is independently selected from hydrogen, C1-C6alkyl, and C6-C14aryl (e.g., R5is C6-C14aryl substituted by 0-5 halogen). In another aspect of the foregoing embodiment, RE2is -O(C1-C5alkyl) wherein the C1-C5alkyl of -O(C1-C5alkyl) is substituted by -OR5, wherein R5is hydrogen or C1-C3alkyl (e.g., R5is –CH3or isopropyl). In another aspect of the foregoing embodiment, RE2is -O(C1-C2alkyl) wherein the C1-C2alkyl of -O(C1-C2alkyl) is substituted by -OR5, wherein R5is C6-C14aryl (e.g., phenyl) substituted by 0-5 halogen (e.g., R5is phenyl substituted by two fluoro groups). In another aspect of the foregoing embodiment, RE2is - O(C1-C5alkyl) wherein the C1-C5alkyl of -O(C1-C5alkyl) is substituted by 1-5 RE2agroups, wherein at least one of the RE2agroups is -CN, -NR6R7, -NR5C(O)OR6, or -S(O)2R5(e.g., RE2ais –CN, -NH2, or -NHC(O)OCH3). In another aspect of the foregoing embodiment, RE2is -O(C1-C5alkyl) wherein the C1-C5alkyl of -O(C1-C5alkyl) is substituted by 2-5 RE2agroups, wherein each RE2ais independently selected from halogen, C1-C6alkyl, C3-C8cycloalkyl, 5- to 10-membered heteroaryl, C6-C14aryl, -CN, -OR5, and -NR5C(O)OR6. In another aspect of the foregoing embodiment, RE2is - O(C1-C5alkyl) (e.g., C1-C3alkyl) wherein the C1-C5alkyl of -O(C1-C5alkyl) is substituted by 2-5 RE2agroups, wherein at least one RE2agroup is phenyl substituted by 0-5 halogen (e.g., RE2ais unsubstituted phenyl, RE2ais phenyl substituted by one fluoro group, or RE2ais phenyl substituted by one chloro group) and at least one RE2agroup is –OR5, wherein each R5is independently selected from hydrogen and C1-C6alkyl (e.g., RE2ais –OH or –OCH3). In another aspect of the foregoing embodiment, RE2is -O(C1-C5alkyl) (e.g., C1-C3alkyl) wherein the C1-C5alkyl of -O(C1-C5alkyl) is substituted by 2-5 RE2agroups, wherein at least one RE2agroup is phenyl substituted by 0-5 halogen (e.g., RE2ais unsubstituted phenyl or RE2ais phenyl substituted by one fluoro group) and at least one RE2agroup is halogen (e.g., RE2ais fluoro). In another aspect of the foregoing embodiment, RE2is - O(C1-C5alkyl) (e.g., C1-C4alkyl, such as isobutyl) wherein the C1-C5alkyl of -O(C1-C5alkyl) is substituted by 2-5 RE2agroups, wherein at least one RE2agroup is halogen (e.g., RE2ais fluoro) and at least one RE2agroup is –OR5, wherein each R5is independently selected from hydrogen and C1-C6alkyl (e.g., RE2ais –OH). In another aspect of the foregoing embodiment, RE2is -O(C1-C5alkyl) (e.g., C1alkyl) wherein the C1-C5alkyl of -O(C1-C5alkyl) is substituted by 2-5 RE2agroups, wherein at least one RE2agroup is C3-C6cycloalkyl (e.g., RE2ais cyclohexyl) and at least one RE2agroup is –OR5, wherein each R5is independently selected from hydrogen and C1-C6alkyl (e.g., RE2ais –OH or – OCH3).

[0264] Also provided is a compound of formula (I), or a salt thereof, wherein RE2is -O(C1-C6alkyl) substituted by RE2a, and the C1-C6alkyl of -O(C1-C6alkyl) is selected from the group consisting of:

[0265] Also provided is a compound of formula (I), or a salt thereof, wherein RE2is -O(C1-C6alkyl) RE2asubstituted by RE2a, and the C1-C6alkyl of -O(C1-C6alkyl) is, wherein each RE2ais C4-C5alkyl or C3-C6cycloalkyl, wherein the C3-C6cycloalkyl of RE2ais optionally substituted by C1-C3alkyl.

[0266] Also provided is a compound of formula (I), or a salt thereof, wherein RE2is -O(C1-C6alkyl) optionally substituted by RE2a, wherein the C1-C6alkyl optionally substituted by RE2ais selected from

[0267] Also provided in another embodiment is a compound of formula (I), or a salt thereof, wherein RE2is -O(C3-C8cycloalkyl) wherein the C3-C8cycloalkyl of -O(C3-C8cycloalkyl) is substituted by 0-5 RE2bgroups. In another aspect of the foregoing embodiment, the C3-C8cycloalkyl of -O(C3-C8cycloalkyl) of RE2is monocyclic. In another aspect, the C3-C8cycloalkyl of - O(C3-C8cycloalkyl) of RE2is bicyclic (e.g., fused, spiro, or bridged). In another aspect, RE2is - O(unsubstituted C3-C8cycloalkyl) (e.g., cyclopropyl, cyclobutyl, cyclohexyl, and spiro[2.5]octanyl). In another aspect of the foregoing embodiment, RE2is -O(C3-C8cycloalkyl) wherein the C3-C8cycloalkyl of -O(C3-C8cycloalkyl) is substituted by 1-5 RE2bgroups, wherein each RE2bis independently selected from halogen, C1-C6alkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, 5- to 10-membered heteroaryl, and -OR5, wherein the C1-C6alkyl, 3- to 12-membered heterocyclyl, C6- C14aryl, and 5- to 10-membered heteroaryl of RE2bare substituted by 0-5 R4agroups. In another aspect of the foregoing embodiment, RE2is -O(C3-C6cycloalkyl) (e.g., cyclopropyl or cyclohexyl) wherein the C3-C6cycloalkyl of -O(C3-C6cycloalkyl) is substituted by 1-5 RE2bgroups, wherein at least one of the RE2bgroups is halogen (e.g., fluoro). In another aspect of the foregoing embodiment, RE2is - O(C3-C6cycloalkyl) wherein the C3-C6cycloalkyl of -O(C3-C6cycloalkyl) is substituted by 1-5 RE2bgroups, wherein at least one of the RE2bgroups is C1-C6alkyl, wherein the C1-C6alkyl of RE2bis substituted by 0-5 R4agroups (e.g., RE2bis C1-C2alkyl substituted by 1-5 R4agroups, wherein each R4agroups is independently selected from phenyl substituted by 0-5 halogen and 6-membered heteroaryl substituted by 0-5 halogen). In another aspect of the foregoing embodiment, RE2is - O(C3-C6cycloalkyl) wherein the C3-C6cycloalkyl of -O(C3-C6cycloalkyl) is substituted by 1-5 RE2bgroups, wherein at least one of the RE2bgroups is C1-C3alkyl (e.g., RE2is cyclohexyl substituted by two –CH3groups). In another aspect of the foregoing embodiment, RE2is -O(C3-C6cycloalkyl) wherein the C3-C6cycloalkyl of -O(C3-C6cycloalkyl) is substituted by 1-5 RE2bgroups, wherein at least one of the RE2bgroups is 3- to 12-membered heterocyclyl (e.g., tetrahydro-2H-pyranyl or benzodioxolyl). In another aspect of the foregoing embodiment, RE2is -O(C3-C4cycloalkyl) whereinthe C3-C4cycloalkyl of -O(C3-C4cycloalkyl) is substituted by 1-5 RE2bgroups, wherein at least one of the RE2bgroups is C6-C14aryl (e.g., phenyl) substituted by 0-5 R4agroups, wherein each R4ais independently selected from halogen, C1-C6alkyl, and -OR8(e.g., RE2bis unsubstituted phenyl or RE2bis phenyl substituted by fluoro, methyl, tert-butyl, or –OCF3). In another aspect of the foregoing embodiment, RE2is -O(C3-C7cycloalkyl) wherein the C3-C7cycloalkyl of -O(C3-C7cycloalkyl) is substituted by 1-5 RE2bgroups, wherein at least one of the RE2bgroups is 5- to 10-membered heteroaryl (e.g., pyridinyl or isoquinolinyl). In another aspect of the foregoing embodiment, RE2is - O(C3-C6cycloalkyl) wherein the C3-C6cycloalkyl of -O(C3-C6cycloalkyl) is substituted by 2-5 RE2bgroups, wherein each RE2bis independently selected from halogen (e.g., fluoro), C1-C6alkyl, C6- C14aryl (e.g., phenyl), and -OR5(e.g., -OH). In another aspect of the foregoing embodiment, RE2is - O(C3-C6cycloalkyl) wherein the C3-C6cycloalkyl of -O(C3-C6cycloalkyl) is substituted by 2-5 RE2bgroups, wherein at least one RE2bgroup is halogen (e.g., fluoro) and at least one RE2bgroup is phenyl substituted by 0-5 C1-C6alkyl (e.g., -CH3). In another aspect of the foregoing embodiment, RE2is - O(C3-C6cycloalkyl) (e.g., cyclobutyl) wherein the C3-C6cycloalkyl of -O(C3-C6cycloalkyl) is substituted by 2-5 RE2bgroups, wherein at least one RE2bgroup is -OH and at least one RE2bgroup is phenyl.

[0268] Also provided is a compound of formula (I), or a salt thereof, wherein RE2is - O(C3-C8cycloalkyl) substituted by 0-5 RE2band the C3-C8cycloalkyl of -O(C3-C8cycloalkyl) is selected from the group consisting of:, wherein RE2bis as defined for formula (I), and n is 0, 1, 2, or 3. In one variation, n is 0. In another variation, n is 1. In another variation, n is 2. In yet another variation, n is 3.

[0269] Also provided in another embodiment is a compound of formula (I), or a salt thereof, wherein RE2is -O(3- to 12-membered heterocyclyl) wherein the 3- to 12-membered heterocyclyl of - O(3- to 12-membered heterocyclyl) is substituted by 0-5 RE2cgroups. In another aspect of the foregoing embodiment, the 3- to 12-membered heterocyclyl of -O(3- to 12-membered heterocyclyl) of RE2is monocyclic. In another aspect of the foregoing embodiment, the 3- to 12-membered heterocyclyl of -O(3- to 12-membered heterocyclyl) of RE2is bicyclic (e.g., fused, spiro, or bridged). In another aspect of the foregoing embodiment, RE2is -O(unsubstituted 4- to 10-membered heterocyclyl) (e.g., pyrrolidinyl, tetrahydropyranyl, or morpholinyl). In another aspect of the foregoing embodiment, RE2is -O(3- to 12-membered heterocyclyl) wherein the 3- to 12-membered heterocyclyl of -O(3- to 12-membered heterocyclyl) is substituted by 1-5 RE2cgroups, wherein each RE2cis independently selected from oxo, halogen, C1-C6alkyl, C6-C14aryl, 5- to 10-memberedheteroaryl, -CN, -OR5, -C(O)R5, -C(O)OR5, and -S(O)2R5. In another aspect of the foregoing embodiment, RE2is -O(4- to 6-membered heterocyclyl) wherein the 4- to 6-membered heterocyclyl of -O(4- to 6-membered heterocyclyl) is substituted by 1-5 RE2cgroups, wherein at least one of the RE2cgroups is halogen (e.g., fluoro). In another aspect of the foregoing embodiment, RE2is -O(4- to 6- membered heterocyclyl) (e.g., oxetanyl, pyrrolidinyl, tetrahydropyranyl, or azetidinyl) wherein the 4- to 6-membered heterocyclyl of -O(4- to 6-membered heterocyclyl) is substituted by 1-5 RE2cgroups, wherein at least one of the RE2cgroups is C1-C6alkyl, wherein the C1-C6alkyl of RE2cis substituted by 0-5 R4agroups. In another aspect of the foregoing embodiment, RE2cis C1-C2alkyl substituted by 1-5 R4agroups, wherein each R4agroups is independently selected from halogen, phenyl 6-membered heteroaryl, and -NR8C(O)OR10(e.g. –NHC(O)O-t-butyl), wherein the phenyl and 6-membered heteroaryl of R4aare each independently substituted by 0-5 halogen (e.g., R4ais unsubstituted phenyl, unsubstituted pyridinyl, or unsubstituted pyrimidinyl). In another aspect of the foregoing embodiment, RE2is -O(4- to 6-membered heterocyclyl) (e.g., 4-membered heterocyclyl, such as oxetanyl) wherein the 4- to 6-membered heterocyclyl of -O(4- to 6-membered heterocyclyl) is substituted by 1-5 RE2cgroups, wherein at least one of the RE2cgroups is unsubstituted C6-C14aryl (e.g., C6-C10aryl, such as phenyl). In another aspect of the foregoing embodiment, RE2is -O(4- to 6-membered heterocyclyl) (e.g., 5-membered heterocyclyl) wherein the 4- to 6-membered heterocyclyl of -O(4- to 6-membered heterocyclyl) is substituted by 1-5 RE2cgroups, wherein at least one of the RE2cgroups is 5- to 10- membered heteroaryl substituted by 0-5 C1-C6alkyl (e.g., RE2cis pyrazolyl substituted by –CH3). In another aspect of the foregoing embodiment, RE2is -O(4- to 6-membered heterocyclyl) (e.g., 5- to 6- membered heterocyclyl, such as pyrrolidinyl or piperidinyl) wherein the 4- to 6-membered heterocyclyl of -O(4- to 6-membered heterocyclyl) is substituted by 1-5 RE2cgroups, wherein at least one RE2cgroup is -OR5, -C(O)R5, or -C(O)OR5, wherein each R5is independently hydrogen or C1-C6alkyl (e.g., RE2cis –OH, -C(O)(CH2)3CH3, or -C(O)OCH3). In another aspect of the foregoing embodiment, RE2is -O(4- to 6-membered heterocyclyl) (e.g., 1,2-dihydropyridinyl) wherein the 4- to 6-membered heterocyclyl of -O(4- to 6-membered heterocyclyl) is substituted by 1-5 RE2cgroups, wherein at least one RE2cgroup is oxo. In another aspect of the foregoing embodiment, RE2is -O(4- to 6-membered heterocyclyl) (e.g., 6-membered heterocyclyl, such as piperidinyl) wherein the 4- to 6- membered heterocyclyl of -O(4- to 6-membered heterocyclyl) is substituted by 2-5 RE2cgroups, wherein each RE2cis independently selected from halogen, C1-C6alkyl, -C(O)R5, and -C(O)OR5, wherein each R5is independently C1-C6alkyl (e.g., RE2cis independently selected from fluoro and – C(O)O-tert-butyl). In another aspect of the foregoing embodiment, RE2is -O(4- to 6-membered heterocyclyl) wherein the 4- to 6-membered heterocyclyl of -O(4- to 6-membered heterocyclyl) is substituted by 2-5 RE2cgroups, wherein at least one RE2cgroup is C1-C6alkyl substituted by 0-5 halogen and at least one RE2cgroup is -C(O)R5or -C(O)OR5(e.g., RE2cis independently selected from –CF3, -C(O)CH3, and –C(O)O-tert-butyl). In another aspect of the foregoing embodiment, the 3- to 12-membered heterocyclyl of -O(3- to 12-membered heterocyclyl) of RE2is azetidinyl, pyrrolidinyl,piperidinyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxabicyclohexanyl, oxabicyclooctanyl, tetrahydro-2H-thiopyranyl, morpholinyl, or benzodioxanyl, each of which is independently substituted by 0-5 RE2cgroups.

[0270] Also provided is a compound of formula (I), or a salt thereof, wherein RE2is -O(3- to 12- membered saturated heterocyclyl) substituted by RE2cand the 3- to 12-membered saturated heterocyclyl of -O(3- to 12-membered saturated heterocyclyl) substituted bwherein RE2cis as defined for formula (I), and n is 0, 1, 2, or 3. In one variation, n is 0. In another variation, n is 1. In another variation, n is 2. In yet another variation, n is 3.

[0271] Also provided in another embodiment is a compound of formula (I), or a salt thereof, wherein RE2is -O(C6-C14aryl) wherein the C6-C14aryl of -O(C6-C14aryl) is substituted by 0-5 RE2dgroups. In another aspect of the foregoing embodiment, RE2is -O(unsubstituted C6-C10aryl) (e.g., phenyl, indanyl, or 1,2,3,4-tetrahydronaphthalenyl). In another aspect of the foregoing embodiment, RE2is -O(C6-C14aryl) wherein the C6-C14aryl of -O(C6-C14aryl) substituted by 1-5 RE2dgroups, wherein each RE2dis independently selected from halogen, C1-C6alkyl, C3-C8cycloalkyl, 3- to 12- membered heterocyclyl, 5- to 10-membered heteroaryl, -CN, and -OR5, wherein the C1-C6alkyl, C3- C8cycloalkyl, 3- to 12-membered heterocyclyl and 5- to 10-membered heteroaryl of RE2dare each independently substituted by 0-5 halogen, C1-C6alkyl or OR8. In another aspect of the foregoing embodiment, RE2is -O(C6-C14aryl) (e.g., phenyl) wherein the C6-C14aryl of -O(C6-C14aryl) is substituted by 1-5 RE2dgroups, wherein at least one of the RE2dgroups is halogen (e.g., fluoro or chloro). In another aspect of the foregoing embodiment, RE2is -O(C6-C14aryl) (e.g., phenyl) wherein the C6-C14aryl of -O(C6-C14aryl) is substituted by 1-5 RE2dgroups, wherein at least one of the RE2dgroups is C1-C6alkyl, wherein the C1-C6alkyl of RE2dis substituted by 0-5 R4agroups (e.g., RE2dis - CF3). In another aspect of the foregoing embodiment, RE2dis C1-C2alkyl substituted by 1-5 R4agroups, wherein each R4agroups is independently selected from halogen and OR8(e.g., RE2dis - CH2(OH), or -CF3). In another aspect of the foregoing embodiment, RE2is -O(C6-C14aryl) (e.g., phenyl) wherein the C6-C14aryl of -O(C6-C14aryl) is substituted by 1-5 RE2dgroups, wherein at least one of the RE2dgroups is C3-C6cycloalkyl (e.g., cyclopropyl). In another aspect of the foregoing embodiment, RE2is -O(C6-C14aryl) (e.g., phenyl) substituted by 1-5 RE2dgroups, wherein at least one of the RE2dgroups is 6-membered heterocyclyl (e.g., morpholinyl). In another aspect of the foregoing embodiment, RE2is -O(C6-C14aryl) (e.g., phenyl) wherein the C6-C14aryl of -O(C6-C14aryl) is substituted by 1-5 RE2dgroups, wherein at least one of the RE2dgroups is 5- to 6-membered heteroaryl (e.g., pyrazolyl, thiazolyl, or pyridinyl), wherein the heteroaryl of RE2dis substituted by 0-5 C1-C6alkyl groups (e.g., C1-C3alkyl, such as -CH3). In another aspect of the foregoing embodiment, RE2is - O(C6-C14aryl) (e.g., phenyl) wherein the C6-C14aryl of -O(C6-C14aryl) is substituted by 1-5 RE2dgroups, wherein at least one of the RE2dgroups is -OR5, wherein each R5is independently C1-C2alkyl (e.g., C2alkyl) substituted by 0-5 groups selected from halogen (e.g., fluoro) and -OR10(e.g., -OCH3). In another aspect of the foregoing embodiment, RE2is -O(C6-C14aryl) (e.g., phenyl) wherein the C6-C14aryl of -O(C6-C14aryl) is substituted by 2-5 RE2dgroups, wherein each RE2dis independently selected from halogen, C1-C6alkyl, -CN, and -OR5. In another aspect of the foregoing embodiment, RE2is -O(C6-C14aryl) (e.g., phenyl) wherein the C6-C14aryl of -O(C6-C14aryl) is substituted by 1-3 RE2dgroups, wherein each RE2dis halogen. In another aspect of the foregoing embodiment, RE2is - O(C6-C14aryl) (e.g., phenyl) wherein the C6-C14aryl of -O(C6-C14aryl) is substituted by 2-5 RE2dgroups, wherein at least two of the RE2dgroups are halogen (e.g., RE2is phenyl substituted by two fluoro groups, phenyl substituted by two chloro groups, or phenyl substituted by one fluoro group and one chloro group). In another aspect of the foregoing embodiment, RE2is -O(C6-C14aryl) (e.g., phenyl) wherein the C6-C14aryl of -O(C6-C14aryl) is substituted by 2-5 RE2dgroups, wherein at least one of the RE2dgroups is C1-C6alkyl substituted by 0-5 halogen and at least one of the RE2dgroups is selected from the group consisting of halogen, -CN, and -OR5(e.g., RE2is phenyl substituted by -CF3and fluoro). In another aspect of the foregoing embodiment, RE2is phenyl, indanyl, or 1,2,3,4- tetrahydronaphthalenyl, each of which is substituted by 0-5 RE2dgroups.

[0272] Also provided is a compound of formula (I), or a salt thereof, wherein RE2is -O(C6-C14aryl) substituted by RE2d, and the C6-C14aryl of -O(C6-C14aryl) substituted by RE2dis selected from the group consisting of: , whereinE2dR is as defined for formula (I), and n is 0, 1, 2, or 3. In one variation, n is 0. In another variation, n is 1. In another variation, n is 2. In yet another variation, n is 3.

[0273] Also provided is a compound of formula (I), or a salt thereof, wherein RE2is -O(C6-C14aryl) substituted by RE2d, and the C6-C14aryl of -O(C6-C14aryl) substituted by RE2dis selected from the

[0274] Also provided in another embodiment is a compound of formula (I), or a salt thereof, wherein RE2is -O(5- to 10-membered heteroaryl) wherein the 5- to 10-membered heteroaryl of -O(5-to 10-membered heteroaryl) is substituted by 0-5 RE2egroups. In another aspect of the foregoing embodiment, RE2is -O(unsubstituted 5- to 10-membered heteroaryl) (e.g., pyridinyl, pyrrolopyridinyl, quinolinyl, or 4,5,6,7-tetrahydro-indazolyl). In another aspect of the foregoing embodiment, RE2is - O(5- to 10-membered heteroaryl) wherein the 5- to 10-membered heteroaryl of -O(5- to 10-membered heteroaryl) is substituted by 1-5 RE2egroups, wherein each RE2eis independently selected from halogen (e.g., fluoro or chloro), C1-C6alkyl substituted by 0-5 halogen (e.g., -CH3, ethyl, -CF3, or isobutyl), -OR5(e.g., -OCH3), C3-C6cycloalkyl (e.g., cyclopropyl), -CN, and -NR6R7(e.g., -N(CH3)2). In another aspect of the foregoing embodiment, RE2is -O(5- to 10-membered heteroaryl) (e.g., pyridinyl) wherein the 5- to 10-membered heteroaryl of -O(5- to 10-membered heteroaryl) is substituted by 1-5 RE2egroups, wherein at least one of the RE2egroups is halogen (e.g., chloro). In another aspect of the foregoing embodiment, RE2is -O(5- to 10-membered heteroaryl) (e.g., pyridinyl, pyrimidinyl, pyrrolopyridinyl, or indazolyl) wherein the 5- to 10-membered heteroaryl of -O(5- to 10- membered heteroaryl) is substituted by 1-5 RE2egroups, wherein at least one of the RE2egroups is C1- C4alkyl, wherein the C1-C4alkyl of RE2eis substituted by 0-5 halogen groups (e.g., RE2eis –CH3, – CF3, or isobutyl). In another aspect of the foregoing embodiment, RE2is -O(6-membered heteroaryl) wherein the 5- to 10-membered heteroaryl of -O(5- to 10-membered heteroaryl) is substituted by 1-5 RE2egroups, wherein at least one of the RE2egroups is -OR5, wherein each R5is independently selected from hydrogen and C1-C3alkyl (e.g., RE2eis –OCH3). In another aspect of the foregoing embodiment, RE2is -O(5- to 10-membered heteroaryl) wherein the 5- to 10-membered heteroaryl of - O(5- to 10-membered heteroaryl) is substituted by 2-5 RE2egroups, wherein each RE2eis independently selected from halogen, C1-C6alkyl, and –CN. In another aspect of the foregoing embodiment, RE2is -O(5- to 10-membered heteroaryl) wherein the 5- to 10-membered heteroaryl of - O(5- to 10-membered heteroaryl) is substituted by 2-5 RE2egroups, wherein at least two of the RE2egroups are halogen (e.g., RE2is -O-pyridinyl substituted by two chloro groups). In another aspect of the foregoing embodiment, RE2is -O(5- to 10-membered heteroaryl) wherein the 5- to 10-membered heteroaryl of -O(5- to 10-membered heteroaryl) is substituted by 2-5 RE2egroups, wherein at least two of the RE2egroups are C1-C6alkyl. In another aspect of the foregoing embodiment, RE2is -O(5- to 10- membered heteroaryl) (e.g., pyridinyl or pyrimidinyl) wherein the 5- to 10-membered heteroaryl of - O(5- to 10-membered heteroaryl) is substituted by 3-5 RE2egroups, wherein each RE2eis independently selected from halogen, C1-C6alkyl, and –CN. In another aspect of the foregoing embodiment, RE2is -O(5- to 10-membered heteroaryl) (e.g., pyridinyl or pyrimidinyl) wherein the 5- to 10-membered heteroaryl of -O(5- to 10-membered heteroaryl) is substituted by three –CH3groups. In another aspect of the foregoing embodiment, RE2is -O(5- to 10-membered heteroaryl) (e.g., pyridinyl or pyrimidinyl) wherein the 5- to 10-membered heteroaryl of -O(5- to 10-membered heteroaryl) is substituted by two –CH3groups and one halogen group.

[0275] Also provided is a compound of formula (I), or a salt thereof, wherein RE2is -O(5- to 10- membered heteroaryl) substituted by RE2eand the 5- to 10-membered heteroaryl of -O(5- to 10-membered heteroaryl) substituted by RE2eis selected from the group consisting, RE2eis as defined for formula (I), and n is 0, 1, 2, or 3. In one variation, n is 0. In another variation, n is 1. In another variation, n is 2. In yet another variation, n is 3.

[0276] Also provided is a compound of formula (I), or a salt thereof, wherein RE2is -O(5- to 10- membered heteroaryl) and the 5- to 10-membered heteroaryl of -O(5- to 10-membered heteroaryl) is selected from the group consisting

[0277] Also provided is a compound of formula (I), or a salt thereof, wherein RE2is selected from

[0278] Also provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein one or more hydrogen atoms on the R2group is replaced by deuterium.

[0279] In one aspect, provided is a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein the compound has any one or more of the following features:(b) -L1-X-L2-Y-L3- are taken together to form a moiety selected from the group consisting of:(c) R2is RB2, wherein RB2is: (i) C1-C6alkyl optionally substituted by RB2a, such as methyl, ethyl, propyl, or butyl, each of which is optionally substituted by 1-5 RB2agroups; (ii) C3-C8cycloalkyl optionally substituted by RB2b, such as cyclopropyl, cyclobutyl, cyclohexyl, or spiro[2.5]octanyl, each of which is optionally substituted by 1-5 RB2bgroups; or (iii) 3- to 12-membered saturated heterocyclyl containing 1 or 2 heteroatoms selected from O and N (e.g., 4- to 6-membered heterocyclyl containing 1 or 2 heteroatoms selected from O and N) optionally substituted by RB2c, such as pyrrolidinyl, piperidinyl, oxetanyl, tetrahydropyranyl, or morpholinyl, each of which is optionally substituted by 1-5 RB2cgroups, such that the atom of the 3- to 12-membered heterocyclyl that is bonded to the –C(O) is a carbon; wherein: each RB2a, RB2b, and RB2cis, where possible, independently halogen, C1-C6alkyl, C3- C8cycloalkyl, 3- to 12-membered saturated heterocyclyl, -CN, -OR5, -NR6R7, -C(O)R5, -C(O)OR5, or -NR5C(O)OR6, wherein the C1-C6alkyl, C3-C8cycloalkyl, and 3- to 12-membered saturated heterocyclyl of RB2a, RB2b, and RB2care independently optionally substituted by one or more R4a, each R4ais independently halogen, oxo, -OR8, -NR8R9, -CN, C3-C8cycloalkyl, 5- to 10- membered heteroaryl, or C1-C6alkyl, wherein the C1-C6alkyl of R4ais independently optionally substituted by one or more R4b, each R4bis independently halogen, each R5is independently hydrogen, C1-C6alkyl, C3-C6cycloalkyl, C6-C14aryl, or 5- to 10- membered heteroaryl, wherein the C1-C6alkyl, C3-C6cycloalkyl, C6-C14aryl, and 5- to 10-membered heteroaryl of R5are each independently optionally substituted by one or more R5a, each R5ais independently halogen, deuterium, -OR10, or C1-C6alkyl, each R6is independently hydrogen or C1-C6alkyl, each R7is hydrogen, each R8is independently hydrogen or C1-C6alkyl, each R9is hydrogen, and each R10is independently C1-C6alkyl; and (d) X is -N(Rx)- wherein Rxis: (i) unsubstituted C3-C8alkyl; (ii) C1-C8alkyl (e.g., C1-C5alkyl) substituted by 1-5 Rxagroups;(iii) C3-C6cycloalkyl (e.g., cyclopropyl) optionally substituted by 1-5 Rxbgroups; (iv) 3- to 12-membered heterocyclyl (e.g., 4- to 6-membered heterocyclyl, such as oxetanyl) optionally substituted by 1-5 Rxcgroups; (v) 5- to 10-membered heteroaryl (e.g., 5-membered heteroaryl, such as thiazolyl) optionally substituted by 1-5 Rxegroups; or (vi) -S(O)2Rxf, wherein Rxfis C1-C6alkyl (e.g., methyl) optionally substituted by one or more Rxg.

[0280] In one aspect of this variation, (a), (b), and (c)(i) apply. In another variation, (a), (b), and (c)(ii) apply. In another variation, (a), (b), and (c)(iii) apply.

[0281] In the variations in the preceding paragraph, it is understood that each combination of variables is described. For example, it is understood that each variation of feature (c) may be combined with each variation of feature (d) the same as if each and every variation of features (c) and (d) were specifically and individually listed. Thus, it is understood that the following combinations are described: (c)(i) + (d)(i); (c)(i) + (d)(ii); (c)(i) + (d)(iii); (c)(i) + (d)(iv); (c)(i) + (d)(v); (c)(i) + (d)(vi); (c)(ii) + (d)(i); (c)(ii) + (d)(ii); (c)(ii) + (d)(iii); (c)(ii) + (d)(iv); (c)(ii) + (d)(v); (c)(ii) + (d)(vi); (c)(iii) + (d)(i); (c)(iii) + (d)(ii); (c)(iii) + (d)(iii); (c)(iii) + (d)(iv); (c)(iii) + (d)(v); (c)(iii) + (d)(vi).

[0282] In one aspect, provided is a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein the compound has any one or more of the following features:(c) R2is RC2, wherein RC2is:(i) C6-C12aryl optionally substituted by one or more RC2a(e.g., C6-C9aryl substituted by 0-5 RC2agroups); (ii) 5- to 12-membered heteroaryl optionally substituted by one or more RC2b(e.g., 5- to 9- membered heteroaryl substituted by 0-5 RC2bgroups); (iii) C3-C10cycloalkenyl optionally substituted by one or more RC2c; (iv) 3- to 12-membered partially unsaturated heterocyclyl optionally substituted by one or more RC2d(e.g., 3- to 10-membered partially unsaturated heterocyclyl substituted by 0-5 RC2dgroups); (v) C1-C6alkyl substituted by one or more RC2e(e.g., C1-C4alkyl substituted by 1-5 RC2egroups), wherein at least one RC2egroup is 3- to 12-membered partially unsaturated heterocyclyl, C6- C14aryl, or 5- to 10-membered heteroaryl, wherein the 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of RC2eare independently optionally substituted by one or more R4a, and each of the other RC2egroups, when present, is independently R4; (vi) C2-C6alkenyl substituted by one or more RC2f, wherein at least one RC2fgroup is 3- to 12- membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl, wherein the 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of RC2fare independently optionally substituted by one or more R4a, and each of the other RC2fgroups, when present, is independently R4; (vii) C3-C8cycloalkyl substituted by one or more RC2g(e.g., C3-C4cycloalkyl substituted by 1- 5 RC2ggroups), wherein at least one RC2ggroup is 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl, wherein the 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of RC2gare independently optionally substituted by one or more R4a, and each of the other RC2ggroups, when present, is independently R4; or (viii) 3- to 12-membered fully saturated heterocyclyl substituted by one or more RC2h(e.g., 4- to 6-membered fully saturated heterocyclyl substituted by 1-5 RC2hgroups), wherein at least one RC2hgroup is 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl, wherein the 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of RC2hare independently optionally substituted by one or more R4a, and each of the other RC2hgroups, when present, is independently oxo or R4; wherein: each RC2a, RC2b, RC2cand RC2dis independently R4, each R4is independently halogen, C1-C6alkyl, 5- to 10-membered heteroaryl, -CN, -OR5, -S(O)2R5, or -S(O)2OH, wherein the C1-C6alkyl and 5- to 10-membered heteroaryl of R4are independently optionally substituted by one or more R4a, each R4ais independently halogen, oxo, -OR8, -CN, -S(O)2R8, or C1-C6alkyl, wherein the C1- C6alkyl of R4aare independently optionally substituted by one or more halogen,each R5is independently hydrogen, C1-C6alkyl, C3-C6cycloalkyl, C6-C14aryl, or 5- to 10- membered heteroaryl, wherein the C1-C6alkyl, C3-C6cycloalkyl, C6-C14aryl, and 5- to 10-membered heteroaryl of R5are each independently optionally substituted by one or more R5a, each R5ais independently halogen, -OR10, C3-C6cycloalkyl, or C1-C6alkyl optionally substituted by one or more deuterium, halogen, -OH, -O(2H), or oxo, each R8is independently hydrogen or C1-C6alkyl optionally substituted by one or more deuterium, halogen, or oxo, and each R10is independently C1-C6alkyl optionally substituted by one or more deuterium, halogen, or oxo; and (d) X is -N(Rx)- wherein Rxis: (i) unsubstituted C3-C8alkyl (e.g., unsubstituted C3alkyl); (ii) C1-C8alkyl (e.g., C1-C5alkyl) substituted by 1-5 Rxagroups; (ii) C3-C6cycloalkyl (e.g., C3-C4cycloalkyl) substituted by 0-5 Rxbgroups; (iii) 3- to 12-membered heterocyclyl (e.g., 4- to 6-membered heterocyclyl, such as oxetanyl) substituted by 0-5 Rxcgroups; (iv) C6-C14aryl optionally substituted by one or more Rxd; (v) 5- to 10-membered heteroaryl (e.g., 5-membered heteroaryl, such as thiazolyl) substituted by 0-5 Rxegroups; or (vi) -S(O)2Rxf, wherein Rxfis C1-C6alkyl (e.g., methyl) optionally substituted by one or more Rxg.

[0283] In one aspect of this variation, (a), (b), and (c)(i) apply. In another variation, (a), (b), and (c)(ii) apply. In another variation, (a), (b), and (c)(iii) apply. In another variation, (a), (b), and (c)(iv) apply. In another variation, (a), (b), and (c)(v) apply. In another variation, (a), (b), and (c)(vi) apply. In another variation, (a), (b), and (c)(vii) apply. In another variation, (a), (b), and (c)(viii) apply.

[0284] In the variations in the preceding paragraph, it is understood that each combination of variables is described. For example, it is understood that each variation of feature (c) may be combined with each variation of feature (d) the same as if each and every variation of features (c) and (d) were specifically and individually listed. Thus, it is understood that the following combinations are described: (c)(i) + (d)(i); (c)(i) + (d)(ii); (c)(i) + (d)(iii); (c)(i) + (d)(iv); (c)(i) + (d)(v); (c)(i) + (d)(vi); (c)(ii) + (d)(i); (c)(ii) + (d)(ii); (c)(ii) + (d)(iii); (c)(ii) + (d)(iv); (c)(ii) + (d)(v); (c)(ii) + (d)(vi); (c)(iii) + (d)(i); (c)(iii) + (d)(ii); (c)(iii) + (d)(iii); (c)(iii) + (d)(iv); (c)(iii) + (d)(v); (c)(iii) + (d)(vi); (c)(iv) + (d)(i); (c)(iv) + (d)(ii); (c)(iv) + (d)(iii); (c)(iv) + (d)(iv); (c)(iv) + (d)(v); (c)(iv) + (d)(vi); (c)(v) + (d)(i); (c)(v) + (d)(ii); (c)(v) + (d)(iii); (c)(v) + (d)(iv); (c)(v) + (d)(v); (c)(v) + (d)(vi); (c)(vi) + (d)(i); (c)(vi) + (d)(ii); (c)(vi) + (d)(iii); (c)(vi) + (d)(iv); (c)(vi) + (d)(v); (c)(vi) + (d)(vi); (c)(vii) + (d)(i); (c)(vii) + (d)(ii); (c)(vii) + (d)(iii); (c)(vii) + (d)(iv); (c)(vii) + (d)(v); (c)(vi) + (d)(vi); (c)(viii) + (d)(i); (c)(viii) + (d)(ii); (c)(viii) + (d)(iii); (c)(viii) + (d)(iv); (c)(viii) + (d)(v); and (c)(viii) + (d)(vi).

[0285] In one aspect, provided is a compound of formula (I) or a salt thereof, wherein the compound has any one or more of the following features:onsisting of:(III) R2is RD2wherein RD2is: (i) -NRD3(C1-C6alkyl) optionally substituted by RD2a, such as -NRD3(methyl), -NRD3(ethyl), - NRD3(propyl), or -NRD3(butyl), each of which is substituted by 0-5 RD2agroups; (ii) -NRD3(C3-C8cycloalkyl optionally substituted by RD2b, such as -NRD3(cyclopropyl), - NRD3(cyclobutyl), -NRD3(cyclohexyl), or -NRD3(spiro[2.5]octanyl), each of which is substituted by 0- 5 RD2bgroups; (iii) -NRD3(3- to 12-membered heterocyclyl containing 1 or 2 heteroatoms selected from O and N) [e.g., -NRD3(4- to 6-membered heterocyclyl containing 1 or 2 heteroatoms selected from O and N)] optionally substituted by RD2c, such as -NRD3(pyrrolidinyl), -NRD3(piperidinyl), -NRD3(oxetanyl), -NRD3(tetrahydropyranyl), or -NRD3(morpholinyl), each of which is substituted by 0-5 RD2cgroups; (iv) 3- to 12-membered heterocyclyl containing 1 N and 0 or 1 additional heteroatoms selected from O and N (e.g., 4- to 6-membered heterocyclyl containing 1 N and 0 or 1 additional heteroatoms selected from O and N)] optionally substituted by RD2d, such as pyrrolidinyl, piperidinyl, morpholinyl, each of which is substituted by 0-5 RD2dgroups; or (v) 5- to 10-membered N-containing heteroaryl optionally substituted by RD2e, such as pyrazolyl, pyridinyl, or indazolyl, each of which is substituted by 0-5 RD2egroups; wherein each RD2a, RD2b, RD2c, RD2d, and RD2eis independently R4, and each R4is independently halogen, C1-C6alkyl, C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, 5- to 10-membered heteroaryl, -CN, -OR5, -C(O)R5, -C(O)OR5, -NR6R7, or -NR5C(O)OR6, wherein theC1-C6alkyl, C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of R4are independently optionally substituted by R4a, wherein R4ais halogen, -OR8, -NR8R9, -C(O)OR8, -NR8C(O)OR10, -CN, 5- to 10-membered heteroaryl, C6-C14aryl, or C1-C6alkyl independently optionally substituted by halogen, wherein R5is hydrogen, C1-C6alkyl optionally substituted by halogen or -OR10, or C6-C14aryl optionally substituted by halogen, R6is hydrogen or C1-C6alkyl, R7is hydrogen, R8is hydrogen or C1-C6alkyl optionally substituted by halogen, R9is hydrogen, and R10is C1-C6alkyl optionally substituted by halogen; and (IV) X is -N(Rx)- wherein Rxis: (i) C1-C6alkyl (e.g., C1-C5alkyl) substituted by 0-5 Rxagroups; (ii) C3-C6cycloalkyl (e.g., cyclopropyl) substituted by 0-5 Rxbgroups; (iii) 3- to 12-membered heterocyclyl (e.g., 4- to 6-membered heterocyclyl, such as oxetanyl) substituted by 0-5 Rxcgroups; (iv) 5- to 10-membered heteroaryl (e.g., 5-membered heteroaryl, such as thiazolyl) substituted by 0-5 Rxegroups; or (v) -S(O)2Rxf, wherein Rxfis C1-C6alkyl (e.g., -CH3) optionally substituted by Rxg.

[0286] In one aspect of this variation, (I), (II), and (III)(i) apply. In another variation, (I), (II), and (III)(ii) apply. In another variation, (I), (II), and (III)(iii) apply. In another variation, (I), (II), and (III)(iv) apply. In another variation, (I), (II), and (III)(v) apply. In another variation, (I), (II), and (III)(vi) apply. In another variation, (I), (II), and (III)(vii) apply.

[0287] In the variations in the preceding paragraph, it is understood that each combination of variables is described. For example, it is understood that each variation of feature (III) may be combined with each variation of feature (IV) the same as if each and every variation of features (III) and (IV) were specifically and individually listed. Thus, it is understood that the following combinations are described: (III)(i) + (IV)(i); (III)(i) + (IV)(ii); (III)(i) + (IV)(iii); (III)(i) + (IV)(iv); (III)(i) + (IV)(v); (III)(ii) + (IV)(i); (III)(ii) + (IV)(ii); (III)(ii) + (IV)(iii); (III)(ii) + (IV)(iv); (III)(ii) + (IV)(v); (III)(iii) + (IV)(i); (III)(iii) + (IV)(ii); (III)(iii) + (IV)(iii); (III)(iii) + (IV)(iv); (III)(iii) + (IV)(v); (III)(iv) + (IV)(i); (III)(iv) + (IV)(ii); (III)(iv) + (IV)(iii); (III)(iv) + (IV)(iv); (III)(iv) + (IV)(v); (III)(v) + (IV)(i); (III)(v) + (IV)(ii); (III)(v) + (IV)(iii); (III)(v) + (IV)(iv); (III)(v) + (IV)(v); (III)(vi) + (IV)(i); (III)(vi) + (IV)(ii); (III)(vi) + (IV)(iii); (III)(vi) + (IV)(iv); (III)(vi) + (IV)(v); (III)(vii) + (IV)(i); (III)(vii) + (IV)(ii); (III)(vii) + (IV)(iii); (III)(vii) + (IV)(iv); and (III)(vii) + (IV)(v).

[0288] Also provided is a compound of formula (I), or a salt thereof, wherein R2is RD2, RD2is - NRD3(C1-C6alkyl), -NRD3(C3-C8cycloalkyl), -NRD3(3- to 12-membered heterocyclyl), 3- to 12-membered heterocyclyl containing 1 N and 0 or 1 additional heteroatoms selected from O and N, or 5- to 10-membered N-containing heteroaryl, wherein the C1-C6alkyl of the -NRD3(C1-C6alkyl) of RD2is optionally substituted by RD2a, the C3-C8cycloalkyl of the -NRD3(C3-C8cycloalkyl) of RD2is optionally substituted by RD2b, the 3- to 12-membered heterocyclyl of the -NRD3(3- to 12-membered heterocyclyl) of RD2is optionally substituted by RD2c, the 3- to 12-membered heterocyclyl containing 1 N and 0 or 1 additional heteroatoms selected from O and N of RD2is optionally substituted by RD2d, the 5- to 10-membered N-containing heteroaryl is optionally substituted by RD2e, wherein each RD2a, RD2b, RD2c, RD2d, and RD2eis independently R4, wherein each R4is independently selected from the group consisting of:, wherein each R4ais independently halogen, -OR8, -NR8R9, -C(O)OR8, -NR8C(O)OR10, -CN, 5- to 10-membered heteroaryl, C6-C14aryl, or C1-C6alkyl, wherein R8, R9, and R10are as defined for formula (I), and n is 0, 1, or 2. In one variation, n is 0. In another variation, n is 1. In yet another variation, n is 2.

[0289] Also provided is a compound of formula (I), or a salt thereof, wherein R2is RD2, wherein RD2is -NRD3(C1-C6alkyl) optionally substituted by RD2a, -NRD3(C3-C8cycloalkyl optionally substituted by RD2b, -NRD3(3- to 12-membered heterocyclyl containing 1 or 2 heteroatoms selected from O and N) optionally substituted by RD2c, or 3- to 12-membered heterocyclyl containing 1 N and 0 or 1 additional heteroatoms selected from O and N optionally substituted by RD2d, or 5- to 10- membered N-containing heteroaryl substituted by 0-5 RD2e, wherein each RD2a, RD2b, RD2c, RD2d, and RD2eis independently R4, wherein each R4is independently selected from the group consisting of:

[0290] In one aspect, provided is a compound of formula (I) or a salt thereof, wherein the compound has any one or more of the following features:(II) -L1-X-L2-Y-L3- are taken together to form a moiety selected from the group consisting of:(III) R2is RE2wherein RE2is: (i) -O(C1-C6alkyl) wherein the C1-C6alkyl of -O(C1-C6alkyl) is optionally substituted by RE2a, such as -O(methyl), -O(ethyl), -O(propyl), or -O(butyl), each of which is substituted by 0-5 RE2agroups; (ii) -O(C3-C8cycloalkyl) wherein the C3-C8cycloalkyl of -O(C3-C8cycloalkyl) is optionally substituted by RE2b, such as -O(cyclopropyl), -O(cyclobutyl), -O(cyclohexyl), or - O(spiro[2.5]octanyl), each of which is substituted by 0-5 RE2bgroups; or (iii) -O(3- to 12-membered heterocyclyl) [e.g., -O(4- to 6-membered heterocyclyl containing 1 or 2 heteroatoms selected from O and N)] wherein the 4- to 6-membered heterocyclyl of -O(4- to 6- membered heterocyclyl) is optionally substituted by RE2c, such as -O(pyrrolidinyl), -O(piperidinyl), -O(oxetanyl), -O(tetrahydropyranyl), or -O(morpholinyl), each of which is substituted by 0-5 RE2cgroups; (iv) -O(C6-C10aryl) [e.g., -O(phenyl)] wherein the C6-C10aryl of -O(C6-C10aryl) is optionally substituted by RE2d, such as -O(phenyl), -O(indenyl), or -O(2,3-dihydro-1H-indenyl), each of which is substituted by 0-5 RE2dgroups; (iv) -O(5- to 10-membered heteroaryl) [e.g., -O(pyridinyl)] wherein the 5- to 10-membered heteroaryl of -O(5- to 10-membered heteroaryl) is optionally substituted by RE2e; wherein each RE2a, RE2b, RE2c, RE2d, and RE2eis independently R4, and R4is halogen, C1- C6alkyl, C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, 5- to 10-membered heteroaryl, -CN, -OR5, -C(O)R5, -C(O)OR5, -NR6R7, or -NR5C(O)OR6, wherein the C1-C6alkyl, C3- C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of R4are independently optionally substituted by R4a, wherein R4ais halogen, -OR8, -NR8R9, -C(O)OR8, -NR8C(O)OR10, -CN, 5- to 10-membered heteroaryl, C6-C14aryl, or C1-C6alkyl independently optionally substituted by halogen, wherein R5is hydrogen, C1-C6alkyl optionally substituted by halogen or -OR10, or C6-C14aryl optionally substituted by halogen, R6is hydrogen or C1-C6alkyl, R7is hydrogen, R8is hydrogen or C1-C6alkyl optionally substituted by halogen, R9is hydrogen, and R10is C1-C6alkyl optionally substituted by halogen; and (IV) X is -N(Rx)- wherein Rxis: (i) C1-C6alkyl (e.g., C1-C5alkyl) substituted by 0-5 Rxagroups; (ii) C3-C6cycloalkyl (e.g., cyclopropyl) substituted by 0-5 Rxbgroups; (iii) 3- to 12-membered heterocyclyl (e.g., 4- to 6-membered heterocyclyl, such as oxetanyl) substituted by 0-5 Rxcgroups; (iv) 5- to 10-membered heteroaryl (e.g., 5-membered heteroaryl, such as thiazolyl) substituted by 0-5 Rxegroups; or (v) -S(O)2Rxf, wherein Rxfis C1-C6alkyl (e.g., -CH3) optionally substituted by Rxg.

[0291] In one aspect of this variation, (I), (II), and (III)(i) apply. In another variation, (I), (II), and (III)(ii) apply. In another variation, (I), (II), and (III)(iii) apply. In another variation, (I), (II), and (III)(iv) apply. In another variation, (I), (II), and (III)(v) apply. In another variation, (I), (II), and (III)(vi) apply. In another variation, (I), (II), and (III)(vii) apply.

[0292] In the variations in the preceding paragraph, it is understood that each combination of variables is described. For example, it is understood that each variation of feature (III) may be combined with each variation of feature (IV) the same as if each and every variation of features (III) and (IV) were specifically and individually listed. Thus, it is understood that the followingcombinations are described: (III)(i) + (IV)(i); (III)(i) + (IV)(ii); (III)(i) + (IV)(iii); (III)(i) + (IV)(iv); (III)(i) + (IV)(v); (III)(ii) + (IV)(i); (III)(ii) + (IV)(ii); (III)(ii) + (IV)(iii); (III)(ii) + (IV)(iv); (III)(ii) + (IV)(v); (III)(iii) + (IV)(i); (III)(iii) + (IV)(ii); (III)(iii) + (IV)(iii); (III)(iii) + (IV)(iv); (III)(iii) + (IV)(v); (III)(iv) + (IV)(i); (III)(iv) + (IV)(ii); (III)(iv) + (IV)(iii); (III)(iv) + (IV)(iv); (III)(iv) + (IV)(v); (III)(v) + (IV)(i); (III)(v) + (IV)(ii); (III)(v) + (IV)(iii); (III)(v) + (IV)(iv); (III)(v) + (IV)(v); (III)(vi) + (IV)(i); (III)(vi) + (IV)(ii); (III)(vi) + (IV)(iii); (III)(vi) + (IV)(iv); (III)(vi) + (IV)(v); (III)(vii) + (IV)(i); (III)(vii) + (IV)(ii); (III)(vii) + (IV)(iii); (III)(vii) + (IV)(iv); and (III)(vii) + (IV)(v).

[0293] Also provided is a compound of formula (I), or a salt thereof, wherein R2is RE2, wherein RE2is -O(C1-C6alkyl) wherein the C1-C6alkyl of -O(C1-C6alkyl) is optionally substituted by RE2a, - O(C3-C8cycloalkyl) wherein the C3-C8cycloalkyl of -O(C3-C8cycloalkyl) is optionally substituted by RE2b, -O(3- to 12-membered heterocyclyl containing 1 or 2 heteroatoms selected from O and N) wherein the 3- to 12-membered heterocyclyl of -O(3- to 12-membered heterocyclyl) is optionally substituted by RE2c, -O(C6-C10aryl) wherein the C6-C10aryl of -O(C6-C10aryl) is optionally substituted by RE2d, or -O(5- to 10-membered heteroaryl) wherein the 5- to 10-membered heteroaryl of -O(5- to 10-membered heteroaryl) is optionally substituted by RE2egroups, wherein each R4is independently selected from the group consisting of:, , ,wherein each R4ais independently halogen, -OR8, -NR8R9, -C(O)OR8, -NR8C(O)OR10, -CN, 5- to 10-membered heteroaryl, C6-C14aryl, or C1-C6alkyl, wherein R8, R9, and R10are as defined for formula (I), and n is 0, 1, or 2. In one variation, n is 0. In another variation, n is 1. In yet another variation, n is 2.

[0294] Also provided is a compound of formula (I), or a salt thereof, wherein R2is RE2, wherein RE2is -O(C1-C6alkyl) wherein the C1-C6alkyl of -O(C1-C6alkyl) is optionally substituted by RE2a, - O(C3-C8cycloalkyl) wherein the C3-C8cycloalkyl of -O(C3-C8cycloalkyl) is optionally substituted by RE2b, -O(3- to 12-membered heterocyclyl containing 1 or 2 heteroatoms selected from O and N) wherein the 3- to 12-membered heterocyclyl of -O(3- to 12-membered heterocyclyl) is optionally substituted by RE2c, -O(C6-C10aryl) wherein the C6-C10aryl of -O(C6-C10aryl) is optionally substituted by RE2d, or -O(5- to 10-membered heteroaryl) wherein the 5- to 10-membered heteroaryl of -O(5- to 10-membered heteroaryl) is optionally substituted by RE2egroups, wherein each RE2a, RE2b, RE2c, RE2d, and RE2eis independently R4, wherein each R4is independently selected from the group

[0295] When a moiety is contemplated, it is understood that the moiety can be attached to the rest of the structure at any available position. For example, 3-chloro-5-methylpyridinyl may be attached to the rest of the structure at the 2-, 4-, or 6-position (i.e., 3-chloro-5-methylpyridin-2-yl, 3-chloro-5- methylpyridin-4-yl or 3-chloro-5-methylpyridin-6-yl, respectively). The R2groups described herein are shown as attached at specific positions (e.g., pyrimid-4-yl, quinazolin-4-yl, or isoquinolin-1-yl) but they can also be attached via any other available valence (e.g., pyrimid-2-yl, quinazolin-2-yl, or isoquinolin-3-yl, respectively).

[0296] In various embodiments, the compound can be selected from the group consisting of the compounds in Table B1, Table C1, Table D1, or Table E1, or a pharmaceutically acceptable salt thereof.

[0297] In one embodiment, provided is a compound selected from the group consisting of the compounds in Table B1: Table B1 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(2- ethylbutanoylamino)butanoic acid; 2-(2-ethylbutanoylamino)-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid;4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- methylbutanoylamino)butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(2,2- dimethylpropanoylamino)butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(2- methoxyacetyl)amino]butanoic acid; 2-(cyclopropanecarbonylamino)-4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(cyclobutanecarbonylamino)-4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(2-ethylbutanoylamino)-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl-[2- (trifluoromethoxy)ethyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2- (pentanoylamino)butanoic acid; 2-[(2-cyclopropylacetyl)amino]-4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3,3- dimethylbutanoylamino)butanoic acid; 2-(3-cyclopropylpropanoylamino)-4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(2- isopropoxyacetyl)amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[1- pentanoylpiperidine-3-carbonyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[1- methoxycarbonylpiperidine-3-carbonyl]amino]butanoic acid; 2-(cyclohexanecarbonylamino)-4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(tetrahydropyran-4- carbonylamino)butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(4,4- difluorocyclohexanecarbonyl)amino]butanoic acid; 4-[cyclopropyl-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentyl]amino]-2-(2- ethylbutanoylamino)butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2- methylbutanoyl]amino]butanoic acid;4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(4,4- difluorocyclohexyl)acetyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- ethylpentanoylamino)butanoic acid; 2-(2-ethylbutanoylamino)-4-[2-methoxyethyl-[[1-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl]cyclopropyl]methyl]amino]butanoic acid; 2-(2-ethylbutanoylamino)-4-[2-isopropoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(4,4- dimethylcyclohexanecarbonyl)amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(spiro[2.5]octane-6- carbonylamino)butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(4,4- dimethylcyclohexyl)acetyl]amino]butanoic acid; 2-(2-ethylbutanoylamino)-4-[[1-(hydroxymethyl)cyclopropyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(1-tert-butoxycarbonyl-5,5-difluoro-piperidine-3-carbonyl)amino]-4-[cyclopropyl-[4-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(2- ethylbutanoylamino)butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(3,3- difluorocyclohexanecarbonyl)amino]butanoic acid; 2-(2-ethylbutanoylamino)-4-[(3-hydroxy-3-methyl-butyl)-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[(1-tert-butoxycarbonyl-5,5-difluoro-piperidine-3-carbonyl)amino]-4-[2-methoxyethyl-[4- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(2-ethylbutanoylamino)-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl-(3,3,3- trifluoropropyl)amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[3- methylpentanoyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(5,5,5- trifluoropentanoylamino)butanoic acid; 2-(4-aminobutanoylamino)-4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(2,2- difluorohexanoylamino)butanoic acid;2-(2-ethylbutanoylamino)-4-[(3-methoxy-3-methyl-butyl)-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[(3-methoxy-3-methyl-butyl)-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(2,2-difluorohexanoylamino)-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(2-ethylbutanoylamino)-4-[(2-hydroxy-2-methyl-propyl)-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)butyl]amino]butanoic acid; 2-(2-ethylbutanoylamino)-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl-[2- (trideuteriomethoxy)ethyl]amino]butanoic acid; 2-[[2-hydroxypentanoyl]amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[2-(oxetan-3-yl)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[(2-fluoro-3-methoxy-propyl)-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)butyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(3-hydroxy-3-propyl- hexanoyl)amino]butanoic acid; 4-[2,2-difluoroethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- ethylpentanoylamino)butanoic acid; 2-(3-ethylpentanoylamino)-4-[2-fluoroethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[[2-fluoro-3-hydroxy-3-methyl-butyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[3-fluoropropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[3,3-difluoropropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- ethylpentanoylamino)butanoic acid; 2-(cyclopropanecarbonylamino)-4-[(2-fluoro-3-methoxy-propyl)-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[(2-fluoro-3-methoxy-propyl)-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[(1-cyanocyclopropyl)methyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- ethylpentanoylamino)butanoic acid;2-(3-ethylpentanoylamino)-4-[[2-fluoro-3-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)butyl]amino]butanoic acid; 4-[(2-cyano-2-methyl-propyl)-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- ethylpentanoylamino)butanoic acid; 4-[(2-tert-butoxy-2-oxo-ethyl)-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- ethylpentanoylamino)butanoic acid; 4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(2-methoxy-2- methyl-propanoyl)amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[(4-methoxyphenyl)methyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-cyclohexyl-2-hydroxy-acetyl]amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butylamino]butanoic acid; 2-[[2-(methoxycarbonylamino)-3-methyl-butanoyl]amino]-4-[2-methoxyethyl-[4-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[(2-fluoro-3-methoxy-2-methyl-propyl)-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(3-hydroxy-2,2- dimethyl-propanoyl)amino]butanoic acid; 2-[[2-cyclohexyl-2-hydroxy-acetyl]amino]-4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)butyl]amino]butanoic acid; 4-[benzyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- ethylpentanoylamino)butanoic acid; 2-[[2-(methoxycarbonylamino)-3-methyl-butanoyl]amino]-4-[2-methoxyethyl-[4-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[(4-fluorophenyl)methyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(3-methyloxetane-3- carbonyl)amino]butanoic acid; 2-acetamido-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(3-methyloxetane- 3-carbonyl)amino]butanoic acid; 2-[(3-hydroxy-2,2-dimethyl-propanoyl)amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid;4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(3-methoxy-2,2- dimethyl-propanoyl)amino]butanoic acid; 2-[(3-cyano-2,2-dimethyl-propanoyl)amino]-4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(3-methoxy-2,2-dimethyl-propanoyl)amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(3-cyano-2,2-dimethyl-propanoyl)amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(2-cyclohexyl-2-methoxy-acetyl)amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(2,2-difluoro-3-hydroxy-3-methyl-butanoyl)amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[[2-methoxypropyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[2-methylsulfonylethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[2-pyrazol-1-ylethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[[3,3-difluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- ethylpentanoylamino)butanoic acid; 2-(3-ethylpentanoylamino)-4-[2-(2-oxopyrrolidin-1-yl)ethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[2-phenylethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[3-phenylpropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[(3,3-difluorocyclobutyl)methyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- ethylpentanoylamino)butanoic acid; 4-[2-(difluoromethoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- ethylpentanoylamino)butanoic acid; 2-[(3,3-difluorocyclohexanecarbonyl)amino]-4-[[2-fluoro-3-methoxy-propyl]-[4-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid;4-[[2-fluoro-3-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(2- methoxy-2-methyl-propanoyl)amino]butanoic acid; 2-[(2-cyclohexyl-2-methoxy-acetyl)amino]-4-[[2-fluoro-3-methoxy-propyl]-[4-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(2-cyclohexyl-2-methyl-propanoyl)amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(4,4-dimethylcyclohexanecarbonyl)amino]-4-[[2-fluoro-3-methoxy-propyl]-[4-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl-[2-(2,2,2- trifluoroethoxy)ethyl]amino]butanoic acid; 4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(2- tetrahydropyran-4-ylacetyl)amino]butanoic acid; 2-[(2-cyclohexylacetyl)amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[[2-methoxypropyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[2-(4-fluorophenoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[2-(2,2-difluorocyclopropoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2- (3-ethylpentanoylamino)butanoic acid; 2-[(2-ethyl-4,4,4-trifluoro-butanoyl)amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(2-ethyl-4,4-difluoro-butanoyl)amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-(3,5-dimethylpyrazol-1-yl)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2- (3-ethylpentanoylamino)butanoic acid; 4-[[2-fluoro-3-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(2- tetrahydropyran-4-ylacetyl)amino]butanoic acid; 4-[[2-fluoro-3-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(3- methoxy-3-methyl-butanoyl)amino]butanoic acid; 4-[[2-fluoro-3-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(3- hydroxy-3-methyl-butanoyl)amino]butanoic acid; 4-[2-(3,5-difluorophenoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- ethylpentanoylamino)butanoic acid; 4-[[2-fluoro-3-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(3- methyloxetane-3-carbonyl)amino]butanoic acid;2-[(3-cyano-2,2-dimethyl-propanoyl)amino]-4-[[2-fluoro-3-methoxy-propyl]-[4-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[2-(2-pyridyloxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[2-[(5-fluoro-3-pyridyl)oxy]ethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-ethoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- ethylpentanoylamino)butanoic acid; 2-(3-ethylpentanoylamino)-4-[2-[(2-methyl-3-pyridyl)oxy]ethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[2-[(6-methyl-3-pyridyl)oxy]ethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[[2-fluoro-3-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(2-cyano-2-methyl-propanoyl)amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl-thiazol-2-yl- amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[2-morpholinoethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[[2-hydroxypropyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[(2-methoxy-2-methyl-propyl)-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(3-methoxy-3-methyl-butanoyl)amino]-4-[[2-methoxypropyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(3-methoxy-3-methyl-butanoyl)amino]-4-[(2-methoxy-2-methyl-propyl)-[4-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[[2-methoxypropyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[[2-methoxypropyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(1- methylcyclopropyl)acetyl]amino]butanoic acid; 2-[(2-cyclobutylacetyl)amino]-4-[[2-methoxypropyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid;4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(1- methylcyclopropyl)acetyl]amino]butanoic acid; 2-[(2-cyclohexylacetyl)amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(2-cyclobutylacetyl)amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(2- tetrahydropyran-4-ylacetyl)amino]butanoic acid; 2-[(2-cyclopropylacetyl)amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(3- methoxy-3-methyl-butanoyl)amino]butanoic acid; 2-[(2-cyclopentylacetyl)amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[[2-methoxypropyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- methylbutanoylamino)butanoic acid; 2-[[2-(3,3-difluorocyclobutyl)acetyl]amino]-4-[[2-methoxypropyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(4,4-difluoro-3,3-dimethyl-butanoyl)amino]-4-[[2-methoxypropyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[[2-methoxypropyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(4,4,4-trifluoro- 3,3-dimethyl-butanoyl)amino]butanoic acid; 2-[(2-cyclohexylacetyl)amino]-4-[[2-methoxypropyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[(2-cyclopropylacetyl)amino]-4-[[2-methoxypropyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-(3,3-difluorocyclobutyl)acetyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(4,4-difluoro-3,3-dimethyl-butanoyl)amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[[2-methoxypropyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(1- methylcyclopentyl)acetyl]amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2- [(4,4,4-trifluoro-3,3-dimethyl-butanoyl)amino]butanoic acid; 2-[(3-ethyl-5,5,5-trifluoro-pentanoyl)amino]-4-[[2-methoxypropyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid;2-[(2-cyclopropylacetyl)amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[(2-cyclopentylacetyl)amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(3-methylbutanoylamino)-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(2- tetrahydropyran-4-ylacetyl)amino]butanoic acid; 2-[[2-(1-methyl-4-piperidyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(2-cyclobutylacetyl)amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-(3,3-difluorocyclobutyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(2-cyclohexylacetyl)amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-(4,4-difluorocyclohexyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[[2-methoxypropyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(1- methylcyclobutyl)acetyl]amino]butanoic acid; 4-[[2-methoxypropyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(1- methylcyclohexyl)acetyl]amino]butanoic acid; 2-[(2-cyclopentylacetyl)amino]-4-[[2-methoxypropyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(1- methylcyclobutyl)acetyl]amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(1- methylcyclopentyl)acetyl]amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(1- methylcyclohexyl)acetyl]amino]butanoic acid; 2-[(3-ethyl-5,5,5-trifluoro-pentanoyl)amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(4- piperidyl)acetyl]amino]butanoic acid;2-(2,2-dimethylpropanoylamino)-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(2-methylpropanoylamino)-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(cyclobutanecarbonylamino)-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[(3-methylcyclobutanecarbonyl)amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(3,3-dimethylcyclobutanecarbonyl)amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-(oxetan-3-yl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(cyclopropanecarbonylamino)-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-(1-methylcyclobutyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(4,4-difluoro-3,3-dimethyl-butanoyl)amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(3-ethyl-5,5,5-trifluoro-pentanoyl)amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-(1-methylcyclopropyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[(3-methoxy-3-methyl-butanoyl)amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(4,4,4-trifluoro- 3,3-dimethyl-butanoyl)amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[2-(2-methoxyphenoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)butyl]amino]butanoic acid; 4-[2-(4-methoxyphenoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- methylbutanoylamino)butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[2-(4-methoxyphenoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-(2-methoxyphenoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- methylbutanoylamino)butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[2-(2-methoxyphenoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid;2-(3-ethylpentanoylamino)-4-[2-(3-methoxyphenoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)butyl]amino]butanoic acid; 4-[2-(3-methoxyphenoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- methylbutanoylamino)butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[2-(3-methoxyphenoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[2-(4-methoxyphenoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)butyl]amino]butanoic acid; 4-[2-benzyloxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- ethylpentanoylamino)butanoic acid; 4-[2-benzyloxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- methylbutanoylamino)butanoic acid; 4-[2-benzyloxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3,3- dimethylbutanoylamino)butanoic acid; 2-(3-ethylpentanoylamino)-4-[3-phenoxypropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(3-methylbutanoylamino)-4-[3-phenoxypropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[3-phenoxypropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[2-carboxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- ethylpentanoylamino)butanoic acid; 4-[2-carboxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3,3- dimethylbutanoylamino)butanoic acid; 4-[3-carboxypropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- ethylpentanoylamino)butanoic acid; 4-[3-carboxypropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3,3- dimethylbutanoylamino)butanoic acid; 4-[2-(3,5-dimethoxyphenoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- ethylpentanoylamino)butanoic acid; 2-(3-ethylpentanoylamino)-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl-[2-(3,4,5- trimethoxyphenoxy)ethyl]amino]butanoic acid; 2-(3-methylbutanoylamino)-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl-[2-(3,4,5- trimethoxyphenoxy)ethyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl-[2-(3,4,5- trimethoxyphenoxy)ethyl]amino]butanoic acid;5-[[3-carboxy-3-(3-ethylpentanoylamino)propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]pentanoic acid; 5-[[3-carboxy-3-(3,3-dimethylbutanoylamino)propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]pentanoic acid; 2-(2,2-difluoropentanoylamino)-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(2,2-difluoropentanoylamino)-4-[[2-methoxypropyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[2-(3,5-dimethoxyphenoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- methylbutanoylamino)butanoic acid; 2-[[2-(3,3-difluorocyclopentyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-(3,5-dimethoxyphenoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2- (3,3-dimethylbutanoylamino)butanoic acid; 2-[[2-[3,3-difluorocyclopentyl]acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-[1- (trifluoromethyl)cyclopropyl]acetyl]amino]butanoic acid; 2-[[2-(3-methyloxetan-3-yl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[4-phenylbutyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[4-phenylbutyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[2-(benzenesulfonyl)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3,3- dimethylbutanoylamino)butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[2-(2-methylpyrimidin-4-yl)oxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[2-(2-methylpyrimidin-5-yl)oxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[2-(5-methylpyrazin-2-yl)oxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[2-(6-methylpyridazin-3-yl)oxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[2-(2,5-dimethylpyrazol-3-yl)oxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid;2-(cyclobutanecarbonylamino)-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- methylbutanoylamino)butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[2-(3,5-dimethylpyrazol-1-yl)ethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[[3-fluoro-2-methoxy-propyl]-[4-(5-methyl-5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[[3-fluoro-2-methoxy-propyl]-[4-(6-methyl-5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[[3-fluoro-2-methoxy-propyl]-[4-(7-methyl-5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(2- oxo-1-piperidyl)acetyl]amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-[1- (trifluoromethyl)cyclopropyl]acetyl]amino]butanoic acid; 2-[(1-fluorocyclohexanecarbonyl)amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[1- (trifluoromethyl)cyclopropanecarbonyl]amino]butanoic acid; 2-[(4-methyltetrahydropyran-4-carbonyl)amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-ethoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[4- (trifluoromethyl)tetrahydropyran-4-carbonyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[2-ethoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[4- (trifluoromethyl)tetrahydropyran-4-carbonyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[2-isopropoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-(4-methyltetrahydropyran-4-yl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-tert-butoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3,3- dimethylbutanoylamino)butanoic acid;4-[2-isopropoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[4- (trifluoromethyl)tetrahydropyran-4-carbonyl]amino]butanoic acid; 4-[2-tert-butoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[4- (trifluoromethyl)tetrahydropyran-4-carbonyl]amino]butanoic acid; 4-[2-(cyclopropoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3,3- dimethylbutanoylamino)butanoic acid; 4-[2-(cyclopropoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(4,4,4- trifluoro-3,3-dimethyl-butanoyl)amino]butanoic acid; 4-[2-(cyclopropoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- ethylpentanoylamino)butanoic acid; 4-[2-(cyclopropoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- methylbutanoylamino)butanoic acid; 4-[2-(cyclopropoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(1- methylcyclopropyl)acetyl]amino]butanoic acid; 4-[2-(cyclopropoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(4,4- difluoro-3,3-dimethyl-butanoyl)amino]butanoic acid; 4-[2-ethoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(1- methylcyclopropyl)acetyl]amino]butanoic acid; 4-[2-tert-butoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(1- methylcyclopropyl)acetyl]amino]butanoic acid; 2-[(4,4-difluoro-3,3-dimethyl-butanoyl)amino]-4-[2-ethoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-ethoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(1- methylcyclobutyl)acetyl]amino]butanoic acid; 4-[2-isopropoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(1- methylcyclopropyl)acetyl]amino]butanoic acid; 2-[(4,4-difluoro-3,3-dimethyl-butanoyl)amino]-4-[2-isopropoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-tert-butoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(4,4,4-trifluoro- 3,3-dimethyl-butanoyl)amino]butanoic acid; 4-[2-tert-butoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(4,4-difluoro- 3,3-dimethyl-butanoyl)amino]butanoic acid; 4-[2-(1-methylethoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[3,3,3- tris(fluoranyl)propanoylamino]butanoic acid; 4-[2-isopropoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(4,4,4-trifluoro- 3,3-dimethyl-butanoyl)amino]butanoic acid;4-[2-isopropoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(1- methylcyclobutyl)acetyl]amino]butanoic acid; 4-[2-(1-methylcyclopropoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[4- (trifluoromethyl)tetrahydropyran-4-carbonyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[2-(1-methylcyclopropoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-(cyclobutoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3,3- dimethylbutanoylamino)butanoic acid; 4-[2-ethoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(4,4,4-trifluoro-3,3- dimethyl-butanoyl)amino]butanoic acid; 2-(3,3-dimethylpentanoylamino)-4-[2-ethoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-(3-bicyclo[1.1.1]pentanyl)acetyl]amino]-4-[2-ethoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-ethoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[3- (trifluoromethyl)bicyclo[1.1.1]pentane-1-carbonyl]amino]butanoic acid; 4-[2-(2,2-difluoroethoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3,3- dimethylbutanoylamino)butanoic acid; 4-[2-ethoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(2-isopropyl-3- methyl-butanoyl)amino]butanoic acid; 4-[2-(cyclopentoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3,3- dimethylbutanoylamino)butanoic acid; 2-(3,3-dimethylpentanoylamino)-4-[2-isopropoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[[tetrahydrofuran-2-yl]methyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-(3-bicyclo[1.1.1]pentanyl)acetyl]amino]-4-[2-isopropoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-isopropoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[3- (trifluoromethyl)bicyclo[1.1.1]pentane-1-carbonyl]amino]butanoic acid; 4-[2-tert-butoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3,3- dimethylpentanoylamino)butanoic acid; 2-[[2-(3-bicyclo[1.1.1]pentanyl)acetyl]amino]-4-[2-tert-butoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-tert-butoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[3- (trifluoromethyl)bicyclo[1.1.1]pentane-1-carbonyl]amino]butanoic acid;4-[2-(cyclopropylmethoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3,3- dimethylbutanoylamino)butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl-[2-(2,2,2- trifluoroethoxy)ethyl]amino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[2-propoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[4,4-di(methyl)pentanoylamino]-4-[2-ethoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[4,4-di(methyl)pentanoylamino]-4-[2-(1-methylethoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-(1,1-dimethylethoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[4,4- di(methyl)pentanoylamino]butanoic acid; 4-[2-ethoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[3,3,3- tris(fluoranyl)propanoylamino]butanoic acid; 2-[3,3-bis(fluoranyl)butanoylamino]-4-[2-ethoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[3,3-bis(fluoranyl)butanoylamino]-4-[2-(1-methylethoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-(1,1-dimethylethoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[3,3,3- tris(fluoranyl)propanoylamino]butanoic acid; 2-(3,3-dimethylbutanoylamino)-4-[[2-ethoxy-1-methyl-ethyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[cyclopropyl-[4-[1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl]butyl]amino]-2-(2- ethylbutanoylamino)butanoic acid; 4-[cyclopropyl-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutyl]amino]-2-(2- ethylbutanoylamino)butanoic acid; 2-(2-ethylbutanoylamino)-4-[2-methoxyethyl-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl]cyclobutyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[2-methoxyethyl-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl]cyclobutyl]amino]butanoic acid; 4-[2-tert-butoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(1- methylcyclobutyl)acetyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[1-(3- pyridylmethyl)pyrrolidine-2-carbonyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[1-(pyrazin-2- ylmethyl)pyrrolidine-2-carbonyl]amino]butanoic acid;4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[1-(pyrimidin-2- ylmethyl)pyrrolidine-2-carbonyl]amino]butanoic acid; 2-[[1-benzylpyrrolidine-2-carbonyl]amino]-4-[isopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[1-benzylpyrrolidine-2-carbonyl]amino]-4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)butyl]amino]butanoic acid; 2-[[2-(2,4-difluorophenoxy)acetyl]amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-(3-ethylpentanoylamino)-4-[methyl-[2-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl]cyclopropyl]amino]butanoic acid; 2-(2-ethylbutanoylamino)-4-[methyl-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethyl]cyclobutyl]amino]butanoic acid; 4-((2-(tert-butoxy)ethyl)(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)amino)-2-(2-(1- methylcyclobutyl)acetamido)butanoic acid; and 4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[1-(2- pyridylmethyl)cyclopropanecarbonyl]amino]butanoic acid, or a pharmaceutically acceptable salt thereof.

[0298] In one aspect, provided is a compound is selected from the group consisting of the compounds of Examples B1-B309, or a pharmaceutically acceptable salt thereof.

[0299] In one embodiment, provided is a compound selected from the group consisting of the compounds in Table C1: Table C1 2-[3-(4-fluorophenyl)propanoylamino]-4-[2-methoxyethyl-[[1-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)ethyl]cyclopropyl]methyl]amino]butanoic acid; 2-[[2-(2-chloro-3-fluoro-phenyl)acetyl]amino]-4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)butyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-[3-fluoro-5- (trifluoromethyl)phenyl]acetyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2- phenylpropanoyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[3-(4- fluorophenyl)propanoylamino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(2- phenylcyclopropanecarbonyl)amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- phenylpentanoylamino)butanoic acid;4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[3-hydroxy-2-phenyl- propanoyl]amino]butanoic acid; 2-[(3-hydroxy-2-phenyl-propanoyl)amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)butyl]amino]butanoic acid; 2-[(2,2-difluoro-2-phenyl-acetyl)amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(4-fluorophenyl)-3- hydroxy-propanoyl]amino]butanoic acid; 2-[(3-cyano-2-phenyl-propanoyl)amino]-4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-hydroxy-2-phenyl- acetyl]amino]butanoic acid; 2-[[2-hydroxy-2-phenyl-acetyl]amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[3-hydroxy-2-methyl-2- phenyl-propanoyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(4-fluorophenyl)-2- hydroxy-acetyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(2-methyl-2-phenyl- propanoyl)amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(1- phenylcyclopropanecarbonyl)amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(1- phenylcyclobutanecarbonyl)amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(2,2-dimethyl-3-phenyl- propanoyl)amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(4-fluorophenyl)-2- methyl-propanoyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(indane-2- carbonylamino)butanoic acid; 2-[(2,2-dimethyl-3-phenyl-propanoyl)amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-(4-fluorophenyl)-2-methyl-propanoyl]amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[3,3-difluoropropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-hydroxy-2- phenyl-acetyl]amino]butanoic acid;4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(3-phenyloxetane-3- carbonyl)amino]butanoic acid; 4-[(2,2-difluoro-3-methoxy-propyl)-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2- hydroxy-2-phenyl-acetyl]amino]butanoic acid; 2-[[2-(2-chlorophenyl)-2-hydroxy-acetyl]amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-(2-fluorophenyl)-2-hydroxy-acetyl]amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-methoxy-2-phenyl- acetyl]amino]butanoic acid; 4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(3-phenyloxetane-3- carbonyl)amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(3-hydroxy-1-phenyl- cyclobutanecarbonyl)amino]butanoic acid; 2-[[2-hydroxy-2-phenyl-propanoyl]amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)butyl]amino]butanoic acid; 2-[[indane-1-carbonyl]amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[cyclopropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[indane-1- carbonyl]amino]butanoic acid; 2-[(2-fluoro-2-phenyl-acetyl)amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2,2-difluoro-2-(4-fluorophenyl)acetyl]amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-(2,4-difluorophenyl)-2-methyl-propanoyl]amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-hydroxy-2-phenyl-propanoyl]amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)butyl]amino]butanoic acid; 2-[[2-(3,5-difluorophenyl)-2-methyl-propanoyl]amino]-4-[2-methoxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[3,3-difluoropropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-hydroxy-2- phenyl-propanoyl]amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2- hydroxy-2-phenyl-propanoyl]amino]butanoic acid; 4-[[3,3-difluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2- hydroxy-2-phenyl-propanoyl]amino]butanoic acid;4-[[2-fluoro-3-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2- hydroxy-2-phenyl-propanoyl]amino]butanoic acid; 4-[3-fluoropropyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-hydroxy-2-phenyl- propanoyl]amino]butanoic acid; 2-[(2,2-dimethyl-3-phenyl-propanoyl)amino]-4-[[2-fluoro-3-methoxy-propyl]-[4-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[[2-fluoro-3-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(4- fluorophenyl)-2-methyl-propanoyl]amino]butanoic acid; 4-[[2-fluoro-3-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[indane- 1-carbonyl]amino]butanoic acid; 4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(2- phenylacetyl)amino]butanoic acid; 2-[[2-(4-chlorophenyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-(2-chlorophenyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[(2,2-difluoro-2-phenyl-acetyl)amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-methoxy-2-phenyl-acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-(2-methoxyphenyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-(3-methoxyphenyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-(4-methoxyphenyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-hydroxy-2-phenyl-acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-(3-chlorophenyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[(2-fluoro-2-phenyl-acetyl)amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2- phenylpropanoyl]amino]butanoic acid; 2-[(2-methyl-2-phenyl-propanoyl)amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)butyl]amino]butanoic acid;4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(1- phenylcyclopropanecarbonyl)amino]butanoic acid; 2-[[2-(o-tolyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-(m-tolyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(p- tolyl)acetyl]amino]butanoic acid; 2-[[2-(2-fluorophenyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-(3-fluorophenyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-(4-fluorophenyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-(2-cyanophenyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-(3-cyanophenyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 2-[[2-(4-cyanophenyl)acetyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)butyl]amino]butanoic acid; 4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(3-phenyloxetane-3- carbonyl)amino]butanoic acid; 4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[3,3,3-trifluoro-2- methoxy-2-phenyl-propanoyl]amino]butanoic acid; 4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-(3- phenylpropanoylamino)butanoic acid; 2-[[2-hydroxy-2-phenyl-propanoyl]amino]-4-[2-phenoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin- 2-yl)butyl]amino]butanoic acid; 2-[[2-(2-fluorophenyl)acetyl]amino]-4-[2-(5-fluoropyrimidin-2-yl)oxyethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-(5-fluoropyrimidin-2-yl)oxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2- [[2-(2-methoxyphenyl)acetyl]amino]butanoic acid; 4-[2-(5-fluoropyrimidin-2-yl)oxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2- [[2-phenylpropanoyl]amino]butanoic acid; 2-[[2-(2-methoxyphenyl)acetyl]amino]-4-[2-(2-oxo-1-pyridyl)ethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid;2-[[2-(2-fluorophenyl)acetyl]amino]-4-[2-(2-oxo-1-pyridyl)ethyl-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-(2-oxo-1-pyridyl)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2- phenylpropanoyl]amino]butanoic acid; 4-[2-(benzenesulfonyl)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(2- phenylacetyl)amino]butanoic acid; 4-[2-(2-methylpyrimidin-4-yl)oxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2- [(2-phenylacetyl)amino]butanoic acid; 4-[2-(2-methylpyrimidin-5-yl)oxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2- [(2-phenylacetyl)amino]butanoic acid; 4-[2-(5-methylpyrazin-2-yl)oxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(2- phenylacetyl)amino]butanoic acid; 4-[2-(6-methylpyridazin-3-yl)oxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2- [(2-phenylacetyl)amino]butanoic acid; 4-[2-(2,5-dimethylpyrazol-3-yl)oxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2- [(2-phenylacetyl)amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(2- phenylacetyl)amino]butanoic acid; 2-[[2-(2-chlorophenyl)acetyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-(3-chlorophenyl)acetyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-(3-cyanophenyl)acetyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(3- phenyloxetane-3-carbonyl)amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2- phenylpropanoyl]amino]butanoic acid; 2-[(2,2-difluoro-2-phenyl-acetyl)amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2-(2- fluorophenyl)acetyl]amino]butanoic acid; 2-[2-(2,6-difluorophenyl)propanoylamino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-(3,5-difluoro-2-methoxy-phenyl)acetyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid;2-[[2-(2,5-difluorophenyl)acetyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2- methoxy-2-phenyl-acetyl]amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2- (isochromane-1-carbonylamino)butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(2- methyl-2-phenyl-propanoyl)amino]butanoic acid; 2-[[2-(2-cyanophenyl)acetyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-(3,5-dimethylpyrazol-1-yl)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2- phenylpropanoyl]amino]butanoic acid; 2-[[2-(2-fluoro-6-methoxy-phenyl)acetyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-(2-chloro-6-methoxy-phenyl)acetyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-(2-fluoro-6-methoxy-phenyl)propanoyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-(2-chloro-6-methoxy-phenyl)propanoyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-(2-cyano-6-methoxy-phenyl)acetyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-(2-cyano-6-fluoro-phenyl)acetyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-(2-cyano-6-methoxy-phenyl)propanoyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[1-(2-chloro-6-methoxy-phenyl)cyclopropanecarbonyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-(2-chloro-6-methoxy-phenyl)-2-methyl-propanoyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-(2,4-difluoro-6-methoxy-phenyl)-2-methyl-propanoyl]amino]-4-[[3-fluoro-2-methoxy-propyl]- [4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[2-(5-fluoro-2-methoxy-phenyl)-2-methyl-propanoyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[4- methylisochromane-4-carbonyl]amino]butanoic acid;2-[[1-(2,4-difluoro-6-methoxy-phenyl)cyclopropanecarbonyl]amino]-4-[[3-fluoro-2-methoxy-propyl]- [4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[(1- phenylcyclopropanecarbonyl)amino]butanoic acid; 2-[[1-(2-cyanophenyl)cyclopropanecarbonyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[1-(2-cyano-6-fluoro-phenyl)cyclopropanecarbonyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[1-(3-cyanophenyl)cyclopropanecarbonyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[1-(2-cyano-6-methoxy-phenyl)cyclopropanecarbonyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[1-(2-chloro-6-cyano-phenyl)cyclopropanecarbonyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[1-(2-cyano-4-fluoro-phenyl)cyclopropanecarbonyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[[3-fluoro-2-methoxy-propyl]-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[1-(2- methylsulfonylphenyl)cyclopropanecarbonyl]amino]butanoic acid; 2-[[1-(5-cyano-2-fluoro-phenyl)cyclopropanecarbonyl]amino]-4-[[3-fluoro-2-methoxy-propyl]-[4- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 2-[[1-(2-chloro-6-methoxy-phenyl)cyclopropanecarbonyl]amino]-4-[2-ethoxyethyl-[4-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-ethoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2- phenylpropanoyl]amino]butanoic acid; 2-[[1-(2-chloro-6-methoxy-phenyl)cyclopropanecarbonyl]amino]-4-[2-isopropoxyethyl-[4-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]butanoic acid; 4-[2-tert-butoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2- phenylpropanoyl]amino]butanoic acid; 4-[2-isopropoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[2- phenylpropanoyl]amino]butanoic acid; 4-[2-tert-butoxyethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]-2-[[1-(2-chloro-6- methoxy-phenyl)cyclopropanecarbonyl]amino]butanoic acid; 4-[2-(cyclopropoxy)ethyl-[4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl]amino]...

Claims

CLAIMS What is claimed is:

1. A compound of formula (I): 2 H R N L1L2L3X Y R1(I), or a pharmaceutical R1is 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl optionally substituted by one or more R4, 1,2,3,4- tetrahydro-1,8-naphthyridin-2-yl optionally substituted by one or more R4, 6-aminopyridin-2-yl optionally substituted by one or more R4, or (pyridin-2-yl)amino optionally substituted by one or more R4; Q is H or C1-C6alkyl; R2is: (i) RB2, wherein: RB2is C1-C6alkyl optionally substituted by one or more RB2a, C3-C8cycloalkyl optionally substituted by one or more RB2b, 3- to 12-membered saturated heterocyclyl optionally substituted by one or more RB2c, wherein a carbon atom of the 3- to 12- membered saturated heterocyclyl is bonded to the –C(O), or C2-C6alkenyl optionally substituted by one or more RB2d; wherein each RB2a, RB2b, RB2c, and RB2dis, where possible, independently oxo, deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3- C8cycloalkyl, 3- to 12-membered saturated heterocyclyl, -CN, -OR5, -SR5, -NR6R7, -NO2, -C=NH(OR5), -C(O)R5, -OC(O)R5, -C(O)OR5, -C(O)NR6R7, -NR5C(O)R6, -NR5C(O)OR6, -NR5C(O)NR6R7, -S(O)R5, -S(O)2R5, -NR5S(O)R6, -NR5S(O)2R6, -S(O)NR6R7, -S(O)2NR6R7, or -P(O)(OR5)(OR6), wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, 3- to 12-membered saturated heterocyclyl of RB2a, RB2b, RB2c, and RB2dare independently optionally substituted by one or more R4a; (ii) RC2, wherein: RC2is C6-C12aryl optionally substituted by one or more RC2a, 5- to 12-membered heteroaryl optionally substituted by one or more RC2b, C3-C10cycloalkenyl optionally substituted by one or more RC2c, 3- to 12-membered partially unsaturated heterocyclyl optionally substituted by one or more RC2d, C1-C6alkyl substituted by one or more RC2e,C2-C6alkenyl substituted by one or more RC2f, C3-C8cycloalkyl substituted by one or more RC2g, or 3- to 12-membered fully saturated heterocyclyl substituted by one or more RC2h; wherein at least one RC2egroup, when present, is 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl, wherein the 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of RC2eare independently optionally substituted by one or more R4a; and each of the other RC2egroups, when present, is independently R4; at least one RC2fgroup, when present, is 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl, wherein the 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of RC2fare independently optionally substituted by one or more R4a; and each of the other RC2fgroups, when present, is independently R4; at least one RC2ggroup, when present, is 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl, wherein the 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of RC2gare independently optionally substituted by one or more R4a; and each of the other RC2ggroups, when present, is independently R4; at least one RC2hgroup, when present, is 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl, wherein the 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of RC2hare independently optionally substituted by one or more R4a; and each of the other RC2hgroups, when present, is independently oxo or R4; and each RC2a, RC2b, RC2c, and RC2dis, where possible, independently oxo or R4; (iii) RD2, wherein RD2is -NRD3(C1-C6alkyl), -NRD3(C3-C8cycloalkyl), -NRD3(3- to 12-membered saturated heterocyclyl) such that a carbon atom of the 3- to 12-membered saturated heterocyclyl of -NRD3(3- to 12-membered saturated heterocyclyl) is bonded to the N of - NRD3, or 3- to 12-membered N-containing saturated heterocyclyl such that a nitrogen atom of the 3- to 12-membered N-containing saturated heterocyclyl is bonded to thecarbon of -C(O)-, or 5- to 10-membered heteroaryl such that a nitrogen atom of the 5- to 10-membered heteroaryl is bonded to the carbon of -C(O)-, wherein the C1-C6alkyl of the -NRD3(C1-C6alkyl) of RD2is optionally substituted by one or more RD2a, the C3-C8cycloalkyl of the - NRD3(C3-C8cycloalkyl) of RD2is optionally substituted by one or more RD2b, the 3- to 12-membered saturated heterocyclyl of the -NRD3(3- to 12-membered saturated heterocyclyl) of RD2is optionally substituted by one or more RD2c, the 3- to 12-membered N-containing saturated heterocyclyl of RD2is optionally substituted by one or more RD2d, and the 5- to 10-membered heteroaryl is optionally substituted by one or more RD2e; RD3is H, deuterium, C1-C6alkyl, C3-C8cycloalkyl, or 3- to 12-membered saturated heterocyclyl, wherein the C1-C6alkyl of RD3is optionally substituted by one or more RD3a, the C3-C8cycloalkyl of RD3is optionally substituted by one or more RD3b, and the 3- to 12-membered saturated heterocyclyl of RD3is optionally substituted by one or more RD3c; and each RD2a, RD2b, RD2c, RD2d, RD2e, RD3a, RD3b, and RD3cis, where possible, independently oxo or R4, or (iv) RE2, wherein RE2is -O(C1-C6alkyl), -O(C3-C8cycloalkyl), -O(3- to 12-membered saturated heterocyclyl) such that a carbon atom of the 3- to 12-membered saturated heterocyclyl of -O(3- to 12-membered saturated heterocyclyl) is bonded to the -OC(O)-, -O(5- to 10- membered aryl) such that a carbon atom of the 5- to 10-membered aryl of -O(C6-C14aryl) is bonded to the -OC(O)-, or -O(5- to 10-membered heteroaryl) such that a carbon atom of the 5- to 10-membered heteroaryl of -O(5- to 10-membered heteroaryl) is bonded to the -OC(O)-, wherein the C1-C6alkyl of -O(C1-C6alkyl) of RE2is optionally substituted by one or more RE2a, the C3-C8cycloalkyl -O(C3-C8cycloalkyl) of RE2is optionally substituted by one or more RE2b, the 3- to 12-membered saturated heterocyclyl of -O(3- to 12-membered saturated heterocyclyl) of RE2is optionally substituted by one or more RE2c, the 5- to 10-membered heteroaryl of -O(C6-C14aryl) of RE2is optionally substituted by one or more RE2d, the 5- to 10-membered heteroaryl of -O(5- to 10-membered heteroaryl) of RE2eis optionally substituted by one or more RE2e; andeach RE2a, RE2b, RE2c, RE2d, and RE2eis, where possible, independently oxo or R4; L1is C2-C4alkylene optionally substituted by one or more by R4; L2is a bond or C1-C6alkylene optionally substituted by one or more R4; L3is C2-C4alkylene optionally substituted by one or more R4; Y is a bond or C3-C5cycloalkylene optionally substituted by one or more Ya; X is -N(Rx)-; Rxis unsubstituted C3-C8alkyl, C1-C8alkyl substituted by one or more Rxa, C3-C6cycloalkyl optionally substituted by one or more Rxb, 3- to 12-membered heterocyclyl optionally substituted by one or more Rxc, C6-C14aryl optionally substituted by one or more Rxd, 5- to 10-membered heteroaryl optionally substituted by one or more Rxe, or -S(O)2Rxf; each Rxais independently halogen, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, 3- to 12- membered heterocyclyl, C6-C14aryl, 5- to 10-membered heteroaryl, oxo, -CN, -OR5, -SR5, -NR6R7, -NO2, -N3, -C=NH(OR5), -C(O)R5, -OC(O)R5, -C(O)OR5, -C(O)NR6R7, -NR5C(O)R6, -NR5C(O)OR6, -NR5C(O)NR6R7, -S(O)R5, -S(O)2R5, -NR5S(O)R6, -NR5S(O)2R6, -S(O)NR6R7, -S(O)2NR6R7, or -P(O)(OR5)(OR6), wherein the C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of Rxaare independently optionally substituted by one or more R4a; Rxfis C1-C6alkyl optionally substituted by one or more Rxgor C3-C5cycloalkyl optionally substituted by one or more Rxh; each Rxb, Rxc, Rxd, Rxe, Rxg, Rxh, and Yais independently oxo or R4; each R4is independently deuterium, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3- C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, 5- to 10-membered heteroaryl, -CN, -OR5, -SR5, -NR6R7, -NO2, -N3, -C=NH(OR5), -C(O)R5, -OC(O)R5, -C(O)OR5, -C(O)NR6R7, -NR5C(O)R6, -NR5C(O)OR6, -NR5C(O)NR6R7, -S(O)R5, -S(O)2R5, -S(O)2OH, -NR5S(O)R6, -NR5S(O)2R6, -S(O)NR6R7, -S(O)2NR6R7, or -P(O)(OR5)(OR6), wherein the C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3- C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of R4are independently optionally substituted by one or more R4a; each R4ais independently deuterium, halogen, oxo, -OR8, -NR8R9, -C(O)R8, -C(O)OR8, -NR8C(O)OR10, -CN, -S(O)R8, -S(O)2R8, -P(O)(OR8)(OR9), C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, 5- to 10-membered heteroaryl, C6-C14aryl, or C1-C6alkyl, wherein the 3- to 12-membered heterocyclyl, 5- to 10-membered heteroaryl, C6-C14aryl, and C1-C6alkyl of R4aare independently optionally substituted by one or more R4b;each R4bis independently deuterium, oxo, -OH, -O-C1-C6alkyl, -O(2H), halogen, or C1-C6alkyl optionally substituted by one or more deuterium, halogen, -OH, -O(2H), or oxo; each R5is independently hydrogen, deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C14aryl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocyclyl, wherein the C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C14aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocyclyl of R5are each independently optionally substituted by one or more R5a; each R5ais independently halogen, deuterium, oxo, -CN, -OR10, -NR11R12, -P(O)(OR11)(OR12), C3-C6cycloalkyl, 3- to 12-membered heterocyclyl, or C1-C6alkyl optionally substituted by one or more deuterium, halogen, -OH, -O(2H), or oxo; each R6is independently hydrogen, deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C14aryl, 5- to 10-membered heteroaryl, or 3- to 6-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C14aryl, 5- to 10-membered heteroaryl, and 3- to 6-membered heterocyclyl of R6are independently optionally substituted by one or more deuterium, halogen, oxo, -CN, -OR10, -NR11R12, or C1-C6alkyl optionally substituted by one or more deuterium, halogen, -OH, -O(2H), or oxo; each R7is independently hydrogen, deuterium, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C14aryl, 5- to 10-membered heteroaryl, or 3- to 6-membered heterocyclyl, wherein the C1- C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C6-C14aryl, 5- to 10-membered heteroaryl, and 3- to 6-membered heterocyclyl of R7are independently optionally substituted by one or more deuterium, halogen, oxo, -CN, -OR10, -NR11R12, or C1-C6alkyl optionally substituted by one or more deuterium, halogen, -OH, -O(2H), or oxo; or R6and R7are taken together with the atom to which they are attached to form a 3- to 10- membered heterocyclyl optionally substituted by one or more deuterium, halogen, oxo, -OR10, -NR11R12, or C1-C6alkyl optionally substituted by one or more deuterium, halogen, oxo, -OH, or -O(2H); each R8, R9, and R10is independently hydrogen, deuterium, C1-C6alkyl, C2-C6alkenyl, or C2- C6alkynyl, wherein the C1-C6alkyl, C2-C6alkenyl and C2-C6alkynyl are optionally substituted by one or more deuterium, halogen, or oxo; and each R11and R12is independently hydrogen, deuterium, C1-C6alkyl, C2-C6alkenyl, or C2- C6alkynyl, wherein the C1-C6alkyl, C2-C6alkenyl and C2-C6alkynyl are optionally substituted by one or more deuterium, halogen, or oxo; or R11and R12are taken together with the atom to which they are attached to form a 3-6 membered heterocyclyl optionally substituted by one or more deuterium, halogen, oxo, or C1-C6alkyl optionally substituted by one or more deuterium, oxo, or halogen.

2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein -L1-X-L2-Y-L3- are taken together to form a moiety selected from the group consisting ofe are each independently optionally substituted by one or more R4;ed by one or more R4, A the C0-C3n-alkylene is optionally substituted by one or more R4, the moiety is a C3-C5cycloalkylene optionally substituted by one or more Ya, and the C2-C4n-alkylene to the right of the A moiety is optionally substituted by one or more R4; andtituted by one or more R4, A the C0-C3n-alkylene is optionally substituted by one or more R4, the moiety is a C3-C5cycloalkylene A optionally substituted by one or more Ya, and the C2-C4n-alkylene to the right of the moiety is optionally substituted by one or more R4.

3. The compound of claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, wherein -L1- X-L2-Y-L3- are taken together to form a moiety selected from the group consisting ofx4. The compound of any one of claims 1-3, or a pharmaceutically acceptable salt thereof, wherein - L1-X-L2-Y-L3- are taken together to form a moiety with the formula5. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt thereof, wherein Rxis unsubstituted C3-C8alkyl or C1-C8alkyl substituted by 1-5 Rxagroups.

6. The compound of claim 5, or a pharmaceutically acceptable salt thereof, wherein Rxis C1-C6alkyl substituted by 1-5 Rxagroups, wherein each Rxais independently selected from halogen, C3- C8cycloalkyl, 3- to 12-membered heterocyclyl, C6-C14aryl, 5- to 10-membered heteroaryl, -CN, -OR5, -C(O)OR5, and -S(O)2R5; wherein the C3-C8cycloalkyl, 3- to 12-membered heterocyclyl, C6- C14aryl, and 5- to 10-membered heteroaryl of Rxaare independently optionally substituted by one or more R4a.

7. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt thereof, wherein Rxis C3-C6cycloalkyl optionally substituted by 1-5 Rxbgroups.

8. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt thereof, wherein Rxis 5- to 10-membered heteroaryl optionally substituted by 1-5 Rxegroups.

9. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt thereof, wherein Rxis 5- to 10-membered heteroaryl optionally substituted by 1-5 Rxegroups.

10. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt thereof, wherein Rxis -S(O)2Rxf, and wherein Rxfis unsubstituted C1-C6alkyl.

11. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt thereof, wherein , ,12. The compound of any one of claims 1-11, or a pharmaceutically acceptable salt thereof, wherein H H H N NN N N NR1is selected from the group consisting o , H NN HN N N N .

13. The compound of any one of claims 1-12, or a pharmaceutically acceptable salt thereof, wherein Q is H.

14. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of O R2O R2O , , , ,15. The compound of any one of claims 1-14, or a pharmaceutically acceptable salt thereof, wherein R2is RB2.

16. The compound of claim 15, or a pharmaceutically acceptable salt thereof, wherein RB2is C1-C6alkyl substituted by 1-5 RB2agroups, wherein each RB2ais independently selected from the group consisting of halogen, C1-C6alkyl, C3-C8cycloalkyl, 3- to 12-membered saturated heterocyclyl, -CN, -OR5, -NR6R7, and-NR5C(O)OR6; wherein the C1-C6alkyl, C3-C8cycloalkyl, and 3- to 12-membered saturated heterocyclyl of RB2aare independently optionally substituted by one or more R4a.

17. The compound of claim 15, or a pharmaceutically acceptable salt thereof, wherein RB2is C3-C8cycloalkyl substituted by 1-5 RB2bgroups, wherein each RB2bis independently selected from the group consisting of halogen and C1-C6alkyl; wherein the C1-C6alkyl of RB2bare optionally substituted by 1-5 R4agroups.

18. The compound of claim 15, or a pharmaceutically acceptable salt thereof, wherein RB2is 3- to 12- membered saturated heterocyclyl optionally substituted by 1-5 RB2cgroups, such that the atom of the 3- to 12-membered saturated heterocyclyl that is bonded to the –C(O) is a carbon.

19. The compound of claim 15, or a pharmaceutically acceptable salt thereof, wherein RB2is selected from the group consisting o, ,20. The compound of any one of claims 1-14, or a pharmaceutically acceptable salt thereof, wherein R2is RC2.

21. The compound of claim 20, or a pharmaceutically acceptable salt thereof, wherein RC2is C1-C5alkyl substituted by 1-5 RC2egroups, wherein at least one RC2egroup is 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, or 5- to 10-membered heteroaryl; and each of the other RC2egroups, when present, is independently selected from the group consisting of halogen, C1-C6alkyl, -CN, and -OR5; and wherein the 3- to 12-membered partially unsaturated heterocyclyl, C6-C14aryl, 5- to 10- membered heteroaryl, and C1-C6alkyl of RC2eare independently optionally substituted by one or more R4a.

22. The compound of claim 20, or a pharmaceutically acceptable salt thereof, wherein RC2is C3-C8cycloalkyl substituted by 1-5 RC2ggroups, wherein at least one RC2ggroup is selected from the group consisting of C6-C14aryl, 5- to 10-membered heteroaryl, and 3- to 10 membered partially unsaturated heterocyclyl; and each of the other RC2ggroups, when present, is independently -OR5; and wherein the 3- to 10-membered partially unsaturated heterocyclyl, C6-C14aryl, and 5- to 10-membered heteroaryl of RC2gare optionally substituted by 1-5 R4agroups.

23. The compound of claim 20, or a pharmaceutically acceptable salt thereof, wherein RC2is 3- to 12- membered partially unsaturated heterocyclyl substituted by 1-5 RC2dgroups, such that the atom of the 3-to 12-membered partially unsaturated heterocyclyl that is bonded to the –C(O) is a carbon; and wherein each RC2dis independently selected from the group consisting of oxo and C1-C6alkyl.

24. The compound of claim 20, or a pharmaceutically acceptable salt thereof, wherein RC2is C6-C12aryl optionally substituted by 1-5 RC2agroups.

25. The compound of claim 20, or a pharmaceutically acceptable salt thereof, wherein RC2is 5- to 12- membered heteroaryl optionally substituted by 1-5 RC2bgroups.

26. The compound of claim 20, or a pharmaceutically acceptable salt thereof, wherein RC2is selected FCl CNĊ ,,27. The compound of any one of claims 1-14, or a pharmaceutically acceptable salt thereof, wherein R2is RD2.

28. The compound of claim 27, or a pharmaceutically acceptable salt thereof, wherein RD2is - NRD3(C1-C6alkyl) wherein the C1-C6alkyl is substituted by 1-5 RD2agroups, wherein each RD2ais independently selected from the group consisting of halogen, C1-C6alkyl, C3-C8cycloalkyl, 3- to 12- membered saturated heterocyclyl, -CN, -OR5, -NR6R7, and-NR5C(O)OR6; wherein the C1-C6alkyl, C3- C8cycloalkyl, and 3- to 12-membered saturated heterocyclyl of RD2aare independently optionally substituted by one or more R4a.

29. The compound of claim 27, or a pharmaceutically acceptable salt thereof, wherein RD2is - NRD3(C3-C8cycloalkyl) wherein the C3-C8cycloalkyl of -NRD3(C3-C8cycloalkyl) is substituted by 0-5 RD2bgroups.

30. The compound of claim 27, or a pharmaceutically acceptable salt thereof, wherein RD2is - NRD3(3- to 12-membered heterocyclyl) such that a carbon atom of the 3- to 12-membered saturated heterocyclyl is bonded to the N of -NRD3, wherein the 3- to 12-membered heterocyclyl is substituted by 0- 5 RD2cgroups.

31. The compound of claim 27, or a pharmaceutically acceptable salt thereof, wherein RD2is 3- to 12- membered N-containing saturated or partially saturated heterocyclyl substituted by 0-5 RD2dgroups, such that a nitrogen atom of the 3- to 12-membered N-containing saturated or partially saturated heterocyclyl is bonded to the carbon of -C(O)-.

32. The compound of claim 27, or a pharmaceutically acceptable salt thereof, wherein RD2is selected from the group consisting o ,, nd33. The compound of any one of claims 114, or a pharmaceutically acceptable salt thereof, wherein R2is RE2.

34. The compound of claim 33, or a pharmaceutically acceptable salt thereof, wherein RE2is - O(C1-C6alkyl) wherein the C1-C6alkyl is substituted by 1-5 RE2agroups, wherein each RE2ais independently selected from the group consisting of halogen, C1-C6alkyl, C3-C8cycloalkyl, 3- to 12- membered saturated heterocyclyl, -CN, -OR5, -NR6R7, and-NR5C(O)OR6; wherein the C1-C6alkyl, C3- C8cycloalkyl, and 3- to 12-membered saturated heterocyclyl of RE2aare independently optionally substituted by one or more R4a.

35. The compound of claim 33, or a pharmaceutically acceptable salt thereof, wherein RE2is - O(C3-C8cycloalkyl) wherein the C3-C8cycloalkyl of -O(C3-C8cycloalkyl) is substituted by 0-5 RE2bgroups.

36. The compound of claim 33, or a pharmaceutically acceptable salt thereof, wherein RE2is -O(3- to 12-membered heterocyclyl) such that a carbon atom of the 3- to 12-membered saturated heterocyclyl is bonded to the N of -O, wherein the 3- to 12-membered heterocyclyl is substituted by 0-5 RE2cgroups.

37. The compound of claim 33, or a pharmaceutically acceptable salt thereof, wherein RE2is - O(C6-C14aryl) wherein the C6-C14aryl is substituted by 0-5 RE2dgroups.

38. The compound of claim 33, or a pharmaceutically acceptable salt thereof, wherein RE2is -O(5- to 10-membered heteroaryl), wherein the 5- to 10-membered heteroaryl is substituted by 0-5 RE2egroups.

39. The compound of claim 33, or a pharmaceutically acceptable salt thereof, wherein RE2is selected40. A compound selected from the group consisting of the compounds of Table B1, Table C1, Table D1, and Table E1, or a pharmaceutically acceptable salt of any of the foregoing.

41. A compound selected from the group consisting of the compounds of Examples B1-B309, Examples C1-C641, Examples D1-D178, and Example E1-E146, or a pharmaceutically acceptable salt of any of the foregoing.

42. A pharmaceutical composition comprising a compound of any one of claims 1-41, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable carrier or excipient.

43. A method of inhibiting TGFβ activation in a cell, comprising contacting the cell with a compound of any one of claims 1-41, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 42.

44. A method of treating a fibrotic disease in an individual in need thereof comprising administering a compound of any one of claims 1-41, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 42.

45. The method of claim 44, wherein the fibrotic disease is pulmonary fibrosis, liver fibrosis, skin fibrosis, scleroderma, cardiac fibrosis, renal fibrosis, gastrointestinal fibrosis, primary sclerosing cholangitis, or biliary fibrosis.

46. A method of treating cancer in a subject in need thereof, comprising administering to the subject a compound of any one of claims 1-41, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 42.

47. The method of claim 46, further comprising administering to the individual a checkpoint inhibitor.

48. The method of claim 47, wherein the checkpoint inhibitor inhibits PD-1, PD-L1, or CTLA-4.

49. The method of claim 47, wherein the checkpoint inhibitor is selected from the group consisting of pembrolizumab, nivolumab, cemiplimab, spartalizumab, camrelizumab, sintilimab, tislelizumab, toripalimab, dostarlimab, INCMGA00012, AMP-224, AMP-514, atezolizumab, avelumab, durvalumab, KN035, CK-301, AUNP12, CA-170, BMS-986189, ipilimumab, and tremelimumab.

50. The method of any one of claims 46-49, wherein the individual has head and neck squamous cell carcinoma, squamous cell lung cancer, cutaneous squamous cell carcinoma (CSCC), prostate carcinoma, pancreatic cancer, or breast cancer.

51. The method of any one of claims 46-49, wherein the individual has breast cancer.

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